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Sample records for pin1 determines parathyroid

  1. Complete determination of the Pin1 catalytic domain thermodynamic cycle by NMR lineshape analysis.

    Science.gov (United States)

    Greenwood, Alexander I; Rogals, Monique J; De, Soumya; Lu, Kun Ping; Kovrigin, Evgenii L; Nicholson, Linda K

    2011-09-01

    The phosphorylation-specific peptidyl-prolyl isomerase Pin1 catalyzes the isomerization of the peptide bond preceding a proline residue between cis and trans isomers. To best understand the mechanisms of Pin1 regulation, rigorous enzymatic assays of isomerization are required. However, most measures of isomerase activity require significant constraints on substrate sequence and only yield rate constants for the cis isomer, [Formula: see text] and apparent Michaelis constants, [Formula: see text]. By contrast, NMR lineshape analysis is a powerful tool for determining microscopic rates and populations of each state in a complex binding scheme. The isolated catalytic domain of Pin1 was employed as a first step towards elucidating the reaction scheme of the full-length enzyme. A 24-residue phosphopeptide derived from the amyloid precurser protein intracellular domain (AICD) phosphorylated at Thr668 served as a biologically-relevant Pin1 substrate. Specific (13)C labeling at the Pin1-targeted proline residue provided multiple reporters sensitive to individual isomer binding and on-enzyme catalysis. We have performed titration experiments and employed lineshape analysis of phosphopeptide (13)C-(1)H constant time HSQC spectra to determine [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] for the catalytic domain of Pin1 acting on this AICD substrate. The on-enzyme equilibrium value of [E·trans]/[E·cis] = 3.9 suggests that the catalytic domain of Pin1 is optimized to operate on this substrate near equilibrium in the cellular context. This highlights the power of lineshape analysis for determining the microscopic parameters of enzyme catalysis, and demonstrates the feasibility of future studies of Pin1-PPIase mutants to gain insights on the catalytic mechanism of this important enzyme.

  2. Complete determination of the Pin1 catalytic domain thermodynamic cycle by NMR lineshape analysis

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, Alexander I.; Rogals, Monique J.; De, Soumya [Cornell University, Department of Molecular Biology and Genetics (United States); Lu, Kun Ping [Cancer Biology Program and Biology of Aging Program, Beth Israel Deaconess Medical Center, Harvard Medical School (United States); Kovrigin, Evgenii L. [Marquette University, Chemistry Department (United States); Nicholson, Linda K., E-mail: lkn2@cornell.edu [Cornell University, Department of Molecular Biology and Genetics (United States)

    2011-09-15

    The phosphorylation-specific peptidyl-prolyl isomerase Pin1 catalyzes the isomerization of the peptide bond preceding a proline residue between cis and trans isomers. To best understand the mechanisms of Pin1 regulation, rigorous enzymatic assays of isomerization are required. However, most measures of isomerase activity require significant constraints on substrate sequence and only yield rate constants for the cis isomer, k{sub cat}{sup cis} and apparent Michaelis constants, K{sub M}{sup App}. By contrast, NMR lineshape analysis is a powerful tool for determining microscopic rates and populations of each state in a complex binding scheme. The isolated catalytic domain of Pin1 was employed as a first step towards elucidating the reaction scheme of the full-length enzyme. A 24-residue phosphopeptide derived from the amyloid precurser protein intracellular domain (AICD) phosphorylated at Thr668 served as a biologically-relevant Pin1 substrate. Specific {sup 13}C labeling at the Pin1-targeted proline residue provided multiple reporters sensitive to individual isomer binding and on-enzyme catalysis. We have performed titration experiments and employed lineshape analysis of phosphopeptide {sup 13}C-{sup 1}H constant time HSQC spectra to determine k{sub cat}{sup cis}, k{sub cat}{sup trans}, K{sub D}{sup cis}, and K{sub D}{sup trans} for the catalytic domain of Pin1 acting on this AICD substrate. The on-enzyme equilibrium value of [E{center_dot}trans]/[E{center_dot}cis] = 3.9 suggests that the catalytic domain of Pin1 is optimized to operate on this substrate near equilibrium in the cellular context. This highlights the power of lineshape analysis for determining the microscopic parameters of enzyme catalysis, and demonstrates the feasibility of future studies of Pin1-PPIase mutants to gain insights on the catalytic mechanism of this important enzyme.

  3. Parathyroid hyperplasia

    Science.gov (United States)

    Enlarged parathyroid glands; Osteoporosis - parathyroid hyperplasia; Bone thinning - parathyroid hyperplasia; Osteopenia - parathyroid hyperplasia; High calcium level - parathyroid hyperplasia; Chronic ...

  4. Dipentamethylene thiuram monosulfide is a novel inhibitor of Pin1

    Energy Technology Data Exchange (ETDEWEB)

    Tatara, Yota; Lin, Yi-Chin; Bamba, Yoshimasa; Mori, Tadashi [Molecular Enzymology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Amamiya, Tsutsumidori, Aoba, Sendai, Miyagi 981-8555 (Japan); Uchida, Takafumi, E-mail: uchidat@biochem.tohoku.ac.jp [Molecular Enzymology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Amamiya, Tsutsumidori, Aoba, Sendai, Miyagi 981-8555 (Japan)

    2009-07-03

    Pin1 is involved in eukaryotic cell proliferation by changing the structure and function of phosphorylated proteins. PiB, the Pin1 specific inhibitor, blocks cancer cell proliferation. However, low solubility of PiB in DMSO has limited studies of its effectiveness. We screened for additional Pin1 inhibitors and identified the DMSO-soluble compound dipentamethylene thiuram monosulfide (DTM) that inhibits Pin1 activity with an EC50 value of 4.1 {mu}M. Molecular modeling and enzyme kinetic analysis indicated that DTM competitively inhibits Pin1 activity, with a K{sub i} value of 0.05 {mu}M. The K{sub D} value of DTM with Pin1 was determined to be 0.06 {mu}M by SPR technology. Moreover, DTM specifically inhibited peptidyl-prolyl cis/trans isomerase activity in HeLa cells. FACS analysis showed that DTM induced G0 arrest of the HCT116 cells. Our results suggest that DTM has the potential to guide the development of novel antifungal and/or anticancer drugs.

  5. Dipentamethylene thiuram monosulfide is a novel inhibitor of Pin1.

    Science.gov (United States)

    Tatara, Yota; Lin, Yi-Chin; Bamba, Yoshimasa; Mori, Tadashi; Uchida, Takafumi

    2009-07-03

    Pin1 is involved in eukaryotic cell proliferation by changing the structure and function of phosphorylated proteins. PiB, the Pin1 specific inhibitor, blocks cancer cell proliferation. However, low solubility of PiB in DMSO has limited studies of its effectiveness. We screened for additional Pin1 inhibitors and identified the DMSO-soluble compound dipentamethylene thiuram monosulfide (DTM) that inhibits Pin1 activity with an EC50 value of 4.1 microM. Molecular modeling and enzyme kinetic analysis indicated that DTM competitively inhibits Pin1 activity, with a K(i) value of 0.05 microM. The K(D) value of DTM with Pin1 was determined to be 0.06 microM by SPR technology. Moreover, DTM specifically inhibited peptidyl-prolyl cis/trans isomerase activity in HeLa cells. FACS analysis showed that DTM induced G0 arrest of the HCT116 cells. Our results suggest that DTM has the potential to guide the development of novel antifungal and/or anticancer drugs.

  6. PIN1 gene variants in Alzheimer's disease

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    Siedlecki Janusz

    2009-11-01

    Full Text Available Abstract Background Peptidyl-prolyl isomerase, NIMA-interacting 1 (PIN1 plays a significant role in the brain and is implicated in numerous cellular processes related to Alzheimer's disease (AD and other neurodegenerative conditions. There are confounding results concerning PIN1 activity in AD brains. Also PIN1 genetic variation was inconsistently associated with AD risk. Methods We performed analysis of coding and promoter regions of PIN1 in early- and late-onset AD and frontotemporal dementia (FTD patients in comparison with healthy controls. Results Analysis of eighteen PIN1 common polymorphisms and their haplotypes in EOAD, LOAD and FTD individuals in comparison with the control group did not reveal their contribution to disease risk. In six unrelated familial AD patients four novel PIN1 sequence variants were detected. c.58+64C>T substitution that was identified in three patients, was located in an alternative exon. In silico analysis suggested that this variant highly increases a potential affinity for a splicing factor and introduces two intronic splicing enhancers. In the peripheral leukocytes of one living patient carrying the variant, a 2.82 fold decrease in PIN1 expression was observed. Conclusion Our data does not support the role of PIN1 common polymorphisms as AD risk factor. However, we suggest that the identified rare sequence variants could be directly connected with AD pathology, influencing PIN1 splicing and/or expression.

  7. Pin1 inhibitor Juglone prevents diabetic vascular dysfunction.

    Science.gov (United States)

    Costantino, Sarah; Paneni, Francesco; Lüscher, Thomas F; Cosentino, Francesco

    2016-01-15

    Atherosclerosis is a major cause of mortality in patients with diabetes. However, novel breakthrough therapies have yet to be approved in this setting. Prolyl-isomerase-1 (Pin1) is emerging as a key molecule implicated in vascular oxidative stress and inflammation. In the present study, we investigate whether pharmacological inhibition of Pin1 may protect against diabetes-induced oxidative stress, endothelial dysfunction and vascular inflammation. Experiments were performed in human aortic endothelial cells (HAECs) exposed to normal (5 mmol/L) or high glucose (25 mmol/L) concentrations, in the presence of Pin1 inhibitor Juglone (10 μM) or vehicle (kB-dependent inflammatory signatures were determined both in HAECs and aortas from diabetic mice. In HAECs, ambient hyperglycemia increased mitochondrial superoxide anion generation while treatment with Juglone prevented this phenomenon. Pharmacological inhibition of Pin1 also preserved mitochondrial integrity, nitric oxide availability and endothelial expression of adhesion molecules. Interestingly enough, endothelial dysfunction, oxidative stress and NF-kB-driven inflammation were significantly attenuated in diabetic mice chronically treated with Juglone as compared to vehicle-treated animals. Pharmacological inhibition of Pin1 by Juglone prevents hyperglycemia-induced vascular dysfunction. Taken together, our findings may set the stage for novel therapeutic approaches to prevent vascular complications in patients with diabetes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Parathyroid adenoma

    Science.gov (United States)

    Hyperparathyroidism - parathryoid adenoma; Overactive parathyroid gland - parathyroid adenoma ... The parathyroid glands in the neck help control calcium use and removal by the body. They do this by ...

  9. Pin1 promotes GR transactivation by enhancing recruitment to target genes.

    Science.gov (United States)

    Poolman, Toryn M; Farrow, Stuart N; Matthews, Laura; Loudon, Andrew S; Ray, David W

    2013-10-01

    The glucocorticoid receptor (GR) is a ligand activated transcription factor, serving to regulate both energy metabolism and immune functions. Factors that influence cellular sensitivity to glucocorticoids (GC) are therefore of great interest. The N-terminal of the GR contains numerous potential proline-directed phosphorylation sites, some of which can regulate GR transactivation. Unrestricted proline isomerisation can be inhibited by adjacent serine phosphorylation and requires a prolyl isomerise, Pin1. Pin1 therefore determines the functional outcome of proline-directed kinases acting on the GR, as cis/trans isomers are distinct pools with different interacting proteins. We show that Pin1 mediates GR transactivation, but not GR trans-repression. Two N-terminal GR serines, S203 and S211, are targets for Pin1 potentiation of GR transactivation, establishing a direct link between Pin1 and the GR. We also demonstrate GC-activated co-recruitment of GR and Pin1 to the GILZ gene promoter. The Pin1 effect required both its WW and catalytic domains, and GR recruitment to its GRE was Pin1-dependent. Therefore, Pin1 is a selective regulator of GR transactivation, acting through N-terminal phospho-serine residues to regulate GR recruitment to its target sites in the genome. As Pin1 is dysregulated in disease states, this interaction may contribute to altered GC action in inflammatory conditions.

  10. The PIN1 family gene PvPIN1 is involved in auxin-dependent root emergence and tillering in switchgrass

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    Kaijie Xu

    2016-03-01

    Full Text Available Abstract Switchgrass (Panicum virgatum L.; family Poaceae is a warm-season C4 perennial grass. Tillering plays an important role in determining the morphology of aboveground parts and the final biomass yield of switchgrass. Auxin distribution in plants can affect a variety of important growth and developmental processes, including the regulation of shoot and root branching, plant resistance and biological yield. Auxin transport and gradients in plants are mediated by influx and efflux carriers. PvPIN1, a switchgrass PIN1-like gene that is involved in regulating polar transport, is a putative auxin efflux carrier. Neighbor-joining analysis using sequences deposited in NCBI databases showed that the PvPIN1gene belongs to the PIN1 family and is evolutionarily closer to the Oryza sativa japonica group. Tiller emergence and development was significantly promoted in plants subjected toPvPIN1 RNA interference (RNAi, which yielded a phenotype similar to that of wild-type plants treated with the auxin transport inhibitor TIBA (2,3,5-triiodobenzoic acid. A transgenic approach that inducedPvPIN1 gene overexpression or suppression altered tiller number and the shoot/root ratio. These data suggest that PvPIN1plays an important role in auxin-dependent adventitious root emergence and tillering.

  11. Solution structural analysis of the single-domain parvulin TbPin1.

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    Lifang Sun

    Full Text Available BACKGROUND: Pin1-type parvulins are phosphorylation-dependent peptidyl-prolyl cis-trans isomerases. Their functions have been widely reported to be involved in a variety of cellular responses or processes, such as cell division, transcription, and apoptosis, as well as in human diseases including Alzheimer's disease and cancers. TbPin1 was identified as a novel class of Pin1-type parvulins from Trypanosoma brucei, containing a unique PPIase domain, which can catalyze the isomerization of phosphorylated Ser/Thr-Pro peptide bond. METHODOLOGY/PRINCIPAL FINDINGS: We determined the solution structure of TbPin1 and performed (15N relaxation measurements to analyze its backbone dynamics using multi-dimensional heteronuclear NMR spectroscopy. The average RMSD values of the 20 lowest energy structures are 0.50±0.05 Å for backbone heavy atoms and 0.85±0.08 Å for all heavy atoms. TbPin1 adopts the typical catalytic tertiary structure of Pin1-type parvulins, which comprises a globular fold with a four-stranded anti-parallel β-sheet core surrounded by three α-helices and one 3(10-helix. The global structure of TbPin1 is relatively rigid except the active site. The 2D EXSY spectra illustrate that TbPin1 possesses a phosphorylation-dependent PPIase activity. The binding sites of TbPin1 for a phosphorylated peptide substrate {SSYFSG[p]TPLEDDSD} were determined by the chemical shift perturbation approach. Residues Ser15, Arg18, Asn19, Val21, Ser22, Val32, Gly66, Ser67, Met83, Asp105 and Gly107 are involved in substantial contact with the substrate. CONCLUSIONS/SIGNIFICANCE: The solution structure of TbPin1 and the binding sites of the phosphorylated peptide substrate on TbPin1 were determined. The work is helpful for further understanding the molecular basis of the substrate specificity for Pin1-type parvulin family and enzyme catalysis.

  12. Enzyme-linked enzyme-binding assay for Pin1 WW domain ligands.

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    Mercedes-Camacho, Ana Y; Etzkorn, Felicia A

    2010-07-01

    Peptidyl prolyl cis-trans isomerase (PPIase) interacting with NIMA-1 (Pin1) catalyzes the cis-trans isomerization of pSer/pThr-Pro amide bonds. Pin1 is a two-domain protein that represents a promising target for the treatment of cancer. Both domains of Pin1 bind the pSer/pThr-Pro motif; PPIase enzymatic activity occurs in the catalytic domain, and the WW domain acts as a recognition module for the pSer/pThr-Pro motif. An assay we call an enzyme-linked enzyme-binding assay (ELEBA) was developed to measure the K(d) of ligands that bind selectively to the WW domain. A ligand specific for the WW domain of Pin1 was covalently immobilized in a 96-well plate. Commercially available Pin1 conjugated to horseradish peroxidase was used for chemiluminescent detection of ligands that block the association of the WW domain with immobilized ligand. The peptide ligands were derived from the cell cycle regulatory phosphatase, Cdc25c, residues 45-50. The K(d) values for Fmoc-VPRpTPVGGGK-NH2 and Ac-VPRpTPV-NH2 were determined to be 36+/-4 and 110+/-30 microM, respectively. The ELEBA offers a selective approach for detecting ligands that bind to the Pin1 WW domain, even in the presence of the catalytic domain. This method may be applied to any dual specificity, multidomain protein. 2010 Elsevier Inc. All rights reserved.

  13. Maternal control of PIN1 is required for female gametophyte development in Arabidopsis.

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    Luca Ceccato

    Full Text Available Land plants are characterised by haplo-diploid life cycles, and developing ovules are the organs in which the haploid and diploid generations coexist. Recently it has been shown that hormones such as auxin and cytokinins play important roles in ovule development and patterning. The establishment and regulation of auxin levels in cells is predominantly determined by the activity of the auxin efflux carrier proteins PIN-FORMED (PIN. To study the roles of PIN1 and PIN3 during ovule development we have used mutant alleles of both genes and also perturbed PIN1 and PIN3 expression using micro-RNAs controlled by the ovule specific DEFH9 (DEFIFICENS Homologue 9 promoter. PIN1 down-regulation and pin1-5 mutation severely affect female gametophyte development since embryo sacs arrest at the mono- and/or bi-nuclear stages (FG1 and FG3 stage. PIN3 function is not required for ovule development in wild-type or PIN1-silenced plants. We show that sporophytically expressed PIN1 is required for megagametogenesis, suggesting that sporophytic auxin flux might control the early stages of female gametophyte development, although auxin response is not visible in developing embryo sacs.

  14. Determining the Levels of Vitamin D and Parathyroid Hormone in Patients on Hemodialysis

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    Mihaylov R.

    2016-03-01

    Full Text Available Vitamin D deficiency is fequently observed in chronic kidney disease. We conducted this study to determine the concentration of the above-mentioned parameters and the correlation between them in order to optimize therapy with vitamin D in patients with end-stage renal disease (ESRD on hemodialysis. In 53 patients on hemodialysis due to ESRD, vitamin D [Calcidiol (25(OHD], parathyroid hormone (PTH, calcium, phosphorus, albuminuria, albumin:creatinine ratio (ACR and other parameters have been followed up. Analysis of the levels of vitamin D has been carried out by High Performance Liquid Chromatography (HPLC, the PTH is determined by the system Centaur XP, Siemens Diagnostic, Electro-chemiluminescence immunoassay (ECLIA, and for albumin in urine we used immunological method [Miltigent microalbumin assay (Abbott Laboratories Diagnostics. We found out deficiency and insufficiency of vitamin D in 56.6% and 37.7%, as well as average 4.5 times increase in the PTH, hyperphosphatemia, hypocalcemia, albuminuria (A2 or A3, over 10 times increase in the ACR, secondary hyperparathyroidism. We registered a negative correlation between vitamin D and PTH. We confirmed the increase in creatinine and cystatin C in the patients on hemodialysis. There are few literature data for patients on hemodialysis, however, regarding the extent of the vitamin deficiency and its relationship with PTH, albuminuria, calcium, phosphorus, etc. Our data have indicated that patients on hemodialysis due to ESRD are associated with high incidence of vitamin D insufficiency or deficiency.

  15. Serum parathyroid hormone (PTH) in pregnant women determined by an immunoradiometric assay for intact PTH

    Energy Technology Data Exchange (ETDEWEB)

    Davis, O.K.; Hawkins, D.S.; Rubin, L.P.; Posillico, J.T.; Brown, E.M.; Schiff, I.

    1988-10-01

    Most studies of circulating PTH levels using traditional RIAs have supported the concept of physiological hyperparathyroidism of pregnancy, with pregnant women having serum immunoreactive PTH levels significantly higher than those in nonpregnant subjects. However, such RIAs are insensitive and often detect inactive PTH fragments, so that the correlation between PTH immunoreactivity and bioactivity is poor. Employing a new intact PTH immunoradiometric assay (Allegro-Nichols), we reassessed the effects of pregnancy on parathyroid function. The mean serum PTH level in 81 pregnant women was 14.4 +/- 6.3 (+/- SD) compared to 24.8 +/- 9.0 ng/L in 11 normally cycling nonpregnant women (P less than 0.001). The mean serum total and ionized calcium levels in the 2 groups were similar. In 5 of the pregnant women, serum bioactive PTH, determined by cytochemical bioassay, was slightly lower (7.7 +/- 3.4 ng/L) than in normal individuals (11.1 +/- 1.9 ng/L). Our findings suggest, in contrast with the results of most previous studies, that serum intact PTH may decline during pregnancy.

  16. Parathyroid Imaging

    NARCIS (Netherlands)

    Kluijfhout, WP

    2017-01-01

    A colloquial saying described the best localization before parathyroid surgery was finding a good surgeon. While it is still important to have a high volume parathyroid surgeon, the trend away from bilateral neck exploration towards that of minimal invasive parathyroidectomy (MIP) has changed the

  17. Dissecting Pin1 and phospho-pRb regulation.

    Science.gov (United States)

    Rizzolio, Flavio; Caligiuri, Isabella; Lucchetti, Chiara; Fratamico, Robert; Tomei, Valentina; Gallo, Gaia; Agelan, Alexis; Ferrari, Giovanni; Toffoli, Giuseppe; Klein-Szanto, Andres J; Giordano, Antonio

    2013-01-01

    The activity of the Retinoblastoma protein, the master regulator of the cell cycle, is finely regulated by phosphorylation. CDKs and cyclins are major players in phosphorylation and it has been recently discovered that the prolyl isomerase Pin1 is an essential protein that orchestrates this process. In this article, we report new findings regarding the role of Pin1 in the pRb pathway. Our data suggest that PI3K, CDKs, and the Pin1 axis have a critical role in sustaining the complete phosphorylation of pRb. Furthermore, we analyze the correlation between Pin1 and pRb phosphorylation in vivo. We show that, in human malignant glioma tissue microarrays (TMA) and in Pin1 knockout (KO) mice, there is a positive correlation between Pin1 and pRb phosphorylation. Prospectively, our findings suggest that the synergism between CDKs, Pin1, and PI3K inhibitors hold great promise for targeted pharmacological treatment of cancer patients, with the possibility of reaching high effectiveness at tolerated doses.

  18. PIN1 in breast development and cancer: a clinical perspective.

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    Rustighi, Alessandra; Zannini, Alessandro; Campaner, Elena; Ciani, Yari; Piazza, Silvano; Del Sal, Giannino

    2017-02-01

    Mammary gland development, various stages of mammary tumorigenesis and breast cancer progression have the peptidyl-prolyl cis/trans isomerase PIN1 at their centerpiece, in virtue of the ability of this unique enzyme to fine-tune the dynamic crosstalk between multiple molecular pathways. PIN1 exerts its action by inducing conformational and functional changes on key cellular proteins, following proline-directed phosphorylation. Through this post-phosphorylation signal transduction mechanism, PIN1 controls the extent and direction of the cellular response to a variety of inputs, in physiology and disease. This review discusses PIN1's roles in normal mammary development and cancerous progression, as well as the clinical impact of targeting this enzyme in breast cancer patients.

  19. A reduced-amide inhibitor of Pin1 binds in a conformation resembling a twisted-amide transition state.

    Science.gov (United States)

    Xu, Guoyan G; Zhang, Yan; Mercedes-Camacho, Ana Y; Etzkorn, Felicia A

    2011-11-08

    The mechanism of the cell cycle regulatory peptidyl prolyl isomerase (PPIase), Pin1, was investigated using reduced-amide inhibitors designed to mimic the twisted-amide transition state. Inhibitors, R-pSer-Ψ[CH(2)N]-Pro-2-(indol-3-yl)ethylamine, 1 [R = fluorenylmethoxycarbonyl (Fmoc)] and 2 (R = Ac), of Pin1 were synthesized and bioassayed. Inhibitor 1 had an IC(50) value of 6.3 μM, which is 4.5-fold better for Pin1 than our comparable ground-state analogue, a cis-amide alkene isostere-containing inhibitor. The change of Fmoc to Ac in 2 improved aqueous solubility for structural determination and resulted in an IC(50) value of 12 μM. The X-ray structure of the complex of 2 bound to Pin1 was determined to 1.76 Å resolution. The structure revealed that the reduced amide adopted a conformation similar to the proposed twisted-amide transition state of Pin1, with a trans-pyrrolidine conformation of the prolyl ring. A similar conformation of substrate would be destabilized relative to the planar amide conformation. Three additional reduced amides, with Thr replacing Ser and l- or d-pipecolate (Pip) replacing Pro, were slightly weaker inhibitors of Pin1.

  20. Pin1 and neurodegeneration: a new player for prion disorders?

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    Elisa Isopi

    2015-07-01

    Full Text Available Pin1 is a peptidyl-prolyl isomerase that catalyzes the cis/trans conversion of phosphorylated proteins at serine or threonine residues which precede a proline. The peptidyl-prolyl isomerization induces a conformational change of the proteins involved in cell signaling process. Pin1 dysregulation has been associated with some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Proline-directed phosphorylation is a common regulator of these pathologies and a recent work showed that it is also involved in prion disorders. In fact, prion protein phosphorylation at the Ser-43-Pro motif induces prion protein conversion into a disease-associated form. Furthermore, phosphorylation at Ser-43-Pro has been observed to increase in the cerebral spinal fluid of sporadic Creutzfeldt-Jakob Disease patients. These findings provide new insights into the pathogenesis of prion disorders, suggesting Pin1 as a potential new player in the disease. In this paper, we review the mechanisms underlying Pin1 involvement in the aforementioned neurodegenerative pathologies focusing on the potential role of Pin1 in prion disorders.

  1. Parathyroid carcinoma

    DEFF Research Database (Denmark)

    Qvist, N; Krøll, L; Ladefoged, C;

    1986-01-01

    Parathyroid carcinoma is a slow growing tumor, and the patients most often die from complications to the hypercalcemia. Therefore, any attempt should be made to remove local recurrence and metastasis surgically, as medical treatment is disappointing. A case treated with extensive vascular surgery...

  2. Increased expression of PIN1 gene in papillary thyroid carcinoma

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    Lewiński Andrzej

    2011-01-01

    Full Text Available Abstract Background Peptidyl-prolyl cis/trans isomerase (Pin1, encoded by PIN1 gene with locus in chromosome 19p13, is an enzyme that catalytically induces conformational changes in proteins after phosphorylation on serine or threonine residues preceding proline (pSer/Thr-Pro motifs; in this way, it has an influence on protein interactions and intracellular localizations of proteins. The aim of the study were: 1 an assessment of PIN1 gene expression level in benign and malignant thyroid lesions; 2 the evaluation of possible correlations between gene expression and histopathological variants of papillary thyroid carcinoma (PTC or tumour size, classified according to TNM classification of primary tumours (in case of PTC only; 3 the estimation of possible relationships between expression of the gene in question and patients' sex or age. Methods Seventy (70 tissue samples were analyzed: 32 cases of PTC, 7 cases of medullary thyroid carcinoma (MTC, 7 cases of follicular adenoma (FA, and 24 cases of nodular goitre (NG. In real-time polymerase chain reaction (real-time PCR, two-step RT-PCR (reverse transcriptase-polymerase chain reaction in an ABI PRISM 7500 Sequence Detection System was employed. The PIN1 gene expression level was assessed, calculating the mean relative quantification rate (RQ rate increase for each sample. Results The level of PIN1 gene expression (compared to that in macroscopically unchanged thyroid tissue was higher in PTC group than those in FA, MTC and/or NG groups, but the statistical significance was noted for difference between PTC and NG groups only. On the other hand, the differences of RQ rate value between different PTC variants were statistically insignificant. No correlations were found between RQ values and tumour size, as well as between RQ values and patients' sex or age in PTC group. Conclusions The PIN1 gene expression may have - in future - an important meaning in the diagnostics of PTC and in understanding its

  3. Parathyroid gland removal

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    Removal of parathyroid gland; Parathyroidectomy; Hyperparathyroidism - parathyroidectomy; PTH - parathyroidectomy ... and pain-free) for this surgery. Usually the parathyroid glands are removed using a 2- to 4-inch ( ...

  4. Overexpression of PvPin1, a Bamboo Homolog of PIN1-Type Parvulin 1, Delays Flowering Time in Transgenic Arabidopsis and Rice

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    Zhigang Zheng

    2017-09-01

    Full Text Available Because of the long and unpredictable flowering period in bamboo, the molecular mechanism of bamboo flowering is unclear. Recent study showed that Arabidopsis PIN1-type parvulin 1 (Pin1At is an important floral activator and regulates floral transition by facilitating the cis/trans isomerization of the phosphorylated Ser/Thr residues preceding proline motifs in suppressor of overexpression of CO 1 (SOC1 and agamous-like 24 (AGL24. Whether bamboo has a Pin1 homolog and whether it works in bamboo flowering are still unknown. In this study, we cloned PvPin1, a homolog of Pin1At, from Phyllostachys violascens (Bambusoideae. Bioinformatics analysis showed that PvPin1 is closely related to Pin1-like proteins in monocots. PvPin1 was widely expressed in all tested bamboo tissues, with the highest expression in young leaf and lowest in floral bud. Moreover, PvPin1 expression was high in leaves before bamboo flowering then declined during flower development. Overexpression of PvPin1 significantly delayed flowering time by downregulating SOC1 and AGL24 expression in Arabidopsis under greenhouse conditions and conferred a significantly late flowering phenotype by upregulating OsMADS56 in rice under field conditions. PvPin1 showed subcellular localization in both the nucleus and cytolemma. The 1500-bp sequence of the PvPin1 promoter was cloned, and cis-acting element prediction showed that ABRE and TGACG-motif elements, which responded to abscisic acid (ABA and methyl jasmonate (MeJA, respectively, were characteristic of P. violascens in comparison with Arabidopsis. On promoter activity analysis, exogenous ABA and MeJA could significantly inhibit PvPin1 expression. These findings suggested that PvPin1 may be a repressor in flowering, and its delay of flowering time could be regulated by ABA and MeJA in bamboo.

  5. Decreasing Pin1 suppresses telomerase activity by NF-κB in HCT116 cells colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jianwen Sun; Lijun Fan; Meining Li; Yuehong Zhang; Niuliang Cheng

    2013-01-01

    Objective: The aim of our study was to investigate the effect of Pin1 on the telomerase activity in human colorectal carcinoma HCT116 cells. Methods: Firstly, we transfected plasmid pGenesil-1-Pin1 (p-shRNA) using liposome (Lipofectamine 2000) into colorectal cancer HCT-116 cells to down-regulate the expression of Pin1. To detect the apoptotic rate of HCT116 cells was by cytometry (FCM). The expression of Pin1 and hTERT at RNA levels in human colorectal cancer HCT116 cells were determined by RT-PCR. To evaluate the activity of telomerase was by TRAP-silver staining. The subcellular localization and accumulative level of p-NF-κB/p65 protein at the nuclear was detected by Immunofluorescence and Western blotting. The DNA-binding activity of NF-κB/p65 was detected by electrophoretic mobility shift assay (EMSA). Results: Using liposome into colorectal cancer HCT-116 cells, and down-regulate the expression of Pin1 (0.392 ± 0.072-fold; P = 0.001), and the apoptotic rate was increased (11.40% ± 1.54%; P < 0.05). Compared with transfected p-CON cell group, in transfected p-shRNA cell group, the transcription of hTERT was lower (0.171 ± 0.060-fold; P = 0.001) by quantitative real-time RT-PCR, and the results of TRAP-silver staining analysis suggested that the telomerase activity was significantly declined (0.384 ± 0.015-fold; P < 0.05). Furthermore, it was demonstrated by Immunofluorescence that p-NF-κB/p65 had a nuclear localization, and the level of p-NF-κB/p65 protein at the nuclear was reduced with silencing the expression of Pin1 by Western blotting. Using EMSA, it was suggested that NF-κB/p65 was able to bind to hTERT promoter, and the direct interaction was declined with silencing the expression of Pin1. Conclusion: Taken together, silencing Pin1 may suppress activity of telomerase and the expression of hTERT by inhibiting NF-κB/p65 activity and reducing the combination of NF-κB/p65 and hTERT gene promoter.

  6. The prolyl isomerase Pin1 increases β-cell proliferation and enhances insulin secretion.

    Science.gov (United States)

    Nakatsu, Yusuke; Mori, Keiichi; Matsunaga, Yasuka; Yamamotoya, Takeshi; Ueda, Koji; Inoue, Yuki; Mitsuzaki-Miyoshi, Keiko; Sakoda, Hideyuki; Fujishiro, Midori; Yamaguchi, Suguru; Kushiyama, Akifumi; Ono, Hiraku; Ishihara, Hisamitsu; Asano, Tomoichiro

    2017-07-14

    The prolyl isomerase Pin1 binds to the phosphorylated Ser/Thr-Pro motif of target proteins and enhances their cis-trans conversion. This report is the first to show that Pin1 expression in pancreatic β cells is markedly elevated by high-fat diet feeding and in ob/ob mice. To elucidate the role of Pin1 in pancreatic β cells, we generated β-cell-specific Pin1 KO (βPin1 KO) mice. These mutant mice showed exacerbation of glucose intolerance but had normal insulin sensitivity. We identified two independent factors underlying impaired insulin secretion in the βPin1 KO mice. Pin1 enhanced pancreatic β-cell proliferation, as indicated by a reduced β-cell mass in βPin1 KO mice compared with control mice. Moreover, a diet high in fat and sucrose failed to increase pancreatic β-cell growth in the βPin1 KO mice, an observation to which up-regulation of the cell cycle protein cyclin D appeared to contribute. The other role of Pin1 was to activate the insulin-secretory step: Pin1 KO β cells showed impairments in glucose- and KCl-induced elevation of the intracellular Ca(2+) concentration and insulin secretion. We also identified salt-inducible kinase 2 (SIK2) as a Pin1-binding protein that affected the regulation of Ca(2+) influx and found Pin1 to enhance SIK2 kinase activity, resulting in a decrease in p35 protein, a negative regulator of Ca(2+) influx. Taken together, our observations demonstrate critical roles of Pin1 in pancreatic β cells and that Pin1 both promotes β-cell proliferation and activates insulin secretion. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Aluminum(III) interferes with the structure and the activity of the peptidyl-prolyl cis-trans isomerase (Pin1): a new mechanism contributing to the pathogenesis of Alzheimer's disease and cancers?

    Science.gov (United States)

    Wang, Jing-Zhang; Liu, Ji; Lin, Tao; Han, Yong-Guang; Luo, Yue; Xi, Lei; Du, Lin-Fang

    2013-09-01

    The enzyme peptidyl-prolyl cis-trans isomerase (Pin1) may play an important role in preventing the development of Alzheimer's disease (AD). The structural and functional stability of Pin1 is extremely important. Previously, we have determined the stability of Pin1 under stressed conditions, such as thermal treatment and acidic-pH. Considering that aluminum (Al(III)) is well known for its potential neurotoxicity in the pathogenesis of AD, we examined whether Al(III) affects the structure and function of Pin1, by means of a PPIase activity assay, intrinsic fluorescence, circular dichroism (CD) spectroscopy, FTIR, and differential scanning calorimetry (DSC). The intrinsic tryptophan fluorescence measurements mainly show that Al(III) may bind to the clusters nearby W11 and W34 in the WW domain of Pin1, quenching the intrinsic fluorescence of the two tryptophan residues, which possibly results in the decreased binding affinity of Pin1 to substrates. The secondary structural analysis as revealed by FTIR and CD measurements indicate that Al(III) induces the increase in β-sheet and the decrease in α-helix in Pin1. Furthermore, the changes of the thermodynamic parameters for Pin1 as monitored by DSC confirm that the thermal stability of Pin1 significantly increases in the presence of Al(III). The Al(III)-induced structural changes of Pin1 result in a sharp decrease of the PPIase activity of Pin1. To some extent, our research is suggestive that Al(III) may inhibit the isomerization activity of Pin1 in vivo, which may contribute to the pathogenesis of AD.

  8. PIN1 in hepatocellular carcinoma is associated with TP53 gene status.

    Science.gov (United States)

    Bae, Jun Sang; Noh, Sang Jae; Kim, Kyoung Min; Jang, Kyu Yun; Park, Ho Sung; Chung, Myoung Ja; Park, Byung-Hyun; Moon, Woo Sung

    2016-10-01

    Phosphorylation of proteins on serine/threonine residues that precede proline (pSer/Thr-Pro) is specifically catalyzed by the peptidyl-prolyl cis-trans isomerase PIN1. PIN1-mediated prolyl-isomerization induces cell cycle arrest and growth inhibition through the regulation of target proteins, including TP53. We examined whether PIN1 acts in a different manner according to TP53 gene status in hepatocellular carcinoma (HCC). We investigated the expression of PIN1 and TP53 proteins in 119 HCC tissue samples. We also analyzed PIN1 expression in combination with TP53 gene mutation and its correlation with the clinical outcome. In addition, we used synthetic small interfering RNA to silence PIN1 gene expression in TP53 wild-type and TP53 mutant HCC cell lines, and then evaluated cell proliferation, migration and invasion. Expression of PIN1 was strongly associated with expression of TP53 protein or TP53 mutation of HCC samples. PIN1 and TP53 expression in TP53 mutant HCC cell lines was higher than that in TP53 wild-type HCC cell lines. Silencing of PIN1 in HLE cells containing mutant TP53 significantly decreased cell proliferation, migration and invasion. In contrast to PIN1 silencing in HLE cells, PIN1 silencing in HepG2 cells containing functional wild-type TP53 resulted in enhanced tumor cell proliferation. HCC patients bearing PIN1 expression with wild-type TP53 were predicted to demonstrate favorable relapse-free survival. Our results suggest that PIN1 plays a role in cancer cell proliferation, migration and invasion in a different manner according to the TP53 gene mutation status in HCC. In particular, interaction of PIN1 with mutant TP53 can act as a tumor promoter and increase its oncogenic activities in HCC.

  9. Parathyroid glands (image)

    Science.gov (United States)

    The 4 parathyroid glands are located near or attached to the back side of the thyroid gland and produce pararthyroid hormone (PTH). Parathyroid hormone regulates calcium, phosphorus, and magnesium balance within ...

  10. Expression of Pin1 and Ki67 in Cervical Cancer and Their Significance

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to investigate the expression levels of Pin1 mRNA and protein in cervical cancer and its association with Ki67 and their clinical significance, amplification of Pin1 gene was examined by RT-PCR, and the expression of both Pin1 and Ki67 protein was detected by immunohistochemistry in cervical cancer tissues. It was shown that the expression levels of Pin1 were higher in cervical cancer than in normal cervical tissues (P<0.05). The expression of Pin1 protein was increased progressively along with the disease process from normal cervix to CIN and to cervical cancer (P<0. 05). No significant difference in the Pin1 expression was found between disease stages (FIGO),pathological grades or pelvic lymph node metastasis status (P>0.05). The expression of Pin1 was significantly higher in adenocarcinoma than insquamous carcinoma of the uterine cervix (P<0.05).In cervical cancer, the overexpression of Pin1 was positively correlated with that of Ki67 (P<0.05). These results suggested that the overexpression of Pin1 was closely related with cancer cell proliferation or progression of cervical cancer and contributed to oncogenesis. Pin1 may serve as a potential marker for cervical cancer diagnosis.

  11. Effects of Pin1 loss in HdhQ111 knock-in mice

    Directory of Open Access Journals (Sweden)

    Elena eAgostoni

    2016-05-01

    Full Text Available Huntington’s disease (HD is a fatal, dominantly inherited, neurodegenerative disorder due to a pathological expansion of the CAG repeat in the coding region of the HTT gene. In the quest for understanding the molecular basis of neurodegeneration, we have previously demonstrated that the prolyl isomerase Pin1 plays a crucial role in mediating p53-dependent apoptosis triggered by mutant huntingtin (mHtt in vitro. To assess the effects of the lack of Pin1 in vivo, we have bred Pin1 knock-out mice with HdhQ111 knock-in mice, a genetically precise model of HD. We show that Pin1 genetic ablation modifies a portion of HdhQ111 phenotypes in a time-dependent fashion. As an early event, Pin1 activity reduces the DNA damage response. In midlife mice, by taking advantage of next-generation sequencing technology, we show that Pin1 activity modulates a portion of the alterations triggered by mHtt, extending the role of Pin1 to two additional HdhQ111 phenotypes: the unbalance in the synthesis/concentration of hormones, as well as the alteration of Wnt/β-catenin signaling. In aging animals, Pin1 significantly increases the number of mHtt-positive nuclear inclusions while it reduces gliosis. In summary, this work provides further support for a role of Pin1 in HD pathogenesis.

  12. A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action

    Science.gov (United States)

    Campaner, Elena; Rustighi, Alessandra; Zannini, Alessandro; Cristiani, Alberto; Piazza, Silvano; Ciani, Yari; Kalid, Ori; Golan, Gali; Baloglu, Erkan; Shacham, Sharon; Valsasina, Barbara; Cucchi, Ulisse; Pippione, Agnese Chiara; Lolli, Marco Lucio; Giabbai, Barbara; Storici, Paola; Carloni, Paolo; Rossetti, Giulia; Benvenuti, Federica; Bello, Ezia; D'Incalci, Maurizio; Cappuzzello, Elisa; Rosato, Antonio; Del Sal, Giannino

    2017-06-01

    The prolyl isomerase PIN1, a critical modifier of multiple signalling pathways, is overexpressed in the majority of cancers and its activity strongly contributes to tumour initiation and progression. Inactivation of PIN1 function conversely curbs tumour growth and cancer stem cell expansion, restores chemosensitivity and blocks metastatic spread, thus providing the rationale for a therapeutic strategy based on PIN1 inhibition. Notwithstanding, potent PIN1 inhibitors are still missing from the arsenal of anti-cancer drugs. By a mechanism-based screening, we have identified a novel covalent PIN1 inhibitor, KPT-6566, able to selectively inhibit PIN1 and target it for degradation. We demonstrate that KPT-6566 covalently binds to the catalytic site of PIN1. This interaction results in the release of a quinone-mimicking drug that generates reactive oxygen species and DNA damage, inducing cell death specifically in cancer cells. Accordingly, KPT-6566 treatment impairs PIN1-dependent cancer phenotypes in vitro and growth of lung metastasis in vivo.

  13. Cryopreservation of Parathyroid Glands

    Directory of Open Access Journals (Sweden)

    Marlon A. Guerrero

    2010-01-01

    Full Text Available The risk of permanent hypoparathyroidism following thyroid and parathyroid surgery is around 1% in the hands of experienced endocrine surgeons. Although this complication is rare, rendering a patient permanently aparathyroid has significant consequences on the health and quality of life of the patient. Immediate autotransplantation of parathyroid glands that are injured or unintentionally removed offers the best possibility of graft viability and functionality. However, since the majority of cases of hypoparathyroidism are transient, immediate autotransplantation can complicate postoperative surveillance in certain patients, especially those with primary hyperparathyroidism. Cryopreservation of parathyroid tissue is an alternate technique that was developed to treat patients with permanent hypoparathyroidism. This method allows for parathyroid tissue to be stored and then autotransplanted in a delayed fashion once permanent hypoparathyroidism is confirmed. This article provides a contemporary review on cryopreservation of parathyroid tissue and its current role in thyroid and parathyroid surgery.

  14. Pin1 Modulates the Synaptic Content of NMDA Receptors via Prolyl-Isomerization of PSD-95.

    Science.gov (United States)

    Antonelli, Roberta; De Filippo, Roberto; Middei, Silvia; Stancheva, Stefka; Pastore, Beatrice; Ammassari-Teule, Martine; Barberis, Andrea; Cherubini, Enrico; Zacchi, Paola

    2016-05-18

    Phosphorylation of serine/threonine residues preceding a proline regulates the fate of its targets through postphosphorylation conformational changes catalyzed by the peptidyl-prolyl cis-/trans isomerase Pin1. By flipping the substrate between two different functional conformations, this enzyme exerts a fine-tuning of phosphorylation signals. Pin1 has been detected in dendritic spines and shafts where it regulates protein synthesis required to sustain the late phase of long-term potentiation (LTP). Here, we demonstrate that Pin1 residing in postsynaptic structures can interact with postsynaptic density protein-95 (PSD-95), a key scaffold protein that anchors NMDA receptors (NMDARs) in PSD via GluN2-type receptor subunits. Pin1 recruitment by PSD-95 occurs at specific serine-threonine/proline consensus motifs localized in the linker region connecting PDZ2 to PDZ3 domains. Upon binding, Pin1 triggers structural changes in PSD-95, thus negatively affecting its ability to interact with NMDARs. In electrophysiological experiments, larger NMDA-mediated synaptic currents, evoked in CA1 principal cells by Schaffer collateral stimulation, were detected in hippocampal slices obtained from Pin1(-/-) mice compared with controls. Similar results were obtained in cultured hippocampal cells expressing a PSD-95 mutant unable to undergo prolyl-isomerization, thus indicating that the action of Pin1 on PSD-95 is critical for this effect. In addition, an enhancement in spine density and size was detected in CA1 principal cells of Pin1(-/-) or in Thy-1GFP mice treated with the pharmacological inhibitor of Pin1 catalytic activity PiB.Our data indicate that Pin1 controls synaptic content of NMDARs via PSD-95 prolyl-isomerization and the expression of dendritic spines, both required for LTP maintenance. PSD-95, a membrane-associated guanylate kinase, is the major scaffolding protein at excitatory postsynaptic densities and a potent regulator of synaptic strength and plasticity. The

  15. Intraoperative nuclear guidance in benign hyperparathyroidism and parathyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bonjer, H.J. [Univ. Hospital Dijkzigt, Rotterdam (Netherlands). Dept. of Surgery; Bruining, H.A. [Univ. Hospital Dijkzigt, Rotterdam (Netherlands). Dept. of Surgery; Pols, H.A.P. [Univ. Hospital Dijkzigt, Rotterdam (Netherlands). Dept. of Internal Medicine 3; Herder, W.W. de [Univ. Hospital Dijkzigt, Rotterdam (Netherlands). Dept. of Internal Medicine 3; Eijck, C.H.J. [Univ. Hospital Dijkzigt, Rotterdam (Netherlands). Dept. of Surgery; Breeman, W.A.P. [Univ. Hospital Dijkzigt, Rotterdam (Netherlands). Dept. of Nuclear Medicine; Krenning, E.P. [Univ. Hospital Dijkzigt, Rotterdam (Netherlands). Dept. of Nuclear Medicine

    1997-03-01

    The success of parathyroid surgery is determined by the identification and removal of all hyperactive parathyroid tissue. Ectopic location of parathyroid tumours and fibrosis due to previous operations can cause failure of parathyroidectomy. Parathyroid tumours accumulate and retain 2-methoxyisobutylisonitrile (MIBI) labelled with technetium-99m. This study assesses the value of intra-operative localization of parathyroid tumours using a hand-held gamma detector in patients with hyperparathyroidism and parathyroid cancer. Twenty patients undergoing their first operations for hyperparathyroidism, 15 patients undergoing reoperations for either persistent or recurrent hyperparathyroidism and two patients with parathyroid cancer were studied. Radioactivity in the neck and the mediastinum was recorded by a gamma detector after administration of 370 MBq {sup 99m}Tc-MIBI. Surgical findings and postoperative serum levels of calcium were documented. The sensitivity of the gamma detector in identifying parathyroid tumours was 90.5% in first parathyroidectomies, 88.9% in reoperations for either persistent or recurrent hyperparathyroidism and 100% in parathyroid cancer. One false-positive result was due to a thyroid nodule. Hypercalcaemia ceased in all but one patient postoperatively. It is concluded that employment of the gamma detector is to be advocated in first parathyroidectomies when a parathyroid tumour cannot be discovered, in reoperations for either persistent or recurrent hyperparathyroidism and in surgery for parathyroid cancer. (orig.)

  16. Cyclohexyl Ketone Inhibitors of Pin1 Dock in a Trans-Diaxial Cyclohexane Conformation

    Science.gov (United States)

    Xu, Guoyan G.; Slebodnick, Carla; Etzkorn, Felicia A.

    2012-01-01

    Cyclohexyl ketone substrate analogue inhibitors (Ac–pSer-Ψ[C = OCH]-Pip–tryptamine) of Pin1, the cell cycle regulatory peptidyl-prolyl isomerase (PPIase), were designed and synthesized as potential electrophilic acceptors for the Pin1 active site Cys113 nucleophile to test a proposed nucleophilic addition-isomerization mechanism. Because they were weak inhibitors, models of all three stereoisomers were docked into the active site of Pin1. Each isomer consistently minimized to a trans-diaxial cyclohexane conformation. From this, we hypothesize that Pin1 stretches substrates into a trans-pyrrolidine conformation to lower the barrier to isomerization. Our reduced amide inhibitor of Pin1 adopted a similar trans-pyrrolidine conformation in the crystal structure. The molecular model of 1, which mimics the l-Ser-l-Pro stereochemistry, in the Pin1 active site showed a distance of 4.4 Å, and an angle of 31° between Cys113-S and the ketone carbon. The computational models suggest that the mechanism of Pin1 PPIase is not likely to proceed through nucleophilic addition. PMID:23028504

  17. Cyclohexyl ketone inhibitors of Pin1 dock in a trans-diaxial cyclohexane conformation.

    Directory of Open Access Journals (Sweden)

    Guoyan G Xu

    Full Text Available Cyclohexyl ketone substrate analogue inhibitors (Ac-pSer-Ψ[C = OCH]-Pip-tryptamine of Pin1, the cell cycle regulatory peptidyl-prolyl isomerase (PPIase, were designed and synthesized as potential electrophilic acceptors for the Pin1 active site Cys113 nucleophile to test a proposed nucleophilic addition-isomerization mechanism. Because they were weak inhibitors, models of all three stereoisomers were docked into the active site of Pin1. Each isomer consistently minimized to a trans-diaxial cyclohexane conformation. From this, we hypothesize that Pin1 stretches substrates into a trans-pyrrolidine conformation to lower the barrier to isomerization. Our reduced amide inhibitor of Pin1 adopted a similar trans-pyrrolidine conformation in the crystal structure. The molecular model of 1, which mimics the l-Ser-l-Pro stereochemistry, in the Pin1 active site showed a distance of 4.4 Å, and an angle of 31° between Cys113-S and the ketone carbon. The computational models suggest that the mechanism of Pin1 PPIase is not likely to proceed through nucleophilic addition.

  18. Down-regulation of Pin1 in Temporal Lobe Epilepsy Patients and Mouse Model.

    Science.gov (United States)

    Tang, Lan; Zhang, Yanke; Chen, Guojun; Xiong, Yan; Wang, Xuefeng; Zhu, Binglin

    2017-02-27

    Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) is a unique PPIase belonging to the parvulin family, and it isomerizes peptide bond between phospho-(Ser/Thr) and Pro. Pin1 has been linked to the pathogenesis of various human diseases; however, its exact biological functions remain unclear. The aim of the present study is to explore the expression pattern of Pin1 in patients with refractory epilepsy and in a chronic pilocarpine-induced epileptic mouse model. Using Western blot, immunofluorescence and immunoprecipitation analysis, we found that Pin1 protein was mainly distributed in neurons, demonstrated by colocalization with the dendritic marker, MAP2. However, the expression of Pin1 decreased remarkably in epileptic patients and experimental mice. Furthermore, the reciprocal coimmunoprecipitation analysis showed that Pin1 interacted with NR2A and NR2B-containing NMDA receptors not AMPA receptors in epileptic mouse models. Our results are the first to indicate that the expression of Pin1 in epileptic brain tissue could play important roles in epilepsy.

  19. Parathyroid incidentalomas detected during thyroid ultrasonography and effect of chronic thyroiditis on false positive parathyroid lesions.

    Science.gov (United States)

    Ozdemir, Didem; Arpaci, Dilek; Ucler, Rifki; Cuhaci, Neslihan; Ersoy, Reyhan; Cakir, Bekir

    2012-12-01

    We aimed to determine the prevalence of parathyroid incidentalomas in patients referred for thyroid ultrasonography (US) and investigate the role of chronic thyroiditis on false positive lesions. Patients suspected to have parathyroid lesions during thyroid US were recorded prospectively between August 2009 and January 2010. Patients referred for parathyroid US and patients with known high serum calcium or parathyroid hormone (PTH) levels were excluded. Suspected parathyroid lesions were defined as hypoechoic, homogeneous, solid lesions with regular margins located outside the thyroid lobe, most commonly inferior to the thyroid gland. Thyroid US was performed in 6,528 patients. There were 78 patients (1.19 %) (73 female and 5 male) with suspected parathyroid lesion. The diagnosis of a true parathyroid adenoma was confirmed in 6 (7.69 %) patients. In patients with true adenoma, mean serum calcium, phosphorus, and PTH levels were 10.57 ± 0.48 mg/dl, 3.03 ± 0.52 mg/dl, and 182.91 ± 46.62 pg/ml, respectively. Among 72 patients with false positive parathyroid lesion, antithyroid peroxidase antibody was positive in 50 (69.4 %), antithyroglobulin antibody was positive in 46 (63.9 %), and one of these antibodies were positive in 59 (81.9 %) patients. Also, 46 (63.9 %) of these patients had thyroid dysfunctions (43 hypothyroidism and 3 hyperthyroidism) and 59 (81.9 %) had chronic thyroiditis ultrasonographically. Parathyroid incidentaloma was detected in 0.09 % of patients referred for thyroid US. The presence of clinically or ultrasonographically chronic thyroiditis might cause inadvertent interpretation of a hypoechoic lesion as a parathyroid pathology during thyroid US.

  20. Imaging diagnosis of ectopic parathyroid lesions in patients with hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Okuda, Itsuko; Kokubo, Takashi; Kurosaki, Atsuko; Suzuki, Noriyuki; Maruno, Hirotaka; Murata, Hajime [Toranomon Hospital, Tokyo (Japan)

    1998-10-01

    We present 9 cases of ectopic parathyroid lesions in which histological diagnosis is confirmed. We analyze the findings of imaging modalities including {sup 99m}Tc-MIBI scintigraphy, Tl-Tc subtraction imaging, ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI), and we assess the usefulness of those imagings in determination of the location of the ectopic parathyroid lesion. MIBI scintigraphy was thought to be most useful for detection of the ectopic parathyroid lesion. (author)

  1. Cellular peptidyl-prolyl cis/trans isomerase Pin1 facilitates replication of feline coronavirus.

    Science.gov (United States)

    Tanaka, Yoshikazu; Amano, Arisa; Morisaki, Masateru; Sato, Yuka; Sasaki, Takashi

    2016-02-01

    Although feline coronavirus (FCoV) causes feline infectious peritonitis (FIP), which is a fatal infectious disease, there are no effective therapeutic medicines or vaccines. Previously, in vitro studies have shown that cyclosporin (CsA) and FK506 inhibit virus replication in diverse coronaviruses. CsA and FK506 are targets of clinically relevant immunosuppressive drugs and bind to cellular cyclophilins (Cyps) or FK506 binding proteins (FKBPs), respectively. Both Cyp and FKBP have peptidyl-prolyl cis-trans isomerase (PPIase) activity. However, protein interacting with NIMA (Pin1), a member of the parvulin subfamily of PPIases that differs from Cyps and FKBPs, is essential for various signaling pathways. Here we demonstrated that genetic silencing or knockout of Pin1 resulted in decreased FCoV replication in vitro. Dipentamethylene thiuram monosulfide, a specific inhibitor of Pin1, inhibited FCoV replication. These data indicate that Pin1 modulates FCoV propagation.

  2. Inhibition of Proliferation of Human Osteosarcoma Cells Transfected with PIN1 Antisense Gene

    Institute of Scientific and Technical Information of China (English)

    XIONG Wenhua; CHEN Anmin; GUO Fengjin

    2006-01-01

    Objective: To evaluate the inhibition of proliferation of human osteosarcoma cells transfected with Pin1 anti-sense gene. Methods: Different doses of antisense Pin1 gene (0, 20, 50, 100, 200, 250μL) were transfected into osteosarcoma MG-63 cells. The cells and culture supernatant before and after transfection were collected. The curve of cell growth was made by MTT method. The cell growth cycle and apoptosis were detected by FCM. The expression of Pin1 was detected by Western-blot and that of Pin1 mRNA by polymerase chain reaction (RT-PCR) respectively. Results: MTT and FCM assays indicated that the transfection by antisense Pin1 gene could inhibit MG-63 proliferation and induce apoptosis. Western-blot assays revealed that the antisense Pin1 gene-transfected MG-63 cells had weaker staining than those without transfected with antisense Pin1 gene, and staining intensity was negatively related with doses. The cells transfected by different doses of gene (0, 20, 50, 100, 200, 250μL) had different absorbance rate: 0.854±0.136, 0.866±0.138, 0.732±0.154, 0.611±0.121, 0.547±0.109, 0.398±0.113,0.320±0.151 respectively, with the difference being significant by F and q test (P<0.05). The expression of Pin1 mRNA had the similar results and its absorbance rate was 0.983±0.125, 0.988±0.127, 0.915±0.157,0.786±0.125, 0.608±0.124, 0.433±0.130, 0.410±0.158 respectively (P<0.05). Conclusion: The expression of Pin1 mRNA in MG-63 cells could be inhibited by antisense Pin1 gene, so to reduce the expression of Pin1 and depress the proliferation of human osteosarcoma cells MG-63.

  3. Cyclic Peptidyl Inhibitors against Human Peptidyl-Prolyl Isomerase Pin1

    Science.gov (United States)

    Liu, Tao; Liu, Yu; Kao, Hung-Ying; Pei, Dehua

    2010-01-01

    Peptidyl-prolyl isomerase Pin1 regulates the function and/or stability of phosphoproteins by altering the conformation of specific pSer/pThr-Pro peptide bonds. In this work, a cyclic peptide library was synthesized and screened against the catalytic domain of human Pin1. The selected inhibitors contained a consensus motif of D-pThr-Pip-Nal (where Pip is L-piperidine-2-carboxylic acid and Nal is L-2-naphthylalanine). Representative compounds were tested for binding to Pin1 by isothermal titration calorimetry and inhibition of Pin1 activity and the most potent inhibitors had KD (and KI) values in the low nanomolar range. Treatment of breast cancer cells with the inhibitors, which were rendered membrane permeable by attachment of an octaarginine sequence, inhibited cell proliferation and increased the protein levels of two previously established Pin1 substrates, PML and SMRT. Finally, a second generation of cell permeable Pin1 inhibitors was designed by replacing the noncritical residues within the cyclic peptide ring with arginine residues and shown to have anti-proliferative activity against the cancer cells. PMID:20180533

  4. Pin1: Intimate involvement with the regulatory protein kinase networks in the global phosphorylation landscape.

    Science.gov (United States)

    Litchfield, David W; Shilton, Brian H; Brandl, Christopher J; Gyenis, Laszlo

    2015-10-01

    Protein phosphorylation is a universal regulatory mechanism that involves an extensive network of protein kinases. The discovery of the phosphorylation-dependent peptidyl-prolyl isomerase Pin1 added an additional layer of complexity to these regulatory networks. We have evaluated interactions between Pin1 and the regulatory kinome and proline-dependent phosphoproteome taking into consideration findings from targeted studies as well as data that has emerged from systematic phosphoproteomic workflows and from curated protein interaction databases. The relationship between Pin1 and the regulatory protein kinase networks is not restricted simply to the recognition of proteins that are substrates for proline-directed kinases. In this respect, Pin1 itself is phosphorylated in cells by protein kinases that modulate its functional properties. Furthermore, the phosphorylation-dependent targets of Pin1 include a number of protein kinases as well as other enzymes such as phosphatases and regulatory subunits of kinases that modulate the actions of protein kinases. As a result of its interactions with numerous protein kinases and their substrates, as well as itself being a target for phosphorylation, Pin1 has an intricate relationship with the regulatory protein kinase and phosphoproteomic networks that orchestrate complex cellular processes and respond to environmental cues. This article is part of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts and Drug Targets. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Parathyroid carcinoma: case report

    Science.gov (United States)

    STURNIOLO, G.; GAGLIANO, E.; TONANTE, A.; TARANTO, F.; PAPALIA, E.; CASCIO, R.; DAMIANO, C.; VERMIGLIO, F.; STURNIOLO, G.

    2013-01-01

    Summary: The authors present a case of parathyroid carcinoma in a patient with primary hyperparathyroidism. Following a literature review, the clinical and diagnostic profile, treatment and prognosis of this rare disease are discussed. PMID:23837957

  6. Parathyroid Cancer Treatment

    Science.gov (United States)

    ... parathyroid glands. The thyroid gland lies at the base of the throat near the trachea. It is ... the neck and takes pictures. Blood flow and metabolism are higher than normal in areas where cancer ...

  7. Calpastatin is regulated by protein never in mitosis gene A interacting-1 (PIN1) in endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Tongzheng, E-mail: liu.tongzheng@mayo.edu [Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905 (United States); Schneider, Ryan A., E-mail: schneiderr@findlay.edu [College of Pharmacy, The University of Findlay, Findlay, OH 45840 (United States); Hoyt, Dale G., E-mail: hoyt.27@osu.edu [The Dorothy M. Davis Heart and Lung Research Institute, and the Division of Pharmacology, College of Pharmacy, The Ohio State University, 500 West Twelfth Avenue, Columbus, OH 43210 (United States)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer Depletion of PIN1 increases inhibitory effect of calpastatin against calpain in endothelial cells. Black-Right-Pointing-Pointer PIN1 associates with calpastatin. Black-Right-Pointing-Pointer PIN1, but not mutants, reduces the inhibitory activity of calpastatin in vitro. Black-Right-Pointing-Pointer Depletion of calpastatin shows that it is required for PIN1 depletion to reduce calpain activity. -- Abstract: The peptidyl-proline isomerase, protein never in mitosis gene A interacting-1 (PIN1) binds and isomerizes proteins phosphorylated on serine/threonine before a proline. It was previously found that depletion of PIN1 greatly increased induction of cyclooxygenase-2 and inducible nitric oxide synthase by lowering calpain activity in murine aortic endothelial cells (MAEC). Here we investigated the effect of PIN1 on the endogenous inhibitor of heterodimeric {mu}- and m-calpains, calpastatin. MAEC were transduced with small hairpin (sh) RNA to knock down PIN1 (KD) or an inactive Control shRNA. Cells were also treated with non-targeted double stranded small inhibitory RNA (siRNA) or siRNA designed to deplete calpastatin. Despite reducing calpain activity, PIN1 KD did not significantly affect the expression of {mu}- and m-calpains, or calpastatin, compared to Control shRNA. Instead, depletion of PIN1 increased the inhibitory activity of calpastatin. Calpastatin co-immunoprecipitated with endogenous PIN1 and was pulled down with glutathione-S-transferase (GST)-PIN1 fusion protein. Adding GST-PIN1 to KD cell extracts lacking PIN1 reduced calpastatin inhibitory activity. Substrate binding and catalytic domain mutants of PIN1 failed to do so. These results suggest that protein interaction and the proline isomerase functions of PIN1 are required for it to inhibit calpastatin. Furthermore, depletion of calpastatin raised calpain activity and reduced calpain inhibitory activity to similar levels in KD and Control MAEC, indicating that

  8. Glucose inhibits root meristem growth via ABA INSENSITIVE 5, which represses PIN1 accumulation and auxin activity in Arabidopsis.

    Science.gov (United States)

    Yuan, Ting-Ting; Xu, Heng-Hao; Zhang, Kun-Xiao; Guo, Ting-Ting; Lu, Ying-Tang

    2014-06-01

    Glucose functions as a hormone-like signalling molecule that modulates plant growth and development in Arabidopsis thaliana. However, the role of glucose in root elongation remains elusive. Our study demonstrates that high concentrations of glucose reduce the size of the root meristem zone by repressing PIN1 accumulation and thereby reducing auxin levels. In addition, we verified the involvement of ABA INSENSITIVE 5 (ABI5) in this process by showing that abi5-1 is less sensitive to glucose than the wild type, whereas glucose induces ABI5 expression and the inducible overexpression of ABI5 reduces the size of the root meristem zone. Furthermore, the inducible overexpression of ABI5 in PIN1::PIN1-GFP plants reduces the level of PIN1-GFP, but glucose reduces the level of PIN1-GFP to a lesser extent in abi5-1 PIN1::PIN1-GFP plants than in the PIN1::PIN1-GFP control, suggesting that ABI5 is involved in glucose-regulated PIN1 accumulation. Taken together, our data suggest that ABI5 functions in the glucose-mediated inhibition of the root meristem zone by repressing PIN1 accumulation, thus leading to reduced auxin levels in roots. © 2013 John Wiley & Sons Ltd.

  9. Inhibitory effects of PIN1 antisense gene on the proliferation of human osteosarcoma cells

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To evaluate the inhibitory effects of PIN1 antisense gene on the proliferation of human osteosarcoma cells. Methods: Different doses of antisense PIN1 gene (0,20,50,100,200,250μl) were transfected into osteosarcoma MG-63 cells. The cells and the culture supernatants before and after transfection were collected. The cell growth curve was made using MTT method. The cell growth cycle and apoptosis were detected by FCM. The expression of PIN1 was detected by Western blot. The expression of PIN1 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Results: MTT and FCM assays indicated that the transfection of antisense PIN1 gene could inhibit proliferation of MG-63 cells and lead to cell apoptosis. Western-blot assays revealed the MG-63 cells transfected with antisense PIN1 gene had weaker expression than those without transfection with antisense PIN1 gene, and the band intensity was negatively related with doses. The cells transfected with different doses of gene (0,20,50,100,200,250 μl) had different absorbance rate(0.854 ± 0.136,0. 866 ± 0. 138,0. 732 ± 0. 154, 0. 611 ± 0. 121,0. 547 ± 0. 109,0. 398 ± 0. 113,0. 320 ± 0. 151 ), with significant difference assessed by F and q test ( P < 0.05). The absorbance rate of PINI mRNA was 0. 983 ± 0.125,0.988 ± 0.127, 0.915 ± 0.157,0.786 ± 0.125,0.608 ± 0.124,0.433 ± 0.130,0.410 ± 0. 158 respectively ( P < 0.05). Conclusion: The expression of PINlmRNA in MG-63 cells could be inhibited by antisense PIN1 gene, and then the expression of PIN1 was reduced and depressed, and so the proliferation of human osteosarcoma cells MG-63 was inhibited.

  10. Structural Basis for High-Affinity Peptide Inhibition of Human Pin1

    Science.gov (United States)

    Zhang, Yan; Daum, Sebastian; Wildemann, Dirk; Zhou, Xiao Zhen; Verdecia, Mark A.; Bowman, Marianne E.; Lücke, Christian; Hunter, Tony; Lu, Kun-Ping; Fischer, Gunter; Noel, Joseph P.

    2009-01-01

    Human Pin1 is a key regulator of cell-cycle progression and plays growth-promoting roles in human cancers. High-affinity inhibitors of Pin1 may provide a unique opportunity for disrupting oncogenic pathways. Here we report two high-resolution X-ray crystal structures of human Pin1 bound to non-natural peptide inhibitors. The structures of the bound high-affinity peptides identify a type-I β-turn conformation for Pin1 prolyl peptide isomerase domain–peptide binding and an extensive molecular interface for high-affinity recognition. Moreover, these structures suggest chemical elements that may further improve the affinity and pharmacological properties of future peptide-based Pin inhibitors. Finally, an intramolecular hydrogen bond observed in both peptide complexes mimics the cyclic conformation of FK506 and rapamycin. Both FK506 and rapamycin are clinically important inhibitors of other peptidyl-prolyl cis-trans isomerases. This comparative discovery suggests that a cyclic peptide polyketide bridge, like that found in FK506 and rapamycin or a similar linkage, may significantly improve the binding affinity of structure-based Pin1 inhibitors. PMID:17518432

  11. Exploring the molecular function of PIN1 by nuclear magnetic resonance.

    Science.gov (United States)

    Landrieu, Isabelle; Smet, C; Wieruszeski, J-M; Sambo, A-V; Wintjens, R; Buée, L; Lippens, G

    2006-06-01

    PIN1 participates in the regulation of a number of signalling pathways in the cell involving protein phosphorylation/dephosphorylation. Its role seems to be an essential control level in addition to the protein phosphorylation by proline-directed kinases. Its cellular function includes regulation of the cell cycle by interaction with phosphorylated mitotic proteins such as Cdc25 and transcription factors such as p53. PIN1 was shown to be involved in the malignant transformation of cells in breast cancer, by up regulation of cyclinD1 and is thought to be involved in the development of the AD by regulating the function of phosphorylated Tau. We propose here to discuss the molecular function of PIN1 at the atomic level based on data from the recent literature and our own results obtained by the technique of Nuclear Magnetic Resonance. PIN1 specifically interacts with pThr/pSer-Pro motifs and is constituted by two domains: a WW N-terminal domain that binds pThr/pSer-Pro epitopes and a prolyl cis/trans isomerase C-terminal catalytic domain. An exception to this organisation is found in the plant PIN1 homologous enzymes, like PIN1At from Arabidopsis thaliana, that are constituted of the sole catalytic domain. The molecular function of PIN1, binding to and isomerization of pThr/pSer-Pro bonds, are thought to lead to several functional consequences. In a first mode of action, exemplified by its competition with the CKS protein, the interaction with PIN1 prevents interaction with other regulatory proteins, like ubiquitin-ligases that lead to degradation pathways. In a second mode of action, the idea is largely accepted that the local isomerization modifies the global conformation of the protein substrate and hence its intrinsic activity, although this has never been directly demonstrated. Finally, isomerization catalysis is thought to regulate the (de)phosphorylation of specific pThr/pSer-Pro motifs, exemplified by the stimulation of the dephosphorylation of pThr231 of Tau

  12. Parathyroid gland adenoma: Case report

    OpenAIRE

    Bojković Gradimir; Čaparević Zorica; Stojanović Dragoš Lj.; Lalošević Đorđe J.; Stojanović Mirjana

    2003-01-01

    Introduction Primary hyperparathyroidism is a generalized disorder resulting from excessive secretion of parathyroid hormone involving one or more parathyroid glands. Both familial and sporadic forms exist. Histologic examination reveals parathyroid adenoma in about 90% of patients, although it is sometimes difficult to distinguish an adenoma from a normal gland. Primary hyperparathyroidism is commonly characterized by hypercalcaemia, hypophosphatemia and excessive bone resorption. Case repor...

  13. Parathyroid Carcinoma: Current Understanding and New Insights into Gene Expression and Intraoperative Parathyroid Hormone Kinetics

    OpenAIRE

    Abdelgadir Adam, Mohamed; Untch, Brian R.; Olson, John A.

    2010-01-01

    This review summarizes the current knowledge on parathyroid carcinoma and describes new information on parathyroid carcinoma gene expression and operative management using intraoperative parathyroid hormone monitoring.

  14. Thyroid and parathyroid imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sandler, M.P.; Patton, J.A.; Partain, C.L.

    1986-01-01

    This book describes the numerous modalities currently used in the diagnosis and treatment of both thyroid and parathyroid disorders. Each modality is fully explained and then evaluated in terms of benefits and limitations in the clinical context. Contents: Production and Quality Control of Radiopharmaceutics Used for Diagnosis and Therapy in Thyroid and Parathyroid Disorders. Basic Physics. Nuclear Instrumentation. Radioimmunoassay: Thyroid Function Tests. Quality Control. Embryology, Anatomy, Physiology, and Thyroid Function Studies. Scintigraphic Thyroid Imaging. Neonatal and Pediatric Thyroid Imaging. Radioiodine Thyroid Uptake Measurement. Radioiodine Treatment of Thyroid Disorders. Radiation Dosimetry of Diagnostic Procedures. Radiation Safety Procedures for High-Level I-131 Therapies. X-Ray Fluorescent Scanning. Thyroid Sonography. Computed Tomography in Thyroid Disease. Magnetic Resonance Imaging in Thyroid Disease. Parathyroid Imaging.

  15. Peptidyl-prolyl isomerase 1 (Pin1) preserves the phosphorylation state of tissue factor and prolongs its release within microvesicles.

    Science.gov (United States)

    Ettelaie, Camille; Collier, Mary E W; Featherby, Sophie; Greenman, John; Maraveyas, Anthony

    2017-09-26

    The exposure and release of TF is regulated by post-translational modifications of its cytoplasmic domain. Here, the potential of Pin1 to interact with the cytoplasmic domain of TF, and the outcome on TF function was examined. MDA-MB-231 and transfected-primary endothelial cells were incubated with either Pin1 deactivator Juglone, or its control Plumbagin, as well as transfected with Pin1-specific or control siRNA. TF release into microvesicles following activation, and also phosphorylation and ubiquitination states of cellular-TF were then assessed. Furthermore, the ability of Pin1 to bind wild-type and mutant forms of overexpressed TF-tGFP was investigated by co-immunoprecipitation. Additionally, the ability of recombinant or cellular Pin1 to bind to peptides of the C-terminus of TF, synthesised in different phosphorylation states was examined by binding assays and spectroscopically. Finally, the influence of recombinant Pin1 on the ubiquitination and dephosphorylation of the TF-peptides was examined. Pre-incubation of Pin1 with Juglone but not Plumbagin, reduced TF release as microvesicles and was also achievable following transfection with Pin1-siRNA. This was concurrent with early ubiquitination and dephosphorylation of cellular TF at Ser253. Pin1 co-immunoprecipitated with overexpressed wild-type TF-tGFP but not Ser258→Ala or Pro259→Ala substituted mutants. Pin1 did interact with Ser258-phosphorylated and double-phosphorylated TF-peptides, with the former having higher affinity. Finally, recombinant Pin1 was capable of interfering with the ubiquitination and dephosphorylation of TF-derived peptides. In conclusion, Pin1 is a fast-acting enzyme which may be utilised by cells to protect the phosphorylation state of TF in activated cells prolonging TF activity and release, and therefore ensuring adequate haemostasis. Copyright © 2017. Published by Elsevier B.V.

  16. Magnetic Resonance Imaging of Thyroid and Parathyroid

    Directory of Open Access Journals (Sweden)

    Miguel Gonzalo-Domínguez

    2016-11-01

    Full Text Available Introduction: The assessment of the thyroid and parathyroid pathology is usually achieved with ultrasounds. There are several systems of classification that are internationally accepted in neoplastic disease, such as TIRADS system, and there are well-defined patterns for ultrasound imaging in inflammatory disease. Material and methods: However, there are specific needs that require magnetic resonance imaging. We review the main indications of MRI in the evaluation of thyroid and parathyroid in 64 patients and determine which protocols are more appropriate and which sequences are better for a proper characterization. Results: Then we review the semiology obtained by this technique, making correlation with disease processes affecting these cervical structures.

  17. Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations

    Directory of Open Access Journals (Sweden)

    Yusuke Nakatsu

    2016-09-01

    Full Text Available Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14. Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer’s disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions.

  18. Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations.

    Science.gov (United States)

    Nakatsu, Yusuke; Matsunaga, Yasuka; Yamamotoya, Takeshi; Ueda, Koji; Inoue, Yuki; Mori, Keiichi; Sakoda, Hideyuki; Fujishiro, Midori; Ono, Hiraku; Kushiyama, Akifumi; Asano, Tomoichiro

    2016-09-07

    Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14). Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer's disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions.

  19. Structure of human Sp140 PHD finger: an atypical fold interacting with Pin1.

    Science.gov (United States)

    Zucchelli, Chiara; Tamburri, Simone; Quilici, Giacomo; Palagano, Eleonora; Berardi, Andrea; Saare, Mario; Peterson, Pärt; Bachi, Angela; Musco, Giovanna

    2014-01-01

    Sp140 is a nuclear leukocyte-specific protein involved in primary biliary cirrhosis and a risk factor in chronic lymphocytic leukemia. The presence of several chromatin related modules such as plant homeodomain (PHD), bromodomain and SAND domain suggests a role in chromatin-mediated regulation of gene expression; however, its real function is still elusive. Herein we present the solution structure of Sp140-PHD finger and investigate its role as epigenetic reader in vitro. Sp140-PHD presents an atypical PHD finger fold which does not bind to histone H3 tails but is recognized by peptidylprolyl isomerase Pin1. Pin1 specifically binds to a phosphopeptide corresponding to the L3 loop of Sp140-PHD and catalyzes cis-trans isomerization of a pThr-Pro bond. Moreover co-immunoprecipitation experiments demonstrate FLAG-Sp140 interaction with endogenous Pin1 in vivo. Overall these data include Sp140 in the list of the increasing number of Pin1 binders and expand the regulatory potential of PHD fingers as versatile structural platforms for diversified interactions. © 2013 FEBS.

  20. [Inflammation of the parathyroid glands].

    Science.gov (United States)

    Ting, S; Synoracki, S; Sheu, S-Y; Schmid, K W

    2016-05-01

    Inflammation of the parathyroid glands is rare when compared to other endocrine organs. This leads to the use of descriptive terms as well as the lack of a generally accepted classification for inflammatory disorders of the parathyroid glands. This review article proposes that parathyroid inflammation be subdivided morphologically into (a) non-specific lymphocytic infiltration, which is more an expression of damage to small vessels, due to e. g. severe systemic inflammation or myocardial infarction, (b) autoimmunogenic lymphocytic parathyroiditis, (c) nonimmunogenic inflammation caused by granulomatous diseases or infections and (d) invasive sclerosing (peri) parathyroiditis. As only parathyroid glands removed due to hyperparathyroidism and normal parathyroid glands incidentally removed during thyroid surgery are seen almost exclusively in routine histopathology, virtually no information about the morphological correlate of hypoparathyroidism is available.

  1. Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKD.

    Science.gov (United States)

    Miller, Gerald; Davis, James; Shatzen, Edward; Colloton, Matthew; Martin, David; Henley, Charles M

    2012-06-01

    Secondary hyperparathyroidism (sHPT) represents an adaptive response to progressively impaired control of calcium, phosphorus and vitamin D in chronic kidney disease (CKD). It is characterized by parathyroid hyperplasia and excessive synthesis and secretion of parathyroid hormone (PTH). Parathyroid hyperplasia in uremic rats can be prevented by calcium-sensing receptor (CaSR) activation with the calcimimetic cinacalcet (Sensipar®/Mimpara®); however, it is unknown, how long the effects of cinacalcet persist after withdrawal of treatment or if cinacalcet is efficacious in uremic rats with established sHPT. We sought to determine the effect of cinacalcet discontinuation in uremic rats and whether cinacalcet was capable of influencing parathyroid hyperplasia in animals with established sHPT. Discontinuation of cinacalcet resulted in reversal of the beneficial effects on serum PTH and parathyroid hyperplasia. In rats with established sHPT, cinacalcet decreased serum PTH and mediated regression of parathyroid hyperplasia. The cinacalcet-mediated decrease in parathyroid gland size was accompanied by increased expression of the cyclin-dependent kinase inhibitor p21. Prevention of cellular proliferation with cinacalcet occurred despite increased serum phosphorus and decreased serum calcium. The animal data provided suggest established parathyroid hyperplasia can be reversed by modulating CaSR activity with cinacalcet and that continued treatment may be necessary to maintain reductions in PTH.

  2. Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKD

    Science.gov (United States)

    Miller, Gerald; Davis, James; Shatzen, Edward; Colloton, Matthew; Martin, David

    2012-01-01

    Background. Secondary hyperparathyroidism (sHPT) represents an adaptive response to progressively impaired control of calcium, phosphorus and vitamin D in chronic kidney disease (CKD). It is characterized by parathyroid hyperplasia and excessive synthesis and secretion of parathyroid hormone (PTH). Parathyroid hyperplasia in uremic rats can be prevented by calcium-sensing receptor (CaSR) activation with the calcimimetic cinacalcet (Sensipar®/Mimpara®); however, it is unknown, how long the effects of cinacalcet persist after withdrawal of treatment or if cinacalcet is efficacious in uremic rats with established sHPT. Methods. We sought to determine the effect of cinacalcet discontinuation in uremic rats and whether cinacalcet was capable of influencing parathyroid hyperplasia in animals with established sHPT. Results. Discontinuation of cinacalcet resulted in reversal of the beneficial effects on serum PTH and parathyroid hyperplasia. In rats with established sHPT, cinacalcet decreased serum PTH and mediated regression of parathyroid hyperplasia. The cinacalcet-mediated decrease in parathyroid gland size was accompanied by increased expression of the cyclin-dependent kinase inhibitor p21. Prevention of cellular proliferation with cinacalcet occurred despite increased serum phosphorus and decreased serum calcium. Conclusions. The animal data provided suggest established parathyroid hyperplasia can be reversed by modulating CaSR activity with cinacalcet and that continued treatment may be necessary to maintain reductions in PTH. PMID:22036941

  3. Pin1-mediated Modification Prolongs the Nuclear Retention of β-Catenin in Wnt3a-induced Osteoblast Differentiation*

    Science.gov (United States)

    Shin, Hye-Rim; Islam, Rabia; Yoon, Won-Joon; Lee, Taegyung; Cho, Young-Dan; Bae, Han-sol; Kim, Bong-Su; Woo, Kyung-Mi; Baek, Jeong-Hwa; Ryoo, Hyun-Mo

    2016-01-01

    The canonical Wnt signaling pathway, in which β-catenin nuclear localization is a crucial step, plays an important role in osteoblast differentiation. Pin1, a prolyl isomerase, is also known as a key enzyme in osteogenesis. However, the role of Pin1 in canonical Wnt signal-induced osteoblast differentiation is poorly understood. We found that Pin1 deficiency caused osteopenia and reduction of β-catenin in bone lining cells. Similarly, Pin1 knockdown or treatment with Pin1 inhibitors strongly decreased the nuclear β-catenin level, TOP flash activity, and expression of bone marker genes induced by canonical Wnt activation and vice versa in Pin1 overexpression. Pin1 interacts directly with and isomerizes β-catenin in the nucleus. The isomerized β-catenin could not bind to nuclear adenomatous polyposis coli, which drives β-catenin out of the nucleus for proteasomal degradation, which consequently increases the retention of β-catenin in the nucleus and might explain the decrease of β-catenin ubiquitination. These results indicate that Pin1 could be a critical target to modulate β-catenin-mediated osteogenesis. PMID:26740630

  4. Characterizing the interactions between prolyl isomerase pin1 and phosphatase inhibitor-2 in living cells with FRET and FCS

    Science.gov (United States)

    Sun, Yuansheng; Wang, Lifu; Jyothikumar, Vinod; Brautigan, David L.; Periasamy, Ammasi

    2012-03-01

    Phosphatase inhibitor-2 (I2) was discovered as a regulator of protein Ser/Thr phosphatase-1 and is conserved from yeast to human. Binding between purified recombinant I2 from different species and the prolyl isomerase Pin1 has been demonstrated with pull-down assays, size exclusion chromatography and nuclear magnetic resonance spectroscopy. Despite this, questions persist as to whether these proteins associate together in living cells. In this study, we prepared fluorescent protein (FP) fusions of I2 and Pin1 and employed both Förster Resonance Energy Transfer (FRET) and Fluorescence Correlation Spectroscopy (FCS) imaging techniques to characterize their interactions in living cells. In both intensity-based and time-resolved FRET studies, we observed FRET uniformly across whole cells co-expressing I2-Cerulean and Pin1-Venus that was significantly higher than in negative controls expressing Cerulean FP (without fusing to I2) as the FRET donor and Pin1-Venus, showing a specific interaction between I2-Cerulean and Pin1-Venus in living cells. We also observed the co-diffusion of I2-Cerulean and Pin1-mCherry in Fluorescence Cross Correlation Spectroscopy (FCCS) measurements. We further showed that I2 itself as well as I2-Pin1 formed complexes in living cells (predicted from in vitro studies) via a quantitative FRET assay, and demonstrated from FCS measurements that both I2 and Pin1 (fused to Cerulean) are highly mobile in living cells.

  5. BARREN INFLORESCENCE2 interaction with ZmPIN1a suggests a role in auxin transport during maize inflorescence development.

    Science.gov (United States)

    Skirpan, Andrea; Culler, Angela Hendrickson; Gallavotti, Andrea; Jackson, David; Cohen, Jerry D; McSteen, Paula

    2009-03-01

    Polar auxin transport, mediated by the PIN-FORMED (PIN) class of auxin efflux carriers, controls organ initiation in plants. In maize, BARREN INFLORESCENCE2 (BIF2) encodes a serine/threonine protein kinase co-orthologous to PINOID (PID), which regulates the subcellular localization of AtPIN1 in Arabidopsis. We show that BIF2 phosphorylates ZmPIN1a, a maize homolog of AtPIN1, in vitro and regulates ZmPIN1a subcellular localization in vivo, similar to the role of PID in Arabidopsis. In addition, bif2 mutant inflorescences have lower auxin levels later in development. We propose that BIF2 regulates auxin transport through direct regulation of ZmPIN1a during maize inflorescence development.

  6. [Phosphate sensing and parathyroid gland].

    Science.gov (United States)

    Mizobuchi, Masahide; Suzuki, Taihei

    2012-10-01

    In the latter 1990s, phosphate, as well as calcium, has been shown to have a direct action on parathyroid function. Since then although many researchers have tried to detect the phosphate sensor in parathyroid gland, none has found it yet. In 2000s, the importance of FGF23 was revealed in patients with autosomal dominant hypophosphatemic rickets and then investigating the role of FGF23 in mineral metabolism has spread. FGF23 target organs comprise those that express coreceptor Klotho, such as kidney and parathyroid glands. While associations of calcium sensing receptor or vitamin D receptor with parathyroid function have been mainly investigated for parathyroid dysfunction, many efforts recently have made to study the effects of FGF23 on parathyroid glands.

  7. [Mediastinal parathyroid cyst].

    Science.gov (United States)

    Togashi, K; Sato, Y; Yazawa, M

    1991-07-01

    A 66-year-old woman, having no complaint, admitted our clinic, because of a mass in the right superior mediastinum detected three years ago on chest X-ray. The operation was performed through the right thoracotomy in December of 1989. The thin-walled cyst located adjacent to the trachea between superior vena cava and back bones, occupied from beneath the innominate artery to the right main bronchus. The tumor (7 x 5 x 5 cm) weighing 80 grams had a smooth surface and contained watery fluid. Histological examination showed a cyst lined a monolayer of cuboidal epithelium. The cyst wall consisted of parathyroid tissue. Mediastinal parathyroid cyst is very rare. Since the first report of DeQuervain, 15 cases have been reported. These reports are reviewed.

  8. Parathyroid adenoma. Case presentation

    Directory of Open Access Journals (Sweden)

    Daniel Olivera Fajardo

    2016-10-01

    Full Text Available Parathyroid Adenoma is a non-malignant tumor of the thyroid glands, which increases the levels of parathormone. This hormone regulates blood and bone levels of calcium, phosphorus and Vitamin D. Its classic triad is characterized by the increase of the levels of parathormone, hyperkalimia and Hipophosphatemia. This entity affects between 500-1000 inhabitants and is the main cause of primary Hyperparathyroidism in about 80-85% of the patients. It is presented a case of a 69 year old female patient, admitted due to pathologic fractures of hip, clavicle, and fingers, caused by primary hyperparathyroidism originated by parathyroid adenoma. For the low incidence of this entity, its publication is considered of interest for the scientific staff.

  9. Targeting prolyl-isomerase Pin1 prevents mitochondrial oxidative stress and vascular dysfunction: insights in patients with diabetes.

    Science.gov (United States)

    Paneni, Francesco; Costantino, Sarah; Castello, Lorenzo; Battista, Rodolfo; Capretti, Giuliana; Chiandotto, Sergio; D'Amario, Domenico; Scavone, Giuseppe; Villano, Angelo; Rustighi, Alessandra; Crea, Filippo; Pitocco, Dario; Lanza, Gaetano; Volpe, Massimo; Del Sal, Giannino; Lüscher, Thomas F; Cosentino, Francesco

    2015-04-01

    Diabetes is a major driver of cardiovascular disease, but the underlying mechanisms remain elusive. Prolyl-isomerase Pin1 recognizes specific peptide bonds and modulates function of proteins altering cellular homoeostasis. The present study investigates Pin1 role in diabetes-induced vascular disease. In human aortic endothelial cells (HAECs) exposed to high glucose, up-regulation of Pin1-induced mitochondrial translocation of pro-oxidant adaptor p66(Shc) and subsequent organelle disruption. In this setting, Pin1 recognizes Ser-116 inhibitory phosphorylation of endothelial nitric oxide synthase (eNOS) leading to eNOS-caveolin-1 interaction and reduced NO availability. Pin1 also mediates hyperglycaemia-induced nuclear translocation of NF-κB p65, triggering VCAM-1, ICAM-1, and MCP-1 expression. Indeed, gene silencing of Pin1 in HAECs suppressed p66(Shc)-dependent ROS production, restored NO release and blunted NF-kB p65 nuclear translocation. Consistently, diabetic Pin1(-/-) mice were protected against mitochondrial oxidative stress, endothelial dysfunction, and vascular inflammation. Increased expression and activity of Pin1 were also found in peripheral blood monocytes isolated from diabetic patients when compared with age-matched healthy controls. Interestingly, enough, Pin1 up-regulation was associated with impaired flow-mediated dilation, increased urinary 8-iso-prostaglandin F2α and plasma levels of adhesion molecules. Pin1 drives diabetic vascular disease by causing mitochondrial oxidative stress, eNOS dysregulation as well as NF-kB-induced inflammation. These findings provide molecular insights for novel mechanism-based therapeutic strategies in patients with diabetes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  10. Parathyroid scintigraphy during hypocalcaemia in primary hyperparathyroidism

    DEFF Research Database (Denmark)

    Øgard, Christina G; Thomsen, Jørn Bo; Jakobsen, Henrik

    2005-01-01

    Minimally invasive parathyroid surgery in patients with primary hyperparathyroidism (PHPT) demands high imaging accuracy. By increasing blood flow to the parathyroid adenoma before injection of a perfusion marker, we intended to improve the parathyroid scintigraphy. We have named the technique...

  11. The carcinoma of parathyroid gland

    OpenAIRE

    Kulkarni P; Parikh Purvish

    2004-01-01

    Parathyroid carcinoma constitutes less than 1% of primary hyperparathyroidism. The exact etiology is not known. Prior radiation to neck, chronic renal failure and genetic factors are thought to play a role. The male to female ratio is one. Parathyroid carcinomas are slow growing, have a tendency to recur locally and metastasize late. 95% of parathyroid carcinomas are functioning. The major distinguishing features of malignant hyperparathyroidism are presence of a palpable mass i...

  12. Pin1-Induced Proline Isomerization in Cytosolic p53 Mediates BAX Activation and Apoptosis.

    Science.gov (United States)

    Follis, Ariele Viacava; Llambi, Fabien; Merritt, Parker; Chipuk, Jerry E; Green, Douglas R; Kriwacki, Richard W

    2015-08-20

    The cytosolic fraction of the tumor suppressor p53 activates the apoptotic effector protein BAX to trigger apoptosis. Here we report that p53 activates BAX through a mechanism different from that associated with activation by BH3 only proteins (BIM and BID). We observed that cis-trans isomerization of proline 47 (Pro47) within p53, an inherently rare molecular event, was required for BAX activation. The prolyl isomerase Pin1 enhanced p53-dependent BAX activation by catalyzing cis-trans interconversion of p53 Pro47. Our results reveal a signaling mechanism whereby proline cis-trans isomerization in one protein triggers conformational and functional changes in a downstream signaling partner. Activation of BAX through the concerted action of cytosolic p53 and Pin1 may integrate cell stress signals to induce a direct apoptotic response. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Association of Parathyroid Gland Biopsy Excision Technique With Ex Vivo Radiation Counts During Radioguided Parathyroid Surgery.

    Science.gov (United States)

    Hinson, Andrew M; Lawson, Bradley R; Franco, Aime T; Stack, Brendan C

    2017-06-01

    Parathyroid biopsy represents a means for normal and hyperfunctional glands to be distinguished intraoperatively. However, no data exist to guide surgeons regarding how much of a parathyroid gland must be biopsied to satisfy the 20% rule. To quantify the relative proportion of a hyperfunctional parathyroid gland that must be evaluated with the gamma probe to satisfy the 20% rule. A retrospective review of surgical data for 24 consecutive patients (16 women, 18 men; mean [SD] age, 66.6 [10] years; range, 51-83 years) who underwent surgery for primary hyperparathyroidism between May and October, 2015, in a tertieary academic medical center. Extirpated parathyroid glands were sectioned into parallel or pie-shaped biopsies and evaluated ex vivo with a gamma probe to determine what percentage of a hyperfunctional gland must be sampled to meet the Norman 20% rule. The hypothesis was formulated during data collection. In total, 253 ex vivo biopsy specimens were obtained from 33 surgically removed parathyroid glands. Parathyroid biopsies satisfied the 20% rule with an accuracy that depended on the relative proportion of the parent gland represented: half or more (96.6%; 95% CI, 91.7%-100.0%), a quarter to one-half (87.0%; 95% CI, 79.3%-94.7%), less than a quarter (63.6%; 95% CI, 54.5%-72.8%). When less than a quarter of the gland was removed, pie-shaped biopsies were more likely to satisfy the 20% rule compared with parallel biopsies of the same weight (78.4% vs 56.2%; absolute difference, 22.2%; 95% CI, 4.7%-39.7%). Unless half of a parathyroid gland is biopsied during radioguided parathyroidectomy, the 20% rule cannot reliably rule out the presence of a hyperfunctional parathyroid lesion. Pie-shaped biopsies originating from the center of the gland are associated with a lower rate of false-negative results compared with peripheral biopsies of similar size. Pie-shaped biopsies and biopsy of half or more of each nonexcised parathyroid gland for ex vivo counts may increase

  14. Brown Algae Polyphenol, a Prolyl Isomerase Pin1 Inhibitor, Prevents Obesity by Inhibiting the Differentiation of Stem Cells into Adipocytes

    Science.gov (United States)

    Suzuki, Atsuko; Saeki, Toshiyuki; Ikuji, Hiroko; Uchida, Chiyoko; Uchida, Takafumi

    2016-01-01

    Background While screening for an inhibitor of the peptidyl prolyl cis/trans isomerase, Pin1, we came across a brown algae polyphenol that blocks the differentiation of fibroblasts into adipocytes. However, its effectiveness on the accumulation of fat in the body has never been studied. Methodology/Principal Findings Oral administration of brown algae polyphenol to mice fed with a high fat diet, suppressed the increase in fat volume to a level observed in mice fed with a normal diet. We speculate that Pin1 might be required for the differentiation of stem cell to adipocytes. We established wild type (WT) and Pin1-/- (Pin1-KO) adipose-derived mesenchymal stem cell (ASC) lines and found that WT ASCs differentiate to adipocytes but Pin1-KO ASCs do not. Conclusion and Significance Oral administration of brown algae polyphenol, a Pin1 inhibitor, reduced fat buildup in mice. We showed that Pin1 is required for the differentiation of stem cells into adipocytes. We propose that oral intake of brown algae polyphenol is useful for the treatment of obesity. PMID:28036348

  15. Pin1 associates with and induces translocation of CRTC2 to the cytosol, thereby suppressing cAMP-responsive element transcriptional activity.

    Science.gov (United States)

    Nakatsu, Yusuke; Sakoda, Hideyuki; Kushiyama, Akifumi; Ono, Hiraku; Fujishiro, Midori; Horike, Nanao; Yoneda, Masayasu; Ohno, Haruya; Tsuchiya, Yoshihiro; Kamata, Hideaki; Tahara, Hidetoshi; Isobe, Toshiaki; Nishimura, Fusanori; Katagiri, Hideki; Oka, Yoshitomo; Fukushima, Toshiaki; Takahashi, Shin-Ichiro; Kurihara, Hiroki; Uchida, Takafumi; Asano, Tomoichiro

    2010-10-22

    Pin1 is a unique regulator, which catalyzes the conversion of a specific phospho-Ser/Thr-Pro-containing motif in target proteins. Herein, we identified CRTC2 as a Pin1-binding protein by overexpressing Pin1 with Myc and FLAG tags in mouse livers and subsequent purification of the complex containing Pin1. The association between Pin1 and CRTC2 was observed not only in overexpression experiments but also endogenously in the mouse liver. Interestingly, Ser(136) in the nuclear localization signal of CRTC2 was shown to be involved in the association with Pin1. Pin1 overexpression in HepG2 cells attenuated forskolin-induced nuclear localization of CRTC2 and cAMP-responsive element (CRE) transcriptional activity, whereas gene knockdown of Pin1 by siRNA enhanced both. Pin1 also associated with CRTC1, leading to their cytosol localization, essentially similar to the action of CRTC2. Furthermore, it was shown that CRTC2 associated with Pin1 did not bind to CREB. Taken together, these observations indicate the association of Pin1 with CRTC2 to decrease the nuclear CBP·CRTC·CREB complex. Indeed, adenoviral gene transfer of Pin1 into diabetic mice improved hyperglycemia in conjunction with normalizing phosphoenolpyruvate carboxykinase mRNA expression levels, which is regulated by CRE transcriptional activity. In conclusion, Pin1 regulates CRE transcriptional activity, by associating with CRTC1 or CRTC2.

  16. Nonfunctional parathyroid cyst: case report

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Molinari Nardi

    Full Text Available CONTEXT: Parathyroid cysts are rare clinical and pathological entities, with less than 300 cases reported. The inferior parathyroid glands are most commonly involved, with left-side predominance. Parathyroid cysts may be functional or nonfunctional, depending on their association with hypercalcemia. CASE REPORT: A 25-year-old man presented a palpable asymptomatic left-side neck mass. Ultrasound revealed a cystic structure contiguous with the left thyroid lobe. Serum ionic calcium was normal. The patient underwent left thyroid lobectomy plus isthmectomy with excision of the cyst. The histological findings revealed a parathyroid cyst. Parathyroid cysts typically present as asymptomatic neck masses, and surgical excision appears to be the treatment of choice.

  17. Calcium-sensing receptor expression and parathyroid hormone secretion in hyperplastic parathyroid glands from humans.

    Science.gov (United States)

    Cañadillas, Sagrario; Canalejo, Antonio; Santamaría, Rafael; Rodríguez, Maria E; Estepa, Jose C; Martín-Malo, Alejandro; Bravo, Juan; Ramos, Blanca; Aguilera-Tejero, Escolastico; Rodríguez, Mariano; Almadén, Yolanda

    2005-07-01

    In uremic patients, severe parathyroid hyperplasia is associated with reduced parathyroid calcium-sensing receptor (CaR) expression. Thus, in these patients, a high serum Ca concentration may be required to inhibit parathyroid hormone (PTH) secretion. This study compares the magnitude of reduction in CaR expression and the degree of the abnormality in Ca-regulated PTH release in vitro. A total of 50 glands from 23 hemodialysis patients with refractory hyperparathyroidism were studied. Tissue slices were incubated in vitro to evaluate (1) the PTH secretory output in a normal Ca concentration (1.25 mM) and (2) the PTH secretory response to high (1.5 mM) and low (0.6 mM) Ca concentration. Tissue aliquots were processed for determination of CaRmRNA expression. The results showed that, corrected for DNA, parathyroid tissue with lowest CaR expression secreted more PTH than that with relatively high CaR expression (146 +/- 23 versus 60 +/- 2 pg/microg DNA; P < 0.01). Furthermore, glands with low CaR expression demonstrated a blunted PTH secretory response to both the inhibitory effect of high Ca and the stimulatory effect of low Ca. The study also showed that the larger the gland, the lower the CaRmRNA expression. Thus, large parathyroid glands produce a large amount of PTH not only as a result of the increased gland size but also because the parathyroid tissue secretory output is increased. These abnormalities in PTH regulation are related to low CaR expression.

  18. PARATHYROID CYTOLOGY: A DIAGNOSTIC DILEMMA

    Directory of Open Access Journals (Sweden)

    Naval Kishore Bajaj

    2016-09-01

    Full Text Available INTRODUCTION Neck nodules are common in clinical practice which are accessible to Fine needle aspiration cytology (FNAC. Thyroid being the commonest organ to present as the nodular lesions. Parathyroid lesions can be incidentally encountered during FNA of a thyroid nodule Fine needle aspiration cytology is a safe economical and leading investigation in the diagnosis of neck nodules. Thyroid and parathyroid nodules are indistinguishable clinically. An attempt is made to familiarise the pathologist about the cytomorphological features of parathyroid nodules and simple approach to differentiate from thyroid nodules. MATERIALS AND METHODS It is a retrospective study conducted over a period of 5 years from 2011-2016. Twelve cases of histologically proven parathyroidal lesions are the subjects of study of which 4 cases were diagnosed as parathyroidal cyst and rest as parathyroid adenoma. All the cases underwent fine needle aspiration cytology under ultrasound guidance, Smears were made, stained by H & E and PAP staining method, the slides were reviewed by two cytopathologists. Biochemical and radiological findings were evaluated before giving definitive cytological diagnosis. RESULTS A total number of 12 cases which were histologically proven as parathyroidal lesion. Out of which 4 were cystic lesions which were excluded from the study. Rest of the 8 cases confirmed as parathyroid adenoma which had FNAC were evaluated. 5 cases had positive cytohistological correlation. Three out of 8 cases were diagnosed as papillary carcinoma of thyroid, Toxic nodular goitre and Hurthle cell neoplasm due to varied cytomorphology. CONCLUSION Parathyroidal lesions has got low sensitivity and specificity in cytology. The confident diagnosis of parathyroid neoplasm was made in conjunction with biochemical and advanced radiological imaging. In neck nodules which are asymptomatic and at abnormal locations, FNAC through its cytomorphological features has an edge in

  19. The rotamase Pin1 is up-regulated, hypophosphorylated and required for cell cycle progression in head and neck squamous cell carcinomas.

    Science.gov (United States)

    Wiegand, Susanne; Dakic, Branka; Rath, Ariane F E; Makarova, Galina; Sterz, Carolina; Meissner, Wolfgang; Bette, Michael; Adamkiewicz, Jürgen; Müller-Brüsselbach, Sabine; Müller, Rolf; Werner, Jochen A; Mandic, Robert

    2009-10-01

    The peptidyl-prolyl cis/trans isomerase Pin1 has been implicated in malignant transformation in multiple studies, however, little is known about its potential impact in head and neck cancer. This study evaluates the role of Pin1 in head and neck squamous cell carcinomas (HNSCCs). Pin1 expression and level of phosphorylation was evaluated by Western blot analysis and 2D-gel-electrophoresis. Pin1 was inhibited with juglone (5-hydroxy-1,4-naphthalenedione) or Pin1 specific siRNA and its influence on cell cycle checkpoint distribution was assessed by FACS analysis. Pin1 overexpression was found in HNSCC tissues and cell lines. 2D-gel-electrophoresis data pointed to Pin1 being hypophosphorylated in HNSCC cells which is consistent with overactivation of this rotamase. Inhibition of HNSCC cells with juglone or Pin1 siRNA induced the cell cycle inhibitor p21(WAF1/Cip1) with a concomitant reduction of cells in G2/M and an increased fraction of cells with fragmented DNA. Cell death did not correlate with significant levels of apoptosis in Pin1 depleted HNSCC cells. In summary, the data shows that Pin1 is overexpressed and hypophosphorylated in HNSCC, and that inhibition of Pin1 blocks cell cycle progression and triggers tumor cell death. Pin1 therefore could represent a new target for the development of improved HNSCC targeting drugs.

  20. Prolyl isomerase Pin1 regulates doxorubicin-inducible P-glycoprotein level by reducing Foxo3 stability.

    Science.gov (United States)

    Shimizu, Taiki; Bamba, Yoshimasa; Kawabe, Yosuke; Fukuda, Tomokazu; Fujimori, Fumihiro; Takahashi, Katsuhiko; Uchida, Chiyoko; Uchida, Takafumi

    2016-03-01

    It has been known that the phosphoSer/Thr-Pro-specific peptidyl prolyl cis/trans isomerase Pin1 regulates a variety of intracellular signaling pathways, including the response to the genotoxic drug doxorubicin. Pin1 binds phosphorylated p53 and stabilizes p53 to cause cell cycle arrest and apoptosis quickly in response to doxorubicin. Here we show another mechanism of Pin1 to maintain cell sensitivity to genotoxic stress, irrespective of whether p53 is present or not. In response to the genotoxic drug, Pin1 binds and decreases levels of the phosphorylated Foxo3, the positive transcription factor of P-glycoprotein (P-gp) gene. Through this mechanism of action, Pin1 decreases the level of P-gp and signals the cell to pump the genotoxic drugs out. This shows that Pin1 is implemented in maintaining the susceptibility to the genotoxic drugs by controlling P-gp level as well as p53-dependent apoptosis and cell cycle signaling pathways.

  1. Modeling conformational ensembles of slow functional motions in Pin1-WW.

    Directory of Open Access Journals (Sweden)

    Faruck Morcos

    Full Text Available Protein-protein interactions are often mediated by flexible loops that experience conformational dynamics on the microsecond to millisecond time scales. NMR relaxation studies can map these dynamics. However, defining the network of inter-converting conformers that underlie the relaxation data remains generally challenging. Here, we combine NMR relaxation experiments with simulation to visualize networks of inter-converting conformers. We demonstrate our approach with the apo Pin1-WW domain, for which NMR has revealed conformational dynamics of a flexible loop in the millisecond range. We sample and cluster the free energy landscape using Markov State Models (MSM with major and minor exchange states with high correlation with the NMR relaxation data and low NOE violations. These MSM are hierarchical ensembles of slowly interconverting, metastable macrostates and rapidly interconverting microstates. We found a low population state that consists primarily of holo-like conformations and is a "hub" visited by most pathways between macrostates. These results suggest that conformational equilibria between holo-like and alternative conformers pre-exist in the intrinsic dynamics of apo Pin1-WW. Analysis using MutInf, a mutual information method for quantifying correlated motions, reveals that WW dynamics not only play a role in substrate recognition, but also may help couple the substrate binding site on the WW domain to the one on the catalytic domain. Our work represents an important step towards building networks of inter-converting conformational states and is generally applicable.

  2. General Information about Parathyroid Cancer

    Science.gov (United States)

    ... parathyroid glands. The thyroid gland lies at the base of the throat near the trachea. It is ... the neck and takes pictures. Blood flow and metabolism are higher than normal in areas where cancer ...

  3. Parathyroid hormone (PTH) blood test

    Science.gov (United States)

    ... excess calcium supplements or certain antacids, that contain calcium carbonate or sodium bicarbonate (baking soda) Parathyroid glands do ... More 25-hydroxy vitamin D test Bone tumor Calcium ... level Malabsorption Milk-alkali syndrome Multiple endocrine neoplasia (MEN) I Multiple ...

  4. [Applied embryology of parathyroid glands].

    Science.gov (United States)

    Henry, J F; Sebag, F

    2006-01-01

    The article describes the normal structure of the parathyroid glands (PTG) and their development, anomalies of migration in the process of embryogenesis and congenital ectopias of PTG as well as possible supplementary PTG and their congenital ectopias.

  5. Multisite phosphorylation of Pin1-associated mitotic phosphoproteins revealed by monoclonal antibodies MPM-2 and CC-3

    Directory of Open Access Journals (Sweden)

    Vincent Michel

    2004-06-01

    Full Text Available Abstract Background The peptidyl-prolyl isomerase Pin1 recently revealed itself as a new player in the regulation of protein function by phosphorylation. Pin1 isomerizes the peptide bond of specific phosphorylated serine or threonine residues preceding proline in several proteins involved in various cellular events including mitosis, transcription, differentiation and DNA damage response. Many Pin1 substrates are antigens of the phosphodependent monoclonal antibody MPM-2, which reacts with a subset of proteins phosphorylated at the G2/M transition. Results As MPM-2 is not a general marker of mitotic phosphoproteins, and as most mitotic substrates are phosphorylated more than once, we used a different phosphodependent antibody, mAb CC-3, to identify additional mitotic phosphoproteins and eventual Pin1 substrates by combining affinity purification, MALDI-TOF mass spectrometry and immunoblotting. Most CC-3-reactive phosphoproteins appeared to be known or novel MPM-2 antigens and included the RNA-binding protein p54nrb/nmt55, the spliceosomal protein SAP155, the Ki-67 antigen, MAP-1B, DNA topoisomerases II α and β, the elongation factor hSpt5 and the largest subunit of RNA polymerase II. The CC-3 mitotic antigens were also shown to be Pin1 targets. The fine CC-3- and MPM-2-epitope mapping of the RNA polymerase II carboxy-terminal domain confirmed that the epitopes were different and could be generated in vitro by distinct kinases. Finally, the post-mitotic dephosphorylation of both CC-3 and MPM-2 antigens was prevented when cellular Pin1 activity was blocked by the selective inhibitor juglone. Conclusion These observations indicate that the mitotic phosphoproteins associated with Pin1 are phosphorylated on multiple sites, suggesting combinatorial regulation of substrate recognition and isomerization.

  6. Molecular implication of PP2A and Pin1 in the Alzheimer's disease specific hyperphosphorylation of Tau.

    Directory of Open Access Journals (Sweden)

    Isabelle Landrieu

    Full Text Available BACKGROUND: Tau phosphorylation and dephosphorylation regulate in a poorly understood manner its physiological role of microtubule stabilization, and equally its integration in Alzheimer disease (AD related fibrils. A specific phospho-pattern will result from the balance between kinases and phosphatases. The heterotrimeric Protein Phosphatase type 2A encompassing regulatory subunit PR55/Bα (PP2A(T55α is a major Tau phosphatase in vivo, which contributes to its final phosphorylation state. We use NMR spectroscopy to determine the dephosphorylation rates of phospho-Tau by this major brain phosphatase, and present site-specific and kinetic data for the individual sites including the pS202/pT205 AT8 and pT231 AT180 phospho-epitopes. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate the importance of the PR55/Bα regulatory subunit of PP2A within this enzymatic process, and show that, unexpectedly, phosphorylation at the pT231 AT180 site negatively interferes with the dephosphorylation of the pS202/pT205 AT8 site. This inhibitory effect can be released by the phosphorylation dependent prolyl cis/trans isomerase Pin1. Because the stimulatory effect is lost with the dimeric PP2A core enzyme (PP2A(D or with a phospho-Tau T231A mutant, we propose that Pin1 regulates the interaction between the PR55/Bα subunit and the AT180 phospho-epitope on Tau. CONCLUSIONS/SIGNIFICANCE: Our results show that phosphorylation of T231 (AT180 can negatively influence the dephosphorylation of the pS202/pT205 AT8 epitope, even without an altered PP2A pool. Thus, a priming dephosphorylation of pT231 AT180 is required for efficient PP2A(T55α-mediated dephosphorylation of pS202/pT205 AT8. The sophisticated interplay between priming mechanisms reported for certain Tau kinases and the one described here for Tau phosphatase PP2A(T55α may contribute to the hyperphosphorylation of Tau observed in AD neurons.

  7. Prolyl isomerase Pin1 negatively regulates AMP-activated protein kinase (AMPK) by associating with the CBS domain in the γ subunit.

    Science.gov (United States)

    Nakatsu, Yusuke; Iwashita, Misaki; Sakoda, Hideyuki; Ono, Hiraku; Nagata, Kengo; Matsunaga, Yasuka; Fukushima, Toshiaki; Fujishiro, Midori; Kushiyama, Akifumi; Kamata, Hideaki; Takahashi, Shin-Ichiro; Katagiri, Hideki; Honda, Hiroaki; Kiyonari, Hiroshi; Uchida, Takafumi; Asano, Tomoichiro

    2015-10-02

    AMP-activated protein kinase (AMPK) plays a critical role in metabolic regulation. In this study, first, it was revealed that Pin1 associates with any isoform of γ, but not with either the α or the β subunit, of AMPK. The association between Pin1 and the AMPK γ1 subunit is mediated by the WW domain of Pin1 and the Thr(211)-Pro-containing motif located in the CBS domain of the γ1 subunit. Importantly, overexpression of Pin1 suppressed AMPK phosphorylation in response to either 2-deoxyglucose or biguanide stimulation, whereas Pin1 knockdown by siRNAs or treatment with Pin1 inhibitors enhanced it. The experiments using recombinant Pin1, AMPK, LKB1, and PP2C proteins revealed that the protective effect of AMP against PP2C-induced AMPKα subunit dephosphorylation was markedly suppressed by the addition of Pin1. In good agreement with the in vitro data, the level of AMPK phosphorylation as well as the expressions of mitochondria-related genes, such as PGC-1α, which are known to be positively regulated by AMPK, were markedly higher with reduced triglyceride accumulation in the muscles of Pin1 KO mice as compared with controls. These findings suggest that Pin1 plays an important role in the pathogenic mechanisms underlying impaired glucose and lipid metabolism, functioning as a negative regulator of AMPK. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. The peptidyl-prolyl isomerase Pin1 up-regulation and proapoptotic function in dopaminergic neurons: relevance to the pathogenesis of Parkinson disease.

    Science.gov (United States)

    Ghosh, Anamitra; Saminathan, Hariharan; Kanthasamy, Arthi; Anantharam, Vellareddy; Jin, Huajun; Sondarva, Gautam; Harischandra, Dilshan S; Qian, Ziqing; Rana, Ajay; Kanthasamy, Anumantha G

    2013-07-26

    Parkinson disease (PD) is a chronic neurodegenerative disease characterized by a slow and progressive degeneration of dopaminergic neurons in substantia nigra. The pathophysiological mechanisms underlying PD remain unclear. Pin1, a major peptidyl-prolyl isomerase, has recently been associated with certain diseases. Notably, Ryo et al. (Ryo, A., Togo, T., Nakai, T., Hirai, A., Nishi, M., Yamaguchi, A., Suzuki, K., Hirayasu, Y., Kobayashi, H., Perrem, K., Liou, Y. C., and Aoki, I. (2006) J. Biol. Chem. 281, 4117-4125) implicated Pin1 in PD pathology. Therefore, we sought to systematically characterize the role of Pin1 in PD using cell culture and animal models. To our surprise we observed a dramatic up-regulation of Pin1 mRNA and protein levels in dopaminergic MN9D neuronal cells treated with the parkinsonian toxicant 1-methyl-4-phenylpyridinium (MPP(+)) as well as in the substantia nigra of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Notably, a marked expression of Pin1 was also observed in the substantia nigra of human PD brains along with a high co-localization of Pin1 within dopaminergic neurons. In functional studies, siRNA-mediated knockdown of Pin1 almost completely prevented MPP(+)-induced caspase-3 activation and DNA fragmentation, indicating that Pin1 plays a proapoptotic role. Interestingly, multiple pharmacological Pin1 inhibitors, including juglone, attenuated MPP(+)-induced Pin1 up-regulation, α-synuclein aggregation, caspase-3 activation, and cell death. Furthermore, juglone treatment in the MPTP mouse model of PD suppressed Pin1 levels and improved locomotor deficits, dopamine depletion, and nigral dopaminergic neuronal loss. Collectively, our findings demonstrate for the first time that Pin1 is up-regulated in PD and has a pathophysiological role in the nigrostriatal dopaminergic system and suggest that modulation of Pin1 levels may be a useful translational therapeutic strategy in PD.

  9. Differential Roles of PIN1 and PIN2 in Root Meristem Maintenance Under Low-B Conditions in Arabidopsis thaliana.

    Science.gov (United States)

    Li, Ke; Kamiya, Takehiro; Fujiwara, Toru

    2015-06-01

    Boron (B) is an essential element for plants; its deficiency causes rapid cessation of root elongation. In addition, B influences auxin accumulation in plants. To assess the importance of auxin transport in B-dependent root elongation, Arabidopsis thaliana pin1-pin4 mutants were grown under low-B conditions. Among them, only the pin2/eir1-1 mutant showed a significantly shorter root under low-B conditions than under control conditions. Moreover, the root meristem size of pin2/eir1-1 was reduced under low-B conditions. Among the PIN-FORMED (PIN) family, PIN1 and PIN2 are important for root meristem growth/maintenance under normal conditions. To investigate the differential response of pin1 and pin2 mutants under low-B conditions, the effect of low-B on PIN1-green fluorescent protein (GFP) and PIN2-GFP accumulation and localization was examined. Low-B did not affect PIN2-GFP, while it reduced the accumulation of PIN1-GFP. Moreover, no signal from DII-VENUS, an auxin sensor, was detected under the low-B condition in the stele of wild-type root meristems. Taken together, these results indicate that under low-B conditions PIN1 is down-regulated and PIN2 plays an important role in root meristem maintenance. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Correlation of subtraction parathyroid scintigraphy with weight, pathohistologic finding and oxyphil cell content of parathyroid glands in parathyroid hyperplasia

    Directory of Open Access Journals (Sweden)

    Dugonjić Sanja

    2012-01-01

    patients nodular PHP. There was no statistically significant difference in SPS results compared to hyperplasia type, and between OC content and hyperplasia type. A significant positive correlation (p = 0.05 was found between PG weight and hyperplasia type. Conclusion. A high positive correlation was found between SPS results and PG weight, PG weight and OC content and PG weight and hyperplasia type. Between SPS results and OC content, and between SPS results and hyperplasia type, an insignificant correlation was found. Our results showed that SPS is a reliable and very sensitive diagnostic tool in detecting abnormal PG in parathyroid hyperplasia, reaching 100% sensitivity in detecting a “dominant gland” and sensitivity per localized gland of 70%. Causes that affect increased uptake of liposolubile Tc99m radiopharmaceuticals (RF in the hyperfunctional PG tissue and conditions which prevent RF admission into the PG cells still remain to be accurately and precisely determined.

  11. Parathyroid Disorders - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Parathyroid Disorders URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Parathyroid Disorders - Multiple Languages To use the sharing features ...

  12. Parathyroid hormone-related protein blood test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003691.htm Parathyroid hormone-related protein blood test To use the ... features on this page, please enable JavaScript. The parathyroid hormone-related protein (PTH-RP) test measures the ...

  13. The Origin of the Parathyroid Gland

    National Research Council Canada - National Science Library

    Masataka Okabe; Anthony Graham; John C. Gerhart

    2004-01-01

    It has long been held that the parathyroid glands and parathyroid hormone evolved with the emergence of the tetrapods, reflecting a need for new controls on calcium homeostasis in terrestrial, rather...

  14. Epigenetic Alterations in Parathyroid Cancers

    Directory of Open Access Journals (Sweden)

    Chiara Verdelli

    2017-02-01

    Full Text Available Parathyroid cancers (PCas are rare malignancies representing approximately 0.005% of all cancers. PCas are a rare cause of primary hyperparathyroidism, which is the third most common endocrine disease, mainly related to parathyroid benign tumors. About 90% of PCas are hormonally active hypersecreting parathormone (PTH; consequently patients present with complications of severe hypercalcemia. Pre-operative diagnosis is often difficult due to clinical features shared with benign parathyroid lesions. Surgery provides the current best chance of cure, though persistent or recurrent disease occurs in about 50% of patients with PCas. Somatic inactivating mutations of CDC73/HRPT2 gene, encoding parafibromin, are the most frequent genetic anomalies occurring in PCas. Recently, the aberrant DNA methylation signature and microRNA expression profile have been identified in PCas, providing evidence that parathyroid malignancies are distinct entities from parathyroid benign lesions, showing an epigenetic signature resembling some embryonic aspects. The present paper reviews data about epigenetic alterations in PCas, up to now limited to DNA methylation, chromatin regulators and microRNA profile.

  15. Epigenetic Alterations in Parathyroid Cancers

    Science.gov (United States)

    Verdelli, Chiara; Corbetta, Sabrina

    2017-01-01

    Parathyroid cancers (PCas) are rare malignancies representing approximately 0.005% of all cancers. PCas are a rare cause of primary hyperparathyroidism, which is the third most common endocrine disease, mainly related to parathyroid benign tumors. About 90% of PCas are hormonally active hypersecreting parathormone (PTH); consequently patients present with complications of severe hypercalcemia. Pre-operative diagnosis is often difficult due to clinical features shared with benign parathyroid lesions. Surgery provides the current best chance of cure, though persistent or recurrent disease occurs in about 50% of patients with PCas. Somatic inactivating mutations of CDC73/HRPT2 gene, encoding parafibromin, are the most frequent genetic anomalies occurring in PCas. Recently, the aberrant DNA methylation signature and microRNA expression profile have been identified in PCas, providing evidence that parathyroid malignancies are distinct entities from parathyroid benign lesions, showing an epigenetic signature resembling some embryonic aspects. The present paper reviews data about epigenetic alterations in PCas, up to now limited to DNA methylation, chromatin regulators and microRNA profile. PMID:28157158

  16. Peptidyl prolyl isomerase Pin1-inhibitory activity of D-glutamic and D-aspartic acid derivatives bearing a cyclic aliphatic amine moiety.

    Science.gov (United States)

    Nakagawa, Hidehiko; Seike, Suguru; Sugimoto, Masatoshi; Ieda, Naoya; Kawaguchi, Mitsuyasu; Suzuki, Takayoshi; Miyata, Naoki

    2015-12-01

    Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis-trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic aliphatic amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity.

  17. Pathology of the parathyroid glands in hyperparathyroidism.

    Science.gov (United States)

    Baloch, Zubair W; LiVolsi, Virginia A

    2013-08-01

    This paper reviews the embryology, histology and pathology of the human parathyroid glands. It emphasizes those pathologic lesions which are found in the setting of clinical hyperparathyroidism. Also discussed are certain molecular features of hyperfunctioning parathyroid glands. The difficulties encountered in parathyroid FNA are reviewed and illustrated.

  18. Digestive manifestations of parathyroid disorders

    Institute of Scientific and Technical Information of China (English)

    Bassam Abboud; Ronald Daher; Joe Boujaoude

    2011-01-01

    The parathyroid glands are the main regulator of plasma calcium and have a direct influence on the digestive tract. Parathyroid disturbances often result in unknown long-standing symptoms. The main manifestation of hypoparathyroidism is steatorrhea due to a deficit in exocrine pancreas secretion. The association with celiac sprue may contribute to malabsorption. Hyperparathyroidism causes smooth-muscle atony, with upper and lower gastrointestinal symptoms such as nausea, heartburn and constipation. Hyperparathyroidism and peptic ulcer were strongly linked before the advent of proton pump inhibitors. Nowadays, this association remains likely only in the particular context of multiple endocrine neoplasia type 1/Zollinger-Ellison syndrome. In contrast to chronic pancreatitis, acute pancreatitis due to primary hyperparathyroidism is one of the most studied topics. The causative effect of high calcium level is confirmed and the distinction from secondary hyperparathyroidism is mandatory. The digestive manifestations of parathyroid malfunction are often overlooked and serum calcium level must be included in the routine workup for abdominal symptoms.

  19. Octreotide Uptake in Parathyroid Adenoma

    Science.gov (United States)

    Karaçavuş, Seyhan; Kula, Mustafa; Cihan Karaca, Züleyha; Ünlühızarcı, Kürşad; Tutuş, Ahmet; Bayram, Fahri; Çoban, Ganime

    2012-01-01

    The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB) and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive Conflict of interest:None declared. PMID:23487397

  20. Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability

    Directory of Open Access Journals (Sweden)

    Lu Kun

    2008-12-01

    Full Text Available Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7% stained positive for Her2 (IHC 3+, and 54% (122/223 of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5% were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2

  1. Methylation of specific CpG sites in the P2 promoter of parathyroid hormone-related protein determines the invasive potential of breast cancer cell lines.

    Science.gov (United States)

    Tost, Jörg; Hamzaoui, Hinda; Busato, Florence; Neyret, Aymeric; Mourah, Samia; Dupont, Jean-Michel; Bouizar, Zhor

    2011-08-01

    Parathyroid hormone-related protein (PTHrP) is upregulated in primary breast cancers and a major candidate for osteoclastic bone resorption present at sites of breast cancer to bone metastases. Using a human model of mammary epithelial cell lines differing in tumorigenicity and PTHrP expression, we investigated the role of epigenetic modifications for PTHrP expression. Quantitative analysis of the DNA methylation patterns at a total of 104 CpGs in the promoter region of PTHrP by pyrosequencing showed the absence of methylation in all analyzed cell lines in the large CpG island upstream of exon 1C. In the second intron of promoter 2 (P2) a region was identified containing 4 CpG nucleotides for which differential methylation correlated with the PTHrP expression level. The functional importance of this control mechanism was confirmed by the ability of the demethylating agent 5'-azacytidine to induce PTHrP mRNA and iPTHrP protein expression in previously non-expressing cell lines and increase their production by metastatic NS2T2A1 cells. In particular, transcription from P2 was activated non-tumoral S1T3 cells upon treatment with 5'-azacytidine. Our findings support the hypothesis that the methylation status of specific CpG dinucleotides is the dominant mechanism involved in silencing of PTHrP expression rather than the overall methylation of the CpG island. Methylation of the PTHrP P2 is a potential marker of breast cancer progression and might be used to evaluate the metastatic potential of breast tumors.

  2. The role of menin in parathyroid tumorigenesis.

    LENUS (Irish Health Repository)

    Davenport, Colin

    2009-01-01

    Primary hyperparathyroidism is a common disorder that involves the pathological enlargement of one or more parathyroid glands resulting in excessive production of parathyroid hormone (PTH). The exact pathogenesis of this disease remains to be fully understood. In recent years interest has focussed on the interaction between menin protein and the transforming growth factor (TGF)-beta\\/Smad signalling pathway. In vitro experimentation has demonstrated that the presence of menin is required for TGF-beta to effectively inhibit parathyroid cell proliferation and PTH production. This observation correlates with the almost universal occurrence of parathyroid tumors accompanying the inactivation of menin in multiple endocrine neoplasia Type 1 (MEN1) syndrome and the high rate of somatic menin gene mutations seen in sporadic parathyroid adenomas. This chapter aims to review the role of menin in primary hyperparathyroidism and parathyroid hormone-regulation, including the influences of MEN1 gene mutations on parathyroid cell proliferation, differentiation and tumorigenesis.

  3. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, pParathyroid hormone may be associated with cognitive performance.

  4. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, pcognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  5. Parathyroid Hormone in Osteoporosis Treatment

    Directory of Open Access Journals (Sweden)

    İ. Özkul

    2002-03-01

    Full Text Available Parathyroid hormone stimulates bone formation, prevents or reverses bone loss, increases bone mass, bone strength and provides protection against fractures. PTH treatment for postmenopausal, male and glucocorticoid- induced osteoporosis proved to be effective in a number of RCTs.

  6. Octreotide Uptake in Parathyroid Adenoma

    Directory of Open Access Journals (Sweden)

    Seyhan Karaçavuş

    2012-08-01

    Full Text Available The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive parathyroid tumors. (MIRT 2012;21:77-79

  7. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, pself-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  8. Parathyroid diseases and animal models.

    Science.gov (United States)

    Imanishi, Yasuo; Nagata, Yuki; Inaba, Masaaki

    2012-01-01

    CIRCULATING CALCIUM AND PHOSPHATE ARE TIGHTLY REGULATED BY THREE HORMONES: the active form of vitamin D (1,25-dihydroxyvitamin D), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). PTH acts to stimulate a rapid increment in serum calcium and has a crucial role in calcium homeostasis. Major target organs of PTH are kidney and bone. The oversecretion of the hormone results in hypercalcemia, caused by increased intestinal calcium absorption, reduced renal calcium clearance, and mobilization of calcium from bone in primary hyperparathyroidism. In chronic kidney disease, secondary hyperparathyroidism of uremia is observed in its early stages, and this finally develops into the autonomous secretion of PTH during maintenance hemodialysis. Receptors in parathyroid cells, such as the calcium-sensing receptor, vitamin D receptor, and FGF receptor (FGFR)-Klotho complex have crucial roles in the regulation of PTH secretion. Genes such as Cyclin D1, RET, MEN1, HRPT2, and CDKN1B have been identified in parathyroid diseases. Genetically engineered animals with these receptors and the associated genes have provided us with valuable information on the patho-physiology of parathyroid diseases. The application of these animal models is significant for the development of new therapies.

  9. Expression of parathyroid-specific genes in vascular endothelial progenitors of normal and tumoral parathyroid glands.

    Science.gov (United States)

    Corbetta, Sabrina; Belicchi, Marzia; Pisati, Federica; Meregalli, Mirella; Eller-Vainicher, Cristina; Vicentini, Leonardo; Beck-Peccoz, Paolo; Spada, Anna; Torrente, Yvan

    2009-09-01

    Parathyroid tissue is able to spontaneously induce angiogenesis, proliferate, and secrete parathyroid hormone when autotransplanted in patients undergoing total parathyroidectomy. Angiogenesis is also involved in parathyroid tumorigenesis. Here we investigated the anatomical and molecular relationship between endothelial and parathyroid cells within human parathyroid glands. Immunohistochemistry for CD34 antigen identified two subpopulations in normal and tumoral parathyroid glands: one constituted by cells lining small vessels that displayed endothelial antigens (factor VIII, isolectin, laminin, CD146) and the other constituted of single cells scattered throughout the parenchyma that did not express endothelial markers. These parathyroid-derived CD34(+) cells were negative for the hematopoietic and mesenchymal markers CD45, Thy-1/CD90, CD105, and CD117/c-kit; however, a subset of CD34(+) cells co-expressed the parathyroid specific genes glial cell missing B, parathyroid hormone, and calcium sensing receptor. When cultured, these cells released significant amount of parathyroid hormone. Parathyroid-derived CD34(+) cells, but not CD34(-) cells, proliferated slowly and differentiated into mature endothelial cells. CD34(+) cells from parathyroid tumors differed from those derived from normal parathyroid glands as: 1) they were more abundant and mainly scattered throughout the parenchyma; 2) they rarely co-expressed CD146; and 3) a fraction co-expressed nestin. In conclusion, we identified cells expressing endothelial and parathyroid markers in human adult parathyroid glands. These parathyroid/endothelial cells were more abundant and less committed in parathyroid tumors compared with normal glands, showing features of endothelial progenitors, which suggests that they might be involved in parathyroid tumorigenesis.

  10. The parathyroid gland in health and disease.

    Science.gov (United States)

    Ghandur-Mnaymneh, L.; Cassady, J.; Hajianpour, M. A.; Paz, J.; Reiss, E.

    1986-01-01

    The authors studied the parathyroid glands from 100 previously healthy subjects who died suddenly and were admitted to the Dade County Medical Examiner's (ME) morgue and from 66 inpatients who died at Jackson Memorial Hospital (JMH). Parathyroid glands in patients with diseases (JMH series) were heavier than those in healthy persons (ME series), and both groups of glands were significantly heavier than those previously reported. Mean glandular weight in white subjects was 42.6 +/- 20.3 mg, with a range of 22-103 mg. The 95% upper limit of gland weight for healthy white subjects was 73.1 mg and for black subjects, 91.6 mg. The size and weight exhibited a skewed distribution. Gland weight varied with age, increasing to a maximum in the 41-60 year old age group in all subsets except white women, in whom it continued to increase till after age 70. There was slight correlation (r2 = 0.15) of gland weight with body weight within series and race groups; parenchymal content of the glands was not constant but correlated positively with glandular weight. Glands from both series had a comparable fat content. Fat was unevenly distributed throughout the gland, and its amount was highly variable, ranging between 0 and 90%, with a mean of 26% for white subjects and 24% for black subjects in both series. Therefore, percentage fat may not be used as an index of hyperplasia. Healthy back subjects had heavier glands than healthy white subjects, unaccounted for by differences in body weights; this difference was not statistically significant in subjects with disease. Within the black race, glands were not significantly heavier in disease than in health, and in the few cases with serum calcium determinations, the gland weight did not vary inversely with serum calcium levels as in white subjects, suggesting a basic difference in parathyroid calcium metabolism between the two races. PMID:3789088

  11. A high-throughput screen for inhibitors of the prolyl isomerase, Pin1, identifies a seaweed polyphenol that reduces adipose cell differentiation.

    Science.gov (United States)

    Mori, Tadashi; Hidaka, Masafumi; Ikuji, Hiroko; Yoshizawa, Ibuki; Toyohara, Haruhiko; Okuda, Toru; Uchida, Chiyoko; Asano, Tomoichiro; Yotsu-Yamashita, Mari; Uchida, Takafumi

    2014-01-01

    The peptidyl prolyl cis/trans isomerase Pin1 enhances the uptake of triglycerides and the differentiation of fibroblasts into adipose cells in response to insulin stimulation. Pin1 downregulation could be a potential approach to prevent and treat obesity-related disorders. In order to identify an inhibitor of Pin1 that exhibited minimal cytotoxicity, we established a high-throughput screen for Pin1 inhibitors and used this method to identify an inhibitor from 1,056 crude fractions of two natural product libraries. The candidate, a phlorotannin called 974-B, was isolated from the seaweed, Ecklonia kurome. 974-B inhibited the differentiation of mouse embryonic fibroblasts and 3T3-L1 cells into adipose cells without inducing cytotoxicity. We discovered the Pin1 inhibitor, 974-B, from the seaweed, E. kurome, and showed that it blocks the differentiation of fibroblasts into adipose cells, suggesting that 974-B could be a lead drug candidate for obesity-related disorders.

  12. Carcinoma in a mediastinal fifth parathyroid gland

    Energy Technology Data Exchange (ETDEWEB)

    Kastan, D.J.; Kottamasu, S.R.; Frame, B.; Greenwald, K.A.

    1987-03-06

    Commonly four parathyroid glands are located in the neck. The incidence of a fifth supernumery parathyroid gland has been reported to be between 2% and 6%. Most reports of a hyperfunctioning supernumery parathyroid gland have been adenomas. There have been only a few reports of parathyroid gland carcinoma occurring outside of the cervical region, none of which were in a supernumery parathyroid gland. The authors believe this is the first report of a carcinoma occurring in a supernumery parathyroid gland. Following surgery, four views of the chest during a barium swallow examination showed an anterior mediastinal mass. Computed tomographic (CT) scans of the mediastinum confirmed a contrast-enhancing soft-tissue mass anterior to and separate from the aorta.

  13. Phosphorylation switch modulates the interdigitated pattern of PIN1 localization and cell expansion in Arabidopsis leaf epidermis

    Institute of Scientific and Technical Information of China (English)

    Hongjiang Li; Deshu Lin; Pankaj Dhonukshe; Shingo Nagawa; Dandan Chen; Ji(r)í Friml; Ben Scheres; Hongwei Guo; Zhenbiao Yang

    2011-01-01

    Within a multicellular tissue cells may coordinately form a singular or multiple polar axes,but it is unclear whether a common mechanism governs different types of polar axis formation. The phosphorylation status of PIN proteins,which is directly affected by the PINOID (PID) protein kinase and the PP2A protein phosphatase,is known to regulate the apical-basal polarity of PIN localization in bipolar cells of roots and shoot apices. Here,we provide evidence that the phosphorylation status-mediated PIN polarity switch is widely used to modulate cellular processes in Arabidopsis including multipolar pavement cells (PC) with interdigitated lobes and indentations. The degree of PC interdigitation was greatly reduced either when the FYPP1 gene,which encodes a PP2A called phytochromeassociated serine/threonine protein phosphatase,was knocked out or when the PID gene was overexpressed (35S::PID).These genetic modifications caused PIN1 localization to switch from lobe to indentation regions. The PP2A and PID mediated switching of PIN1 localization is strikingly similar to their regulation of the apical-basal polarity switch of PIN proteins in other cells. Our findings suggest a common mechanism for the regulation of PIN1 polarity formation,a fundamental cellular process that is crucial for pattern formation both at the tissue/organ and cellular levels.

  14. Aluminum, parathyroid hormone, and osteomalacia

    Energy Technology Data Exchange (ETDEWEB)

    Burnatowska-Hledin, M.A.; Kaiser, L.; Mayor, G.H.

    1983-01-01

    Aluminum exposure in man is unavoidable. The occurrence of dialysis dementia, vitamin D-resistant osteomalacia, and hypochromic microcytic anemia in dialysis patients underscores the potential for aluminum toxicity. Although exposure via dialysate and hyperalimentation leads to significant tissue aluminum accumulation, the ubiquitous occurrence of aluminum and the severe pathology associated with large aluminum burdens suggest that smaller exposures via the gastrointestinal tract and lungs could represent an important, though largely unrecognized, public health problem. It is clear that some aluminum absorption occurs with the ingestion of small amounts of aluminum in the diet and medicines, and even greater aluminum absorption is seen in individuals consuming large amounts of aluminum present in antacids. Aluminum absorption is enhanced in the presence of elevated circulating parathyroid hormone. In addition, elevated PTH leads to the preferential deposition of aluminum in brain and bone. Consequently, PTH is likely to be involved in the pathogenesis of toxicities in those organs. PTH excess also seems to lead to the deposition of aluminum in the parathyroid gland. The in vitro demonstration that aluminum inhibits parathyroid hormone release is consistent with the findings of a euparathyroid state in dialysis patients with aluminum related vitamin D-resistant osteomalacia. Nevertheless, it seems likely that hyperparathyroidism is at least initially involved in the pathogenesis of aluminum neurotoxicity and osteomalacia; the increases in tissue aluminum stores are followed by suppression of parathyroid hormone release, which is required for the evolution of osteomalacia. Impaired renal function is not a prerequisite for increased tissue aluminum burdens, nor for aluminum-related organ toxicity. Consequently, it is likely that these diseases will be observed in populations other than those with chronic renal disease.

  15. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  16. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  17. The origin of the parathyroid gland

    OpenAIRE

    Okabe, Masataka; Graham, Anthony

    2004-01-01

    It has long been held that the parathyroid glands and parathyroid hormone evolved with the emergence of the tetrapods, reflecting a need for new controls on calcium homeostasis in terrestrial, rather than aquatic, environments. Developmentally, the parathyroid gland is derived from the pharyngeal pouch endoderm, and studies in mice have shown that its formation is under the control of a key regulatory gene, Gcm-2. We have used a phylogenetic analysis of Gcm-2 to probe the evolutionary origins...

  18. [Surgery of the parathyroid gland].

    Science.gov (United States)

    Fukunari, Nobuhiro

    2012-11-01

    The introduction of various techniques for minimally invasive parathyroidectomy (MIP) has changed both the conceptual and surgical approach to parathyroid disease. The perceived advantages of minimally invasive surgery among both clinicians and patients have been a major factor in the development of new surgical techniques, as well as refinement of preoperative localization techniques such as high-sensitive ultrasound and technetium sestamibi scanning. MIP for primary hyperparathyroidism has become an accepted part of endocrine surgical practice worldwide. In recent years, medical management of hyperparathyroidism has been made possible with the use of therapeutics specifically aimed at the calcium-sensing receptor, a cell-surface protein widely viewed as the primary regulator of parathyroid hormone secretion. The calcimimetic agent cinacalcet is approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis and for the treatment of hypercalcemia in patients with parathyroid carcinoma. Cinacalcet is also expected to be useful in the treatment of intractable hypercalcemia in patients with primary hyperparathyroidism for whom parathyroidectomy is indicated but surgery is clinically inappropriate or contraindicated.

  19. Intrathyroidal parathyroid carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    You, Woo Young; Han, You Mie; Choi, Young Hee [Hallym University College of Medicine, Dongtan Sacred Heart Hospital, Hwaseong (Korea, Republic of)

    2015-05-15

    Parathyroid carcinoma is an uncommon malignancy and a rare cause of primary hyperparathyroidism. Intrathyroidal parathyroid carcinoma is even rarer and only few cases have been reported previously. A 33-year-old woman presented with hypercalcemia. CT scan revealed a 5-cm sized intrathyroid nodule with a positive beak sign on the surface in contact with the thyroid gland. The patient underwent total thyroidectomy, and the histopathologic examination confirmed the diagnosis of parathyroid carcinoma. We report a case of intrathyroidal parathyroid carcinoma with brief literature review.

  20. Inflammatory diseases of the parathyroid gland.

    Science.gov (United States)

    Talat, Nadia; Diaz-Cano, Salvador; Schulte, Klaus-Martin

    2011-11-01

    Inflammatory disorders of the parathyroid gland are very rare as compared with those of other endocrine organs. The aim of this study was to provide the first systematic review of this condition. A 42-year-old patient underwent surgery for recurrent secondary hyperparathyroidism. Histology showed hyperplastic parathyroiditis defined by a mixed inflammatory infiltrate with active germinal centres. Molecular markers revealed significant upregulation of CD68 in an ischaemic background (hypoxia-inducible factor 1 upregulation) with mitochondrial reaction (malate dehydrogenase 2 upregulation) and hyperparathyroidism (carbonic anhydrase 4 upregulation). Our case demonstrates true intraparathyroid inflammation with terminal B-cell differentiation. We searched PubMed, ISI Thompson and Google Scholar up to January 2011, using the terms 'parathyroiditis', 'inflammation of parathyroid gland', 'lymphocytic infiltrate', 'tuberculosis of the parathyroid', 'sarcoidosis', and 'graulomatous inflammation'. Three autopsy series, 27 articles and 96 case reports with inflammatory parathyroid disorders were identified. Autopsy series showed lymphocytic infiltrates in up to 16% of all cases. The entire material reported lymphocytic infiltrates (n=69), parathyroiditis with germinal centres (n=15), sarcoidosis (n=6), tuberculosis (n=4), and other granulomatous diseases (n=2). Distinct inflammatory and granulomatous processes in the parathyroid gland are rare. Scanty lymphocytic infiltrates are common, and occur in generalized inflammatory conditions or venous congestion. We note the surprising absence of an association between histological proof of parathyroiditis and hypoparathyroidism. © 2011 Blackwell Publishing Limited.

  1. The Parathyroid Gland and Heart Disease.

    Science.gov (United States)

    Brown, Spandana J; Ruppe, Mary D; Tabatabai, Laila S

    2017-01-01

    The parathyroid glands are critical to maintaining calcium homeostasis through actions of parathyroid hormone (PTH). Recent clinical and molecular research has shown that direct and indirect actions of PTH also affect the heart and vasculature through downstream actions of G protein-coupled receptors in the myocardium and endothelial cells. Patients with disorders of the parathyroid gland have higher incidences of hypertension, arrhythmias, left ventricular hypertrophy, heart failure, and calcific disease which translate into increased cardiac morbidity and mortality. Importantly, clinical research also suggests that early treatment of parathyroid disorders through medical or surgical management may reverse cardiovascular remodeling and mitigate cardiac risk factors.

  2. Aortopulmonary ectopic parathyroid gland and concurrent thymolipoma.

    Science.gov (United States)

    Abu Abeeleh, Mahmoud; Bani Hani, Amjad; Ghaith, Ata; Alodwan, Tareq; Bani Ismail, Zuhair; Alshehabat, Musa

    2016-10-01

    Ectopic parathyroid adenomas are considered the main cause of primary hyperparathyroidism. However, concurrent parathyroid and thymic pathologies are rarely diagnosed in the same patient. A 47-year-old man with history of diabetes mellitus, hypertension, and myasthenia gravis presented with persistent hypercalcemia. Laboratory investigations, computed tomography, and technetium-99 m sestamibi scintigraphy revealed ectopic parathyroid glands, a mediastinal mass, and an enlarged thymus. The patient underwent thymectomy and mass excision via a median sternotomy. Histopathology was consistent with ectopic parathyroid adenoma and thymolipoma. The serum calcium and parathormone concentrations normalized within 48 hours after surgery. © The Author(s) 2016.

  3. A sister of PIN1 gene in tomato (Solanum lycopersicum) defines leaf and flower organ initiation patterns by maintaining epidermal auxin flux.

    Science.gov (United States)

    Martinez, Ciera C; Koenig, Daniel; Chitwood, Daniel H; Sinha, Neelima R

    2016-11-01

    The spatiotemporal localization of the plant hormone auxin acts as a positional cue during early leaf and flower organogenesis. One of the main contributors to auxin localization is the auxin efflux carrier PIN-FORMED1 (PIN1). Phylogenetic analysis has revealed that PIN1 genes are split into two sister clades; PIN1 and the relatively uncharacterized Sister-Of-PIN1 (SoPIN1). In this paper we identify entire-2 as a loss-of-function SlSoPIN1a (Solyc10g078370) mutant in Solanum lycopersicum. The entire-2 plants are unable to specify proper leaf initiation leading to a frequent switch from the wild type spiral phyllotactic pattern to distichous and decussate patterns. Leaves in entire-2 are large and less complex and the leaflets display spatial deformities in lamina expansion, vascular development, and margin specification. During sympodial growth in entire-2 the specification of organ position and identity is greatly affected resulting in variable branching patterns on the main sympodial and inflorescence axes. To understand how SlSoPIN1a functions in establishing proper auxin maxima we used the auxin signaling reporter DR5: Venus to visualize differences in auxin localization between entire-2 and wild type. DR5: Venus visualization shows a widening of auxin localization which spreads to subepidermal tissue layers during early leaf and flower organogenesis, showing that SoPIN1 functions to focus auxin signaling to the epidermal layer. The striking spatial deformities observed in entire-2 help provide a mechanistic framework for explaining the function of the SoPIN1 clade in S.lycopersicum. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. The Prolyl Isomerase Pin1 Promotes the Herpesvirus-Induced Phosphorylation-Dependent Disassembly of the Nuclear Lamina Required for Nucleocytoplasmic Egress.

    Science.gov (United States)

    Milbradt, Jens; Hutterer, Corina; Bahsi, Hanife; Wagner, Sabrina; Sonntag, Eric; Horn, Anselm H C; Kaufer, Benedikt B; Mori, Yasuko; Sticht, Heinrich; Fossen, Torgils; Marschall, Manfred

    2016-08-01

    The nuclear lamina lines the inner nuclear membrane providing a structural framework for the nucleus. Cellular processes, such as nuclear envelope breakdown during mitosis or nuclear export of large ribonucleoprotein complexes, are functionally linked to the disassembly of the nuclear lamina. In general, lamina disassembly is mediated by phosphorylation, but the precise molecular mechanism is still not completely understood. Recently, we suggested a novel mechanism for lamina disassembly during the nuclear egress of herpesviral capsids which involves the cellular isomerase Pin1. In this study, we focused on mechanistic details of herpesviral nuclear replication to demonstrate the general importance of Pin1 for lamina disassembly. In particular, Ser22-specific lamin phosphorylation consistently generates a Pin1-binding motif in cells infected with human and animal alpha-, beta-, and gammaherpesviruses. Using nuclear magnetic resonance spectroscopy, we showed that binding of Pin1 to a synthetic lamin peptide induces its cis/trans isomerization in vitro. A detailed bioinformatic evaluation strongly suggests that this structural conversion induces large-scale secondary structural changes in the lamin N-terminus. Thus, we concluded that a Pin1-induced conformational change of lamins may represent the molecular trigger responsible for lamina disassembly. Consistent with this concept, pharmacological inhibition of Pin1 activity blocked lamina disassembly in herpesvirus-infected fibroblasts and consequently impaired virus replication. In addition, a phospho-mimetic Ser22Glu lamin mutant was still able to form a regular lamina structure and overexpression of a Ser22-phosphorylating kinase did not induce lamina disassembly in Pin1 knockout cells. Intriguingly, this was observed in absence of herpesvirus infection proposing a broader importance of Pin1 for lamina constitution. Thus, our results suggest a functional model of similar events leading to disassembly of the nuclear

  5. An Interesting Case of Life-Threatening Hypercalcemia Secondary to Atypical Parathyroid Adenoma versus Parathyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Ankur Mishra

    2014-01-01

    Full Text Available Context. Severe hypercalcemia is a life-threatening condition. Atypical parathyroid adenoma and parathyroid carcinomas are uncommon causes which can be difficult to differentiate. Objective. We report a case of a 36-year-old male with very high serum calcium due to a possible atypical parathyroid adenoma versus parathyroid carcinoma. Case Illustration. A serum calcium level of 23.2 mg/dl was noted on admission. He was initially treated with IV hydration, pamidronate, and salmon calcitonin to lower his calcium levels. He also underwent a surgical en bloc resection of parathyroid mass. Pathology showed a mixed picture consistent with possible atypical adenoma versus parathyroid carcinoma. However, due to the possible involvement of the recurrent laryngeal nerve, parathyroid carcinoma was more likely. Also after operation the patient developed hungry bones syndrome and his calcium was replaced vigorously. He continues to be on calcium, vitamin D, and calcitriol supplementation. Results. A review of the literature was conducted to identify previous studies pertaining to parathyroid adenomas and parathyroid cancer. Conclusion. We thereby conclude that hypercalcemia requires very careful monitoring especially after operation. Also it can be very difficult to distinguish between atypical parathyroid adenomas and parathyroid carcinomas as in our case and no clear cut guidelines yet exist to differentiate the two based on histology.

  6. Pin1为靶点的肿瘤反义基因治疗研究进展%Progress on Pin1-targeted antisense gene therapy for cancer

    Institute of Scientific and Technical Information of China (English)

    孙环星; 邵荣光

    2007-01-01

    @@ 肽基脯氨酰顺反式异构酶1(peptidyl-prolyl cis/trans isomerase 1,Pin1)是进化上非常保守的肽基脯氨酰异构酶(peptidyl-prolylisomerase,PPIase)家族的成员,属微小菌素蛋白[1],最初报道于1996年,在分离与NIMA(never in mitosis geneA)相互作用的蛋白时得到[2].

  7. Ultrasound guided fine needle aspiration biopsy of parathyroid gland and lesions

    Directory of Open Access Journals (Sweden)

    Dimashkieh Haytham

    2006-03-01

    Full Text Available Abstract Background Parathyroid gland and their tumors comprise a small proportion of non-palpable neck masses that are investigated by ultrasound (US guided fine needle aspiration biopsy. We reviewed our institution's cases of US guided FNAB of parathyroid gland and their lesions to determine the role of cytology for the preoperative diagnosis of parathyroid gland and their lesions. Method All cases of FNAB of parathyroid gland and lesions in the last 10 years were reviewed in detail with respect to clinical history and correlated with the histopathologic findings in available cases. The cytologic parameters that were evaluated included cellularity assessed semiquantitatively as scant, intermediate or abundant (500 cells, cellular distribution (loose clusters, single cells/naked nuclei, rounded clusters, two- and three-dimensional clusters, and presence of prominent vascular proliferation, cellular characteristics (cell size, nuclear shape, presence/absence of a nucleolus, degree of mitosis, amount of cytoplasm, and appearance of nuclear chromatin, and background (colloid-like material and macrophages. Immunostaining for parathyroid hormone (PTH was performed on selected cases using either destained Pap smears or cell block sections. Results Twenty cases of US-guided FNAB of parathyroid glands and their lesions including 13 in the expected locations in the neck, 3 in intrathyroid region, 3 in thyroid bed, and 1 metastatic to liver were studied. Majority of the cases showed intermediate cellularity (51–500 cells with round to oval cells that exhibited a stippled nuclear chromatin, without significant pleomorphism or mitotic activity. The cells were arranged in loose two dimensional groups with many single cells/naked nuclei around the groups. Occasionally macrophages and colloid like material was also encountered. There was no significant difference in the cytomorphologic features between normal gland, hyperplasia adenoma, or carcinoma

  8. Intrathyroidal Parathyroid Cyst: An Unusual Neck Mass

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    Maswood M Ahmad

    2017-03-01

    Full Text Available Parathyroid cyst (PC is a very rare condition. A case of intrathyroidal PC is being reported here in a 53-year-old woman who presented to the endocrine clinic with slowly progressive painless left anterior neck swelling for 1 year with no symptoms of thyroid or parathyroid dysfunction and no compressive symptoms. Ultrasound of the thyroid showed a well-defined cystic lesion measuring 4.7 × 3.6 cm in maximum diameter with internal echoes within the cyst located in the left lobe of the thyroid gland. Fine needle aspiration revealed colorless clear fluid with a high concentration of parathyroid hormone. The patient underwent left hemithyroidectomy at her request. Histopathology revealed parathyroid tissue with unilocular cyst and thyroid tissue with goitrous changes. She was in remission, and there was no evidence of thyroid or parathyroid dysfunction after surgery.

  9. Parathyroid hormone and bone healing

    DEFF Research Database (Denmark)

    Ellegaard, M; Jørgensen, N R; Schwarz, P

    2010-01-01

    , no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial...... in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment...

  10. ShaPINg cell fate upon DNA damage:role of Pin1 isomerase in DNA damage-induced cell death and repair

    Directory of Open Access Journals (Sweden)

    Thomas G Hofmann

    2014-06-01

    Full Text Available The peptidyl-prolyl cis/trans isomerase Pin1 acts as a molecular timer in proline-directed Ser/Thr kinase signaling and shapes cellular responses based on recognition of phosphorylation marks and implementing conformational changes in its substrates. Accordingly, Pin1 has been linked to numerous phosphorylation-controlled signaling pathways and cellular processes such as cell cycle progression, proliferation and differentiation. In addition, Pin1 plays a pivotal role in DNA damage-triggered cell fate decisions. Whereas moderate DNA damage is balanced by DNA repair, cells confronted with massive genotoxic stress are eliminated by the induction of programmed cell death or cellular senescence. In this review we summarize and discuss the current knowledge on how Pin1 specifies cell fate through regulating key players of the apoptotic and the repair branch of the DNA damage response.

  11. Autophagy regulated by prolyl isomerase Pin1 and phospho-Ser-GSK3αβ involved in protection of oral squamous cell carcinoma against cadmium toxicity

    Energy Technology Data Exchange (ETDEWEB)

    So, Keum-Young [Department of Anesthesiology and Pain Medicine College of Dentistry, Chosun University, 309 Pilmundaero, Dong-gu, Gwangju 501-759 (Korea, Republic of); Ahn, Sang-Gun [Department of Pathology, College of Dentistry, Chosun University, 309 Pilmundaero, Dong-gu, Gwangju 501-759 (Korea, Republic of); Oh, Seon-Hee, E-mail: seonh@chosun.ac.kr [Department of Premedicine, School of Medicine, College of Dentistry, Chosun University, 309 Pilmundaero, Dong-gu, Gwangju 501-759 (Korea, Republic of)

    2015-10-23

    Prolyl isomerase Pin1 plays an important role in cell proliferation and is overexpressed in many human tumors. However, its role in autophagy induction remains undefined. Here we show that Pin1 regulates cell survival via autophagy in cadmium (Cd)-exposed oral squamous cell carcinoma (OSCC). OSCC exposure to Cd induced autophagy, as demonstrated by the formation of green fluorescent punctae in transfected cells expressing GFP-conjugated microtubule-associated protein light chain 3 (LC3) and by LC3 flux in the presence of autophagy inhibitors. Suppression of Atg5 enhanced Cd-induced apoptosis, indicating that autophagy is involved in cell protection. In dose–response experiments, cleavage of procaspase-3, PARP-1, and LC3-II was induced by Cd with an IC{sub 50} of 45 μM. Expression of Pin1 was decreased at or above the Cd IC{sub 50} value and was inversely correlated with the level of phospho(p)-Ser-GSK3αβ. Genetic or pharmacologic inhibition of Pin1 suppressed Cd-induced autophagy, but increased p-Akt-mediated p-Ser-GSK3αβ; this was reversed by overexpression of Pin1. However, suppression of GSK3αβ inhibited Cd-induced autophagy and induced apoptosis, which could be reversed by overexpression of GSK3β. The PI3K inhibitor Ly294002 blocked p-Akt-mediated increases in p-Ser-GSK3αβ and autophagy and induced apoptosis. Therefore, p-Ser-GSK3αβ can directly regulate Cd-induced autophagy, although its function is suppressed by Pin1. Collectively, the present results indicate that targeting Pin1 and GSK3αβ at the same time could be an effective therapeutic tool for Cd-induced carcinogenesis. - Highlights: • Pin1 regulated autophagy to protect cells from cadmium toxicity. • Pin1 suppression inhibited cadmium-induced autophagy and induced apoptosis. • Pin1 inhibited the function of p-Ser-GSK3αβ in autophagy regulation. • p-Ser-GSK3αβ regulated autophagy independently of Pin1.

  12. Thyroid and parathyroid gland

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930466 The association of Graves’disease withserum soluble interleukin 2 receptor.RENYuezhong(任跃忠),SONG Zuogui(宋作珪).2ndAffili Hosp,Zhejiang Med Univ,Hangzhou,310009.Natl Med J China 1993;73(5):264—265.The serum soluble interleukin 2 receptor(slL2R)was measured in 38 first visited patientswith Graves’disease and 29 normal controls.The serum sIL2R in 17 patients with Graves’dis-ease was determined after treatment with an-tithyroid drugs(propylthiouracil)for a short pe-riod(1.2±0.5 months).The serum sIL2R was

  13. A case report: Giant cystic parathyroid adenoma presenting with parathyroid crisis after Vitamin D replacement

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    Asghar Ali

    2012-07-01

    Full Text Available Abstract Background Parathyroid adenoma with cystic degeneration is a rare cause of primary hyperparathyroidism. The clinical and biochemical presentation may mimic parathyroid carcinoma. Case presentation We report the case of a 55 year old lady, who had longstanding history of depression and acid peptic disease. Serum calcium eight months prior to presentation was slightly high, but she was never worked up. She was found to be Vitamin D deficient while being investigated for generalized body aches. A month after she was replaced with Vitamin D, she presented to us with parathyroid crisis. Her corrected serum calcium was 23.0 mg/dL. She had severe gastrointestinal symptoms and acute kidney injury. She had unexplained consistent hypokalemia until surgery. Neck ultrasound and CT scan revealed giant parathyroid cyst extending into the mediastinum. After initial medical management for parathyroid crisis, parathyroid cystic adenoma was surgically excised. Her serum calcium, intact parathyroid hormone, creatinine and potassium levels normalized after surgery. Conclusion This case of parathyroid crisis, with very high serum calcium and parathyroid hormone levels, is a rare presentation of parathyroid adenoma with cystic degeneration. This case also highlights that Vitamin D replacement may unmask subclinical hyperparathyroidism. Consistent hypokalemia until surgery merits research into its association with hypercalcemia.

  14. Parathormone, Calcium And Phosphorus In Autotransplanted Parathyroid, Total Thyriodectomized Patients

    OpenAIRE

    Abdel Salam, I. M. [ابراهيم عبد السلام; M. Murad; Gamil, M. M.

    1995-01-01

    The success of parathyroid autotransplantation was indicated by the postoperative assay of serum parathormone in thirteen out of fourteen patients to whom total thyroidectomy was carried out because of thyroid cancer during the past three years. Four glands were autotransplanted in four patients and froam two to three glamds were trasplanted in the remaineng nime patients. All patients were followed up with daily calcium and phosphate determinations. Patients with low ca"1"1" level and with h...

  15. Lipoadenoma of the parathyroid gland - a rare cause of hyperparathyroidism.

    Science.gov (United States)

    Bansal, R; Trivedi, P; Sarin, J; Parikh, B

    2012-01-01

    Lipoadenoma of parathyroid gland is an unusual morphologic variant of parathyroid adenoma in which the glandular elements are associated with abundant mature adipose tissue. The lesion has also been reported as parathyroid lipohyperplasia, parathyroid hamartoma, and parathyroid adenoma with myxoid stroma. Most cases are functioning and are associated with hyperparathyroidism. Lipoadenoma of parathyroid gland are difficult to diagnose as a cause of hyperparathyroidism because of rarity of these lesions and overlap with normal parathyroid tissue on microscopic evaluation. Only few cases have been documented in the literature so far. The lesion may be overlooked by both surgeon and pathologists alike, if they are not aware of this specific clinicopathologic entity.

  16. Stereochemical Control in the Still-Wittig Rearrangement Synthesis of Cyclohexyl (Z-Alkene Inhibitors of Pin1.

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    Xingguo R Chen

    Full Text Available Three stereoisomeric inhibitors of Pin1: (2R,5S-, (2S,5R- and (2S,5S-Ac-pSer-Ψ[(ZCH = C]-pipecolyl(Pip-2-(2-naphthylethylamine 1, that mimic L-pSer-D-Pro, D-pSer-L-Pro, and D-pSer-D-Pro amides respectively, were synthesized by a 13-step route. The newly formed stereogenic centers in the pipecolyl ring were introduced by Luche reduction, followed by stereospecific [2,3]-Still-Wittig rearrangement. The (Z- to (E-alkene ratio in the rearrangements were consistently 5.5 to 1. The stereochemistry at the original Ser α-carbon controlled the stereochemistry of the Luche reduction, but it did not affect the stereochemical outcome of the rearrangement, which consistently gave the (Z-alkene. The epimerized by-product, (2S,5S-10, resulting from the work-up after Na/NH3 debenzylation of (2S,5R-9, was carried on to the (2S,5S-1 isomer. Compound (2S,5S-10 was resynthesized from the Luche reduction by-product, (2R,3R-3, and the stereochemistry was confirmed by comparison of the optical rotations. The IC50 values for (2R,5S-1, (2S,5R-1 and (2S,5S-1 Pin1 inhibition were: 52, 85, and 140 μM, respectively.

  17. Clinical suspicion and parathyroid carcinoma management

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    Fabio Luiz de Menezes Montenegro

    Full Text Available CONTEXT AND OBJECTIVE: Adequate management of parathyroid carcinoma apparently relates to the surgeon’s ability to identify it at the first operation. The objective of this paper was to evaluate the role of clinical suspicion in the management of parathyroid carcinoma. DESIGN AND SETTING: Retrospective analysis of parathyroid carcinoma patients treated in Department of Head and Neck Surgery, Faculdade de Medicina da Universidade de São Paulo. METHODS: Cross-sectional study of 143 patients who underwent surgery from 1995 to 2000, due to hyperparathyroidism. These cases were reviewed to ascertain whether preoperative and intraoperative suspicion of parathyroid carcinoma were helpful during the operation, and which factors demonstrated the suspicion of cancer best. RESULTS: Among 66 patients with primary hyperparathyroidism there were four cases of parathyroid carcinoma (6.1%, and one case was found in secondary hyperparathyroidism (1.3%. Palpable nodules were found in five patients with primary hyperparathyroidism, four of them with parathyroid carcinoma. Preoperative levels of calcium in primary hyperparathyroidism with cancer patients varied from 12.0 mg/dl to 18.2 mg/dl. Two patients had gross macroscopic spread of the tumor to adjacent structures. Except for one patient, with extensive disease, tumors were resected en bloc. In secondary hyperparathyroidism, parathyroid carcinoma was found in a fifth mediastinal gland. One atypical adenoma was observed. CONCLUSIONS: High levels of calcium, palpable tumors and adherence to close structures are more common in parathyroid carcinoma. These clinical signs may be helpful for decision-making during parathyroid surgery.

  18. Sonography of intrathyroid parathyroid adenomas: Are there distinctive features that allow for preoperative identification?

    Energy Technology Data Exchange (ETDEWEB)

    Heller, Matthew T., E-mail: hellermt@upmc.edu [University of Pittsburgh Medical Center, Department of Radiology, 200 Lothrop St, Suite 3950 PUH S. Tower, Pittsburgh, PA 15213 (United States); Yip, Linwah, E-mail: yipl@upmc.edu [University of Pittsburgh Medical Center, Department of Endocrine Surgery, Kaufmann Building, 3471 Fifth Ave, Suite 101, Pittsburgh, PA 15213 (United States); Tublin, Mitchell E., E-mail: tublme@upmc.edu [University of Pittsburgh Medical Center, Department of Radiology, 200 Lothrop St, Suite 3950 PUH S. Tower, Pittsburgh, PA 15213 (United States)

    2013-01-15

    Objective: The purpose of our study was to determine if intra-thyroid parathyroid adenomas can be accurately identified by applying proposed criteria to preoperative ultrasound examinations in patients with primary hyperparathyroidism. Materials/methods: Fifty-three patients with pathology proven intra-thyroid parathyroid adenomas and pre-operative ultrasounds were identified from a surgical database for a blinded, retrospective review. A contemporary, age-matched cohort of 54 patients with extra-thyroid parathyroid adenomas was identified as a control. A total of 64 patients within these cohorts had co-existing thyroid nodules. Proposed ultrasound criteria for identifying a parathyroid adenoma included solid composition, profound hypoechogenicity, and presence of a feeding polar vessel. Parathyroid adenomas were classified as extra-thyroid or intra-thyroid (partial or complete) based on their relationship with the thyroid gland during ultrasound evaluation and results were compared to surgical and histopathology reports as the gold standard. The results from the blinded, retrospective review during which the proposed, specific ultrasound criteria were applied were compared to the initial, pre-operative reports during which the proposed criteria were not applied. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the blinded, retrospective review and initial, pre-operative reports were calculated. Additionally, in patients with co-existing thyroid nodules, an attempt was made to differentiate parathyroid adenomas from the thyroid nodules. Results: Application of the proposed ultrasound criteria during blinded retrospective review yielded a sensitivity and specificity for detecting intra-thyroid parathyroid adenomas of 76% and 92%, respectively. The sensitivity and specificity of ultrasound for detecting intra-thyroid parathyroid adenomas on the initial reports was 29% and 95%, respectively. The sensitivity and

  19. [Parathyroid cyst presenting as a mediastinal tumor].

    Science.gov (United States)

    Shishido, M; Nagao, M

    1996-08-01

    Mediastinal parathyroid cysts are very rare. Since the first report by DeQuervain, 19 cases have been reported. We encountered a case of mediastinal parathyroid cyst presenting as displacement of the trachea. The cyst originated in the lower portion of the left lobe of the thyroid gland and extended to the mediastinum, displacing the trachea and the esophagus. The monolocular mass was a thin walled cyst, and mognetic imaging indicated that it contained watery fluid. The left lobe of the thyroid gland was found to be displaced upward by the tumor, on thyroid scintigram done with technetium-99, which suggested that the cyst originated in the parathyroid gland.

  20. Pin1, a new player in the fate of HIF-1α degradation: an hypothetical mechanism inside vascular damage as Alzheimer’s disease risk factor.

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    Elena eLonati

    2014-01-01

    Full Text Available Aetiology of neurodegenerative mechanisms underlying Alzheimer's disease (AD are still under elucidation. The contribution of cerebrovascular deficiencies (such as cerebral ischemia/stroke has been strongly endorsed in recent years. Reduction of blood supply leading to hypoxic condition is known to activate cellular responses mainly controlled by hypoxia-inducible transcription factor-1 (HIF-1. Thus alterations of oxygen responsive HIF-1α subunit in the central nervous system may contribute to the cognitive decline, especially influencing mechanisms associated to APP (amyloid precursor protein amyloidogenic metabolism. Although HIF-1α protein level is known to be regulated by von Hippel-Lindau (VHL ubiquitin-proteasome system, it has been recently suggested that Gsk-3β (glycogen synthase kinase-3β promotes a VHL-independent HIF-1α degradation. Here we provide evidences that in rat primary hippocampal cell cultures, HIF-1α degradation might be mediated by a synergic action of Gsk-3β and Pin1 (peptidyl-prolyl cis/trans isomerase. In post-ischemic conditions, such as those mimicked with oxygen glucose deprivation (OGD, HIF-1α protein level increases remaining unexpectedly high for long time after normal condition restoration jointly with the increase of LDH (lactate dehydrogenase and BACE1 (β-secretase 1 protein expression (70% and 140% respectively. Interestingly the Pin1 activity decreases about 40%-60% and Pin1S16 inhibitory phosphorylation significantly increases, indicating that Pin1 binding to its substrate and enzymatic activity are reduced by treatment. Co-immunoprecipitation experiments demonstrate that HIF-1α/Pin1 in normoxia are associated, and that in presence of specific Pin1 and Gsk-3β inhibitors their interaction is reduced in parallel to an increase of HIF-1α protein level. Thus we suggest that in post-OGD neurons the high level of HIF-1α might be due to Pin1 binding ability and activity reduction which affects HIF-1

  1. Nerve growth factor stimulates interaction of Cayman ataxia protein BNIP-H/Caytaxin with peptidyl-prolyl isomerase Pin1 in differentiating neurons.

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    Jan Paul Buschdorf

    Full Text Available Mutations in ATCAY that encodes the brain-specific protein BNIP-H (or Caytaxin lead to Cayman cerebellar ataxia. BNIP-H binds to glutaminase, a neurotransmitter-producing enzyme, and affects its activity and intracellular localization. Here we describe the identification and characterization of the binding between BNIP-H and Pin1, a peptidyl-prolyl cis/trans isomerase. BNIP-H interacted with Pin1 after nerve growth factor-stimulation and they co-localized in the neurites and cytosol of differentiating pheochromocytoma PC12 cells and the embryonic carcinoma P19 cells. Deletional mutagenesis revealed two cryptic binding sites within the C-terminus of BNIP-H such that single point mutants affecting the WW domain of Pin1 completely abolished their binding. Although these two sites do not contain any of the canonical Pin1-binding motifs they showed differential binding profiles to Pin1 WW domain mutants S16E, S16A and W34A, and the catalytically inert C113A of its isomerase domain. Furthermore, their direct interaction would occur only upon disrupting the ability of BNIP-H to form an intramolecular interaction by two similar regions. Furthermore, expression of Pin1 disrupted the BNIP-H/glutaminase complex formation in PC12 cells under nerve growth factor-stimulation. These results indicate that nerve growth factor may stimulate the interaction of BNIP-H with Pin1 by releasing its intramolecular inhibition. Such a mechanism could provide a post-translational regulation on the cellular activity of BNIP-H during neuronal differentiation.

  2. Pin1、β-连接素和细胞周期素D1在老年肺癌组织中的表达及临床意义%The expressions of Pin1,β-catenin and cyclin D1 in elderly lung carcinomas and their significance

    Institute of Scientific and Technical Information of China (English)

    Jian Liu; Jun Zhao; Jianming Yang

    2008-01-01

    Objective:To investigate the expressions and correlations of Pin1,β-catenin and cyclin D1 in elderly lung carcinomas.Methods:The expressions of Pin1,β-catenin and cyclin D1 were examined in the specimens of 92 elderly lung carcinomas and 10 normal lung tissues by immunohistochemistry and explored the relationship between the expression levels and clinicopathological factors.Results:(1) The overexpression of Pin1 and cyclin D1 in lung carcinomas was 46 (50%)cases and 60 (65.22%) cases respectively and 56 (60.82%) cases showed positive immunoreactivity for β-catenin in the nuclear and (or) cytoplasmic fraction in tumor tissues,In normal tissue,the expressions of Pin1 and cyclin D1 were negative,the expression of β-catenin was lied in cell membrane.(2) In lung carcinomas the expressions of Pin1,β-catenin and cyclin D1 correlated with tumor differentiation (P<0.05).The pesitive expression rate and intensity of Pin1 correlated with tumor stage (P=0.032) and lymph node positive disease (P=0.041).The expression of β-catenin correlated with lymph node positive disease (P=0.012).(3) High expression levels of Pin1 correlated with aberrant β-catenin expression (P=0.000) but did not show a correlation with cyclin D1 (P=0.157).Conclusion:In elderly lung carcinomas,the positive expression of Pin1 causes abnormal accumulation of β-catenin and actives its target gene,however,this target gene was not cyclin DI.The detection of Pin1 expression had some clinical significance in estimating prognosis of elderly patient with lung carcinomas.

  3. Nonfunctional Parathyroid Carcinoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Sang Gyu [Dankook University College of Medicine, Cheonan (Korea, Republic of)

    2010-11-15

    Parathyroid carcinoma is a rare endocrine malignancy accounting for 0.5% to 4.0% of all cases of hyperparathyroidism and commonly present as hypercalcemia and parathyroid hormone (PTH) elevation. Nonfunctional parathyroid carcinoma does not show symptoms of hyperparathyroidism and only showed a vague indication of being pathologic, even when detected late. The optimal treatment is en bloc resection of the cancer, but frequent local recurrence after surgery has been reported. Adjuvant local treatment such as radiotherapy may improve the likelihood local control in cases with incompletely resected or microscopic residual tumor. The results of this study point to a case of nonfunctional parathyroid carcinoma treated by external beam radiotherapy after en-bloc resection of cancer.

  4. The parathyroid gland in health and disease.

    OpenAIRE

    Ghandur-Mnaymneh, L.; Cassady, J.; Hajianpour, M. A.; Paz, J; Reiss, E

    1986-01-01

    The authors studied the parathyroid glands from 100 previously healthy subjects who died suddenly and were admitted to the Dade County Medical Examiner's (ME) morgue and from 66 inpatients who died at Jackson Memorial Hospital (JMH). Parathyroid glands in patients with diseases (JMH series) were heavier than those in healthy persons (ME series), and both groups of glands were significantly heavier than those previously reported. Mean glandular weight in white subjects was 42.6 +/- 20.3 mg, wi...

  5. Synchronous Parathyroid and Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Shi-Dou Lin

    2005-02-01

    Full Text Available Concomitant thyroid disease is not unusual among patients with primary hyperparathyroidism. However, the simultaneous occurrence of parathyroid and thyroid carcinoma is extremely rare. We report a 38-year-old man with primary hyperparathyroidism who presented with osteitis fibrosa cystica complicated with pathologic femoral neck fracture. Preoperative investigation for exclusion of multiple endocrine neoplasia did not find evidence of medullary thyroid carcinoma or pheochromocytoma, but imaging studies revealed the presence of nodules in the right lobe and a parathyroid lesion over the left inferior pole of the thyroid gland. Total thyroidectomy, left parathyroidectomy, and bipolar hemiarthroplasty of the left hip were then performed simultaneously. The resected specimens were pathologically identified as papillary thyroid carcinoma and parathyroid carcinoma, respectively. After the operation, 131I ablation therapy was administered at a dose of 120 mCi. Additional doses of 30 mCi were given yearly as serum thyroglobulin level became elevated. Serum calcium level remained normal during yearly follow-up. Although parathyroid carcinoma is an uncommon cause of parathyroid hormone-dependent hypercalcemia, it should nonetheless be given due consideration because its surgical approach differs from that of parathyroid adenoma. As the coexistence of parathyroid and non-medullary thyroid carcinoma has previously been reported, the possibility of both malignancies must also be considered in the setting of primary hyperparathyroidism with thyroid nodules. If confirmed with preoperative parathyroid scintigraphic and other laboratory studies, an optimal outcome may be achieved with complete resection of both tumors at the time of initial operation, followed by adjunctive therapy.

  6. Parathyroid cysts: the Latin-American experience

    Science.gov (United States)

    Aristizábal, Natalia; Aguilar, Carolina; Palacios, Karen; Pérez, Juan Camilo; Vélez-Hoyos, Alejandro; Duque, Carlos Simon; Sanabria, Alvaro

    2016-01-01

    Background Parathyroid cyst is an infrequent and unsuspected disease. There are more than 300 hundred cases reported in the world literature, a few of them are from Latin America. The experience of our centers and a review of the cases are presented. Methods Case report of a series of patients with parathyroid cyst from our institutions according to the CARE guidelines (Case Reports). A search of Medline, Embase, BIREME (Biblioteca Regional de Medicina) LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), Google Scholar and Scielo (Scientific Electronic Library on Line) databases and telephonic or email communications with other experts from Latin-America was performed . Results Six patients with parathyroid cyst were found in our centers in Colombia. Most of them were managed with aspiration of the cyst. Two of them required surgery. Only one case was functional. Twelve reports from Latin America were found for a total of 18 cases in our region adding ours. Conclusions Parathyroid cysts are uncommonly reported in Latin America. Most of them are diagnosed postoperatively. Suspicion for parathyroid cyst should be raised when a crystal clear fluid is aspirated from a cyst. The confirmation of the diagnosis may be easily done if parathyroid hormone (PTH) level is measured in the cyst fluid. PMID:28149800

  7. Ultrasonographic evaluation of parathyroid hyperplasia in multiple endocrine neoplasia type 1: Positive correlation between parathyroid volume and circulating parathyroid hormone concentration.

    Science.gov (United States)

    Tamiya, Hiroyuki; Miyakawa, Megumi; Takeshita, Akira; Miura, Daishu; Takeuchi, Yasuhiro

    2015-09-01

    There are few reports on parathyroid ultrasonography of multiple endocrine neoplasia type 1 (MEN1). This study investigated the ultrasonographic features of parathyroid glands in 10 patients with MEN1 who underwent preoperative neck ultrasonography and parathyroidectomy between 2006 and 2010 at Toranomon Hospital. We retrospectively analyzed clinical features, laboratory and ultrasonographic data, and pathological diagnosis. A total of 38 parathyroid glands were surgically removed (three to five glands from each patient). All removed parathyroids were pathologically diagnosed as hyperplasia. Seven cases (70.0 %) had adenomatous thyroid nodules. Twenty-five enlarged parathyroid glands (65.8 %) were detected by preoperative ultrasonography with a detection rate of 81.8 % (9/11) and 59.3 % (16/27) for patients without and with adenomatous nodules, respectively. Total parathyroid gland weight and potentially predictable total parathyroid volume by preoperative ultrasonography were significantly correlated with preoperative serum intact parathyroid hormone (iPTH) concentration (R = 0.97, P parathyroid glands by ultrasonography difficult, the positive correlation between the predictable parathyroid volume by ultrasonography and serum iPTH suggests that their measurement is useful in the preoperative detection and localization of enlarged parathyroid glands in patients with MEN1. Furthermore, the presence of parathyroid glands that should be resected can be predicted before surgery using the equation proposed here.

  8. Parathyroid hyperplasia, adenomas, and carcinomas: differential expression of p27Kip1 protein.

    Science.gov (United States)

    Erickson, L A; Jin, L; Wollan, P; Thompson, G B; van Heerden, J A; Lloyd, R V

    1999-03-01

    The histologic spectrum of proliferative parathyroid lesions (hyperplasia, adenoma, and carcinoma) often overlap, and differentiation between these lesions may at times be difficult. p27kip1 (p27) is a cyclin-dependent kinase inhibitor that helps regulate the transition from the G1 to the S phase of the cell cycle. Significantly higher levels of p27 expression have been detected in some normal tissues than in their neoplastic counterparts. The authors analyzed a series of parathyroid lesions to determine if expression of this cell cycle protein may be useful in distinguishing between parathyroid hyperplasia, adenomas, and carcinomas. Formalin-fixed paraffin-embedded tissues from randomly selected patients (22 histologically normal parathyroid glands, 33 cases of hyperplasia, 43 adenomas, and 17 carcinomas) were analyzed for expression of p27 by immunostaining. All cases were also immunostained for Ki67 with antibody MIB-1. The distribution of immunoreactivity was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index (LI). In situ hybridization (ISH) for p27 mRNA was done using a cRNA probe with 30 of these cases. Normal parathyroid glands had the highest p27 LI (89.6 +/- 1.4), followed by hyperplasia (69.6 +/- 7.5), adenomas (56.8 +/- 3.4), and carcinomas (13.9 +/- 2.6). ISH showed no differences in p27 mRNA, indicating that the expression of the p27 gene was controlled at a posttranslational level in parathyroid tissues. Ki67 expression was significantly higher in carcinomas (LI = 8.4 +/- 1.9) than in adenomas (LI = 2.7 +/- 0.2) and hyperplasia (LI = 3.3 +/- 0.4). These results suggest that both p27 and Ki67 may be helpful in the diagnosis of histologically difficult parathyroid lesions.

  9. ROLE OF IMAGING TESTS FOR PREOPERATIVE LOCATION OF PATHOLOGIC PARATHYROID TISSUE IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM.

    Science.gov (United States)

    Coelho, Maria Caroline Alves; de Oliveira E Silva de Morais, Nathalie Anne; Beuren, Andrea Cristiani; Lopes, Cristiane Bertolino; Santos, Camila Vicente; Cantoni, Joyce; Neto, Leonardo Vieira; Lima, Maurício Barbosa

    2016-09-01

    Primary hyperparathyroidism (PHPT) can be cured by parathyroidectomy, and the preoperative location of enlarged pathologic parathyroid glands is determined by imaging studies, especially cervical ultrasonography and scintigraphy scanning. The aim of this retrospective study was to evaluate the use of preoperative cervical ultrasonography and/or parathyroid scintigraphy in locating pathologic parathyroid tissue in a group of patients with PHPT followed in the same endocrine center. We examined the records of 61 patients who had undergone parathyroidectomy for PHPT following (99m)Tc-sestamibi scintigraphy scan and/or cervical ultrasonography. Scintigraphic and ultrasonographic findings were compared to histopathologic results of the surgical specimens. Ultrasonography detected enlarged parathyroid glands in 87% (48/55) of patients with PHPT and (99m)Tc-sestamibi scintigraphy in 79% (37/47) of the cases. Ultrasonography was able to correctly predict the surgical findings in 75% (41/55) of patients and scintigraphy in 72% (34/47). Of 7 patients who had negative ultrasonography, scintigraphy correctly predicted the surgical results in 2 (29%). Of 10 patients who had negative scintigraphy, ultrasonography correctly predicted the surgical results in 4 (40%). When we analyzed only patients with solitary eutopic parathyroid adenomas, the predictive positive values of ultrasonography and scintigraphy were 90% and 86%, respectively. Cervical ultrasonography had a higher likelihood of a correct positive test and a greater predictive positive value for solitary adenoma compared to (99m)Tc-sestamibi and should be used as the first diagnostic tool for preoperative localization of affected parathyroid glands in PHPT. Ca = calcium IEDE = Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione PHPT = primary hyperparathyroidism PTH = parathyroid hormone.

  10. Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone

    Directory of Open Access Journals (Sweden)

    Lars Rejnmark

    2015-12-01

    Full Text Available Hypoparathyroidism (HypoPT is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH. Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84 as well as therapy with the N-terminal PTH fragment (rhPTH(1-34 have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy.

  11. Preserving Parathyroid Gland Vasculature to Reduce Post-thyroidectomy Hypocalcemia.

    Science.gov (United States)

    Park, Inhye; Rhu, Jinsoo; Woo, Jung-Woo; Choi, Jun-Ho; Kim, Jee Soo; Kim, Jung-Han

    2016-06-01

    The failure to preserve parathyroid function in patients who have undergone total thyroidectomy is of major concern, because hypocalcemia is difficult to prevent and remains a common postoperative complication. Here, we describe procedures designed to preserve the vasculature supplying the parathyroid glands and examine both recent outcomes and retrospective reports of results obtained prior to the application of these preservation techniques. Our technique for preserving parathyroid function during thyroidectomy was adopted in 2009 and involves separating a relatively long segment of a vessel distally from the thyroid gland. We reviewed the medical records of 1,411 patients who underwent total thyroidectomy, with or without lateral neck dissection, at the Samsung Medical Center from January 2006 through June 2014 to determine outcomes. Patients were divided into three groups according to the time period during which the surgery took place: Group A, 2006-2008 (before the vasculature-preserving technique was applied); Group B, 2009-2011 (the time when the technique was first adopted); and Group C, 2012-2014 (more recent results of the technique). We analyzed the incidence of hypoparathyroidism in the three groups, as well as risk factors that influenced its development. The rates of transient and permanent hypoparathyroidism in Group A were 25.4 and 4.3 %, respectively. However, the incidence of hypoparathyroidism decreased significantly over time after the vasculature-preserving procedure was adopted. Transient hypoparathyroidism developed in 4.8 % of Group C patients, and only four (0.7 %) of the 565 patients in this group required calcium supplementation, despite the fact that a greater number of patients were included who underwent total thyroidectomy combined with lateral neck dissection. Although female sex and lateral neck dissection tended to increase the rate of transient hypoparathyroidism, multivariate analysis showed that the vasculature

  12. Intra-Operative Indocyanine Green Angiography of the Parathyroid Gland.

    Science.gov (United States)

    Vidal Fortuny, Jordi; Karenovics, Wolfram; Triponez, Frederic; Sadowski, Samira M

    2016-10-01

    Major complications of thyroid and parathyroid surgery are recurrent laryngeal nerve injuries and definitive hypoparathyroidism. The use of intra-operative Indocyanine Green Angiography for confirmation of vascular status of the parathyroid gland is reported here.

  13. Parathyroid Cancer Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Parathyroid cancer is very rare and is usually treated with surgery. Learn about the diagnosis, risk and genetic factors, staging, treatment, and management of parathyroid cancer in this expert-reviewed summary.

  14. FGF23 and the parathyroid glands.

    Science.gov (United States)

    Silver, Justin; Naveh-Many, Tally

    2010-11-01

    Fibroblast growth factor 23 (FGF23) is a phosphatonin that is secreted by osteocytes and osteoblasts in response to hyperphosphatemia and 1,25-dihydroxyvitamin D (1,25D). It acts on its receptor complex, Klotho-FGFR1c (fibroblast growth factor receptor 1 c-splicing form), in the distal convoluted tubule to repress renal phosphorus reabsorption in the proximal tubule and suppress the renal synthesis of 1,25D. Klotho-FGFR1c is also expressed in the parathyroid glands. FGF23 acts on the receptor complex in the parathyroid glands to decrease parathyroid hormone (PTH) gene expression and PTH secretion through activation of the MAPK pathway. In chronic kidney disease (CKD), both FGF23 and PTH are increased, implying resistance of the parathyroid glands to FGF23. There is a decrease in the Klotho-FGFR1c complex in the parathyroid glands in both experimental CKD and in patients with end-stage renal disease. In addition, in advanced experimental CKD, FGF23 has a decreased ability to inhibit PTH expression.

  15. Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery

    Science.gov (United States)

    Vidal Fortuny, J.; Belfontali, V.; Sadowski, S. M.; Karenovics, W.; Guigard, S.

    2016-01-01

    Background Postoperative hypoparathyroidism remains the most common complication following thyroidectomy. The aim of this pilot study was to evaluate the use of intraoperative parathyroid gland angiography in predicting normal parathyroid gland function after thyroid surgery. Methods Angiography with the fluorescent dye indocyanine green (ICG) was performed in patients undergoing total thyroidectomy, to visualize vascularization of identified parathyroid glands. Results Some 36 patients underwent ICG angiography during thyroidectomy. All patients received standard calcium and vitamin D supplementation. At least one well vascularized parathyroid gland was demonstrated by ICG angiography in 30 patients. All 30 patients had parathyroid hormone (PTH) levels in the normal range on postoperative day (POD) 1 and 10, and only one patient exhibited asymptomatic hypocalcaemia on POD 1. Mean(s.d.) PTH and calcium levels in these patients were 3·3(1·4) pmol/l and 2·27(0·10) mmol/l respectively on POD 1, and 4·0(1.6) pmol/l and 2·32(0·08) mmol/l on POD 10. Two of the six patients in whom no well vascularized parathyroid gland could be demonstrated developed transient hypoparathyroidism. None of the 36 patients presented symptomatic hypocalcaemia, and none received treatment for hypoparathyroidism. Conclusion PTH levels on POD 1 were normal in all patients who had at least one well vascularized parathyroid gland demonstrated during surgery by ICG angiography, and none required treatment for hypoparathyroidism. PMID:26864909

  16. [Rare abnormalities of parathyroid gland function and parathyroid hormone receptor action].

    Science.gov (United States)

    Krysiak, Robert; Bartecka, Anna; Okopień, Bogusław

    2014-01-01

    The parathyroid glands, located near or within the posterior surface of the thyroid gland and secreting parathyroid hormone, are essential organs for the regulation of calcium and phosphate metabolism. As they are necessary to sustain life and maintain homeostasis, undetected or misdiagnosed parathyroid disorders may pose a significant threat to health outcomes, as their presence may increase morbidity and mortality in affected individuals. The clinical picture of some disorders associated with abnormal parathyroid hormone secretion and receptor action is sometimes complicated by coexisting abnormalities, and in these cases establishing the correct diagnosis is challenging. The remarkable progress of recent years in the area of hormonal assessment, imaging procedures and molecular biology, has resulted in a great improvement in the identification, differentiation and treatment of various parathyroid disorders and has made it possible to identify several new clinical entities. In this paper, we discuss the present state-of-art on the etiopathogenesis, clinical manifestations, diagnosis and treatment of chosen rare abnormalities of parathyroid gland function and parathyroid hormone receptor action.

  17. Resection of a large ectopic parathyroid adenoma: A case report

    Directory of Open Access Journals (Sweden)

    Seijiro Sato

    2016-01-01

    Discussion and conclusions: Parathyroid adenomas and parathyroid carcinomas have disparate natural histories, but they can be difficult to differentiate on the basis of preoperative clinical characteristics. We believe that long-term follow-up of these cases is required because there have been few reports on the postoperative natural history of large parathyroid adenomas.

  18. Parathyroid hormone secretion in chronic renal failure

    DEFF Research Database (Denmark)

    Madsen, J C; Rasmussen, A Q; Ladefoged, S D

    1996-01-01

    The aim of study was to introduce and evaluate a method for quantifying the parathyroid hormone (PTH) secretion during hemodialysis in secondary hyperparathyroidism due to end-stage renal failure. We developed a method suitable for inducing sequential hypocalcemia and hypercalcemia during....../ionized calcium curves were constructed, and a mean calcium set-point of 1.16 mmol/liter was estimated compared to the normal mean of about 1.13 mmol/liter. In conclusion, we demonstrate that it is important to use a standardized method to evaluate parathyroid hormone dynamics in chronic renal failure. By the use...... of a standardized method we show that the calcium set-point is normal or slightly elevated, indicating normal parathyroid reactivity to calcium in chronic renal failure....

  19. The prolyl isomerase Pin1 acts synergistically with CDK2 to regulate the basal activity of estrogen receptor α in breast cancer.

    Directory of Open Access Journals (Sweden)

    Chiara Lucchetti

    Full Text Available In hormone receptor-positive breast cancers, most tumors in the early stages of development depend on the activity of the estrogen receptor and its ligand, estradiol. Anti-estrogens, such as tamoxifen, have been used as the first line of therapy for over three decades due to the fact that they elicit cell cycle arrest. Unfortunately, after an initial period, most cells become resistant to hormonal therapy. Peptidylprolyl isomerase 1 (Pin1, a protein overexpressed in many tumor types including breast, has been demonstrated to modulate ERalpha activity and is involved in resistance to hormonal therapy. Here we show a new mechanism through which CDK2 drives an ERalpha-Pin1 interaction under hormone- and growth factor-free conditions. The PI3K/AKT pathway is necessary to activate CDK2, which phosphorylates ERalphaSer294, and mediates the binding between Pin1 and ERalpha. Site-directed mutagenesis demonstrated that ERalphaSer294 is essential for Pin1-ERalpha interaction and modulates ERalpha phosphorylation on Ser118 and Ser167, dimerization and activity. These results open up new drug treatment opportunities for breast cancer patients who are resistant to anti-estrogen therapy.

  20. Parathyroid and bone imaging in primary hyperparathyroidism

    Institute of Scientific and Technical Information of China (English)

    ZHU Rui-Sen; LU Han-Kui; LUO Quan-Yong; CHEN Li-Bo; MA Ji-Xiao

    2004-01-01

    Skeletal derangements occur quite often in patient with primary hyperparathyroidism (PHPT). We investigated parathyroid and bone imagings in 59 cases of pathologically proven PHPT. Forty-nine cases were pathologically proven parathyroid adenomas; 8 presented hyperplasia and the other 2 were adenocarcinomas. Parathyroid imaging (early phase imaging, EPI) was conducted at 30 min after injecting 740~925MBq 99mTc-MIBI and 2~3h later (delayed phase imaging, DPI) separately. The following thyroid imagings were performed at the same posture 10 min after intravenous injection of 74~111MBq 99mTcO4-. The 99mTc- MIBI subtraction imaging data were obtained by subtracting thyroid imaging from that of DPI. Among 49 cases of proven hyperparathyroid adenoma 45 yielded positive imagings. Eight cases with hyperplasia gave negative results. The results were positive in 2 cases of parathyroid adenocarcinoma. Results of 99mTc-MDP/bone imaging: 35 cases of hyperparathyroid adenocarcinoma (disease duration 1-6 months) showed normal bone images, while 14 cases showed superscan images, course being 4-12 months. Bone imaging for 2 cases of adenocarcinoma showed multiple, radioactive aggregated foci (brown tumor imaging); course lasting 10-24 months. The results of bone imaging in 8 cases of hyperplasia/ hyperparathyroidism were normal. It was concluded that diagnostic accuracy for parathyroid was 79.6% and for parathyroid adenoma was 91.8%, and the technique has no diagnostic value for hyperplasia. The 99mTc-MDP / bone imaging results for PHPT can be classified into three categories, i.e. normal, superscan and brown tumor. The imaging results correlated well with the different categories and degrees of bone damage, the duration of clinical course and the pathological types. Therefore, it's important to use bone imaging data in association with therapy to reflect the stage and progress of PHPT.

  1. The history of the parathyroid surgery

    Directory of Open Access Journals (Sweden)

    Marcelo Garcia Toneto

    2016-06-01

    Full Text Available ABSTRACT The authors conducted a review of the major aspects of progression of knowledge about the surgical treatment of hyperparathyroidism. Through literature review, we analyzed articles on the history of the evolution of anatomical, physiological, pathological and surgical knowledge of the parathyroid glands. Because of their unique anatomical features, the parathyroid glands were the last of the endocrine glands to be discovered, which greatly hindered proper treatment until the first decades of the twentieth century. Technological developments in the last 30 years greatly facilitated the location of the glands and hyperparathyroidism surgery. However, an experienced and dedicated surgeon is still essential to the excellence of treatment.

  2. Pin1-mediated Sp1 phosphorylation by CDK1 increases Sp1 stability and decreases its DNA-binding activity during mitosis.

    Science.gov (United States)

    Yang, Hang-Che; Chuang, Jian-Ying; Jeng, Wen-Yih; Liu, Chia-I; Wang, Andrew H-J; Lu, Pei-Jung; Chang, Wen-Chang; Hung, Jan-Jong

    2014-12-16

    We have shown that Sp1 phosphorylation at Thr739 decreases its DNA-binding activity. In this study, we found that phosphorylation of Sp1 at Thr739 alone is necessary, but not sufficient for the inhibition of its DNA-binding activity during mitosis. We demonstrated that Pin1 could be recruited to the Thr739(p)-Pro motif of Sp1 to modulate the interaction between phospho-Sp1 and CDK1, thereby facilitating CDK1-mediated phosphorylation of Sp1 at Ser720, Thr723 and Thr737 during mitosis. Loss of the C-terminal end of Sp1 (amino acids 741-785) significantly increased Sp1 phosphorylation, implying that the C-terminus inhibits CDK1-mediated Sp1 phosphorylation. Binding analysis of Sp1 peptides to Pin1 by isothermal titration calorimetry indicated that Pin1 interacts with Thr739(p)-Sp1 peptide but not with Thr739-Sp1 peptide. X-ray crystallography data showed that the Thr739(p)-Sp1 peptide occupies the active site of Pin1. Increased Sp1 phosphorylation by CDK1 during mitosis not only stabilized Sp1 levels by decreasing interaction with ubiquitin E3-ligase RNF4 but also caused Sp1 to move out of the chromosomes completely by decreasing its DNA-binding activity, thereby facilitating cell cycle progression. Thus, Pin1-mediated conformational changes in the C-terminal region of Sp1 are critical for increased CDK1-mediated Sp1 phosphorylation to facilitate cell cycle progression during mitosis.

  3. Expression of the calcium receptor CaR in the parathyroid of secondary hyperparathyroidism patients

    Institute of Scientific and Technical Information of China (English)

    王宁宁; 王笑云; 彭韬; 吴宏飞; 胡建明; 赵卫红; 俞香宝

    2004-01-01

    @@ The effects of calcium on parathyroid hormone (PTH) has further discovered in recent years. It has been known that calcium ion concentration in the extracellular fluid is a major determinant of PTH secretion. The relationship between serum intact PTH (iPTH) and calcium ion levels is described by a sigmoidal curve. The calcium concentration that produces half-maximal change in PTH release (the midpoint between maximal and minimal change in PTH release) represents the sensitivity of parathyroid cells to serum calcium. In secondary hyperparathyroidism (SHPT) patients, higher calcium concentrations are needed to suppress PTH secretion, as demonstrated by the PTH-calcium sigmoidal curve. The loss of physiological control over the secretory function and growth of parathyroid tissue in hyperparathyroid disease is still incompletely understood.

  4. Hyperparathyroid crisis due to asymmetric parathyroid hyperplasia with a massive ectopic parathyroid gland.

    Science.gov (United States)

    Gratian, Lauren F; Hyland, Kristen A; Scheri, Randall P

    2014-10-01

    To report a rare case of primary hyperparathyroidism presenting with hyperparathyroid crisis due to parathyroid hyperplasia with ectopic glands. We present the initial clinical manifestations, laboratory results, radiologic and surgical findings, and management in a patient who had hyperparathyroid crisis. The pertinent literature and management options are also reviewed. A 60-year-old female presented with hyperparathyroid crisis requiring preoperative stabilization with rehydration, diuresis, bisphosphonate therapy, and ultimately hemodialysis. Parathyroidectomy revealed asymmetric 4-gland hyperplasia, with a massive ectopic parathyroid gland in the tracheoesophageal groove extending into the mediastinum. Her postoperative course was complicated by hungry bone syndrome and hypocalcemia. This case illustrates the rare occurrence of hyperparathyroid crises due to asymmetric parathyroid hyperplasia with a massive ectopic parathyroid gland.

  5. The management of acute parathyroid crisis secondary to parathyroid carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    O'Malley Diarmuid

    2010-01-01

    Full Text Available Abstract Introduction Hypercalcaemic hyperparathyroid crisis is a rare but life-threatening complication of primary hyperparathyroidism. Parathyroid carcinoma is a rare malignancy with an incidence of 0.5% to 4% of all reported cases of primary hyperparathyroidism. Case presentation We report the case of a 60-year-old Caucasian man with hypercalcaemic hyperparathyroid crisis associated with parathyroid carcinoma. He presented with a classic hypercalcaemic syndrome and his serum calcium and parathyroid hormone levels were at 4.65 mmol/L and 1743 ng/L, respectively. He initially presented with a two-week history of weakness and lethargy and a one-week history of vomiting, polyuria and polydipsia. An emergency left thyroid lobectomy and left lower parathyroidectomy were performed. There was a prompt decrease in his parathyroid hormone level immediately after surgery. Histology revealed that our patient had a 4-cm parathyroid carcinoma. Conclusion In patients with parathyroid carcinoma, the optimal surgical treatment is en bloc resection with ipsilateral thyroid lobectomy and removal of any enlarged or abnormal lymph nodes. Surgery is the only curative treatment. In our patient, prompt surgical intervention proved successful. At six months the patient is well with no evidence of disease recurrence. This case highlights the importance of considering a hyperparathyroid storm in the context of a parathyroid carcinoma. Parathyroid carcinoma is a rare entity and our knowledge is mainly derived from case reports and retrospective studies. This case report increases awareness of this serious and life-threatening complication. This report also illustrates how prompt and appropriate management provides the best outcome for the patient.

  6. The management of acute parathyroid crisis secondary to parathyroid carcinoma: a case report.

    LENUS (Irish Health Repository)

    Rock, Kathy

    2010-01-01

    ABSTRACT: INTRODUCTION: Hypercalcaemic hyperparathyroid crisis is a rare but life-threatening complication of primary hyperparathyroidism. Parathyroid carcinoma is a rare malignancy with an incidence of 0.5% to 4% of all reported cases of primary hyperparathyroidism. CASE PRESENTATION: We report the case of a 60-year-old Caucasian man with hypercalcaemic hyperparathyroid crisis associated with parathyroid carcinoma. He presented with a classic hypercalcaemic syndrome and his serum calcium and parathyroid hormone levels were at 4.65 mmol\\/L and 1743 ng\\/L, respectively. He initially presented with a two-week history of weakness and lethargy and a one-week history of vomiting, polyuria and polydipsia. An emergency left thyroid lobectomy and left lower parathyroidectomy were performed. There was a prompt decrease in his parathyroid hormone level immediately after surgery. Histology revealed that our patient had a 4-cm parathyroid carcinoma. CONCLUSION: In patients with parathyroid carcinoma, the optimal surgical treatment is en bloc resection with ipsilateral thyroid lobectomy and removal of any enlarged or abnormal lymph nodes. Surgery is the only curative treatment. In our patient, prompt surgical intervention proved successful. At six months the patient is well with no evidence of disease recurrence. This case highlights the importance of considering a hyperparathyroid storm in the context of a parathyroid carcinoma. Parathyroid carcinoma is a rare entity and our knowledge is mainly derived from case reports and retrospective studies. This case report increases awareness of this serious and life-threatening complication. This report also illustrates how prompt and appropriate management provides the best outcome for the patient.

  7. Transient modulation of calcium and parathyroid hormone stimulates bone formation.

    Science.gov (United States)

    Chen, Andy B; Minami, Kazumasa; Raposo, João F; Matsuura, Nariaki; Koizumi, Masahiko; Yokota, Hiroki; Ferreira, Hugo G

    2016-10-01

    Intermittent administration of parathyroid hormone can stimulate bone formation. Parathyroid hormone is a natural hormone that responds to serum calcium levels. In this study, we examined whether a transient increase and/or decrease in the serum calcium can stimulate bone formation. Using a mathematical model previously developed, we first predicted the effects of administration of parathyroid hormone, neutralizing parathyroid hormone antibody, calcium, and EGTA (calcium chelator) on the serum concentration of parathyroid hormone and calcium. The model predicted that intermittent injection of parathyroid hormone and ethylene glycol tetraacetic acid transiently elevated the serum parathyroid hormone, while that of parathyroid hormone antibody and calcium transiently reduced parathyroid hormone in the serum. In vitro analysis revealed that parathyroid hormone's transient changes (both up and down) elevated activating transcription factor 4-mediated osteocalcin expression. In the mouse model of osteoporosis, both intermittent administration of calcium and ethylene glycol tetraacetic acid showed tendency to increase bone mineral density of the upper limb (ulna and humerus) and spine, but the effects varied in a region-specific manner. Collectively, the study herein supports a common bone response to administration of calcium and its chelator through their effects on parathyroid hormone.

  8. Carcinoma of the parathyroid gland with hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Trevino Canamar, G.; Vogel, H.

    1983-02-01

    A patient with an endocrine-active carcinoma of the parathyroid gland was observed. The typical signs of hyperthyroidism could be seen in the skelettal system. Symptoms of bone and kidney diseases dominated the clinical picture. The symptomatology corresponded to a subchronic primary hyperparathyroidism.

  9. The Fine Structure of the Parathyroid Gland

    Science.gov (United States)

    Trier, Jerry Steven

    1958-01-01

    The fine structure of the parathyroid of the macaque is described, and is correlated with classical parathyroid cytology as seen in the light microscope. The two parenchymal cell types, the chief cells and the oxyphil cells, have been recognized in electron micrographs. The chief cells contain within their cytoplasm mitochondria, endoplasmic reticulum, and Golgi bodies similar to those found in other endocrine tissues as well as frequent PAS-positive granules. The juxtanuclear body of the light microscopists is identified with stacks of parallel lamellar elements of the endoplasmic reticulum of the ergastoplasmic or granular type. Oxyphil cells are characterized by juxtanuclear bodies and by numerous mitochondria found throughout their cytoplasm. Puzzling lamellar whorls are described in the cytoplasm of some oxyphil cells. The endothelium of parathyroid capillaries is extremely thin in some areas and contains numerous fenestrations as well as an extensive system of vesicles. The possible significance of these structures is discussed. The connective tissue elements found in the perivascular spaces of macaque parathyroid are described. PMID:13502423

  10. Place of the parathyroid scintigraphy in the preoperative detection of pathological parathyroid glands; Place de la scintigraphie parathyroidienne dans la detection preoperatoire des glandes parathyroides pathologiques

    Energy Technology Data Exchange (ETDEWEB)

    Rejeb, O.; Sellem, A.; Elbez, I.; Elkadri, N.; Hammami, H. [Service de medecine nucleaire, hopital militaire, Tunis, (Tunisia)

    2009-05-15

    The aim of this work is to evaluate the performances of the scintigraphy in the preoperative localization of pathological parathyroid glands. The parathyroid scintigraphy is a simple, non invasive technique that proved its performances in the preoperative detection of pathological parathyroid glands, mostly in the case of adenoma. It should be indicated in first intention in the topographic diagnosis of a hyperparathyroidism. (N.C.)

  11. Normal Parathyroid Function with Decreased Bone Mineral Density in Treated Celiac Disease

    Directory of Open Access Journals (Sweden)

    Bernard Lemieux

    2001-01-01

    Full Text Available Decreased bone mineral density (BMD has been reported in patients with celiac disease in association with secondary hyperparathyroidism. The present study investigated whether basal parathyroid hormone (PTH remained elevated and whether abnormalities of parathyroid function were still present in celiac disease patients treated with a gluten-free diet. Basal seric measurements of calcium and phosphate homeostasis and BMD were obtained in 17 biopsy-proven patients under treatment for a mean period of 5.7±3.7 years (range 1.1 to 15.9. In addition, parathyroid function was studied with calcium chloride and sodium citrate infusions in seven patients. Basal measurements of patients were compared with those of 26 normal individuals, while parathyroid function results were compared with those of seven sex- and age-matched controls. Basal results were similar in patients and controls except for intact PTH (I-PTH (3.77±0.88 pmol/L versus 2.28±0.63 pmol/L, P<0.001, which was higher in the former group but still within normal limits. Mean 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D values were normal in patients. Parathyroid function results were also found to be similar in both groups. Compared with a reference population of the same age (Z score, patients had significantly lower BMDs of the hip (-0.60±0.96 SDs, P<0.05 and lumbar spine (-0.76±1.15 SDs, P<0.05. T scores were also decreased for the hip (-1.3±0.9 SDs, P<0.0001 and lumbar spine (-1.4±1.35 SDs, P<0.0001, with two to three patients being osteoporotic (T score less than -2.5 SDs and seven to eight osteopenic (T score less than -1 SDs but greater than or equal to -2.5 SDs in at least one site. Height and weight were the only important determinants of BMD values by multivariate or logistical regression analysis in these patients. The results show higher basal I-PTH values with normal parathyroid function in treated celiac disease. Height and weight values are, but I-PTH values are not

  12. Intraoperative Near-infrared Imaging for Parathyroid Gland Identification by Auto-fluorescence: A Feasibility Study.

    Science.gov (United States)

    De Leeuw, Frederic; Breuskin, Ingrid; Abbaci, Muriel; Casiraghi, Odile; Mirghani, Haïtham; Ben Lakhdar, Aïcha; Laplace-Builhé, Corinne; Hartl, Dana

    2016-09-01

    Parathyroid glands (PGs) can be particularly hard to distinguish from surrounding tissue and thus can be damaged or removed during thyroidectomy. Postoperative hypoparathyroidism is the most common complication after thyroidectomy. Very recently, it has been found that the parathyroid tissue shows near-infrared (NIR) auto-fluorescence which could be used for intraoperative detection, without any use of contrast agents. The work described here presents a histological validation ex vivo of the NIR imaging procedure and evaluates intraoperative PG detection by NIR auto-fluorescence using for the first time to our knowledge a commercially available clinical NIR imaging device. Ex vivo study on resected operative specimens combined with a prospective in vivo study of consecutive patients who underwent total or partial thyroid, or parathyroid surgery at a comprehensive cancer center. During surgery, any tissue suspected to be a potential PG by the surgeon was imaged with the Fluobeam 800 (®) system. NIR imaging was compared to conventional histology (ex vivo) and/or visual identification by the surgeon (in vivo). We have validated NIR auto-fluorescence with an ex vivo study including 28 specimens. Sensitivity and specificity were 94.1 and 80 %, respectively. Intraoperative NIR imaging was performed in 35 patients and 81 parathyroids were identified. In 80/81 cases, the fluorescence signal was subjectively obvious on real-time visualization. We determined that PG fluorescence is 2.93 ± 1.59 times greater than thyroid fluorescence in vivo. Real-time NIR imaging based on parathyroid auto-fluorescence is fast, safe, and non-invasive and shows very encouraging results, for intraoperative parathyroid identification.

  13. Intraoperative parathyroid hormone as an indicator for parathyroid gland preservation in thyroid surgery.

    Science.gov (United States)

    Ezzat, Waleed Farag; Fathey, Hanaa; Fawaz, Samya; El-Ashri, Alaa; Youssef, Tamer; Othman, Hala Badr

    2011-11-08

    Intra-operative parathyroid hormone (PTH) levels have successfully been used to assess surgical ablation of parathyroid adenomas, the use of this same test to predict preservation of viable gland has not been widely used. to test the sensitivity and specificity of intraoperative rapid PTH assay test in predicting permanent postoperative hypoparathyroidism, and applicability to guide the search for inadvertently removed parathyroid glands for possible auto transplantation. 52 patients undergoing total thyroidectomy for non-malignant thyroid diseases were included. Intraoperative rapid PTH assay test was performed. If levels were reduced, or less than 3 parathyroid glands were detected, removed thyroid gland was examined for unintentionally removed parathyroid tissue for possible auto transplantation. There was a strong correlation between intraoperative rapid PTH assays and those taken 24 hours after surgery, 16 out of 52 patients had reduction of the PTH intraoperatively to levels below 25 pg/ml, of them, 11 patients (who had values between 15-24 pg/ml) recovered to normal PTH levels within 4 weeks, while the 5 patients with intraoperative PTH levels below 15 pg/ml failed to regain normal PTH levels up to 12 weeks postoperatively, even in those patients where parathyroid tissue was auto transplantated. The 4 patients who had parathyroid tissue reimplanted intraoperatively restored some of their parathyroid function as indicated by relative rise of their PTH levels, but did not reach even the low normal levels. (ROC) curve for prediction of early hypoparathyroidism using intraoperative rapid PTH assay was statistically highly significant with optimal cutoff value for predicting early hypocalcaemia level <27 pg/ml, (sensitivity 100%, specificity 68.2%). (ROC) curves for predicting permanent hypoparathyroidism using intraoperative rapid PTH assay or standard PTH assay taken 24 hours after surgery were statistically significant with optimal cutoff value PTH level <12

  14. Contact endoscopy for identifying the parathyroid glands during thyroidectomy.

    Science.gov (United States)

    Guimarães, A V; Brandão, L G; Dedivitis, R A

    2010-02-01

    Aim of this study was to analyse contact endoscopy as an auxiliary method for identifying parathyroid glands during thyroid surgery and to identify other variables that may interfere with this correlation. Overall, 125 patients underwent thyroid surgery between January 2004 and February 2006. The variables analysed were: the total duration of surgery; time taken to locate and identify parathyroid glands; improvement in identifying these; numbers of parathyroid glands located by the surgeon and confirmed by contact endoscopy; histopathological diagnosis; presence of thyroiditis; thyroid weight; number of parathyroid glands left in thyroid specimens; and number of parathyroid gland autotransplantations. A total of 331 parathyroid glands were observed by the surgeon. However, 282 glands were identified by contact endoscopy. Nine parathyroid glands (7.2%) were observed together with thyroid specimens (Kappa = 0.534). The longer the total duration of surgery (p = 0.03) and time taken to locate and identify (p = 0.00) the parathyroid glands by contact endoscopy, the lower the observed agreement. The second year of performing contact endoscopy led to better agreement between the results (p = 0.02). In conclusion, contact endoscopy is an efficient auxiliary method for identifying parathyroid glands during thyroid surgery. During the period studied, association between total duration of surgery and time taken to locate and identify parathyroid glands was statistically significant.

  15. A Case of Primary Hyperparathyroidism due to Intrathyroidal Parathyroid Cyst

    Directory of Open Access Journals (Sweden)

    Yavuz Yalcin

    2014-01-01

    Full Text Available Parathyroid cysts constitute 0.08–3.41% of all parathyroid masses. Intrathyroidal parathyroid cysts, however, are rare conditions with only a few cases being reported. Most of the parathyroid cysts are found to be nonfunctional and functional cysts are generally thought to be due to cystic degeneration of parathyroid adenomas. A cystic, smooth contoured lesion of 24 × 19 × 16 mm was observed in left thyroid lobe of a 76-year-old woman during ultrasonography which was performed as routine workup for primary hyperparathyroidism. It was defined as a cystic thyroid nodule at first. Tc99m sestamibi scintigraphy was performed to see any parathyroid lesions, but no radioactive uptake was observed. Intact parathormone (iPTH level was found to be >600 pg/mL in cyst aspiration fluid. Left lobectomy was performed, with a diagnosis of primary hyperparathyroidism due to functional parathyroid cyst. Serum iPTH level was decreased >50% postoperatively and histopathological evaluation was consistent with an encapsulated parathyroid adenoma with a cystic center. Parathyroid cysts are among rare causes of primary hyperparathyroidism. Diagnosis is made by markedly increased iPTH level in cyst fluid and observation of parathyroid epithelium lining the cyst wall.

  16. Intraoperative near-infrared autofluorescence imaging of parathyroid glands.

    Science.gov (United States)

    Ladurner, Roland; Sommerey, Sandra; Arabi, Nora Al; Hallfeldt, Klaus K J; Stepp, Herbert; Gallwas, Julia K S

    2017-08-01

    To identify parathyroid glands intraoperatively by exposing their autofluorescence using near-infrared light. Fluorescence imaging was carried out during minimally invasive and open parathyroid and thyroid surgery. After identification, the parathyroid glands as well as the surrounding tissue were exposed to near-infrared (NIR) light with a wavelength of 690-770 nm using a modified Karl Storz near-infrared/indocyanine green (NIR/ICG) endoscopic system. Parathyroid tissue was expected to show near-infrared autofluorescence, captured in the blue channel of the camera. Whenever possible the visual identification of parathyroid tissue was confirmed histologically. In preliminary investigations, using the original NIR/ICG endoscopic system we noticed considerable interference of light in the blue channel overlying the autofluorescence. Therefore, we modified the light source by interposing additional filters. In a second series, we investigated 35 parathyroid glands from 25 patients. Twenty-seven glands were identified correctly based on NIR autofluorescence. Regarding the extent of autofluorescence, there were no noticeable differences between parathyroid adenomas, hyperplasia and normal parathyroid glands. In contrast, thyroid tissue, lymph nodes and adipose tissue revealed no substantial autofluorescence. Parathyroid tissue is characterized by showing autofluorescence in the near-infrared spectrum. This effect can be used to distinguish parathyroid glands from other cervical tissue entities.

  17. Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery.

    Science.gov (United States)

    Vidal Fortuny, J; Belfontali, V; Sadowski, S M; Karenovics, W; Guigard, S; Triponez, F

    2016-04-01

    Postoperative hypoparathyroidism remains the most common complication following thyroidectomy. The aim of this pilot study was to evaluate the use of intraoperative parathyroid gland angiography in predicting normal parathyroid gland function after thyroid surgery. Angiography with the fluorescent dye indocyanine green (ICG) was performed in patients undergoing total thyroidectomy, to visualize vascularization of identified parathyroid glands. Some 36 patients underwent ICG angiography during thyroidectomy. All patients received standard calcium and vitamin D supplementation. At least one well vascularized parathyroid gland was demonstrated by ICG angiography in 30 patients. All 30 patients had parathyroid hormone (PTH) levels in the normal range on postoperative day (POD) 1 and 10, and only one patient exhibited asymptomatic hypocalcaemia on POD 1. Mean(s.d.) PTH and calcium levels in these patients were 3·3(1·4) pmol/l and 2·27(0·10) mmol/l respectively on POD 1, and 4·0(1.6) pmol/l and 2·32(0·08) mmol/l on POD 10. Two of the six patients in whom no well vascularized parathyroid gland could be demonstrated developed transient hypoparathyroidism. None of the 36 patients presented symptomatic hypocalcaemia, and none received treatment for hypoparathyroidism. PTH levels on POD 1 were normal in all patients who had at least one well vascularized parathyroid gland demonstrated during surgery by ICG angiography, and none required treatment for hypoparathyroidism. © 2016 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.

  18. Human apolipoprotein E4 modulates the expression of Pin1, Sirtuin 1, and Presenilin 1 in brain regions of targeted replacement apoE mice.

    Science.gov (United States)

    Lattanzio, F; Carboni, L; Carretta, D; Rimondini, R; Candeletti, S; Romualdi, P

    2014-01-01

    The apolipoprotein E4 (apoE4) allele is consistently associated with increased risk for Alzheimer's disease (AD). We investigated the molecular mechanism of this susceptibility by analyzing the levels of genes involved in AD pathogenesis in transgenic mice expressing human apoE3 or apoE4 isoforms. mRNA and protein levels of Pin1, Sirtuin 1 (Sirt1), Presenilin 1 (PS1), and pro-Brain-derived Neurotrophic Factor (BDNF) were analyzed in brain regions affected by neuropathological changes in AD. Pin1 mRNA was significantly higher in the hippocampus of apoE4 mice than in apoE3 controls, whereas lower expression was detected in the entorhinal and parietal cortices. Reduced Pin1 levels may increase neurofibrillary degeneration and amyloidogenic processes, while compensatory mechanisms may take place in the hippocampus to balance spatial memory deficits. Sirt1 levels were significantly reduced in the frontal cortex of apoE4 mice. Sirt1 reduction may hinder its protective role against the formation of plaques and tangles and diminish its anti-inflammatory actions. Sirt1 decrease may also play a role in apoE4-associated memory impairments. Moreover, in apoE4 mice PS1 mRNA levels were lower in the frontal cortex. Lower PS1 expression may hamper γ-secretase function, thus affecting amyloid precursor protein processing. Pro-BDNF mRNA levels did not differ between apoE3 and apoE4 mice in any region analyzed. This study showed dysregulated expression of Pin1, Sirt1, and PS1 genes in different cerebral areas of apoE4 mice, suggesting that these changes may play a role in the mechanism of AD vulnerability.

  19. Aberrant WNT/β-catenin signaling in parathyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Åkerström Göran

    2010-11-01

    Full Text Available Abstract Background Parathyroid carcinoma (PC is a very rare malignancy with a high tendency to recur locally, and recurrent disease is difficult to eradicate. In most western European countries and United States, these malignant neoplasms cause less than 1% of the cases with primary hyperparathyroidism, whereas incidence as high as 5% have been reported from Italy, Japan, and India. The molecular etiology of PC is poorly understood. Results The APC (adenomatous polyposis coli tumor suppressor gene was inactivated by DNA methylation in five analyzed PCs, as determined by RT-PCR, Western blotting, and quantitative bisulfite pyrosequencing analyses. This was accompanied by accumulation of stabilized active nonphosphorylated β-catenin, strongly suggesting aberrant activation of the WNT/β-catenin signaling pathway in these tumors. Treatment of a primary PC cell culture with the DNA hypomethylating agent 5-aza-2'-deoxycytidine (decitabine, Dacogen(r induced APC expression, reduced active nonphosphorylated β-catenin, inhibited cell growth, and caused apoptosis. Conclusion Aberrant WNT/β-catenin signaling by lost expression and DNA methylation of APC, and accumulation of active nonphosphorylated β-catenin was observed in the analyzed PCs. We suggest that adjuvant epigenetic therapy should be considered as an additional option in the treatment of patients with recurrent or metastatic parathyroid carcinoma.

  20. Parathyroid-specific epidermal growth factor-receptor inactivation prevents uremia-induced parathyroid hyperplasia in mice.

    Science.gov (United States)

    Arcidiacono, Maria Vittoria; Yang, Jing; Fernandez, Elvira; Dusso, Adriana

    2015-03-01

    In chronic kidney disease (CKD), parathyroid hyperplasia contributes to high serum parathyroid hormone (PTH) and also to an impaired suppression of secondary hyperparathyroidism by calcium, vitamin D and fibroblast growth factor 23 (FGF23). In rats, systemic inhibition of epidermal growth factor receptor (EGFR) activation markedly attenuated uremia-induced parathyroid hyperplasia and vitamin D receptor (VDR) loss, hence restoring the response to vitamin D. Therefore, we propose that parathyroid-specific EGFR inactivation should prevent CKD-induced parathyroid hyperplasia. A dominant-negative human EGFR mutant, which forms non-functional heterodimers with full-length endogenous EGFR, was successfully targeted to the parathyroid glands (PTGs) of FVB/N mice, using the 5' regulatory sequence of the PTH promoter. The parathyroid phenotype and serum chemistries of wild-type (WT) and transgenic mice were examined after 14 weeks of either sham operation or 75% renal mass reduction (NX). Both genotypes had similar morphology and body weight, and NX-induction enhanced similarly serum blood urea nitrogen compared with sham-operated controls. However, despite similar serum calcium, phosphate and FGF23 levels in NX mice of both genotypes, parathyroid EGFR inactivation sufficed to completely prevent the marked increases in PTG enlargement, serum PTH and in parathyroid levels of transforming growth factor-α, a powerful EGFR-activator, and the VDR reductions observed in WT mice. In CKD, parathyroid EGFR activation is essential for parathyroid hyperplasia and VDR loss, rendering this transgenic mouse a unique tool to scrutinize the pathogenesis of parathyroid and multiple organ dysfunction of CKD progression unrelated to parathyroid hyperplasia. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  1. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats

    Science.gov (United States)

    Gowen, Maxine; Stroup, George B.; Dodds, Robert A.; James, Ian E.; Votta, Bart J.; Smith, Brian R.; Bhatnagar, Pradip K.; Lago, Amparo M.; Callahan, James F.; DelMar, Eric G.; Miller, Michael A.; Nemeth, Edward F.; Fox, John

    2000-01-01

    Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a “calcilytic”) of the parathyroid cell Ca2+ receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17β-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca2+ receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis. PMID:10841518

  2. Cervical SPECT Camera for Parathyroid Imaging

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2012-08-31

    Primary hyperparathyroidism characterized by one or more enlarged parathyroid glands has become one of the most common endocrine diseases in the world affecting about 1 per 1000 in the United States. Standard treatment is highly invasive exploratory neck surgery called Parathyroidectomy. The surgery has a notable mortality rate because of the close proximity to vital structures. The move to minimally invasive parathyroidectomy is hampered by the lack of high resolution pre-surgical imaging techniques that can accurately localize the parathyroid with respect to surrounding structures. We propose to develop a dedicated ultra-high resolution (~ 1 mm) and high sensitivity (10x conventional camera) cervical scintigraphic imaging device. It will be based on a multiple pinhole-camera SPECT system comprising a novel solid state CZT detector that offers the required performance. The overall system will be configured to fit around the neck and comfortably image a patient.

  3. Quantitative morphological studies of the parathyroid gland

    OpenAIRE

    Larsson, Hans-Olov

    1983-01-01

    This work is based upon a series of quantitative morphological studies of the parathyroid glands of Mongolian gerbils and rats. Standard stereological methods were used on light and electron microscopical levels. Subclassification of the chief cells based on the staining affinity and electron density of the cytoplasm was not correlated with contents (volume and surface densities) of organelles. Compared to fixation by immersion, fixation by perfusion caused a remarkable reduction in the numbe...

  4. Technical aspects of magnetic resonance imaging in parathyroid gland lesions

    Energy Technology Data Exchange (ETDEWEB)

    Hemmingsson, A.; Ericsson, A.; Ljunghall, S.; Juhlin, C.; Jung, B.; Rastad, J.; Thuomas, K.A.; Akerstroem, G.

    Two patients with primary hyperparathyroidism were examined before parathyroid surgery with magnetic resonance imaging at 0.35 telsa in order to analyse optimal methods of visualization. Two large parathyroid glands in the neck had long transverse relaxation times which rendered them clearly visible in T2-weighted images as structures of a signal intensity higher than that of the surrounding. Large parathyroid lesions may thus be easily detected by magnetic resonance imaging provided proper examination parameters are employed.

  5. Ectopic parathyroid glands and their anatomical, clinical and surgical implications.

    Science.gov (United States)

    Noussios, G; Anagnostis, P; Natsis, K

    2012-11-01

    Ectopic parathyroid glands result from aberrant migration during early stages of development and lack of successful identification may lead to lack of success in parathyroid surgery. They constitute a common etiology of persistent or recurrent hyperparathyroidism, when they are missed at initial diagnosis. Their prevalence is about 2-43% in anatomical series and up to 16% and 14% in patients with primary and secondary hyperparathyroidism, respectively. Ectopic inferior parathyroids are most frequently found in the anterior mediastinum, in association with the thymus or the thyroid gland, while the most common position for ectopic superior parathyroids is the tracheoesophageal groove and retroesophageal region. Neck ultrasound and 99mTc Sestamibi scan are first-line imaging modalities, although with low sensitivity and specificity. However, their combination with modern techniques, such as single photon emission computed tomography (SPECT) alone or in combination with CT (SPECT/CT) increases their diagnostic accuracy. Fine needle-aspiration cytology of a lesion suspicious for parathyroid tissue and measurement of parathyroid hormone (PTH) in the aspired material further assist to the successful preoperative localization of ectopic glands. Common sites for surgical investigation are the upper thyroid pole and the upper vascular thyroid stalk behind the hypopharynx and cervical esophagus for the superior parathyroids, and the carotid artery bifurcation and the thymic tongue, for the inferior parathyroids. Radioguided minimally invasive parathyroidectomy after successful localization, assisted by rapid PTH measurement postoperatively, significantly improves surgical outcomes in patients with ectopic parathyroid adenomas.

  6. Identification of parathyroid glands: anatomical study and surgical implications.

    Science.gov (United States)

    Melo, Catarina; Pinheiro, Susana; Carvalho, Lina; Bernardes, António

    2015-03-01

    While performing thyroid surgery, the unintentional lesion of parathyroid glands and laryngeal nerves results in a profound alteration in patient's quality of life. To minimize thyroid surgery morbidity, the surgeon must have an in-depth knowledge of the thyroid gland morphology and its anatomical relations in the anterior compartment of the neck. This work intended to simulate total thyroidectomies using cadaver parts and isolate fragments that may correspond to parathyroid glands. The thyroid glands and "eventual" parathyroid glands were then submitted to histological study. Ninety-two cadaver parts were used for macroscopic dissection. A total of 242 fragments were isolated, 154 of which were confirmed through histological study to be parathyroid glands. In 36 cases, all "eventual" parathyroid glands isolated during dissection were confirmed through histological verification. In 40 cases, some glands were confirmed. In 16 cases, none of the "eventual" parathyroid glands was confirmed. The 92 thyroid glands isolated during dissection were also submitted to histological study. In 21 thyroid glands, 16 parathyroid glands were identified in the histological cuts: 8 sub-capsular, 8 extra-capsular, 6 intra-thyroidal. There was no statistical difference between the dimensions of the parathyroid glands. Parathyroid gland identification and preservation are sometimes a challenge during thyroid surgery, difficulty that has been demonstrated during dissection of cadaver parts.

  7. FGF23 fails to inhibit uremic parathyroid glands.

    Science.gov (United States)

    Canalejo, Rocío; Canalejo, Antonio; Martinez-Moreno, Julio Manuel; Rodriguez-Ortiz, M Encarnacion; Estepa, Jose C; Mendoza, Francisco Javier; Munoz-Castaneda, Juan Rafael; Shalhoub, Victoria; Almaden, Yolanda; Rodriguez, Mariano

    2010-07-01

    Fibroblast growth factor 23 (FGF23) modulates mineral metabolism by promoting phosphaturia and decreasing the production of 1,25-dihydroxyvitamin D(3). FGF23 decreases parathyroid hormone (PTH) mRNA and secretion, but despite a marked elevation in FGF23 in uremia, PTH production increases. Here, we investigated the effect of FGF23 on parathyroid function in normal and uremic hyperplastic parathyroid glands in rats. In normal parathyroid glands, FGF23 decreased PTH production, increased expression of both the parathyroid calcium-sensing receptor and the vitamin D receptor, and reduced cell proliferation. Furthermore, FGF23 induced phosphorylation of extracellular signal-regulated kinase 1/2, which mediates the action of FGF23. In contrast, in hyperplastic parathyroid glands, FGF23 did not reduce PTH production, did not affect expression of the calcium-sensing receptor or vitamin D receptor, and did not affect cell proliferation. In addition, FGF23 failed to activate the extracellular signal-regulated kinase 1/2-mitogen-activated protein kinase pathway in hyperplastic parathyroid glands. We observed very low expression of the FGF23 receptor 1 and the co-receptor Klotho in uremic hyperplastic parathyroid glands, which may explain the lack of response to FGF23 in this tissue. In conclusion, in hyperparathyroidism secondary to renal failure, the parathyroid cells resist the inhibitory effects of FGF23, perhaps as a result of the low expression of FGF23 receptor 1 and Klotho in this condition.

  8. Structural Basis for Antibody Discrimination between Two Hormones That Recognize the Parathyroid Hormone Receptor

    Energy Technology Data Exchange (ETDEWEB)

    McKinstry, William J.; Polekhina, Galina; Diefenbach-Jagger, Hannelore; Ho, Patricia W.M.; Sato, Koh; Onuma, Etsuro; Gillespie, Matthew T.; Martin, T. John; Parker, Michael W.; (SVIMR-A); (Chugai); (Melbourne)

    2009-08-18

    Parathyroid hormone-related protein (PTHrP) plays a vital role in the embryonic development of the skeleton and other tissues. When it is produced in excess by cancers it can cause hypercalcemia, and its local production by breast cancer cells has been implicated in the pathogenesis of bone metastasis formation in that disease. Antibodies have been developed that neutralize the action of PTHrP through its receptor, parathyroid hormone receptor 1, without influencing parathyroid hormone action through the same receptor. Such neutralizing antibodies against PTHrP are therapeutically effective in animal models of the humoral hypercalcemia of malignancy and of bone metastasis formation. We have determined the crystal structure of the complex between PTHrP (residues 1-108) and a neutralizing monoclonal anti-PTHrP antibody that reveals the only point of contact is an {alpha}-helical structure extending from residues 14-29. Another striking feature is that the same residues that interact with the antibody also interact with parathyroid hormone receptor 1, showing that the antibody and the receptor binding site on the hormone closely overlap. The structure explains how the antibody discriminates between the two hormones and provides information that could be used in the development of novel agonists and antagonists of their common receptor.

  9. Genetic Complementation Studies of Human Pin1 in Azotobacter vinelandii Revealed that it Requires Amino Terminus of the NifM to Deliver PPIase Effect to the Fe-protein of Nitrogenase

    OpenAIRE

    Kumaraguru Raja; Lakshmi Pulakat; Narayanan Gavini

    2006-01-01

    The NifM is a peptidyl prolyl cis-trans isomerase and is required for the maturation and activation of the Fe protein of Nitrogenase. Since the carboxyl terminus of NifM is similar to the Human Pin1, we expressed the Human Pin1 in A. vinelandii BG98, a nifM mutant strain containing a kanamycin insertion and found that it could not complement the function of nifM. It was hypothesized that the amino terminus of the NifM might be required for the Pin1 to bind to NifH similar to requirement of th...

  10. Association between serum 25-hydroxyvitamin D3 concentration,parathyroid hormone,and arterial stiffness in patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    马笑堃

    2013-01-01

    Objective To evaluate the association between serum 25-hydroxyvitamin D3[25 (OH) D3],parathyroid hormone,and arterial stiffness in patients with type 2 diabetes.Methods Serum 25 (OH) D3and parathyroid hormone (PTH) were determined in a cross-sectional sample of 258 patients aged 30 years or over.Arterial stiffness was assessed by pulse wave velocity (PWV) obtained with a VP-1000 pulse wave unit.Fasting plasma HbA1C,

  11. Ectopic parathyroid gland. Localization with thallium-201 SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Ziffer, J.A.; Fajman, W.A.

    1987-08-01

    Dual isotope Tl-201/Tc-99m subtraction is a useful technique for localization of abnormal parathyroid glands. A case of tomographic localization of nonsubtracted Tl-201 to a mediastinal parathyroid is reported and the possible benefit of this method discussed.

  12. Anabolic Action Of Bovine Parathyroid Hormone In Male Rats ...

    African Journals Online (AJOL)

    Anabolic Action Of Bovine Parathyroid Hormone In Male Rats. ... bovine parathyroid hormone (bPTH) and to throw more lights on the mechanisms of these ... DNA, RNA and activities of some lipogenic enzymes such as ATP-citrate lyase, malic ...

  13. CYP2D6, GST-M1 and GST-T1 enzymes: expression in parathyroid gland and association with the parathyroid hormone concentration during early renal replacement therapy

    Science.gov (United States)

    Yan, Feng-Xiang; Langub, M Chris; Ihnen, Mark A; Hornung, Carlton; Juronen, Erkki; Rayens, Mary K; Cai, Wei-Min; Wedlund, Peter J; Fanti, Paolo

    2003-01-01

    Aims The purpose of this research was to characterize CYP2D6, GST-M1 and GST-T1 enzyme expression in human parathyroid tissue, and to determine whether or not there is any association between deficiencies in these enzymes and serum parathyroid hormone concentrations in patients with end-stage renal disease. Methods Surgical human parathyroid tissue was obtained and evaluated by immunohistochemistry for cellular localization of CYP2D6, GST-M1 and GST-T1 and colocalization of CYP2D6 with parathyroid hormone. Blood samples were collected from 328 Caucasian patients with end-stage renal disease for genetic testing of CYP2D6*3, *4, *5, *6, *7 and GST-M1*0 and GST-T1*0 alleles. Clinical chemistry data and serum intact parathyroid hormone (iPTH) concentrations were obtained from patient medical records. In 277 of the patients, the same laboratory performed all clinical tests. Results CYP2D6, GST-M1 and GST-T1 were present in human parathyroid tissue. CYP2D6 was colocalized with parathyroid hormone in parathyroid chief cells. Within the end-stage renal disease population, a nonfunctional CYP2D6 genotype was present in 18.2%[95% confidence interval (CI) 8.0, 28.4] of patients in the 1st iPTH concentration quintile (iPTH 347 pg mL−1) (P = 0.001). Out of 12 CYP2D6-deficient females, seven were in the 1st iPTH concentration quintile and the remaining five were in the 5th quintile. Patients deficient in the GST-M1 and GST-T1 enzymes displayed a far more uniform frequency distribution relative to serum iPTH concentrations. Conclusions The presence of CYP2D6, GST-M1 and GST-T1 in parathyroid cells was observed. An association is reported between a lack of CYP2D6 and iPTH concentrations in newly diagnosed end-stage renal disease patients. Gender and concomitant deficiency in GST-M1 and/or GST-T1 appear to define this association further. It remains to be established whether these associations reflect a cause-effect relationship between deficient expression of metabolizing

  14. Value of Prophylactic Cervical Thymectomy in Parathyroid Hyperplasia.

    Science.gov (United States)

    Boltz, Melissa M; Zhang, Ning; Zhao, Carrie; Thiruvengadam, Sujan; Siperstein, Allan E; Jin, Judy

    2015-12-01

    In parathyroid hyperplasia (HPT), parathyroid glands within the cervical thymus are a cause for recurrence. As a result of differences in pathophysiology, variable practice patterns exist regarding performing bilateral cervical thymectomy (BCT) in primary hyperplasia versus hyperplasia from renal failure or familial disease. The objective of this study was to capture patients where thymic tissue was found with subtotal parathyroidectomy (PTX) and intended BCT, identify number of thymic supernumerary glands (SNGs), and determine overall cure rate. Retrospective review of patients with four-gland exploration and intended BCT for HPT from 2000 to 2013 was performed. Identification of thymic tissue and SNGs were determined by operative/pathology reports. Univariate analysis identified differences in cure rate for patients undergoing subtotal PTX with or without BCT. Thymic tissue was found in 52 % of 328 primary HPT (19 % unilateral, 33 % bilateral), 77 % of 128 renal HPT (28 % unilateral, 49 % bilateral), and 100 % of familial HPT (24 % unilateral, 76 % bilateral) patients. Nine percent of primary, 18 % of renal, and 10 % of familial HPT patients had SNGs within thymectomy specimens. Cure rates of primary HPT patients with BCT were 99 % compared to 94 % in subtotal PTX alone. Renal HPT cure rates were 94 % with BCT compared to 89 % without BCT. Renal HPT patients benefited most in cure when thymectomy was performed. Although the rate of SNGs found in primary HPT was lower than renal HPT, the cure rate mimicked the pattern in renal disease. Furthermore, the incidences of SNGs in primary and familial HPT were similar. On the basis of these data, we advocate that BCT be considered in primary HPT when thymic tissue is readily identified.

  15. Parathyroid involvement in thyroid cancer: an unforeseen event

    Directory of Open Access Journals (Sweden)

    Chrisoulidou Alexandra

    2012-06-01

    Full Text Available Abstract Background Parathyroid metastatic disease from thyroid cancer has not been studied extensively, mainly due to the need for parathyroid preservation during thyroid surgery. Methods We reviewed files from 1,770 patients with thyroid cancer followed up in our department and 10 patients with parathyroid metastases (0.5% were identified. Patient and tumor characteristics were recorded. Results Six out of ten patients had metastases from papillary thyroid cancer, three from follicular thyroid cancer and one from anaplastic thyroid cancer. In nine patients parathyroid infiltration from thyroid cancer was found in direct contact with the thyroid cancer, and in one patient metastatic foci were observed not in continuity with the thyroid cancer. Conclusions Parathyroid involvement, although infrequent, may occur in thyroid cancer independently of patient age and tumor size. The clinical significance of such event is not clear. The influence on disease outcome remains to be elucidated.

  16. Ectopic parathyroid adenoma in the soft palate: a case report.

    Science.gov (United States)

    Chang, Brent A; Sharma, Anil; Anderson, Donald W

    2016-10-18

    Ectopic parathyroid adenomas can occur in numerous anatomic locations. While ectopic parathyroid adenomas can rarely occur in the pharyngeal region, this has not previously been described in the soft palate. We report the first case of ectopic parathyroid adenoma within the soft palate. A 59 year old woman presented with hyperparathyroidism. She remained persistently hyperparathyroid after initial parathyroidectomy. Repeat exploration for a lesion suspicious on PET-CT for an ectopic parathyroid adenoma in the parapharyngeal region was unsuccessful in treating the hyperparathyroidism. An ectopic adenoma in the soft palate was eventually discovered. Removal through a transoral approach was successful in treating the hyperparathyroidism. Ectopic parathyroid adenomas can occur in various anatomical locations that may be missed even with the use of the various imaging modalities. The soft palate should be added to the list of possible ectopic locations high in the neck.

  17. Dual-Phase 99MTc-MIBI Parathyroid Imaging Reveals Synchronous Parathyroid Adenoma and Papillary Thyroid Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Ming-Che Chang

    2008-10-01

    Full Text Available The possibility of a coincidental appearance of hyperparathyroidism and thyroid cancer is not often considered because of its low incidence. Here, we present a case of a 49-year-old woman with a parathyroid adenoma coexisting with two sites of papillary thyroid carcinoma. Dual-phase 99mTc-methoxyisobutylisonitrile (MIBI parathyroid imaging before the operation correctly visualized the site of the parathyroid adenoma. In addition, two papillary thyroid carcinomas showed faint uptake of 99mTc-MIBI on delayed image. Total thyroidectomy and parathyroidectomy of a solitary parathyroid adenoma were performed. The patient subsequently underwent radioiodine-131 ablation and was treated with T4 suppression. This case illustrates the need for clinical awareness of concomitant hyperparathyroidism and thyroid cancer. Dual-phase 99mTc-MIBI parathyroid imaging may be useful for detecting indolent thyroid cancer before it becomes a distinct disease.

  18. Parathyroid hormone-related peptide plasma concentrations in patients on hemodialysis

    DEFF Research Database (Denmark)

    Nordholm, Anders; Rix, M.; Olgaard, K.

    2014-01-01

    BACKGROUND: Uremic patients develop hyperplasia of the parathyroid glands due to disturbances in the mineral metabolism. The hyperplastic parathyroids are associated with significant expression of parathyroid hormone (PTH)-related peptide (PTHrP). PTHrP has been shown to have an autocrine...... not derive from the uremic hyperplastic parathyroid glands...

  19. The prognostic significance of β-catenin, cyclin D1 and PIN1 in minor salivary gland carcinoma: β-catenin predicts overall survival.

    Science.gov (United States)

    Schneider, Sven; Thurnher, Dietmar; Seemann, Rudolf; Brunner, Markus; Kadletz, Lorenz; Ghanim, Bahil; Aumayr, Klaus; Heiduschka, Gregor; Lill, Claudia

    2016-05-01

    Minor salivary gland carcinoma is a rare and heterogeneous type of cancer. Molecular prognostic and predictive markers are sparse. The aim of this study was to identify new prognostic and predictive markers in minor salivary gland carcinoma. 50 tissue samples of carcinomas of the minor salivary glands (adenoid cystic carcinoma n = 23, mucoepidermoid carcinoma n = 12, adenocarcinoma n = 10, carcinoma ex pleomorphic adenoma n = 2, salivary duct carcinoma n = 1, clear cell carcinoma n = 1, basal cell carcinoma n = 1) were immunohistochemically stained for β-catenin, cyclin D1 and PIN1. Expression patterns were analyzed and correlated to clinical outcome of 37 patients with complete clinical data. High expression of membranous β-catenin was linked to significantly better overall survival in patients with adenoid cystic carcinoma (log rank test, χ (2) = 13.3, p = .00397, Bonferroni corrected p = .024). PIN1 and cyclin D1 did not show any significant correlation to patients' clinical outcome. Expression of β-catenin in adenoid cystic carcinoma of the minor salivary glands significantly correlates with better overall survival. Hence, evaluation of β-catenin might serve as a clinical prognostic marker.

  20. Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Tomaschitz Andreas

    2012-09-01

    Full Text Available Abstract Background Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess. Methods/design Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease. The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1 parathyroid hormone(1–84 as the primary endpoint and (2 24-h systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24-h urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints. Discussion In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular, renal and bone health in patients with primary hyperparathyroidism. Trial registration ISRCTN33941607

  1. 胶质瘤中PIN1-Nanog相关通路表达的研究%Relation of peptidyl-prolyi isomerase 1 and Nanog expressions in human gliomas

    Institute of Scientific and Technical Information of China (English)

    倪升远; 牛朝诗; 杨洋; 张翔宇

    2015-01-01

    目的 观察肽基脯氨酰异构酶1(PIN1)、Nanog在胶质瘤组织中的表达以及PIN1抑制剂PiB对U87细胞增殖能力及PIN1、Nanog表达的影响. 方法 选取安徽医科大学附属省立医院神经外科自2013年3月至2014年8月间手术切除的84例胶质瘤和10例正常脑组织标本,免疫组化染色检测标本PIN1、Nanog蛋白的表达.体外常规培养U87胶质瘤细胞,用0.2、0.5、1.0、2.0 μg/mL PiB分别作用24、48 h,MTT检测PiB对细胞增殖的抑制作用并计算抑制率;以1.0μmol/L PiB处理U87细胞24 h为1.0 μmol/L PiB组,未经任何处理的U87细胞作为对照组,免疫荧光双染检测细胞PIN1、Nanog的表达,RT-PCR和Westem blotting分别检测细胞PIN1、Nanog mRNA和蛋白的表达. 结果 WHOⅡ级、Ⅲ级、Ⅳ级胶质瘤中PIN1、Nanog高表达率不同,差异有统计学意义(P<0.05),且胶质瘤级别越高,PIN1、Nanog高表达率越高.MTT检测显示PiB对U87细胞的增殖有抑制作用,且呈时间和剂量依赖性.与对照组比较,1.0 μmol/L PiB组PIN1、Nanog及PIN1/Nanog阳性细胞百分比降低,差异有统计学意义(P<0.05);对照组和1.0 μmol/L PiB组细胞PIN1 mRNA的表达量分别为1.82±0.03和0.94±0.20,Nanog mRNA的表达量分别为1.47±0.04和0.82±0.19,差异均有统计学意义(P<0.05);对照组和1.0 μmol/L PiB组细胞PIN1蛋白表达量分别为2.96±0.05和1.15±0.26,Nanog蛋白表达量分别为1.52±0.16和0.75±0.05,差异均有统计学意义(P<0.05). 结论 PIN1、Nanog在胶质瘤的发生发展中起重要作用,且与肿瘤的恶性程度相关.PIN1可参与调控Nanog,两者之间存在相关通路,下调PIN1-Nanog通路后,胶质瘤细胞增殖能力下降.%Objective To obsevre the peptidyl-prolyi isomerase 1 (PIN1) and Nanog expreesions in glioma tissues and the effect of PIN1 inhibitor polyiso-butylene (PiB) on their expressions and U87 cell proliferation.Methods Eighty-four glioma samples (15 with WHO graded Ⅱ,27 with WHO graded

  2. Near-infrared autofluorescence for the detection of parathyroid glands

    Science.gov (United States)

    Paras, Constantine; Keller, Matthew; White, Lisa; Phay, John; Mahadevan-Jansen, Anita

    2011-06-01

    A major challenge in endocrine surgery is the intraoperative detection of parathyroid glands during both thyroidectomies and parathyroidectomies. Current localization techniques such as ultrasound and sestamibi scan are mostly preoperative and rely on an abnormal parathyroid for its detection. In this paper, we present near-infrared (NIR) autofluorescence as a nonintrusive, real-time, automated in vivo method for the detection of the parathyroid gland. A pilot in vivo study was conducted to assess the ability of NIR fluorescence to identify parathyroid glands during thyroid and parathyroidectomies. Fluorescence measurements at 785 nm excitation were obtained intra-operatively from the different tissues exposed in the neck region in 21 patients undergoing endocrine surgery. The fluorescence intensity of the parathyroid gland was found to be consistently greater than that of the thyroid and all other tissues in the neck of all patients. In particular, parathyroid fluorescence was two to eleven times higher than that of the thyroid tissues with peak fluorescence occurring at 820 to 830 nm. These results indicate that NIR fluorescence has the potential to be an excellent optical tool to locate parathyroid tissue during surgery.

  3. Differential Findings of Tc 99m Sestamibi Dual Phase Parathyroid Scintigraphy Between Benign and Malignant Parathyroid Lesions in Patients with Primary Hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Miju; Choi, Joon Young; Chung, Jae Hoon; Lee, Ji Young; Cho, Sook Kyung; Yoo, Jang; Park, Soo Bin; Lee, Kyung Han; Kim, Byung Tae [Sungkyunkwan, Univ. School of Medicine, Seoul (Korea, Republic of)

    2011-12-15

    This study aimed to investigate the differential findings in clinical and biochemical features, and Tc 99m sestamibi (MIBI) dual phase parathyroid lesions in patients with primary hyperparathyroidism. Subjects were 102 parathyroid lesions from 91 patients with primary hyperparathyroidism. Scintigraphic findings included radioactivity grade, uptake pattern, uptake contour lesion size on early and delayed images, and degree of washout. Clinical and biochemical features were also evaluated. Histopathology confirmed the final diagnosis for all the patients. Final diagnoses were 94 benign parathyroid lesions and 8 parathyroid carcinomas. The patients with parathyroid carcinoma were significantly older (p=0.002) and had significantly higher serum parathyroid hormone concentrations than those with benign parathyroid lesions (p<0.001). All malignant parathyroid lesions showed intense radioactivity similar to or greater than the submandibular gland activity on delayed images (p=0.007), and little radioactivity difference between early and delayed images (p=0.012). The cancer incidence for parathyroid lesions with both intense radioactivity and no washout was 17.0% (8/47). When parathyroid lesions with all of the above mentioned findings were regarded as malignant, the cancer incidence significantly increased from 17.0% to 33.3% (8/24, p<0.001). For Tc 99m MIBI dual phase parathyroid scintigraphy, uptake grade on delayed images and washout were significantly useful diagnostic criteria for differentiating benign from malignant parathyroid lesions, along with age and parathyroid hormone serum concentration.

  4. Parathyroid hormone and parathyroid hormone-related protein analogs as therapies for osteoporosis.

    Science.gov (United States)

    Augustine, Marilyn; Horwitz, Mara J

    2013-12-01

    Osteoporotic fractures result in significant morbidity and mortality. Anabolic agents reverse the negative skeletal balance that characterizes osteoporosis by stimulating osteoblast-dependent bone formation to a greater degree than osteoclast-dependent bone resorption. Parathyroid hormone (PTH) and parathyroid hormone- related protein (PTHrP) are peptide hormones, which have anabolic actions when administered intermittently. The only FDA-approved anabolic bone agent for the treatment of osteoporosis in the United States is PTH 1-34, or teriparatide, administered by daily subcutaneous injections. However, PTH 1-84 is also available in Europe. Synthetic human PTHrP 1-36 and a PTHrP 1-34 analog, BA058, have also been shown to increase lumbar spine bone density. These agents and several other PTH and PTHrP analogs, including some which are not administered as injections, continue to be investigated as potential anabolic therapies for osteoporosis.

  5. Parathyroid hormone-related protein and calcium regulation in vitamin D-deficient sea bream (Sparus auratus).

    NARCIS (Netherlands)

    Abbink, W.; Hang, X.M.; Guerreiro, P.M.; Spanings, F.A.T.; Ross, H.A.; Canario, A.V.; Flik, G.

    2007-01-01

    Gilthead sea bream (Sparus auratus L.) were fed a vitamin D-deficient diet for 22 weeks. Growth rate, whole body mineral pools and calcium balance were determined. Plasma parathyroid hormone-related protein (PTHrP) and calcitriol levels were assessed. Expression of mRNA for pthrp and pth1r was

  6. Scintigraphy of parathyroids in secondary hyperparathyroidism; Scintigraphie des parathyroides dans l`hyperparathyroidie secondaire

    Energy Technology Data Exchange (ETDEWEB)

    Hublo, D.; Beauchat, V.; Pattou, F.; Lecomte-Houcke, M.; Prangere, T.; Ziegels, P.; Carnaille, B.; Proye, C.; Marchandise, X.; Steiling, M. [Medecine Nucleaire, Chirurgie Endocrinienne et Anatomie et Cytologie Pathologiques - CHU de Lille - 59037 Lille cedex (France)

    1997-12-31

    Use of pre-surgery imaging of parathyroids is still questioned. The goal of this study is to evaluate the sensitivity of the scintigraphy in the detection of secondary parathyroid anomalies with renal insufficiency. Thirty two patients (20 F, 12 M) of 14 - 74 years old were operated of secondary hyperparathyroidism with renal insufficiency. It was a matter of re-intervention in 9 cases. The acquisitions were achieved 20 min and 2 h after injection of 550 MBq of MIBI-{sup 99m}Tc or of Tetrofosmine - {sup 99m}Tc and 2 h after injection of 5.5 MBq of iodine 123. Eighty seven glands of 28 to 3820 mg were pulled out in 23 first surgeries while the parathyroid tissue was found in thymic prolongations in 5 of these patients. The masses of 41 glands, positive by scintigraphy (from 69 to 3829 mg), were significantly higher (Wilcoxon`s test, p < 10{sup -8}) than the 46 not-seen (from 28 to 1050 mg). The sensitivity of total detection is 47%, of 85% for the 33 glands of 500 mg or more and of 24% for the 54 glands of less than 500 mg. In 9 re-interventions, 12 abnormal glands were pulled out: 11 of 430 to 4500 mg were positive by scintigraphy, while only one gland of 80 mg was not seen. In conclusion, the scintigraphy realised before first surgery for secondary hyperparathyroidism with renal insufficiency presents low sensitivity, related partly, at least, to the low mass of glands and justifies itself only by search for positive ectopic parathyroids. Instead, it appears performing and indispensable in case of re-intervention

  7. Simultaneous Incidental Parathyroid Carcinoma and Intrathyroid Parathyroid Gland in Suspected Renal Failure Induced Hyperparathyroidism.

    Science.gov (United States)

    Pappa, Andrew; Hackman, Trevor

    2017-01-01

    Hyperparathyroidism is a common disorder affecting more than hundreds of thousands of people annually. While most commonly secondary to an adenoma, it may also arise from four-gland hyperplasia or malignancy. In the case of primary hyperparathyroidism, the number of glands involved may be unknown prior to surgery. In contrast, the metabolic disorder associated with renal failure induced hyperparathyroidism ensures a hyperplasia picture. Despite the uniform hyperplasia seen in tertiary disease and the preoperative expectation for four-gland exploration, our case demonstrates the continued need for a surgeon's vigilance during dissection to identify all glands and appropriately use intraoperative parathyroid hormone (PTH) testing. In addition, while intraoperative PTH assessment is an effective method for confirming adequacy of treatment for hyperparathyroidism, only surgical pathology can confirm malignancy, which should be considered with PTH levels > 1,000. The case also underscores the importance of comprehensive surgery management and mindful interpretation of intraoperative PTH levels in the management of hyperparathyroidism. Standard surgical technique includes complete exploration of the central compartment, and thyroid lobectomy when the aforementioned exploration fails to reveal the necessary parathyroid tissue, especially with a persistently elevated PTH. Without a standardized progressive compartment exploration and judicious use of intraoperative hormone testing, intrathyroidal parathyroid glands can be missed.

  8. Effects of Parathyroid Hormone on Immune Function

    Directory of Open Access Journals (Sweden)

    Abdallah Sassine Geara

    2010-01-01

    Full Text Available Parathyroid hormone (PTH function as immunologic mediator has become interesting with the recent usage of PTH analogue (teriparatide in the management of osteoporosis. Since the early 1980s, PTH receptors were found on most immunologic cells (neutrophils, B and T cells. The in vitro evaluations for a possible role of PTH as immunomodulator have shown inconsistent results mainly due to methodological heterogeneity of these studies: it used different PTH formulations (rat, bovine, and human, at different dosages and different incubating periods. In some of these studies, the lymphocytes were collected from uremic patients or animals, which renders the interpretation of the results problematic due to the effect of uremic toxins. Parathyroidectomy has been found to reverse the immunologic defect in patients with high PTH levels. Nonetheless, the clinical significance of these findings is unclear. Further studies are needed to define if PTH does have immunomodulatory effects.

  9. Alignment between PIN1 polarity and microtubule orientation in the shoot apical meristem reveals a tight coupling between morphogenesis and auxin transport.

    Directory of Open Access Journals (Sweden)

    Marcus G Heisler

    Full Text Available Morphogenesis during multicellular development is regulated by intercellular signaling molecules as well as by the mechanical properties of individual cells. In particular, normal patterns of organogenesis in plants require coordination between growth direction and growth magnitude. How this is achieved remains unclear. Here we show that in Arabidopsis thaliana, auxin patterning and cellular growth are linked through a correlated pattern of auxin efflux carrier localization and cortical microtubule orientation. Our experiments reveal that both PIN1 localization and microtubule array orientation are likely to respond to a shared upstream regulator that appears to be biomechanical in nature. Lastly, through mathematical modeling we show that such a biophysical coupling could mediate the feedback loop between auxin and its transport that underlies plant phyllotaxis.

  10. Water-Clear Cell Adenoma of the Mediastinal Parathyroid Gland.

    Science.gov (United States)

    Arik, Deniz; Dündar, Emine; Yilmaz, Evrim; Sivrikoz, Cumhur

    2017-10-06

    Water-clear cell adenoma of the parathyroid gland is a rare neoplasm that consists of cells with abundant clear-pink cytoplasm. There have only been 19 cases reported in the English literature. Here we report a case of water-clear cell adenoma of the mediastinal parathyroid gland. A 70-year-old male patient presented to the hospital with back pain and a mediastinal mass 6 cm in size was detected. After excision and microscopic evaluation, uniform, large clear cells with fine cytoplasmic vacuolization, without nuclear atypia, and arranged in solid and acinar patterns were revealed. The cells formed nests that were separated by fine fibrovascular septae and stained positively with anti-parathyroid hormone. To the best of our knowledge, this has not been previously reported in this location. In the differential diagnosis of clear cell lesions of the mediastinum, water-clear cell parathyroid adenoma should be considered.

  11. Parathyroid Adenoma Presenting as a Brown Tumour of the Mandible

    Directory of Open Access Journals (Sweden)

    Kavit Amin

    2012-01-01

    Full Text Available Background. Parathyroid adenoma is the commonest cause of primary hypercalcaemia and usually presents with symptoms/signs of hypercalcaemia. This paper highlights an unusual presentation. Case Report. A 27-year-old female presented with a painful left mandibular swelling, suspicious of neoplasia. A computed tomography (CT guided biopsy was performed. Based on the histology result, serum calcium was carried out, confirming hypercalcaemia. A left inferior parathyroid adenoma was subsequently removed. CT mandible showed extensive erosive lesions at the left 2nd/3rd inferior molar roots with protrusion to adjacent soft tissues. USS revealed a hypoechoic lesion on the left inferior parathyroid gland. Sestamibi scan showed a focus of MIBI uptake and retention at the inferior aspect of the left thyroid lobe. Conclusion. This case highlights the importance of a thorough history and examination. Clinicians should always bear in mind atypical presentations of parathyroid adenomas, with the need to exclude this differential in the presence of hypercalcaemia.

  12. Strigolactone can promote or inhibit shoot branching by triggering rapid depletion of the auxin efflux protein PIN1 from the plasma membrane.

    Directory of Open Access Journals (Sweden)

    Naoki Shinohara

    Full Text Available Plants continuously extend their root and shoot systems through the action of meristems at their growing tips. By regulating which meristems are active, plants adjust their body plans to suit local environmental conditions. The transport network of the phytohormone auxin has been proposed to mediate this systemic growth coordination, due to its self-organising, environmentally sensitive properties. In particular, a positive feedback mechanism termed auxin transport canalization, which establishes auxin flow from active shoot meristems (auxin sources to the roots (auxin sinks, has been proposed to mediate competition between shoot meristems and to balance shoot and root growth. Here we provide strong support for this hypothesis by demonstrating that a second hormone, strigolactone, regulates growth redistribution in the shoot by rapidly modulating auxin transport. A computational model in which strigolactone action is represented as an increase in the rate of removal of the auxin export protein, PIN1, from the plasma membrane can reproduce both the auxin transport and shoot branching phenotypes observed in various mutant combinations and strigolactone treatments, including the counterintuitive ability of strigolactones either to promote or inhibit shoot branching, depending on the auxin transport status of the plant. Consistent with this predicted mode of action, strigolactone signalling was found to trigger PIN1 depletion from the plasma membrane of xylem parenchyma cells in the stem. This effect could be detected within 10 minutes of strigolactone treatment and was independent of protein synthesis but dependent on clathrin-mediated membrane trafficking. Together these results support the hypothesis that growth across the plant shoot system is balanced by competition between shoot apices for a common auxin transport path to the root and that strigolactones regulate shoot branching by modulating this competition.

  13. [Ectopic parathyroid glands. Imaging methods and surgical access].

    Science.gov (United States)

    Fialová, M; Adámková, J; Adámek, S; Libánský, P; Kubinyi, J

    2014-08-01

    We discuss the benefits of imaging methods in localizing ectopic parathyroid glands in patients with primary hyperparathyroidism. The ectopic localizations are discussed within the context of the orthotopic norm. In the sample of 123 patients, a 23% rate of ectopic parathyroid glands was detected. Three selected case studies are presented, supporting the benefit of SPECT/CT imaging in terms of surgical access strategy selection.

  14. Increased parathyroid expression of klotho in uremic rats

    DEFF Research Database (Denmark)

    Hofman-Bang, J.; Martuseviciene, G.; Santini, M.A.

    2010-01-01

    /6 nephrectomy rat model of secondary hyperparathyroidism. Parathyroid klotho gene expression and protein were significantly increased in severely uremic hyperphosphatemic rats, but not affected by moderate uremia and normal serum phosphorus. Calcitriol suppressed klotho gene and protein expression in severe...... secondary hyperparathyroidism, despite a further increase in plasma phosphate. Both FGFR1 IIIC and Na+/K+-ATPase gene expression were significantly elevated in severe secondary hyperparathyroidism. Parathyroid gland klotho expression and the plasma calcium ion concentration were inversely correlated. Thus...

  15. Intraoperative parathyroid hormone assay-cutting the Gordian knot

    Directory of Open Access Journals (Sweden)

    Chandralekha Tampi

    2014-01-01

    Full Text Available Background: Hyperparathyroidism is treated by surgical excision of the hyperfunctioning parathyroid gland. In case of adenoma the single abnormal gland is removed, while in hyperplasias, a subtotal excision, that is, three-and-a-half of the four glands are removed. This therapeutic decision is made intraoperatively through frozen section evaluation and is sometimes problematic, due to a histological overlap between hyperplasia and the adenoma. The intraoperative parathyroid hormone (IOPTH assay, propogated in recent years, offers an elegant solution, with a high success rate, due to its ability to identify the removal of all hyperfunctioning parathyroid tissue. Aim: To study the feasibility of using IOPTH in our setting. Materials and Methods: Seven patients undergoing surgery for primary hyperparathyroidism had their IOPTH levels evaluated, along with the routine frozen and paraffin sections. Results: All seven patients showed more than a 50% intraoperative fall in serum PTH after excision of the abnormal gland. This was indicative of an adenoma and was confirmed by histopathological examination and normalization of serum calcium postoperatively. Conclusion: The intraoperative parathyroid hormone is a sensitive and specific guide to a complete removal of the abnormal parathyroid tissue. It can be incorporated without difficulty as an intraoperative guide and is superior to frozen section diagnosis in parathyroid surgery.

  16. Persistent renal hyperparathyroidism caused by intrathyroidal parathyroid glands.

    Science.gov (United States)

    Chen, Chin-Li; Lin, Shih-Hua; Yu, Jyh-Cherng; Shih, Ming-Lang

    2014-09-01

    Renal hyperparathyroidism usually occurs in chronic renal failure patients on regular dialysis. However, renal hyperparathyroidism resulting from intrathyroidal parathyroid glands is an uncommon condition. We herein present the case of a 35-year-old woman who has been on hemodialysis for 20 years. She had renal hyperparathyroidism with generalized weakness and bone pain for 2 years. The patient initially underwent parathyroidectomy at a local institution, during which two large parathyroid glands were resected from the right side (no parathyroid glands were found on the left side); however, the surgical procedure was unsuccessful, and the patient had persistent renal hyperparathyroidism after the operation. She was then transferred to our hospital and ectopic intrathyroidal parathyroid glands were localized by neck ultrasonography and technetium-99m sestamibi scans with single-photon emission computed tomography imaging preoperatively. A left thyroid lobectomy was performed and two intrathyroidal parathyroid glands were found. The patient recovered uneventfully and her symptoms resolved. Therefore, clinicians should be aware of the possibility of renal hyperparathyroidism resulting from intrathyroidal parathyroid glands in cases where the renal hyperparathyroidism persists after parathyroidectomy.

  17. Non-functioning parathyroid gland carcinoma: case report.

    Science.gov (United States)

    Krvavica, Ana; Kovacić, Marijan; Baraka, Ivan; Rudić, Milan

    2011-06-01

    Parathyroid gland carcinoma is a rare malignancy. The tumor is mostly functioning, causing severe hyperparathyroidism, with high serum calcium level and severe bone disease. Non-functioning parathyroid carcinomas are extremely rare. We report on a 60-year-old male patient admitted to ENT Department due to a large neck tumor mass compressing the thyroid and trachea. Preoperatively, thyroid hormone, parathyroid hormone (PTH) and calcium serum levels were normal. The following immunohistochemical markers (DAKO, Denmark) were used: bcl-2; CD-10; Chromogranin-A; Cyclin-D1; EMA; Ki-67; Mdm-2; p-53; PGP-9,5; RCC; Synaptophysin; Thyroglobulin; and TTF-1. Immunohistochemical analysis indicated the diagnosis of a primary parathyroid gland carcinoma. Tumor cells showed diffusely positive immunohistochemical staining with chromogranin-A and PGP-9,5, positive staining of variable intensity with synaptophysin, and weakly positive reaction with EMA. Also, the cytoplasm of tumor cells was diffusely positively stained with bcl-2, while the nuclei showed positive reaction with p-53 oncogene and TTF-1. The remaining markers (CD-10, cyclin-D1, Ki-67, Mdm-2, RCC and thyroglobulin) were negative. Four years after the surgery, the patient died from renal carcinoma pulmonary metastases and liver cirrhosis complications. In conclusion, non-functioning parathyroid gland carcinoma is a very rare disease. Detailed immunohistochemical analysis is needed to distinguish it from other thyroid and parathyroid neoplasms and metastatic carcinoma. Surgical treatment is presently the best mode of therapy.

  18. Role of radionuclide scintigraphy in the detection of parathyroid adenoma

    Directory of Open Access Journals (Sweden)

    Singh N

    2007-01-01

    Full Text Available Background: Preoperative detection of parathyroid adenoma is a diagnostic challenge. The sonography and computerized tomography (CT scan demonstrate high sensitivity but low specificity. The advent of radionuclide scanning technique has enhanced the specificity in this context. Aim: We undertook a study to assess the role of radionuclide scanning in suspected cases of parathyroid adenomas. Materials And Methods: Totally 28 cases were incorporated in the study. The suspicion was raised either due to raised PTH levels or recurrent calcinosis. Most of these patients had estimation of calcium done as a routine or specific investigation. The parathyroid scan was performed using either of the two techniques - Dual isotope subtraction or Sestamibi washout technique. We also used the recent approach of fusion imaging (CT + tomographic nuclear images in selected cases. Results: There were 16 true positive, 10 true negative, 1 false negative and 1 equivocal scan findings. The findings were compared with sonography, CT Scan and PTH values. The true positive yield in our study was 57%, true negative 35% and the overall sensitivity and specificity was found to be 94% and 100% respectively. Conclusion: We conclude that parathyroid scintigraphy is a reliable and sensitive technique in the preoperative detection of parathyroid adenomas and should be the first choice of imaging modality in suspicion of parathyroid adenoma.

  19. Impact of hybrid SPECT/CT imaging on the detection of single parathyroid adenoma

    Science.gov (United States)

    Morrison, Antony; Brennan, Patrick C.; Reed, Warren; Pietrzyk, Mariusz; Schembri, Geoff; Bailey, Elizabeth; Roach, Paul; Evanoff, Michael; Kench, Peter L.

    2011-03-01

    Objective: The aim of this investigation is to determine the impact of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) on the detection of parathyroid adenoma. Materials and methods: 16 patients presented with suspected parathyroid adenoma localised within the neck. All patients were injected with Tc-99m sestamibi and were scanned with a GE Infinia Hawkeye SPECT/CT. There were six negative and ten positive confirmed cases. Five expert radiologists specializing in nuclear medicine were asked to report on the 16 planar and SPECT data sets and were then asked to report on the same randomly ordered data sets with the addition of CT. Receiver operating characteristic (ROC) analysis was performed using the Dorfman-Berbaum-Metz multireadermulticase methodology and sensitivity and specificity values were generated. A significance level of p parathyroid adenoma. However the difference in diagnostic efficacy between the two groups was not found to be statistically significant therefore requiring further investigation. These findings have implications beyond the clinical situation described here.

  20. Premenstrual Symptoms in Dysmenorrheic College Students: Prevalence and Relation to Vitamin D and Parathyroid Hormone Levels

    Directory of Open Access Journals (Sweden)

    Bayan A. Obeidat

    2012-11-01

    Full Text Available Objectives: To determine the prevalence of premenstrual symptoms (PMS due to primary dysmenorrhea among a sample of university female students, and to explore possible association with vitamin D and parathyroid (PTH levels, as well as frequency of consumption of dairy products. Design: A cross-sectional study. Setting: One Jordanian university. Subjects: A total of 177 female students aged between 18 and 24 years who experienced primary dysmenorrhea participated in the study and completed a self administered questionnaire to collect information concerning demographics, menstruation- related information, associated specified premenstrual symptoms, and consumption of dairy products. Plasma 25-hydroxyvitamin vitamin D level and intact parathyroid hormone level were measured. Results: Of the 177 participants 91.5% had two or more symptoms among which fatigue, mood swings, anxiety, abdominal bloating, and depression were the most prevalent symptoms. There was no evident association between presence of symptoms and vitamin D status, PTH level or dairy products consumption. Headaches and social withdrawal were significantly lower in those women who consumed high amounts of dairy products. Conclusion: Premenstrual symptoms are very common in young women with primary dysmenorrhea. PMS has no relation to levels of vitamin D, parathyroid hormone or dairy products consumption. Headache and social withdrawal may be affected by dairy product consumption.

  1. Parathyroid hormone 7-84 induces hypocalcemia and inhibits the parathyroid hormone 1-84 secretory response to hypocalcemia in rats with intact parathyroid glands.

    Science.gov (United States)

    Huan, Jinxing; Olgaard, Klaus; Nielsen, Lars Bo; Lewin, Ewa

    2006-07-01

    Biologic effects of large C-terminal parathyroid hormone (PTH) fragments, opposite to those of N-terminal PTH, have been demonstrated. C-terminal PTH fragments are co-secreted with N-terminal PTH from the parathyroids. The aim of our study was to examine whether C-terminal PTH 7-84 regulates secretion of PTH 1-84 and affects the expression of genes of relevance for parathyroid function, PTH, calcium-sensing receptor (CaR), PTH type 1 receptor (PTHR1), and PTH-related peptide (PTHrP) genes in rat parathyroid glands. PTH 7-84 induced a significant decrease in plasma Ca2+ in rats with intact parathyroid glands. Despite the reduction of plasma Ca2+, no stimulation of PTH 1-84 secretion took place. Furthermore, the PTH 1-84 secretory response to EGTA-induced acute and severe hypocalcemia was significantly inhibited by PTH 7-84. During recovery from hypocalcemia, plasma Ca2+ levels were significantly lower in the PTH 7-84-treated group, as compared with the vehicle group, and at the same time plasma PTH 1-84 levels were significantly suppressed. The expression of PTH, CaR, PTHR1, and PTHrP genes in the rat parathyroid glands was not affected by PTH 7-84. The peripheral metabolism of PTH 1-84 was not affected by PTH 7-84. PTH 7-84 did not cross-react with the rat bioactive PTH 1-84 assay. In normal rats with intact parathyroid glands, PTH 7-84 inhibited the PTH 1-84 secretory response to hypocalcemia and induced a significant decrease in plasma Ca2+. These effects of PTH 7-84 on PTH 1-84 secretion and on plasma Ca2+ levels were not associated with significant changes in PTH, PTHR1, CaR, and PTHrP gene expressions in the rat parathyroid glands. It is hypothesized that PTH 7-84 regulates PTH secretion via an autocrine/paracrine regulatory mechanism.

  2. Evaluation of parathyroid gland function using sodium bicarbonate infusion test for 22q11.2 deletion syndrome.

    Science.gov (United States)

    Nagasaki, Keisuke; Iwasaki, Yasumasa; Ogawa, Yohei; Kikuchi, Toru; Uchiyama, Makoto

    2011-01-01

    22q11.2 Deletion syndrome is a congenital malformation syndrome with hypoparathyroidism. The spectrum of parathyroid gland dysfunction ranges from severe neonatal hypocalcemia to subclinical hypoparathyroidism. The parathyroid hormone (PTH) secretory reserve is reduced in a significant number of 22q11.2 deletion syndrome patients with normocalcemia. The aim of this study was to investigate hypoparathyroid function using the bicarbonate infusion test for 22q11.2 deletion syndrome with normocalcemia. sodium bicarbonate solution [7% (w/v); 40 ml/m(2) body surface area] was infused for 2 min, and blood samples for the determination of plasma ionized calcium and plasma intact PTH were serially obtained. The test was conducted on five 22q11.2 deletion syndrome patients with normocalcemia. two patients presented increments of intact PTH levels (peak value - basal value) of 70 pg/ml or higher during the test, whereas the remaining 3 showed PTH level increments of <30 pg/ml. The former 2 patients were diagnosed as having normal parathyroid gland function, and the latter 3 patients as having subclinical hypoparathyroidism. the bicarbonate infusion test may be a valuable method for the evaluation of residual parathyroid gland function in patients with 22q11.2 deletion syndrome. Screening of subclinical hypoparathyroidism should be considered in the regular follow-up of patients with 22q11.2 deletion syndrome, even in cases with normocalcemia. 2010 S. Karger AG, Basel.

  3. Indocyanine green fluorescence angiography for quantitative evaluation of in situ parathyroid gland perfusion and function after total thyroidectomy.

    Science.gov (United States)

    Lang, Brian Hung-Hin; Wong, Carlos K H; Hung, Hing Tsun; Wong, Kai Pun; Mak, Ka Lun; Au, Kin Bun

    2017-01-01

    Because the fluorescent light intensity on an indocyanine green fluorescence angiography reflects the blood perfusion within a focused area, the fluorescent light intensity in the remaining in situ parathyroid glands may predict postoperative hypocalcemia risk after total thyroidectomy. Seventy patients underwent intraoperative indocyanine green fluorescence angiography after total thyroidectomy. Any parathyroid glands with a vascular pedicle was left in situ while any parathyroid glands without pedicle or inadvertently removed was autotransplanted. After total thyroidectomy, an intravenous 2.5 mg indocyanine green fluorescence angiography was given and real-time fluorescent images of the thyroid bed were recorded using the SPY imaging system (Novadaq, Ontario, Canada). The fluorescent light intensity of each indocyanine green fluorescence angiography as well as the average and greatest fluorescent light intensity in each patient were calculated. Postoperative hypocalcemia was defined as adjusted calcium 150% developed postoperative hypocalcemia while 9 (81.8%) patients with a greatest fluorescent light intensity ≤150% did. Similarly, no patients with an average fluorescent light intensity >109% developed PH while 9 (30%) with an average fluorescent light intensity ≤109% did. The greatest fluorescent light intensity was more predictive than day-0 postoperative hypocalcemia (P = .027) and % PTH drop day-0 to 1 (P < .001). Indocyanine green fluorescence angiography is a promising operative adjunct in determining residual parathyroid glands function and predicting postoperative hypocalcemia risk after total thyroidectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Substernal oxyphil parathyroid adenoma producing PTHrP with hypercalcemia and normal PTH level

    Directory of Open Access Journals (Sweden)

    Rubini Domenico

    2008-02-01

    Full Text Available Abstract Background Parathyroid adenoma is the most common cause of primary hyperparathyroidism. Preoperative serum calcium and intact-parathyroid hormone levels are the most useful diagnostic parameters that allow differentiating primary hyperparathyroidism from non-parathyroid-dependent hypercalcemia. Parathyroidectomy is the definitive treatment for primary hyperparathyroidism. Approximately 5% of patients who underwent parathyroidectomy present with persistent or recurrent hyperparathyroidism due to ectopic localization of the adenoma. Functioning oxyphil parathyroid adenoma is an uncommon histological form, seldom causing primary hyperparathyroidism. Parathyroid adenoma with hypercalcemia exhibiting normal parathyroid hormone level is rare. An incidence of 5% to 33% has been documented in the literature; no etiologic explanation has been given. In 1987, parathyroid-hormone-related peptide was isolated as a causative factor of humeral hypercalcemia of malignancy. The presence of parathyroid-hormone-related peptide in parathyroid tissue under normal and pathological conditions has been described in the literature; however, its role in causing hyperparathyroidism has not yet been defined. Case presentation We present a case of persistent hypercalcemia with a normal level of intact-parathyroid hormone due to a substernal parathyroid adenoma, treated with radioguided parathyroidectomy. The final histological diagnosis was oxyphil adenoma, positive for parathyroid-hormone-related peptide antigens. Conclusion In clinical practice, this atypical biochemical presentation of primary hyperparathyroidism should be considered in the differential diagnosis of hypercalcemia. The parathyroid-hormone-related peptide should be considered not only in the presence of malignancy.

  5. Allotransplantation of cultured parathyroid progenitor cells without immunosuppression: clinical results.

    Science.gov (United States)

    Nawrot, Ireneusz; Woźniewicz, Bogdan; Tołłoczko, Tadeusz; Sawicki, Andrzej; Górski, Andrzej; Chudziński, Witold; Wojtaszek, Mikołaj; Grzesiuk, Wiesław; Sladowski, Dariusz; Karwacki, Jerzy; Zawitkowska, Teresa; Szmidt, Jacek

    2007-03-27

    Hypoparathyroidism is a well-known consequence of extensive thyroid and parathyroid surgery. Allotransplantation of cultured parathyroid cells can be considered as an alternative to vitamin D3 and calcium supplementation in treatment of hypoparathyroidism. We present the long-term allotransplant activity in 85 patients who had undergone cellular allotransplantation for surgical hypoparathyroidism. Also, a modified technique to prepare parathyroid explants is described for obtaining a new nonimmunogenic cell population. From March 1990 to December 2004, 85 patients underwent 116 allotransplantations of cultured parathyroid cells. Mean recipient age was 46.2+/-11.1 years. Donors were selected from patients undergoing parathyroidectomy for secondary and tertiary hyperparathyroidism. After 6 weeks of cultivation and freezing, the parathyroid cells decreased their normal human leukocyte antigen (HLA) class I ABC expression and were free of HLA class II positive cells. The viability of cultured cells was 95.15+/-2.94%. Eighty-five patients underwent primary allotransplantation. Of these, 25 patients subsequently underwent a repeat procedure. In six cases, the parathyroid cells were obtained from the same donor and in 19 cases from a different donor. For all patients, the mean cellular allograft survival was 6.35+/-13.08 months. In 64 patients (55.1%), the allografts retained their endocrine function for more than 2 months. The present study has shown that in some patients parathyroid cell allotransplantation may be considered a method of treatment for permanent hypoparathyroidism after thyroid surgery. Graft function and/or survival did not depend on the baseline viability or secretory activity of cultured cells used for transplantation.

  6. SIKs control osteocyte responses to parathyroid hormone

    Science.gov (United States)

    Wein, Marc N.; Liang, Yanke; Goransson, Olga; Sundberg, Thomas B.; Wang, Jinhua; Williams, Elizabeth A.; O'Meara, Maureen J.; Govea, Nicolas; Beqo, Belinda; Nishimori, Shigeki; Nagano, Kenichi; Brooks, Daniel J.; Martins, Janaina S.; Corbin, Braden; Anselmo, Anthony; Sadreyev, Ruslan; Wu, Joy Y.; Sakamoto, Kei; Foretz, Marc; Xavier, Ramnik J.; Baron, Roland; Bouxsein, Mary L.; Gardella, Thomas J.; Divieti-Pajevic, Paola; Gray, Nathanael S.; Kronenberg, Henry M.

    2016-01-01

    Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH. PMID:27759007

  7. Parathyroid Gland Function in Primary Aldosteronism.

    Science.gov (United States)

    Asbach, E; Bekeran, M; Reincke, M

    2015-12-01

    Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. Beyond its effects on intravascular volume and blood pressure, PA causes metabolic alterations and a higher cardiovascular morbidity, which is reduced by PA-directed therapy. Experimental studies demonstrated that mineralocorticoid excess may also influence mineral homeostasis. A role in cardiovascular disease has also been attributed to parathyroid hormone (PTH). Increasing evidence supports a bidirectional interaction between aldosterone and PTH.Primary hyperparathyroidism is associated with arterial hypertension and an increased cardiovascular morbidity and mortality, which might be associated to higher aldosterone values; parathyreoidectomy results in lowered aldosterone and blood pressure levels. PA leads to secondary hyperparathyroidism, which is reversible by PA-directed therapy. A lower bone mineral density and a higher fracture rate were also shown to be reversible by PA-directed therapy. There is a suspicion of a bidirectional interaction between aldosterone and PTH, which might lead to a higher cardiovascular risk. There are more and more reports about coincident PA and primary hyperparathyroidism. From a pathophysiologic point of view this constellation is best characterized as tertiary hyperparathyroidism. Future aspects should further clarify the extent of these endocrine interactions and analyze the influence of this interplay on cardiovascular morbidity and mortality and bone health. © Georg Thieme Verlag KG Stuttgart · New York.

  8. SIKs control osteocyte responses to parathyroid hormone.

    Science.gov (United States)

    Wein, Marc N; Liang, Yanke; Goransson, Olga; Sundberg, Thomas B; Wang, Jinhua; Williams, Elizabeth A; O'Meara, Maureen J; Govea, Nicolas; Beqo, Belinda; Nishimori, Shigeki; Nagano, Kenichi; Brooks, Daniel J; Martins, Janaina S; Corbin, Braden; Anselmo, Anthony; Sadreyev, Ruslan; Wu, Joy Y; Sakamoto, Kei; Foretz, Marc; Xavier, Ramnik J; Baron, Roland; Bouxsein, Mary L; Gardella, Thomas J; Divieti-Pajevic, Paola; Gray, Nathanael S; Kronenberg, Henry M

    2016-10-19

    Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH.

  9. Active acromegaly enhances spontaneous parathyroid hormone pulsatility.

    Science.gov (United States)

    Mazziotti, Gherardo; Cimino, Vincenzo; De Menis, Ernesto; Bonadonna, Stefania; Bugari, Giovanna; De Marinis, Laura; Veldhuis, Johannes D; Giustina, Andrea

    2006-06-01

    In healthy subjects, parathyroid hormone (PTH) is secreted in a dual fashion, with low-amplitude and high-frequency pulses superimposed on tonic secretion. These 2 components of PTH secretion seem to have different effects on target organs. The aim of our study was to evaluate whether growth hormone excess in acromegaly may modify the spontaneous pulsatility of PTH. Five male patients with newly diagnosed active acromegaly and 8 healthy subjects were evaluated by 3-minute blood sampling for 6 hours. Plasma PTH concentrations were evaluated by multiparameter deconvolution analysis. Plasma PTH release profiles were also subjected to an approximate entropy (ApEn) estimate, which provides an ensemble measure of the serial regularity or orderliness of the release process. In acromegalic patients, baseline serum PTH values were not significantly different from those measured in the healthy subjects, as well as tonic PTH secretion rate, number of bursts, fractional pulsatile PTH secretion, and ApEn ratio. Conversely, PTH pulse half-duration was significantly longer in acromegalic patients vs healthy subjects (11.8+/-0.95 vs 6.9+/-1.6 minutes; P=.05), whereas PTH pulse mass showed a tendency (P=.06) to be significantly greater in acromegalic patients. These preliminary data suggest that growth hormone excess may affect PTH secretory dynamics in patients with acromegaly. Potentially negative bone effects of the modifications of PTH secretory pattern in acromegaly should be investigated.

  10. Apoptosis of Parathyroid Cell in 5/6 Nephrectomized Rats and its Change Induced by Calcitrid

    Institute of Scientific and Technical Information of China (English)

    ZhaoWH; WangXY

    2002-01-01

    Objective To study the apoptosis of parathyroid cell in chronic renal failure(CRF) and observe its change induced by calcitriol.Methods In the studies,Sprague-Dawley rats were divided into three groups(8in each group).The five-sixth renal nephrectomy(NX) were performed in group A,5/6 NX treated with calciriol 50ng/d,subcutaneously administared for 8 weeks in group B and sham-operated control in group C.All parathyroid glands of rats were taken under anatomic microscope to evaluate.After 8 weeks apoptosis rate(APO) and cell proliferative cycle of all parathyroid gland of rats were determined by flowmetry,meanwhile the serum Ca2+,P3-,ALP,iPTH and urinary creatinine clearance(CCr) were also measured.Results Both the 5/6 NX rats and 5/6NX rats treated with calcitriol show remarkable decreasing in CCr compared to the sham-operated rats.Serum ALP and iPTH in group A were significantly higher than those of group B and group C.APO in group A was(0.23±0.19)%,it was significantly lower than that of group B(1.32±0.45)%,respectively(P<0.01).While both Speriod cell rate(SPR) and proliferation index(PI) in group A [(11.99±2.73)% and (16.93±3.42)%] were significantly higher than those in group B [(2.95±1.58)%and (5.24±2.29%)]and group Cu [(0.73±0.46)% and (1.76±0.70)%],P<0.01.But SPF and PI in group B were still higher than in group C,P<0.05.Conclusion The outstanding proliferation of parathyroid cells may be partly given off by the reduction of its apoptosis at least and calcitriol may induce apoptosis of parathyroid cells in 5/6 renal nephrectomy rats.

  11. In vivo wide-band reflectance spectrometry during thyroid and parathyroid surgery

    NARCIS (Netherlands)

    Schols, R.M.; Wieringa, F.P.; Alić, L.; Bouvy, N.D.; Stassen, L.P.S.

    2013-01-01

    Distinguishing critical tissues can be challenging in (para-)thyroid surgery. As a first step towards intraoperative image contrast enhancement, we collected and analyzed spectral signatures (350-1830nm) of thyroid, parathyroid and recurrent laryngeal nerve in 10 patients.

  12. Cystic parathyroid glands in MEN1: A rare entity?

    Science.gov (United States)

    Cavalli, Tiziana; Giudici, Francesco; Nesi, Gabriella; Amorosi, Andrea; Santi, Raffaella; Brandi, Maria Luisa; Tonelli, Francesco

    2017-04-01

    Approximately 300 cases of sporadic parathyroid cyst (PCs) have been reported to date. Only two cases have been described in MEN1 so far. Detection by imaging could be challenging, especially in multiglandular primary hyperparathyroidism (HPT) and clinical outcome could be different. During the period 1990-2014, 71 MEN1 patients were operated for primary hyperparathyroidism in our centre. We report three cases of PCs in MEN1 patients affected by HPT, who underwent a total or subtotal parathyroidectomy with transcervical thymectomy. In our series, all three patients had an unsatisfactory postoperative course, at variance with the high percentage (over 90 %) of long-term success in MEN1 patients operated at our centre. One patient affected by cystic degeneration of all the four parathyroid glands reported persistent hypoparathyroidism, despite autografts of parathyroid tissue. For the other two cases, surgery failed to cure hyperparathyroidism, perhaps because of the presence of undetected ectopic parathyroid tissue. In the context of a multiglandular disease such as MEN1 syndrome, PCs seem rare but our experience shows about a 4 % incidence. Furthermore their presence, even in expert hands, could affect the preoperative identification of the parathyroid glands due to the difficult differential diagnosis between PC and other cystic lesions of the neck, and intraoperative detection of the glands as well as the postoperative outcome.

  13. Diagnosis and Surgical Treatment of Parathyroid Adenoma (24 Case Report)

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Junchu Zhang; Daqiao Zhu; Zhiqian Hu; Qiang Wang

    2005-01-01

    OBJECTIVE To summarize the experience in diagnosing and treating parathyroid adenoma.METHODS Twenty-four patients were diagnosed with parathyroid adenoma and received parathyroidectomy in our hospital. Sixteen of them presented with hyperparathyroidism. The patients received ultrasounography, CT or 99mTc-MIBI to locate the tumor site. Serum concentrations of PTH and calcium were checked before the operation. All operations were performed under general anesthesia. The adenomas were resected and the four glands explored.RESULTS All of the patients were cured and there was no mortality in our group. The symptoms of hyperparathyroidism remitted to various degrees after the operation. PTH dropped to the normal range 2 days after operation.Serum calcium concentrations declined to different levels from the first day after operation. Seven patients developed hypocalcemia post-operation but recovered by injection of calcium gluconate. Only one of the patients with parathyroid adenoma recurred 2 years after the operation and was found to have malignancy of the parathyroid adenoma.CONCLUSION Not all the patients with parathyroid adenoma had clinical manifestations. The CT and 99mTc-MIBI were more accurate than ultrasounography in locating the adenoma. The four glands should be explored during the operation. Protecting the recurrent laryngeal nerve from being injuried and maintaning secure hemastasis were most important.

  14. Painful ophthalmoplegia from metastatic nonproducing parathyroid carcinoma : Case study and review of the literature

    NARCIS (Netherlands)

    Eurelings, M; Frijns, CJM; Jeurissen, FJF

    2002-01-01

    Parathyroid carcinoma is an uncommon malignancy. Of the fewer than 400 cases reported, most have been cases of producing parathyroid carcinoma with accompanying hypercalcemia. Only 13 patients with nonproducing parathyroid carcinoma have been described. Nine of these 13 patients had metastatic disea

  15. Difuse optical reflectance spectrometry in thyroid and parathyroid surgery (abstract only)

    NARCIS (Netherlands)

    Schols, R.M.; Bouvy, N.D.; Wieringa, F.P.; Alić, L.; Stassen, L.P.S.

    2012-01-01

    INTRODUCTION: In thyroid and parathyroid surgery iatrogenic injury of the parathyroid glands or the recurrent laryngeal nerve (RLN) is a possible complication that needs to be prevented. The visible contrast between thyroid and parathyroid tissue is delicate to observe. The aim of this pilot study w

  16. Difuse optical reflectance spectrometry in thyroid and parathyroid surgery (abstract only)

    NARCIS (Netherlands)

    Schols, R.M.; Bouvy, N.D.; Wieringa, F.P.; Alić, L.; Stassen, L.P.S.

    2012-01-01

    INTRODUCTION: In thyroid and parathyroid surgery iatrogenic injury of the parathyroid glands or the recurrent laryngeal nerve (RLN) is a possible complication that needs to be prevented. The visible contrast between thyroid and parathyroid tissue is delicate to observe. The aim of this pilot study

  17. Coexisiting adenoma and granuloma involving the right inferior parathyroid gland with adjacent ectopic thymic tissue.

    Science.gov (United States)

    Gupta, Mayank; Kandasamy, Subramaniam

    2014-06-23

    Inflammatory lesions, particularly granulomas, involving adenoma of the parathyroid gland are rare. Ectopic thymic tissue is commonly associated with the thyroid and/or parathyroid gland due to their close embryonic relationship. We report a rare case of coexisting adenoma and granuloma of the parathyroid gland with adjacent ectopic thymic tissue. 2014 BMJ Publishing Group Ltd.

  18. Anatomy of thyroid and parathyroid glands and neurovascular relations.

    Science.gov (United States)

    Mohebati, A; Shaha, A R

    2012-01-01

    Historically, thyroid surgery has been fraught with complications. Injury to the recurrent laryngeal nerve, superior laryngeal nerve, or the parathyroid glands may result in profound life-long consequences for the patient. To minimize the morbidity of the operation, a surgeon must have an in-depth understanding of the anatomy of the thyroid and parathyroid glands and be able to apply this information to perform a safe and effective operation. This article will review the pertinent anatomy and embryology of the thyroid and parathyroid glands and the critical structures that lie in their proximity. This information should aid the surgeon in appropriate identification and preservation of the function of these structures and to avoid the pitfalls of the operation.

  19. Experimental investigations on immunology of the parathyroid gland

    Science.gov (United States)

    Lupulescu, A.; Potorac, E.; Pop, A.; Heitmanek, Constanta; Merculiev, Elena; Chisiu, N.; Oprisan, R.; Neacsu, C.

    1968-01-01

    Repeated inoculation of homologous parathyroid tissue in dogs induced isoimmune hypoparathyroidism, with all the characteristic biochemical and histopathological features and the presence of complement fixing antibodies in the serum. Disturbances of calcium and phosphorus metabolism were similar to, but less severe than, those observed in dogs with hypoparathyroidism induced by complete thyro-parathyroidectomy. Injection of rabbits with crude extracts of dog, rat, hog and human parathyroid or with bovine parathormone (PTH), each incorporated in Freund's adjuvant, resulted in the development of complement fixing and precipitating antibodies: these reacted with the corresponding tissue preparations, but did not show cross-reactivity. Antibodies were not detected in the serum of normal dogs or in control dogs inoculated with Freund's adjuvant alone. Study of the parathyroid glands by electron microscopy provided information on the mechanism of PTH secretion and synthesis in normal dogs and in those with hypoparathyroidism. ImagesFIG. 3FIG. 4-8FIG. 9FIG. 10-11 PMID:4968246

  20. Presentation of parathyroid adenoma with genu valgum and thoracic deformities.

    Science.gov (United States)

    Zil-E-Ali, Ahsan; Latif, Aiza; Rashid, Anam; Malik, Asim; Khan, Haseeb Ahmed

    2016-01-01

    Parathyroid adenoma is the main cause of primary hyperparathyroidism. It is usually asymptomatic and occurs more commonly in adults. It presents with raised parathormone (PTH) and Ca+ levels in serum. Its presentation in adolescence is rare. We report one such incidence of a 14 years old girl who presented with bone pains short stature, and generalized muscle wasting. She was found to have genu valgum at the knee joint, pectus carniatum, scoliosis and cystic changes in pelvis and calvarium. Biochemical investigations and parathyroid Tc-99mMIBI scan confirmed the diagnosis of a parathyroid adenoma. The gland was removed by parathyroidectomy. Till date 12 such cases are reported and none had thoracic, vertebral or calvarium involvement.

  1. Parathyroid gland of the freshwater snake Natrix piscator Schneider.

    Science.gov (United States)

    Singh, R; Kar, I

    1983-07-01

    The structure and function of the parathyroid glands of freshwater snake, Natrix piscator, were studied. N. piscator has two pairs of parathyroid glands which are composed of cell cords of typical endocrine appearance, and follicles are absent. Parathyroidectomy was followed by significant (P less than 0.001) hypocalcemia and hyperphosphatemia throughout the 5th week of experimental period. Following parathyroidectomy, calcium and phosphate concentrations in bone were significantly (P less than 0.05) increased after 5 weeks; however, these values in muscle were not significantly changed. Tetany was also observed in parathyroidectomized snakes. Histological structure and function of the glands do not appear to vary seasonally. Administration of parathyroid gland extract of this ophidian reptile into rats caused significant (P less than 0.05) elevation of serum calcium.

  2. Efficacy and safety of ultrasound-guided radiofrequency ablation of hyperplastic parathyroid gland for secondary hyperparathyroidism associated with chronic kidney disease.

    Science.gov (United States)

    Peng, Chengzhong; Zhang, Zhengxian; Liu, Jibin; Chen, Hongyu; Tu, Xiao; Hu, Rihong; Ni, Jun; Weng, Ning; Pang, Haisu; Xue, Zhengmei

    2017-03-01

    The purpose of this study was to determine if ultrasound-guided radiofrequency ablation (RFA) of hyperplastic parathyroid glands could be used to treat secondary hyperparathyroidism (HPT) in patients with chronic kidney disease. RFA of the hyperplastic parathyroid glands was performed in 34 patients with secondary HPT. Intact parathyroid hormone (iPTH), calcium, and phosphorus were measured. The outcome was based on the ablation extent (ie, 4, 3, and 1-2 glands). The iPTH, calcium, and phosphorus levels decreased in all groups after RFA. One year after ablation, these parameters remained significantly lower in the 4-gland ablation group compared with the 3-gland and 1 to 2-gland groups. The same tendency was observed for the symptom score. The iPTH levels of <272 pg/mL on the day after ablation was the best predictor for maintaining parathyroid hormone (PTH) levels in a reasonable range 1 year after ablation. RFA of hyperplastic parathyroid glands for treating secondary HPT is feasible in selected patients. © 2016 Wiley Periodicals, Inc. Head Neck 39: 564-571, 2017. © 2016 Wiley Periodicals, Inc.

  3. Retropharyngeal thymus and parathyroid gland: a case report.

    Science.gov (United States)

    Schramm, Jordan C; Perry, Deborah A; Sewell, Ryan K

    2014-01-01

    Cervical ectopic thymus occurs when thymic tissue arrests during its embryologic descent through the neck to the upper mediastinum. Most often it presents as an asymptomatic neck mass. Rarely does it present with airway compromise, particularly in neonates. A neonate presented with a retropharyngeal mass causing dynamic upper airway obstruction, mimicking a venolymphatic malformation. Ultimately this proved to be aberrant ectopic thymus with an associated parathyroid gland. While there have been isolated reports of thymus or parathyroid in the retropharyngeal space, none of the prior reports found both within the same patient. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Nonoxidized, biologically active parathyroid hormone determines mortality in hemodialysis patients

    DEFF Research Database (Denmark)

    Tepel, Martin; Armbruster, Franz Paul; Grön, Hans Jürgen;

    2013-01-01

    in the highest n-oxPTH tertile compared with the lowest n-oxPTH tertile (χ(2), 14.3; P = .0008). Median survival was 1702 days in the highest n-oxPTH tertile, whereas it was only 453 days in the lowest n-oxPTH tertile. Multivariable-adjusted Cox regression showed that higher age increased odds for death, whereas...

  5. Parathyroid carcinoma survival: improvements in the era of intact parathyroid hormone monitoring?

    Directory of Open Access Journals (Sweden)

    Steve R. Martinez

    2013-02-01

    Full Text Available The intact parathyroid hormone (iPTH assay is a critical test in the diagnosis and management of PTH-mediated hypercalcemia, including parathyroid carcinoma (PCa. We hypothesized that the survival of patients diagnosed with PCa has improved since adoption of the iPTH assay into clinical practice. We identified all confirmed cases of PCa within the Surveillance, Epidemiology and End Results database from 1973 to 2006. Patients were categorized into two eras based upon introduction of the iPTH assay: 1973 to 1997 (era I and 1997 to 2006 (era II, when the iPTH assay was in standard use. We estimated overall survival (OS and disease-specific survival (DSS using the Kaplan-Meier method, with differences among survival curves assessed via log rank. Multivariate Cox proportional hazards models compared the survival rates between treatment eras while controlling for patient age, sex, race/ethnicity, tumor size, nodal status, extent of disease, and type of surgery. Multivariate models included patients undergoing potentially curative surgery and excluded those with dis- tant metastases. Risks of overall and disease-specific mortality were reported as hazard ratios with 95% confidence intervals. Study criteria were met by 370 patients. Median survival was 15.6 years. Five-year rates of OS and DSS were 78% and 88% for era I and 82% and 96% for era II. On multivariate analysis, age, black race, and unknown extent of disease predicted an increased risk of death from any cause. Treatment era did not predict OS. No factor predicted PCa-specific mortality. In multivariate analysis, neither OS nor DSS have improved in the current era that utilizes iPTH for the detection and management of PCa.

  6. Hysteresis and calcium set-point for the calcium parathyroid hormone relationship in healthy horses.

    Science.gov (United States)

    Toribio, Ramiro E; Kohn, Catherine W; Sams, Richard A; Capen, Charles C; Rosol, Thomas J

    2003-02-15

    Abnormalities in calcium (Ca(2+)) homeostasis are reported in horses with several pathological conditions; however, there is little information on Ca(2+) regulation in horses. The objectives of the present study were to determine the Ca(2+) set-point in healthy horses, to determine whether the Ca(2+)/parathyroid hormone (PTH) response curves were characterized by hysteresis, and to determine if the order of experimentally induced hypocalcemia or hypercalcemia had an effect on PTH secretion. The Ca(2+) set-point and hysteresis were determined in 12 healthy horses by infusing Na(2)EDTA and calcium gluconate. The Ca(2+) set-point was 1.37 +/- 0.05 mmol/L, which is higher than values reported for humans and dogs (1.0-1.2 mmol/L). Hysteresis was present during hypocalcemia and hypercalcemia. Horses in which hypocalcemia was followed by hypercalcemia secreted more PTH (7440 +/- 740 pmol min/L) than horses in which hypercalcemia was followed by hypocalcemia (5990 +/- 570 pmol min/L). This study has demonstrated that the Ca(2+) set-point in the horse is higher than in other domestic animals and man. We have shown that the Ca(2+)/PTH relationship in horses is sigmoidal and displays hysteresis during both hypocalcemia and hypercalcemia, and that extracellular Ca(2+) concentrations may affect the response of the parathyroid gland to hypocalcemia.

  7. Diagnosis of Parathyroid Adenoma Detected during Thyroid Ultrasound: The Role of Parathormone Measurement in Fine-Needle Aspiration Washout

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Sung Soo; Kim, Eun Kyung; Kwak, Jin Young; Kim, Min Jung [Severance Hospital, Yonsei University, College of Medicine, Seoul (Korea, Republic of)

    2009-03-15

    With the widespread use of thyroid ultrasound, the detection rate of parathyroid incidentalomas as well as thyroid nodules has been on the increase. The differentiation between thyroid nodules and parathyroid nodules is occasionally difficult due to considerable overlap in terms of the sonographic findings. A case of parathyroid adenoma diagnosed with a measured parathyroid hormone level after fine needle aspiration washout is presented

  8. Sensitive detection of a small parathyroid adenoma using fluorocholine PET/CT: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Padinhare-Keloth, Thanseer N. T. K.; Bhadada, Sanjay K.; Sood, Ashwani; Kumar, Rajender; Behera, Arunanshu; Radotra, Bishan D.; Mittal, Bhagwant R. [PGIMER, Chandigarh (India)

    2017-06-15

    Primary hyperparathyroidism is caused by parathyroid adenoma in the majority of cases and diagnosis is usually made biochemically. Pre-surgical localization of parathyroid adenoma is essential to limit the extent of surgery and avoid missing them at ectopic sites. Anatomical and functional imaging are used for the localization, but may fail to identify the small and ectopic parathyroid adenoma. We present a case of small sized ectopic parathyroid adenoma at unusual location detected by F-18 fluorocholine (FCH) PET/CT, where other imaging modalities failed. The post-operative histopathology confirmed the diagnosis of ectopic parathyroid adenoma.

  9. Direct demonstration of D1 dopamine receptors in the bovine parathyroid gland using the D1 selective antagonist (/sup 125/I)-SCH 23982

    Energy Technology Data Exchange (ETDEWEB)

    Monsma, F.J. Jr.; Sibley, D.R.

    1989-01-01

    The presence of D1 dopamine receptors in the parathyroid gland has been proposed based on the demonstration of dopaminergic regulation of adenylate cyclase activity and parathyroid hormone release in dispersed bovine parathyroid cells. Using a radioiodinated D1 selective antagonist (125I)-SCH 23982, we have now directly labeled and characterized the D1 dopamine receptors in bovine parathyroid gland membranes. (125I)-SCH 23982 binds in a saturable manner with high affinity and low nonspecific binding to membranes prepared from bovine parathyroid glands. D1 dopamine receptors are present in this preparation at a concentration of approximately 130 fMoles/mg protein and (125I)-SCH 23982 binding increases with increasing protein concentration in a linear fashion. Determination of the Kd using the association (k1) and dissociation (k-1) rate constants revealed good agreement with the Kd determined by saturation analysis (390 pM vs. 682 pM, respectively). Inhibition of 0.3 nM (125I)-SCH 23982 binding by a series of dopaminergic antagonists verified the D1 nature of this binding site, exhibiting appropriate affinities and rank order of potency. The competition curves of all antagonists exhibited Hill coefficients that were not significantly different from 1. Inhibition of (125I)-SCH 23982 binding by dopamine and other dopaminergic agonists revealed the presence of high and low affinity agonist binding sites. Addition of 200 microM GppNHp effected a complete conversion of high affinity dopamine binding sites to a homogeneous population of low affinity dopamine sites. The D1 receptors identified in the parathyroid gland with (125I)-SCH 23982 appear to be pharmacologically identical with those previously characterized in the central nervous system.

  10. Intraoperative Identification of the Parathyroid Gland with a Fluorescence Detection System.

    Science.gov (United States)

    Shinden, Yoshiaki; Nakajo, Akihiro; Arima, Hideo; Tanoue, Kiyonori; Hirata, Munetsugu; Kijima, Yuko; Maemura, Kosei; Natsugoe, Shoji

    2017-06-01

    Intraoperative identification of the difficult-to-spot parathyroid gland is critical during surgery for thyroid and parathyroid disease. Recently, intrinsic fluorescence of the parathyroid gland was identified, and a new method was developed for intraoperative detection of the parathyroid with an original fluorescent detection apparatus. Here, we describe a method for intraoperative detection of the parathyroid using a ready-made photodynamic eye (PDE) system without any fluorescent dye or contrast agents. Seventeen patients who underwent surgical treatment for thyroid or parathyroid disease at Kagoshima University Hospital were enrolled in this study. Intrinsic fluorescence of various tissues was detected with the PDE system. Intraoperative in vivo and ex vivo intrinsic fluorescence of the parathyroid, thyroid, lymph nodes and fat tissues was measured and analyzed. The parathyroid gland had a significantly higher fluorescence intensity than the other tissues, including the thyroid glands, lymph nodes and fat tissues, and we could identify them during surgery using the fluorescence-guided method. Our method could be applicable for two intraoperative clinical procedures: ex vivo tissue identification of parathyroid tissue and in vivo identification of the location of the parathyroid gland, including ectopic glands. The PDE system may be an easy and highly feasible method to identify the parathyroid gland during surgery.

  11. A correlation between decreased parathyroid α-Klotho and fibroblast growth factor receptor 1 expression with pathological category and parathyroid gland volume in dialysis patients.

    Science.gov (United States)

    Yan, Junfang; Jingbo, Chen; Wang, Deguang; Xie, Shengxue; Yuan, Liang; Zhong, Xing; Hao, Li

    2015-04-01

    The objective of this study was to investigate α-Klotho and fibroblast growth factor receptor 1 (FGFR1) expression in hyperplastic parathyroid glands, as well as their role in the development of renal hyperparathyroidism. Hyperplastic parathyroid glands (n = 90) were obtained from 24 patients who received parathyroidectomy due to secondary renal hyperparathyroidism. Normal parathyroid tissue was obtained from glands (n = 6) that were inadvertently removed, in conjunction with thyroidectomy, from patients with thyroid carcinoma. The expression of α-Klotho and FGFR1 in the parathyroid tissue was detected using immunohistochemical staining. The expression of α-Klotho and FGFR1 was significantly reduced in the hyperplastic parathyroid tissue compared to that in the normal parathyroid tissue. The expression of α-Klotho decreased further with increasing parathyroid pathology. A significant positive correlation was observed between α-Klotho and FGFR1 (r = 0.38, P < 0.01). FGFR1 (r = -0.21, P < 0.05) and α-Klotho (r = -0.42, P < 0.01) were negatively correlated with the volume of the hyperplastic parathyroid tissue. The expression of α-Klotho and FGFR1 decreases in the parathyroid glands of dialysis patients with secondary hyperparathyroidism, and this decrease may play an important role in the pathogenesis of secondary renal hyperparathyroidism.

  12. Huge parathyroid carcinoma: Clinical considerations and literature review

    Directory of Open Access Journals (Sweden)

    Marone Ugo

    2005-06-01

    Full Text Available Abstract Background Parathyroid carcinoma is a rare malignancy, with an incidence of 0.5 to 4% of all cases of primary hyperparathyroidism. Surgery is the only curative treatment. Case presentation We report the case of a 66-year-old man referred for a large suspicious substernal goitre associated with severe hypercalcemia due to hyperparathyroidism. After normalization of serum calcium levels, patient underwent surgery. The voluminous cervicomediastinal firm mass could not be removed through the cervical incision; therefore a cervicothoracic approach was employed. Histopathology revealed a giant parathyroid cancer of 450 grams. A review of the literature was also undertaken to summarize the current treatment approaches for this rare malignancy. Conclusion Parathyroid cancer is usually not recognized either preoperatively or intra-operatively. En bloc resection of the tumour with the adjacent tissue is the treatment of choice and it is very important to avoid the rupture of the capsule during operation. Neither tumour size, nor the lymph node status appears to play a role in prognosis. The management of parathyroid carcinoma is a challenge even for experienced surgeons.

  13. Diseases of the parathyroid gland in chronic kidney disease.

    Science.gov (United States)

    Komaba, Hirotaka; Kakuta, Takatoshi; Fukagawa, Masafumi

    2011-12-01

    During the past few years, remarkable advances have been made in the understanding and the management of parathyroid diseases in patients with chronic kidney disease (CKD). One of the important insights is the identification of fibroblastic growth factor 23, which has greatly reshaped our understanding of secondary hyperparathyroidism (SHPT). The recent introduction of calcimimetic cinacalcet hydrochloride has led to a major breakthrough in the management of SHPT. Recognition of circulating molecular forms of parathyroid hormone (PTH) is also a major milestone in the accurate assessment of parathyroid function in CKD. Primary hyperparathyroidism should also be considered in patients with CKD, because it can cause various renal manifestations and can also occur as a sporadic disease in these patients. Hypoparathyroidism is occasionally seen in dialysis patients in the setting of diabetes mellitus and malnutrition-inflammation complex syndrome, as well as after parathyroidectomy for advanced SHPT. For patients with adynamic bone disease due to hypoparathyroidism and/or skeletal resistance to PTH, teriparatide, a PTH analog, may have potential for improving bone metabolism and reducing the risk of fracture. In this review, we summarize our current knowledge on diseases of the parathyroid gland in CKD patients, with a particular focus on recent work in the field.

  14. Echographic diagnosis and localisation of the parathyroid gland

    Energy Technology Data Exchange (ETDEWEB)

    Maier, W.

    1981-04-01

    The sonographic morphology of adenomas is studied on the basis of 7 sonographically identified and surgically confirmed adenomas of the parathyroid gland, taking the available literature into consideration. Information is given on differential diagnosis against normal anatomical structures and phatological processes. A correlation is established between sonomorphological and pathologico-anatomical findings.

  15. Increased parathyroid expression of klotho in uremic rats

    DEFF Research Database (Denmark)

    Hofman-Bang, J.; Martuseviciene, G.; Santini, M.A.

    2010-01-01

    secondary hyperparathyroidism, despite a further increase in plasma phosphate. Both FGFR1 IIIC and Na+/K+-ATPase gene expression were significantly elevated in severe secondary hyperparathyroidism. Parathyroid gland klotho expression and the plasma calcium ion concentration were inversely correlated. Thus...

  16. Superior parathyroid gland approach to the recurrent laryngeal nerve.

    Science.gov (United States)

    Elsheikh, Ezzeddin

    2017-07-01

    The superior parathyroid gland is known to be almost constant in its location under the false thyroid capsule. Could it be a landmark to point to the site of incision of the false thyroid capsule and find the plane of the recurrent laryngeal nerve (RLN) during thyroidectomy? The study included 48 patients with benign goiter scheduled for hemithyroidectomy or total thyroidectomy; there were 16 cases of solitary thyroid nodules, 27 cases of multinodular goiter, and 5 cases of toxic goiter. This study included 80 lobectomies. All patients showed no evidence of postoperative RLN palsy, bleeding, or hypoparathyroidism. The superior parathyroid gland was consistently found within the false capsule in all cases, whereas the inferior parathyroid was found within the same layer in 64 sides (80%). The described approach can accurately guide dissection between true and false capsules of the thyroid to reach and preserve both the RLN and the superior parathyroid gland. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1287-1290, 2017. © 2017 Wiley Periodicals, Inc.

  17. 21 CFR 862.1545 - Parathyroid hormone test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Parathyroid hormone test system. 862.1545 Section 862.1545 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...) resulting from disorders of calcium metabolism. (b) Classification. Class II....

  18. A mathematical/physiological model of parathyroid hormone secretion in response to blood-ionized calcium lowering in vivo

    DEFF Research Database (Denmark)

    Momsen, G; Schwarz, P

    1997-01-01

    The aim of the present study was to test a mathematical model of the biochemical processes in the parathyroid glands responsible for the secretion of parathyroid hormone resulting from extracellular calcium reduction. A double exponential curve described the parathyroid hormone secretion induced...... plasma and the rate of cellular production/secretion was observed. This could be interpreted as an adaptation of the parathyroid gland's ability to produce parathyroid hormone depending on the average demand from the body....

  19. Evaluation of a potential parathyroid dysfunction under treatment with radioactive iodine of benign thyroid diseases; Pruefung einer potentiellen strahleninduzierten Nebenschilddruesenfunktionsstoerung waehrend einer Radioiodtherapie benigner Schilddruesenerkrankung

    Energy Technology Data Exchange (ETDEWEB)

    Schumacher, Serena Christine

    2011-09-28

    The intention of the present thesis was the evaluation of a potential parathyroid dysfunction under treatment with radioactive iodine of benign thyroid diseases. It was to be examined whether a change in the parathyroid function would arise within the first week on treatment. So far there are some minor studies existing describing significant changes in the parathyroid hormone serum level within the first months after radioactive iodine therapy of benign and malignant thyroid diseases. Moreover, it is a fact that external beam-radiotherapy can induce neoplasia and that the risk for the subsequent development of primary hyperparathyroidism doubles or triples after external beam-radiotherapy of the head and neck. Up to now, however, an increased incidence for primary hyperparathyroidism following treatment with radioactive iodine ({sup 131}I) could not be proved. At the department of nuclear medicine of the university hospital Giessen-Marburg GmbH, location Marburg, a prospective cohort study was executed on radioactive iodine therapy of benign thyroid diseases with 105 probands (75 women / 30 men, mean age 60.62 ± 14.3 years). According to their thyroid diseases these 105 probands were classified into following subgroups: thyroid adenoma with 23 patients, multifocal thyroid autonomy with 8 patients, disseminated thyroid autonomy with 37 patients as well as the subgroup Graves' hyperthyroidism (without Graves' ophtalmopathy) and accordingly Graves' disease (with Graves' ophtalmopathy) with 37 patients. The serum level of the intact parathyroid hormone was determined directly before starting the radioactive iodine therapy on the admission day and on day 1, 3 and 5 of the radioactive iodine therapy as well as at the ambulant follow-up examination one month after the start of the therapy. In case of 99 of 105 probands the serum level of parathyroid hormone declined on treatment with {sup 131}I with its nadir on day 3 of therapy (decline by 15.71 ng

  20. Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial

    Science.gov (United States)

    Objective: To determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), serum parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C telopeptide (CTX) in HIV-infected youth receiving and not receiving tenofovir-containing cART (TDF). Design: Ra...

  1. Circulating sclerostin in disorders of parathyroid gland function.

    Science.gov (United States)

    Costa, Aline G; Cremers, Serge; Rubin, Mishaela R; McMahon, Donald J; Sliney, James; Lazaretti-Castro, Marise; Silverberg, Shonni J; Bilezikian, John P

    2011-12-01

    Sclerostin, a protein encoded by the SOST gene in osteocytes and an antagonist of the Wnt signaling pathway, is down-regulated by PTH administration. Disorders of parathyroid function are useful clinical settings to study this relationship. The objective of the study was to evaluate sclerostin in two different disorders of parathyroid function, primary hyperparathyroidism and hypoparathyroidism, and to analyze the relationship between sclerostin and PTH, bone markers, and bone mineral density. This is a cross-sectional study. The study was conducted at a clinical research center. Twenty hypoparathyroid and 20 hyperparathyroid patients were studied and compared to a reference control group. Serum sclerostin was significantly higher in hypoparathyroid subjects than in hyperparathyroid subjects (P < 0.0001) and controls (P < 0.0001). PTH was negatively associated with sclerostin, achieving statistical significance in hypoparathyroidism (r = -0.545; P = 0.02). The bone turnover markers, cross-linked C-telopeptide of type I collagen (CTX) and amino-terminal propeptide of type I collagen (P1NP), were differently associated with sclerostin according to the parathyroid disorder. In primary hyperparathyroidism, bone turnover markers were associated negatively with sclerostin (for P1NP, r = -0.490; P = 0.03). In hypoparathyroidism, bone turnover markers were associated positively with sclerostin (for CTX, r = +0.571; P = 0.01). Although there was no significant correlation between bone mineral density and sclerostin in either parathyroid disorder, there was a significant positive relationship between sclerostin and bone mineral content in hypoparathyroidism. The results are consistent with the hypothesis that PTH is a regulator of sclerostin in human disorders of parathyroid function. In addition, the results suggest that bone mineral content may be another factor that influences sclerostin.

  2. Ras-induced and extracellular signal-regulated kinase 1 and 2 phosphorylation-dependent isomerization of protein tyrosine phosphatase (PTP)-PEST by PIN1 promotes FAK dephosphorylation by PTP-PEST.

    Science.gov (United States)

    Zheng, Yanhua; Yang, Weiwei; Xia, Yan; Hawke, David; Liu, David X; Lu, Zhimin

    2011-11-01

    Protein tyrosine phosphatase (PTP)-PEST is a critical regulator of cell adhesion and migration. However, the mechanism by which PTP-PEST is regulated in response to oncogenic signaling to dephosphorylate its substrates remains unclear. Here, we demonstrate that activated Ras induces extracellular signal-regulated kinase 1 and 2-dependent phosphorylation of PTP-PEST at S571, which recruits PIN1 to bind to PTP-PEST. Isomerization of the phosphorylated PTP-PEST by PIN1 increases the interaction between PTP-PEST and FAK, which leads to the dephosphorylation of FAK Y397 and the promotion of migration, invasion, and metastasis of v-H-Ras-transformed cells. These findings uncover an important mechanism for the regulation of PTP-PEST in activated Ras-induced tumor progression.

  3. Inhibition effects of parathyroid hormone on human medullary thyroid carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Yaqiong Ni; Qinjiang Liu; Shihong Ma; Ruihui Chen

    2014-01-01

    Objective:The purpose of the study was to investigate the ef ects of parathyroid hormone and parathyroid hor-mone receptor monoclonal antibody on in vitro growth and proliferation of human medul ary thyroid carcinoma celllines. Methods:The medul ary thyroid carcinoma cellline was cultured in vitro, with parathyroid hormone and parathyroid hormone receptor monoclonal antibody treatment intervention, the growth of the cells was observed under an inverted contrast micro-scope, the MTT assay was used to detect the cellgrowth inhibition rate. Results:Under the inverted contrast microscope, the cells changed significantly, the parathyroid hormone and parathyroid hormone receptor monoclonal antibodies can ef ectively inhibit the proliferation of medul ary thyroid cancer cells in a time and dose dependent. When parathyroid hormone concentra-tion reached a concentration of 2.0μmol/L, the parathyroid hormone receptor monoclonal antibody reached a concentration of 1.0μmol/L, the cellgrowth was most significantly inhibited (P<0.05). Conclusion:Parathyroid hormone and parathyroid hormone receptor monoclonal antibody were able to inhibit the proliferation of medul ary thyroid carcinoma cells and signifi-cantly reduce the proliferation index.

  4. Right thyroid hemiagenesis with adenoma and hyperplasia of parathyroid glands -case report.

    Science.gov (United States)

    Oruci, Merima; Ito, Yasuhiro; Buta, Marko; Radisavljevic, Ziv; Pupic, Gordana; Djurisic, Igor; Dzodic, Radan

    2012-11-13

    Thyroid hemiagenesis is a rare anomaly, more commonly seen on the left side (ratio 4:1) and in females (ratio 3:1). The first to describe this anomaly was Handfield Jones in 1852. We present a 66 year old female patient with right thyroid hemiagenesis, parathyroid adenoma on the side of hemiagenesis and parathyroid hyperplasia on the contralateral side. The patient had neck pain and was diagnosed as Hashimto thyroiditis with hyperparathyroidism. Parathyroid hormone, thyroglobulin antibodies (Tg-Ab) and thyroid peroxidase antibodies (TPO-Ab) were elevated. Neck ultrasound and technetium 99mTc-methoxyisobutyl isonitrile (MIBI) scintigraphy confirmed the right thyroid hemiagenesis, but not adenoma of parathyroid glands. Intraoperatively, right thyroid hemiagenesis was confirmed and left loboistmectomy was performed with removal of left inferior hyperplastic parathyroid gland. Postoperative PTH (parathyroid hormone) levels were within normal range. Five months after the operation PTH level was elevated again with calcium values at the upper limit. MIBI scintigraphy was performed again which showed increased accumulation of MIBI in the projection of the right parathyroid gland. Surgical reexploration of the neck and excision of the right upper parathyroid adenoma was performed which was located behind cricoid laryngeal cartilage. After surgery a normalization of calcium and PTH occured. From available literature we have not found the case that described parathyroid adenoma on the side of thyroid hemiagenesis,with parathyroid hyperplasia on the contralateral side.

  5. Right thyroid hemiagenesis with adenoma and hyperplasia of parathyroid glands -case report

    Directory of Open Access Journals (Sweden)

    Oruci Merima

    2012-11-01

    Full Text Available Abstract Background Thyroid hemiagenesis is a rare anomaly, more commonly seen on the left side (ratio 4:1 and in females (ratio 3:1. The first to describe this anomaly was Handfield Jones in 1852. Case presentation We present a 66 year old female patient with right thyroid hemiagenesis, parathyroid adenoma on the side of hemiagenesis and parathyroid hyperplasia on the contralateral side. The patient had neck pain and was diagnosed as Hashimto thyroiditis with hyperparathyroidism. Parathyroid hormone, thyroglobulin antibodies (Tg-Ab and thyroid peroxidase antibodies (TPO-Ab were elevated. Neck ultrasound and technetium 99mTc-methoxyisobutyl isonitrile (MIBI scintigraphy confirmed the right thyroid hemiagenesis, but not adenoma of parathyroid glands. Intraoperatively, right thyroid hemiagenesis was confirmed and left loboistmectomy was performed with removal of left inferior hyperplastic parathyroid gland. Postoperative PTH (parathyroid hormone levels were within normal range. Five months after the operation PTH level was elevated again with calcium values at the upper limit. MIBI scintigraphy was performed again which showed increased accumulation of MIBI in the projection of the right parathyroid gland. Surgical reexploration of the neck and excision of the right upper parathyroid adenoma was performed which was located behind cricoid laryngeal cartilage. After surgery a normalization of calcium and PTH occured. Conclusion From available literature we have not found the case that described parathyroid adenoma on the side of thyroid hemiagenesis,with parathyroid hyperplasia on the contralateral side.

  6. Conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid as Pin1 inhibitors displaying anti-prostate cancer ability.

    Science.gov (United States)

    Li, Kun; Ma, Tianyi; Cai, Jingjing; Huang, Min; Guo, Hongye; Zhou, Di; Luan, Shenglin; Yang, Jinyu; Liu, Dan; Jing, Yongkui; Zhao, Linxiang

    2017-08-04

    Twenty-six conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid were designed and synthesized as Pin1 inhibitors. Most of these semi-synthetic compounds showed improved Pin1 inhibitory activity and anti-proliferative effects against prostate cancer cells as compared to 3-(1H-benzo[d]imidazol-2-yl)propanoic acid and GA. Compounds 10a and 12i were the most potent to inhibit growth of prostate cancer PC-3 with GI50 values of 7.80μM and 3.52μM, respectively. The enzyme inhibition ratio of nine compounds at 10μM was over 90%. Structure-activity relationships indicated that both appropriate structure at ring C of GA and suitable length of linker between GA skeleton and benzimidazole moiety had significant impact on improving activity. Western blot assay revealed that 10a decreased the level of cell cycle regulating protein cyclin D1. Thus, these compounds might represent a novel anti-proliferative agent working through Pin1 inhibition. Copyright © 2017. Published by Elsevier Ltd.

  7. The secretory response of parathyroid hormone to acute hypocalcemia in vivo is independent of parathyroid glandular sodium/potassium-ATPase activity

    DEFF Research Database (Denmark)

    Martuseviciene, Giedre; Hofman-Bang, Jacob; Clausen, Torben

    2011-01-01

    -treated parathyroid glands, indicating inhibition of the ATPase. As ouabain induced systemic hyperkalemia, the effect of high potassium on hormone secretion was also examined but was found to have no effect. Thus, inhibition of the parathyroid gland sodium/potassium-ATPase activity in vivo had no effect...

  8. Two Years of Cinacalcet Hydrochloride Treatment Decreased Parathyroid Gland Volume and Serum Parathyroid Hormone Level in Hemodialysis Patients With Advanced Secondary Hyperparathyroidism.

    Science.gov (United States)

    Yamada, Shunsuke; Tokumoto, Masanori; Taniguchi, Masatomo; Toyonaga, Jiro; Suehiro, Takaichi; Eriguchi, Rieko; Fujimi, Satoru; Ooboshi, Hiroaki; Kitazono, Takanari; Tsuruya, Kazuhiko

    2015-08-01

    The long-term effect of cinacalcet hydrochloride treatment on parathyroid gland (PTG) volume has been scarcely investigated in patients with moderate to advanced secondary hyperparathyroidism (SHPT). The present study was a prospective observational study to determine the effect of cinacalcet treatment on PTG volume and serum biochemical parameters in 60 patients with renal SHPT, already treated with intravenous vitamin D receptor activator (VDRA). Measurement of biochemical parameters and PTG volumes were performed periodically, which were analyzed by stratification into tertiles across the baseline parathyroid hormone (PTH) level or PTG volume. We also determined the factors that can estimate the changes in PTG volume and the achievement of the target PTH range by multivariable analyses. Two years of cinacalcet treatment significantly decreased the serum levels of PTH, calcium, and phosphate, followed by the improvement of achieving the target ranges for these parameters recommended by the Japanese Society for Dialysis Therapy. Cinacalcet decreased the maximal and total PTG volume by about 30%, and also decreased the serum PTH level independent of the baseline serum PTH level and PTG volume. Ten out of 60 patients showed 30% increase in maximal PTG after 2 years. Multivariable analysis showed that patients with nodular PTG at baseline and patients with higher serum calcium and PTH levels at 1 year were likely to exceed the target range of PTH at two years. In conclusion, cinacalcet treatment with intravenous VDRA therapy decreased both PTG volume and serum intact PTH level, irrespective of the pretreatment PTG status and past treatment history. © 2015 The Authors. Therapeutic Apheresis and Dialysis © 2015 International Society for Apheresis.

  9. The utility of 99mTc-sestamibi scintigraphy in the localisation of parathyroid adenomas in primary hyperparathyroidism.

    LENUS (Irish Health Repository)

    Glynn, N

    2012-02-01

    BACKGROUND: There are conflicting data in the literature about the sensitivity of sestamibi scintigraphy in parathyroid tumour localisation in primary hyperparathyroidism (PHPT). AIM: We aimed to evaluate the overall sensitivity of this modality in parathyroid tumour localisation and to determine clinical and biochemical factors which influence sensitivity of this method. METHODS: We performed a retrospective review of 57 patients with a biochemical diagnosis of PHPT who had sestamibi scintigraphy performed. RESULTS: The sensitivity of sestamibi scanning was 56% in whole group and 63% in those without nodular thyroid disease. Among the patients with confirmed single gland disease (biochemical cure after surgical removal of a single adenoma), sensitivity was 71%. A positive scan was associated with younger age, greater adenoma weight and higher pre-operative serum calcium. Concordance between the sestamibi and neck ultrasonography was 92% accurate in pre-operative tumour localisation. CONCLUSION: Sestamibi scintigraphy was more likely to be positive in younger patients without nodular thyroid disease who have larger parathyroid adenomas with more severe hyperparathyroidism.

  10. Clinical and Pathological Studies on Severe Parathyroid Hyperplasia in Uremic Patients with Secondary Hyperparathyroidism

    Institute of Scientific and Technical Information of China (English)

    SunB; WangXY

    2002-01-01

    Objective To evaluate clinical significance of parathyroid proliferation in secondary hyperpar athyroidism(SHPT).Methods The specimens of parathyroid were taken from 7 patients with SHPT and resistance to medical therapy.The histological sections were routinely stained with hematoxylin-eoxin(HE) stain,and according to macroscopical and microscopical examinations,divided into two types:diffuse type (D-type) with a normal lobular constitution and nodular type(N-type).The sum of parathyroid cells under HE stain were calculated by computer image analysis system.Results There was 16.1 times increase in the weight of parathyroid of CRF patients with SHPT and 1.86 times increase in sum of parathyroid cells.The proliferation of N-type parathyroid was especially noticeable.Conclusion We suggest that D-type hyperplasia parathryoid should be selected in autotransplantation,expecially quite small piece,in order to prevent symtom recurrence of SHPT.

  11. Sphenoid Brown Tumor Associated with a Parathyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Abelardo Loya-Solís

    2014-01-01

    Full Text Available Brown tumors are osteolytic bone lesions that occur as a result of persistent hyperparathyroidism. They usually appear late in the natural history of the disease and are currently very rare due to an earlier diagnosis of primary hyperparathyroidism. We present the case of a 53-year-old female with a 2-month history of bitemporal hemianopsia and diplopia. A computed tomography showed an osteolytic bone lesion that involved the sphenoid corpus and clivus. A biopsy was made and the histopathology result was consistent with a brown tumor. The aforementioned location is very infrequent to such tumors, and therefore represented a diagnostic challenge. However, in this case, its association to primary hyperparathyroidism was the clue for the diagnosis. The association of a brown tumor secondary to a parathyroid carcinoma has been seldom reported. This case represents, to our knowledge, one of the few brown tumors described in such location and the first secondary to a parathyroid carcinoma.

  12. A Matlab Tool for Tumor Localization in Parathyroid Sestamibi Scintigraphy

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    M. Đurović

    2015-11-01

    Full Text Available Submarine method for localization of parathyroid tumors (PT has proved to be effective in case of typical pitfalls of conventional scintigraphic methods (combined subtraction and double phase methods. It uses images obtained by standard dynamic parathyroid sestamibi scintigraphy suggested by European Association of Nuclear Medicine. This paper presents: 1 the developed Matlab interface that enables the implementation and evaluation of algorithms for the automatic application of Submarine method; 2 the algorithm for automatic extraction of the entire thyroid region from the background radioactivity using operations from mathematical morphology applied on dynamic scintigrams; 3 the results obtained by algorithm for localization and visualization of PTs based on estimation of exponential decreasing trend of time-activity curves. The algorithm was tested on a group of 20 patients with histopathologically proven PTs using developed Matlab interface.

  13. [Optical coherence tomography for differentiation of parathyroid gland tissue].

    Science.gov (United States)

    Ladurner, R; Hallfeldt, K; Al Arabi, N; Gallwas, J; Mortensen, U; Sommerey, S

    2016-05-01

    Optical coherence tomography (OCT) is a high-resolution imaging technique that allows the identification of microarchitectural features in real-time. Can OCT be used to differentiate parathyroid tissue from other cervical tissue entities? All investigations were carried out during cervical operations. Initially, ex vivo images were analyzed to define morphological imaging criteria for each tissue entity. These criteria were used to evaluate a first series of ex vivo images. In a second phase the practicability of the technique was investigated in vivo and in the third phase backscattering intensity measurements were analyzed employing linear discriminant analysis (LDA). In the ex vivo series parathyroid tissue could be differentiated from other tissue entities with a sensitivity and specificity of 84  % and 94  %, respectively. Parathyroid tissue was correctly identified in the in vivo series in only 69.2 %. The analysis of backscattering intensity profiles employing LDA reliably distinguished between the different tissue types. The OCT images displayed typical characteristics for each tissue entity. Due to technical problems in handling the probe the in vivo OCT images were of much poorer quality. Backscattering intensity measurements illustrated that OCT images provide an individual profile for each tissue entity independent of the defined morphological assessment criteria. The results show that OCT is fundamentally suitable for intraoperative differentiation of tissues.

  14. A role for magnesium in neonatal parathyroid gland function

    Energy Technology Data Exchange (ETDEWEB)

    Loughead, J.L.; Mimouni, F.; Tsang, R.C.; Khoury, J.C. (Univ. of Cincinnati College of Medicine, OH (USA))

    1991-04-01

    Little is known of the factors regulating parathyroid function in the neonatal period. Twenty-seven term infants born after uncomplicated pregnancies, labors, and deliveries were studied to test the hypothesis that in normal newborns the amplitude of parathyroid hormone (PTH) response to decreasing serum ionized calcium (iCa) correlates with serum magnesium (Mg) concentrations. Serum iCa (ion selective electrode, Radiometer ICA 1), PTH (1-84 intact molecules, radioimmunoassay) and Mg (atomic absorption) were measured at birth (cord blood) and 24 hours of age. Repeated measures analysis of covariance showed decreasing serum iCa (p less than 0.01) and increasing serum Mg (p less than 0.01) and PTH (p less than 0.01) over time. The change in PTH over the first 24 hours was directly correlated with cord blood (r = 0.38, p less than 0.05) and 24-hr Mg concentrations (r = 0.53, p less than 0.01). We conclude that the ability of the parathyroid gland to respond to decreasing serum iCa after birth is directly related to Mg status. We speculate that neonatal hypomagnesemia may lead to a blunted PTH secretory response, thus contributing to early neonatal hypocalcemia.

  15. Vitamin D metabolism and activity in the parathyroid gland.

    Science.gov (United States)

    Bienaimé, Frank; Prié, Dominique; Friedlander, Gérard; Souberbielle, Jean Claude

    2011-12-05

    Parathormone (PTH) and vitamin D are two critical hormonal regulators of calcium homeostasis. An important cross-talk exists between the PTH and vitamin D hormonal systems. PTH enhances vitamin D hydroxylation on carbon 1 in kidney cells thereby allowing the systemic release of 1-25-dihydroxy-vitamin D, which represents the fully active hormone. Conversely, parathyroid gland represents a direct target for vitamin D. Parathyroid cells express the vitamin D receptor and the 1-α-hydroxylase enzyme, which allows the local formation of 1-25-dihydroxy-vitamin D. Because of its potential implication in several diseases, including osteoporosis or chronic kidney disease, the interplay between PTH and vitamin D has received considerable attention these last two decades. The aim of this review is to summarize our current understanding of the molecular basis of vitamin D action and metabolism in parathyroid cells. The potential clinical implications of the recent advances made in this field will also be discussed. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Expression of parathyroid hormone-related protein in ameloblastomas.

    Science.gov (United States)

    Ohtsuru, Mitsunobu

    2005-12-01

    Parathyroid hormone-related protein (PTHrP) was first discovered as a causative protein for hypercalcemia, which is often seen in the malignant tumor. PTHrP binds to the parathyroid hormone 1 receptor (PTH1R) for signal transduction. PTHrP-PTH1R interactions were associated with bone resorption. The present study, therefore, sought to clarify the expression of PTHrP, parathyroid hormone (PTH) and PTH1R in ameloblastoma, using RT-PCR (N = 8), immunohistochemistry (N = 23) and ELISA (N = 11) techniques. PTHrP and B-actin mRNA were detected in the all samples. Expression of PTHrP was also seen in all of the 23 cases in ameloblastoma by immunohistochemistry. There was a significant difference in PTHrP concentration by ELISA between typical unicystic type and solid type including unicystic type 3 (p = 0.0427). Only one exhibited the weak expression of PTH1R mRNA. PTH1R was observed on osteoblasts in bone around the tumor but no expression was observed on ameloblastoma cells in tumor parenchyma by immunohistochemistry. PTH was not detected in ameloblastoma by RT-PCR, immunohistochemistory as well as ELISA. In addition, hypercalcemia and increase of serum PTHrP level was observed in one case of 8 ameloblastomas. It was suggested that PTHrP level may be associated with local bone infiltration and hypercalcemia in ameloblastoma.

  17. Ultrasonography of histologically normal parathyroid glands and thyroid lobules in normocalcemic dogs.

    Science.gov (United States)

    Liles, Sofija R; Linder, Keith E; Cain, Brandon; Pease, Anthony P

    2010-01-01

    The purpose of this study is to characterize the sonographic appearance of canine parathyroid glands using high-resolution ultrasonography. Ten cadaver dogs were studied after euthanasia for reasons not relating to the parathyroid. The cervical region was examined using a 13-5 MHz linear transducer in right and left recumbency. Ultrasonographic features of the parathyroid and thyroid glands were compared with the gross and histopathologic findings. Thirty-five structures were identified sonographically as parathyroid glands but only 26 of 35 glands (74% positive predictive value) were proven to be normal parathyroid glands histopathologically. Of the nine false positives, five (14%) were proven to be lobular thyroid tissue. The remaining four (11%) structures were visible grossly or found histopathologically. There were no statistical differences between ultrasonographic and gross measurements of the parathyroid glands. The average size as seen sonographically was 3.3 x 2.2 x 1.7 mm and the average gross size was 3.7 x 2.6 x 1.6 mm (length, width, height). The average size of the thyroid lobules assessed sonographically was 2.3 x1.6 x 0.8 mm (length, width, height). Normal parathyroid glands can be identified using high-resolution ultrasonography. But some thyroid lobules will be misinterpreted as parathyroid glands; this will result in false positives when identifying parathyroid glands with ultrasonography.

  18. Non-functional parathyroid gland carcinoma, a rare malignant tumor of the head and neck.

    Science.gov (United States)

    Kotromanović, Zeljko; Birtić, Darija; Vceva, Andrijana; Medić, Darija; Zubcić, Zeljko; Mihalj, Hrvoje; Kotromanović, Zdenka; Erić, Suzana; Dmitrović, Branko; Stefanić, Mario

    2012-11-01

    Carcinoma of the parathyroid gland is a very rare tumor of the head and neck. The largest number of carcinomas are discovered by chance. (intraoperatively, during surgery removal of the parathyroid gland are adenomas). Around 1% of the primary parathyreoidism is caused by the cancer of parathyroid glands. Only 10% of these rare tumors make up dysfunctional cancer of parathyroid glands. There have been 24 cases reported of this disease in the literature. The focus of our study is to present a case of this disease and to review the published literature to date.

  19. [A combination of diseases of the thyroid and asymptomatic adenoma of the parathyroid glands].

    Science.gov (United States)

    Romanchishen, A F; Matveeva, Z S

    2006-01-01

    The authors have analyzed the cases of diagnosis of asymptomatic tumors of the parathyroid gland made during 8814 operations on the thyroid in the period from 1995 through 2004. The probability of detecting parathyroid incidentalomas in different forms of goiter was calculated which reaches 0.4%. A precision technique of operating allows the parathyroid tumors to be detected at the preclinical stage in all patients apart from a removal of the necessary volume of the thyroid tissue, guaranteed preservation of the laryngeal nerves and parathyroid glands.

  20. Successful xenotransplantation of microencapsulated newborn pig parathyroid cells in the treatment of hypoparathyroidism in rats

    Institute of Scientific and Technical Information of China (English)

    林乐岷; 宋一民; 宋纯; 许评; 宋春芳

    2003-01-01

    Objective To study the effect of xenotransplantation with pig parathyroid cells, which was prepared using cell microencapsulation technique, on the treatment of hypoparathyroidism in rats without immunosuppressor. Methods Parathyroid cells were isolated from 10 healthy newborn pigs and encapsulated in alginate-polylysine-alginate (APA) membranes. Thirty-two aparathyroid Wistar rats were randomly allocated to microcapsule, non-microcapsule, empty microcapsule, and control groups. Each rat was injected intraperitoneally with encapsulated porcine parathyroid cells, free porcine parathyroid cells, empty capsules or 0.9% NaCl, respectively. Total serum calcium and parathyroid hormone levels were monitored continuously for 40 weeks. And then, the transplant beds were retrieved and subjected to morphologic and electron microscopic examination. Results In those animals xenotransplanted with microencapsulated porcine parathyroid cells, the calcium and PTH levels were consistently within the normal range during the 40 weeks. In contrast, no therapeutic effects were observed in rats in the non-microcapsule group. Furthermore, neither empty capsules nor 0.9% NaCl were shown to have any effect on the recipient's serum calcium or PTH levels. After 40 weeks, electron microscopic examination demonstrated that the parathyroid cells within the microcapsules had survived well in vivo. Conclusions Xenotransplantation of microencapsulated newborn pig parathyroid cells can successfully treat hypoparathyroidism in rats without using immunosuppressive drugs. The results of this study show the possible clinical use of microencapsulated porcine parathyroid cells.

  1. Calcification of all four parathyroid glands in a hemodialysis patient with secondary hyperparathyroidism revealed by computerized tomography.

    Science.gov (United States)

    Peces, R; Rodríguez, M; González, F; Ablanedo, P

    2001-09-01

    This report describes the parathyroid scan, computerized tomography and histologic findings in a young female hemodialysis patient with severe secondary hyperparathyroidism. These findings included hyperplasia and calcification of all four parathyroid glands.

  2. Interspecies comparison of renal cortical receptors for parathyroid hormone and parathyroid hormone-related protein

    Energy Technology Data Exchange (ETDEWEB)

    Orloff, J.J.; Goumas, D.; Wu, T.L.; Stewart, A.F. (West Haven Veterans Administration Medical Center, CT (USA))

    1991-03-01

    Parathyroid hormone (PTH) and PTH-related proteins (PTHrP) interact with a common receptor in rat bone cells and in canine renal membranes with similar affinity, but PTHrP are substantially less potent than PTH in stimulating adenylate cyclase in canine renal membranes; in contrast, PTH and PTHrP are equipotent in stimulating adenylate cyclase in rat bone cells. This discrepancy has been largely viewed as reflecting differences in the relative efficiency of signal transduction of PTHrP between bone and kidney assay systems. To test the alternative (but not mutually exclusive) hypothesis that these differences could reflect interspecies differences in PTH receptors, we have characterized the bioactivity of amino-terminal PTHrP and PTH in rat and human renal cortical membranes (RCM) and compared them to results we previously reported in canine RCM. The stability of PTH and PTHrP peptides under binding and adenylate cyclase assay conditions was greater than 80% for each species. Competitive inhibition of ({sup 125}I)(Tyr36)hPTHrP-(1-36)NH{sub 2} binding to rat RCM by bPTH-(1-34) and (Tyr36)hPTHrP-(1-36)NH{sub 2} yielded nearly identical binding dissociation constants (3.7 and 3.6 nM, respectively), and binding to human RCM demonstrated slightly greater potency for PTHrP (0.5 nM) than for PTH (0.9 nM). Similarly, adenylate cyclase stimulating activity was equivalent for the two peptides in rat RCM, but PTHrP was twofold more potent than PTH in human RCM. Covalent photoaffinity labeling of protease-protected rat RCM yielded an apparent 80 kD receptor protein, and cross-linking of human RCM labeled an 85 kD receptor, indistinguishable in size from the canine renal PTH receptor. We conclude that rat, canine, and human renal cortical PTH receptors exhibit species specificity.

  3. Histone deacetylase turnover and recovery in sulforaphane-treated colon cancer cells: competing actions of 14-3-3 and Pin1 in HDAC3/SMRT corepressor complex dissociation/reassembly

    Directory of Open Access Journals (Sweden)

    Williams David E

    2011-05-01

    Full Text Available Abstract Background Histone deacetylase (HDAC inhibitors are currently undergoing clinical evaluation as anti-cancer agents. Dietary constituents share certain properties of HDAC inhibitor drugs, including the ability to induce global histone acetylation, turn-on epigenetically-silenced genes, and trigger cell cycle arrest, apoptosis, or differentiation in cancer cells. One such example is sulforaphane (SFN, an isothiocyanate derived from the glucosinolate precursor glucoraphanin, which is abundant in broccoli. Here, we examined the time-course and reversibility of SFN-induced HDAC changes in human colon cancer cells. Results Cells underwent progressive G2/M arrest over the period 6-72 h after SFN treatment, during which time HDAC activity increased in the vehicle-treated controls but not in SFN-treated cells. There was a time-dependent loss of class I and selected class II HDAC proteins, with HDAC3 depletion detected ahead of other HDACs. Mechanism studies revealed no apparent effect of calpain, proteasome, protease or caspase inhibitors, but HDAC3 was rescued by cycloheximide or actinomycin D treatment. Among the protein partners implicated in the HDAC3 turnover mechanism, silencing mediator for retinoid and thyroid hormone receptors (SMRT was phosphorylated in the nucleus within 6 h of SFN treatment, as was HDAC3 itself. Co-immunoprecipitation assays revealed SFN-induced dissociation of HDAC3/SMRT complexes coinciding with increased binding of HDAC3 to 14-3-3 and peptidyl-prolyl cis/trans isomerase 1 (Pin1. Pin1 knockdown blocked the SFN-induced loss of HDAC3. Finally, SFN treatment for 6 or 24 h followed by SFN removal from the culture media led to complete recovery of HDAC activity and HDAC protein expression, during which time cells were released from G2/M arrest. Conclusion The current investigation supports a model in which protein kinase CK2 phosphorylates SMRT and HDAC3 in the nucleus, resulting in dissociation of the corepressor

  4. The effects of cinacalcet treatment on bone mineral metabolism, anemia parameters, left ventricular mass index and parathyroid gland volume in hemodialysis patients with severe secondary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    Dilek Torun

    2016-01-01

    Full Text Available The aim of this study was to investigate the effects of cinacalcet therapy on anemia parameters, bone mineral metabolism, left ventricular mass index (LVMI and parathyroid gland volume in hemodialysis (HD patients with secondary hyperparathyroidism. Twenty-five HD patients (M/F: 11/14, mean age: 45.2 ± 17.9 years, mean HD duration: 96.4 ± 32.7 months were included in this prospective pilot study. The indication to start calcimimetic therapy was persistent serum levels of parathyroid hormone (PTH >1000 pg/mL, refractory to intravenous (i.v. vitamin D and phosphate-binding therapy. The initial and one-year results of adjusted serum calcium (Ca +2 , phosphate (P, Ca × P product, PTH, hemoglobin (Hb and ferritin levels, transferrin saturation index (TSAT, median weekly erythropoietin (EPO dose, LVMI, and parathyroid volume by parathyroid ultrasonography were determined. There were no differences between pre- and post-treatment levels of serum Ca +2 (P = 0.853, P (P = 0.447, Ca × P product (P = 0.587, PTH (P = 0.273, ferritin (P = 0.153 and TSAT (P = 0.104. After 1 year of calcimimetic therapy, the Hb levels were significantly higher than the initial levels (P = 0.048. The weekly dose of EPO decreased with no statistical significance. The dose of cinacalcet was increased from 32.4 ± 12.0 to 60.0 ± 24.4 mg/day (P = 0.01. There were no differences between the pre- and post-treatment results regarding weekly vitamin D dose, parenteral iron dose, LVMI and parathyroid volume. The results of our study suggest that cinacalcet therapy might have an additional benefit in the control anemia in HD patients.

  5. The effects of cinacalcet treatment on bone mineral metabolism, anemia parameters, left ventricular mass index and parathyroid gland volume in hemodialysis patients with severe secondary hyperparathyroidism.

    Science.gov (United States)

    Torun, Dilek; Yildiz, Ismail; Micozkadioglu, Hasan; Nursal, Gul Nihal; Yigit, Fatma; Ozelsancak, Ruya

    2016-01-01

    The aim of this study was to investigate the effects of cinacalcet therapy on anemia parameters, bone mineral metabolism, left ventricular mass index (LVMI) and parathyroid gland volume in hemodialysis (HD) patients with secondary hyperparathyroidism. Twenty-five HD patients (M/F: 11/14, mean age: 45.2±17.9 years, mean HD duration: 96.4±32.7 months) were included in this prospective pilot study. The indication to start calcimimetic therapy was persistent serum levels of parathyroid hormone (PTH)>1000 pg/mL, refractory to intravenous (i.v.) vitamin D and phosphate-binding therapy. The initial and one-year results of adjusted serum calcium (Ca+2), phosphate (P), Ca×P product, PTH, hemoglobin (Hb) and ferritin levels, transferrin saturation index (TSAT), median weekly erythropoietin (EPO) dose, LVMI, and parathyroid volume by parathyroid ultrasonography were determined. There were no differences between pre- and post-treatment levels of serum Ca+2 (P=0.853), P (P=0.447), Ca×P product (P=0.587), PTH (P=0.273), ferritin (P=0.153) and TSAT (P=0.104). After 1 year of calcimimetic therapy, the Hb levels were significantly higher than the initial levels (P=0.048). The weekly dose of EPO decreased with no statistical significance. The dose of cinacalcet was increased from 32.4±12.0 to 60.0±24.4 mg/day (P=0.01). There were no differences between the pre- and post-treatment results regarding weekly vitamin D dose, parenteral iron dose, LVMI and parathyroid volume. The results of our study suggest that cinacalcet therapy might have an additional benefit in the control anemia in HD patients.

  6. Unique expression pattern of the EMT markers Snail, Twist and E-cadherin in benign and malignant parathyroid neoplasia.

    Science.gov (United States)

    Fendrich, Volker; Waldmann, Jens; Feldmann, Georg; Schlosser, Katja; König, Alexander; Ramaswamy, Annette; Bartsch, Detlef K; Karakas, Elias

    2009-04-01

    Epithelial and mesenchymal transitions (EMT) are essential for embryonic development and progression of non-invasive tumor cells into malignant, metastatic carcinomas. During embryogenesis, the parathyroid glands develop from pharyngeal pouches and migrate to their final destinations, densely enclosed by mesenchymal neural crest cells. In this study, we examined the expression of the EMT markers Snail, Twist and E-cadherin in normal parathyroid glands and benign and malignant parathyroid diseases. Using immunohistochemistry, we compared expression of E-cadherin, Snail and Twist in 25 patients with parathyroid adenoma, 25 patients with parathyroid hyperplasia, and nine patients with parathyroid cancer with normal parathyroid glands. Normal parathyroid glands, parathyroid adenomas, and parathyroid hyperplasias showed a typical membranous E-cadherin staining pattern. Expression of Snail was found in 22/25 parathyroid adenomas and in all parathyroid hyperplasias. Twist was expressed in 22/25 of parathyroid adenomas and in 20/25 parathyroid hyperplasias. Snail and Twist positive cells were homogeneously distributed throughout the gland. However, in all nine parathyroid carcinomas, membranous E-cadherin staining was lost. In addition, the expression pattern of Snail and Twist was changed and mostly limited to the invasive front of cancer tissue samples. Expression of Snail and Twist at the invasive front and consecutive loss of E-cadherin in parathyroid carcinomas suggests a key role of EMT in the tumorigenesis of this cancer. The unique expression pattern could help to distinguish between an adenoma and a non-metastatic carcinoma. Loss of E-cadherin and change of the expression pattern of Snail and Twist together should result in an en bloc resection or a close follow-up.

  7. Molecular analysis of the HPJ-JT syndrome and sporadic parathyroid carcinogenesis

    NARCIS (Netherlands)

    Haven, Carola José

    2008-01-01

    HPT-JT syndrome is a rare disease characterized by parathyroid tumours (with a high percentage of carcinomas), jaw and kidney tumours. In this thesis, the clinical and genetic features of the HPT-JT syndrome and the relationship between the HRPT2 gene and parathyroid tumours were investigated. We

  8. Parathyroid gland tumors in A-bomb survivors, autopsy cases, Hiroshima. Preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Takeichi, Nobuo; Fujikura, Toshio (Radiation Effects Research Foundation, Hiroshima (Japan)); Nishida, Toshihiro

    1984-03-01

    Parathyroid gland tumors were observed in 16 of 4,136 autopsy cases (0.4%) based on the life span survey for the population including A-bomb survivors and the control group. All of the cases (5 males and 11 females) had adenoma. The incidence of parathyroid gland tumors tended to increase with increasing the dose.

  9. Primary hyperparathyroidism by parathyroid gland adenoma (Report of 2 cases with review of the literature)

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Seong Sook; Han, Sang Suk [Inje Medical College, Busan (Korea, Republic of); Chae, Yoo Soon [Maryknoll Medical Center, Busan (Korea, Republic of)

    1985-02-15

    The primary hyperparathyroidism is a complex endocrine disease caused by neoplasm or diffuse hyperplasia of parathyroid gland in which excessive parathyroid hormone is secreted. This results in chemical abnormalities of serum, and exerts major influences on the bone, kidney and gastrointestinal tract. The authors report 2 cases of primary hyperparathyroidism with review of the literature.

  10. SUCCESSFUL SURGICAL-TREATMENT OF PARATHYROID CARCINOMA IN 2 HEMODIALYSIS-PATIENTS

    NARCIS (Netherlands)

    RADEMAKER, P; MEIJER, S; OOSTERHUIS, JW; VERMEY, A; ZWIERSTRA, R; VANDERHEM, G; GEERLINGS, W

    1990-01-01

    Parathyroid carcinoma is rare, occurring in less than 2-3% of the patients with clinical features of primary hyperparathyroidism. In haemodialysis patients parathyroid carcinoma has only once been described, although secondary hyperparathyroidism in these patients is common. We discuss two female ha

  11. Coexistence of parathyroid adenoma and papillary thyroid carcinoma: Experience of a single center

    Directory of Open Access Journals (Sweden)

    Ebubekir Gündeş

    2013-01-01

    Full Text Available Objective: The aim of this study was to describe experienceswith concurrent parathyroid adenoma and papillarythyroid carcinoma.Methods: Eight patients with concurrent parathyroid adenomaand papillary thyroid carcinoma were identifiedbetween 2005 and 2012, and their medical records werereviewed retrospectively.Results: Of the eight patients identified, two were maleand six were female; their mean age was 53.6 years.The mean serum calcium concentration was 11.7 mg/dL.Intact parathyroid hormone (iPTH concentrations werehigh in all patients, with a mean concentration of 338 pg/mL. The most frequently used surgical technique was totalthyroidectomy plus parathyroid adenoma excision (n=6.The mean size of the thyroid carcinoma was 1.2 cm, andone case showed metastatic lymph nodes in the centralcompartment. The mean parathyroid adenoma size wasfound to be 2.1(0.6- 3.5 cm, according to the longest sizeof the adenom. Six patients (75% developed postoperativecomplications, including temporary symptomatic hypocalcemiain 4 patients (50%, hematoma developmentin 1 patient (12.5% and temporary vocal cord paralysis inone patient (12.5%.Conclusion: Thyroid carcinoma and parathyroid adenomaare rarely concomitant. Rarely hyperparathyroidismmay be accompanied with thyroid carcinomas so preoperativelythyroid gland should be properly examined. Thyroidwith parathyroid surgery are risk factors of recurrentlaryngeal nerve injury and hypoparathyroidism.Key words: Papillary thyroid cancer; parathyroid adenoma;thyroidectomy

  12. Actions of parathyroid hormone related peptide in mouse parietal endoderm formation

    NARCIS (Netherlands)

    Veltmaat, J.M.

    2001-01-01

    Summary Since about a decade, several reports have strongly suggested a role for parathyroid hormone related peptide (PTHrP) in the formation of parietal endoderm (PE) in the mouse embryo. This thesis is aimed first at elucidating the biological significance of parathyroid hormone related peptide

  13. [Mediastinal parathyroid adenomas on a 5th ectopic gland. 2 case reports].

    Science.gov (United States)

    Emy, P; Combe, H; Marchand, J P; Villeneuve, A; Sicre, G; Chadenas, D

    1992-11-01

    Mediastinal parathyroid adenoma located on the 5th ectopic gland is rare. We report here two new cases diagnosed by scintigraphy. In one case the adenoma was found to be located in the mediastinum prior to cervicotomy. The modern imaging methods capable of locating parathyroid adenomas are evaluated.

  14. Epigenetic Methylation of Parathyroid CaR and VDR Promoters in Experimental Secondary Hyperparathyroidism.

    Science.gov (United States)

    Hofman-Bang, Jacob; Gravesen, Eva; Olgaard, Klaus; Lewin, Ewa

    2012-01-01

    Secondary hyperparathyroidism (s-HPT) in uremia is characterized by decreased expression in the parathyroids of calcium sensing (CaR) and vitamin D receptors (VDR). Parathyroid hormone (PTH) is normalized despite low levels of CaR and VDR after experimental reversal of uremia. The expression of CaR in parathyroid cultures decreases rapidly. Methylation of promoter regions is often detected during epigenetic downregulation of gene expression. Therefore, using an experimental rat model, we examined changes in methylation levels of parathyroid CaR and VDR promoters in vivo and in vitro. Methods. Uremia was induced by 5/6 nephrectomy. Melting temperature profiling of CaR and VDR PCR products after bisulfite treatment of genomic DNA from rat parathyroids was performed. Real-time PCR measured expression of PTH, CaR, VDR, and klotho genes in vitro. Results. Parathyroids from uremic rats had similar low levels of methylation in vivo and in vitro. In culture, a significant downregulation of CaR, VDR, and klotho within two hours of incubation was observed, while housekeeping genes remained stable for 24 hours. Conclusion. In uremic s-HPT and in vitro, no overall changes in methylation levels in the promoter regions of parathyroid CaR and VDR genes were found. Thus, epigenetic methylation of these promoters does not explain decreased parathyroid expression of CaR and VDR genes in uremic s-HPT.

  15. Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease.

    Science.gov (United States)

    Galitzer, H; Ben-Dov, I Z; Silver, Justin; Naveh-Many, Tally

    2010-02-01

    Although fibroblast growth factor 23 (FGF23) acting through its receptor Klotho-FGFR1c decreases parathyroid hormone expression, this hormone is increased in chronic kidney disease despite an elevated serum FGF23. We measured possible factors that might contribute to the resistance of parathyroid glands to FGF23 in rats with the dietary adenine-induced model of chronic kidney disease. Quantitative immunohistochemical and reverse transcription-PCR analysis using laser capture microscopy showed that both Klotho and FGFR1 protein and mRNA levels were decreased in histological sections of the parathyroid glands. Recombinant FGF23 failed to decrease serum parathyroid hormone levels or activate the mitogen-activated protein kinase signaling pathway in the glands of rats with advanced experimental chronic kidney disease. In parathyroid gland organ culture, the addition of FGF23 decreased parathyroid hormone secretion and mRNA levels in control animals or rats with early but not advanced chronic kidney disease. Our results show that because of a downregulation of the Klotho-FGFR1c receptor complex, an increase of circulating FGF23 does not decrease parathyroid hormone levels in established chronic kidney disease. This in vivo resistance is sustained in parathyroid organ culture in vitro.

  16. Epigenetic Methylation of Parathyroid CaR and VDR Promoters in Experimental Secondary Hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    Jacob Hofman-Bang

    2012-01-01

    Full Text Available Secondary hyperparathyroidism (s-HPT in uremia is characterized by decreased expression in the parathyroids of calcium sensing (CaR and vitamin D receptors (VDR. Parathyroid hormone (PTH is normalized despite low levels of CaR and VDR after experimental reversal of uremia. The expression of CaR in parathyroid cultures decreases rapidly. Methylation of promoter regions is often detected during epigenetic downregulation of gene expression. Therefore, using an experimental rat model, we examined changes in methylation levels of parathyroid CaR and VDR promoters in vivo and in vitro. Methods. Uremia was induced by 5/6 nephrectomy. Melting temperature profiling of CaR and VDR PCR products after bisulfite treatment of genomic DNA from rat parathyroids was performed. Real-time PCR measured expression of PTH, CaR, VDR, and klotho genes in vitro. Results. Parathyroids from uremic rats had similar low levels of methylation in vivo and in vitro. In culture, a significant downregulation of CaR, VDR, and klotho within two hours of incubation was observed, while housekeeping genes remained stable for 24 hours. Conclusion. In uremic s-HPT and in vitro, no overall changes in methylation levels in the promoter regions of parathyroid CaR and VDR genes were found. Thus, epigenetic methylation of these promoters does not explain decreased parathyroid expression of CaR and VDR genes in uremic s-HPT.

  17. Hypercalcemic crisis due to a mediastinal parathyroid cyst diagnosed by ultrasound-guided fine needle aspiration

    Institute of Scientific and Technical Information of China (English)

    ZHU Yan; MENG Yun-xiao; LI Nai-shi; LU Lin; CHEN Shi; XING Xiao-ping; MENG Xun-wu; GUAN Heng; TAN Li; LU Ke

    2010-01-01

    @@ Hypercalcemic crisis, generally accepted as serum calcium concentration greater than 3.5 mmol/L,constitues a life-threatening endocrinologic emergency,and is most frequently caused by either primary hyperparathyroidism (PHPT) or malignant diseases.Parathyroid cysts are uncommon lesions, most of that are located in the low part of the neck. By routine neck ultrasound scan investigation in a large series of 6621 patients, only 5 parathyroid cysts were detected, yielding a prevalence of 0.075% in setting of unselected patients.The parathyroid cysts in the mediastinum are much less frequently encountered, with only 106 cases reported in English literature.2,3 Moreover, less than half of these cases presented as functional with elevated serum calcium and parathyroid hormone, and only 10 cases were associated with hypercalcemic crisis.3 Herein, we present a rare case of mediastinal parathyroid cyst associated with recurrent hypercalcemic crisis, which diagnosed by ultrasound-guided fine needle aspiration (FNA).

  18. Parathyroid Carcinoma: A Review with Three Illustrative Cases

    Directory of Open Access Journals (Sweden)

    Antoine Digonnet, Adelaïde Carlier, Esther Willemse, Marie Quiriny, Cécile Dekeyser, Nicolas de Saint Aubain, Marc Lemort, Guy Andry

    2011-01-01

    Full Text Available Parathyroid carcinoma is a rare disease, which accounts for less than 1% of all case of primary hyperparathyroidism and is usually not detected until the time of surgery or thereafter. For most patients preoperative staging is not available. A radical excision remains the standard management; the place of adjuvant radiotherapy is not well established yet. Local recurrence and/or the metastases are unfortunately frequent. The present paper presents an up to date review of the literature illustrated by three clinical cases.

  19. Therapy of hypoparathyroidism by replacement with parathyroid hormone

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Underbjerg, Line; Sikjaer, Tanja

    2014-01-01

    Hypoparathyroidism (HypoPT) is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH). HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (Qo......L) seems impaired and patients are at increased risk of renal complications. A number of studies have suggested subcutaneous injections with PTH as an alternative therapy. By replacement with the missing hormone, urinary calcium may be lowered and QoL may improve. PTH replacement therapy (PTH-RT) possesses...

  20. Evaluation of a potential parathyroid dysfunction under treatment with radioactive iodine of benign thyroid diseases; Pruefung einer potentiellen strahleninduzierten Nebenschilddruesenfunktionsstoerung waehrend einer Radioiodtherapie benigner Schilddruesenerkrankung

    Energy Technology Data Exchange (ETDEWEB)

    Schumacher, Serena Christine

    2011-09-28

    The intention of the present thesis was the evaluation of a potential parathyroid dysfunction under treatment with radioactive iodine of benign thyroid diseases. It was to be examined whether a change in the parathyroid function would arise within the first week on treatment. So far there are some minor studies existing describing significant changes in the parathyroid hormone serum level within the first months after radioactive iodine therapy of benign and malignant thyroid diseases. Moreover, it is a fact that external beam-radiotherapy can induce neoplasia and that the risk for the subsequent development of primary hyperparathyroidism doubles or triples after external beam-radiotherapy of the head and neck. Up to now, however, an increased incidence for primary hyperparathyroidism following treatment with radioactive iodine ({sup 131}I) could not be proved. At the department of nuclear medicine of the university hospital Giessen-Marburg GmbH, location Marburg, a prospective cohort study was executed on radioactive iodine therapy of benign thyroid diseases with 105 probands (75 women / 30 men, mean age 60.62 ± 14.3 years). According to their thyroid diseases these 105 probands were classified into following subgroups: thyroid adenoma with 23 patients, multifocal thyroid autonomy with 8 patients, disseminated thyroid autonomy with 37 patients as well as the subgroup Graves' hyperthyroidism (without Graves' ophtalmopathy) and accordingly Graves' disease (with Graves' ophtalmopathy) with 37 patients. The serum level of the intact parathyroid hormone was determined directly before starting the radioactive iodine therapy on the admission day and on day 1, 3 and 5 of the radioactive iodine therapy as well as at the ambulant follow-up examination one month after the start of the therapy. In case of 99 of 105 probands the serum level of parathyroid hormone declined on treatment with {sup 131}I with its nadir on day 3 of therapy (decline by 15.71 ng

  1. Effect of (131)I 'clear residual thyroid tissue' after surgery on the function of parathyroid gland in differentiated thyroid cancer.

    Science.gov (United States)

    Zhao, Zhi-Hua; Li, Feng-Qi; Han, Jian-Kui; Li, Xian-Jun

    2015-12-01

    Thyroid cancer is a common malignant tumor of the endocrine glands. Although surgery is the optimal treatment utilized, the disease is characterized by recurrence and metastasis. The aim of the present study was to determine the effect of iodine-131 ((131)I) 'clear residual thyroid tissue' following surgery on the treatment of differentiated thyroid cancer (DTC) and its effect on the function of the parathyroid gland. A total of 160 patients diagnosed with DTC, who were consecutively admitted to our Hospital between June 2012 and June 2014 and underwent total thyroidectomy or subtotal resection, were included in the present study. After three months, the patients were administered (131)I 'clear residual thyroid tissue' treatment and underwent a whole body scan after 1 week to determine whether 'clear residual thyroid tissue' treatment was successful or not. The treatment was repeated within 3 months if not successful. Of the 160 patients, 24 patients had cancer metastasis (15.0%). The average dose of (131)I used for the first time was 6.4+1.2 GBq and the treatment was successful in 66 cases (41.3%). The average treatment time was 2.8±0.6 therapy sessions. The results showed that, prior to and following the first treatment and at the end of the follow up, levels of the parathyroid hormone, serum calcium and phosphorus were compared, and no statistically significant difference (P>0.05) was observed. There were 5 patients with persistent hypothyroidism and 8 patients with transient hypothyroidism. The levels of thyroglobulin were significantly decreased, and the difference was statistically significant (P<0.05). A total of 48 patients (30%) with hypothyroidism were identified. In conclusion, the results have shown that DTC resection and (131)I 'clear residual thyroid tissue' treatment did not significantly impair the parathyroid function, thereby improving the treatment effect.

  2. Parathyroid gland function after radioiodine ((131)I) therapy for toxic and non-toxic goitre.

    Science.gov (United States)

    Szumowski, Piotr; Abdelrazek, Saeid; Mojsak, Małgorzata; Rogowski, Franciszek; Kociura-Sawicka, Agnieszka; Myśliwiec, Janusz

    2013-01-01

    The therapeutic effect of radioactive iodine ((131)I) on benign goitre consists of the emission of tissue-destructive beta-radiation. Since the range of beta (131)I radiation in tissue can reach 2.4 mm, it can affect the adjacent parathyroid glands. The purpose of this paper is to assess parathyroid function in patients with toxic and non-toxic goitres, up to five years following (131)I therapy. The study sample consisted of 325 patients with benign goitres (220 with toxic nodular goitre (TNG), 25 with non-toxic nodular goitre (NTNG), and 80 with Graves' disease (GD) treated with (131)I. The therapeutic activity of (131)I for each patient was calculated using Marinelli's formula. The serum levels of fT3, fT4, TSH, iPTH and Ca(2+), Ca and phosphates were determined one week before (131)I administration, as well as every two months up to a year following the therapy, and then after three and five years post-treatment. After two months following the administration of (131)I, all the treated patients showed a statistically significant above normal increase in iPTH concentrations (amounting to a value almost twice the norm in patients with TNG), which remained stable up to ten months after treatment, to return to normal level in the following months. In all the patients, Ca(2+), Ca, phosphates concentration remained within normal range throughout the course of the study. The concentrations of fT3 and fT4 quickly returned to normal after (131)I administration, and remained within normal range until the completion of the study. Radioiodine treatment of benign thyroid disorders results in transient (up to ten months after (131)I administration) hyperparathyroidism. The condition does not influence the level of calcium and phosphates concentration in any significant way.

  3. Does the ultrasound dissector improve parathyroid gland preservation during surgery?

    Science.gov (United States)

    Pelizzo, M R; Sorgato, N; Isabella Merante Boschin, I; Marzola, M C; Colletti, P M; Rubello, D

    2014-07-01

    The most common complication of thyroid surgery is hypoparathyroidism, usually temporary. Ischemic injury or parathyroid avulsion are the causes of surgical hypoparathyroidism. We assessed the value of an ultrasound scalpel, the Harmonic Focus(®) (HF), could prevent surgical-related hypoparathyroidism. Patients consecutively undergoing total thyroidectomy using the HF from November 2009 to February 2011 were recruited and their clinical characteristics, type of operation, histology, and postoperative calcium levels (normal range: 2.10-2.55 mMol/l) were recorded. The prevalence of transient and permanent hypocalcemia was calculated for benign vs. malignant diseases and compared with a control group of 147 patients treated surgically in 2005 using manual technique. 139 patients treated by the same surgeon with a total thyroidectomy (41.7% for a malignant disease) were considered. Prevalence of transient hypoparathyroidism (THP) was 45.2% and of definitive hypoparathyroidism (DHP) 1.4%. None of the patients with malignancies were hypocalcemic at 1-year follow-up. In the control group THP was found in 51.7% of cases and DHP in 5.4% (p < 0.001). Use of the ultrasound scalpel improved the likelihood of the parathyroid glands preservation during thyroid surgery. Paradoxically, the HF appears to be more effective in treating malignant disease, i.e. when central node dissection is required. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Effect of Occupational Cadmium Exposure on Parathyroid Gland.

    Science.gov (United States)

    Ibrahim, Khadiga S; Beshir, Safia; Shahy, Eman M; Shaheen, Weam

    2016-06-15

    Cadmium (Cd) is used in many industries. High-level exposure is associated with severe kidney and bone damage. This study investigates the possible effect of occupational cadmium exposure on parathyroid gland and some minerals in workers. Environmental air monitoring of cadmium was done. Serum and urine cadmium levels, kidney function, some minerals, and plasma parathormone were estimated in the studied groups. The exposed workers had significantly higher Cd concentration in serum and urine than controls. The mean levels of plasma parathyroid hormone, serum phosphorus and magnesium were significantly lower among the exposed group. However, the mean levels of serum creatinine and calcium were significantly higher in the same group when compared to referents. There was a significant positive correlation between Cd concentration in the serum and urine for the exposed group. The biological Cd exposure indices correlated positively with serum calcium and negatively with plasma PTH level. The prevalence of musculoskeletal complaints, bone ache, joint pain and muscle spasm were more prevalent among the exposed workers compared with the controls with odds ratio 4.316, 3.053 and 3.103 respectively. Occupational cadmium exposure has an adverse effect on PTH level and serum human minerals.

  5. Osteopontin negatively regulates parathyroid hormone receptor signaling in osteoblasts.

    Science.gov (United States)

    Ono, Noriaki; Nakashima, Kazuhisa; Rittling, Susan R; Schipani, Ernestina; Hayata, Tadayoshi; Soma, Kunimichi; Denhardt, David T; Kronenberg, Henry M; Ezura, Yoichi; Noda, Masaki

    2008-07-11

    Systemic hormonal control exerts its effect through the regulation of local target tissues, which in turn regulate upstream signals in a feedback loop. The parathyroid hormone (PTH) axis is a well defined hormonal signaling system that regulates calcium levels and bone metabolism. To understand the interplay between systemic and local signaling in bone, we examined the effects of deficiency of the bone matrix protein osteopontin (OPN) on the systemic effects of PTH specifically within osteoblastic cell lineages. Parathyroid hormone receptor (PPR) transgenic mice expressing a constitutively active form of the receptor (caPPR) specifically in cells of the osteoblast lineage have a high bone mass phenotype. In these mice, OPN deficiency further increased bone mass. This increase was associated with conversion of the major intertrabecular cell population from hematopoietic cells to stromal/osteoblastic cells and parallel elevations in histomorphometric and biochemical parameters of bone formation and resorption. Treatment with small interfering RNA (siRNA) for osteopontin enhanced H223R mutant caPPR-induced cAMP-response element (CRE) activity levels by about 10-fold. Thus, in addition to the well known calcemic feedback system for PTH, local feedback regulation by the bone matrix protein OPN also plays a significant role in the regulation of PTH actions.

  6. Purification of human parathyroid hormone: recent studies and further observations.

    Science.gov (United States)

    Keutmann, H T; Hendy, G N; Boehnert, M; O'Riordan, J L; Potts, J T

    1978-07-01

    During the isolation of human parathyroid hormone there is an extensive loss of immuno-assayble hormone over the successive extraction steps, due in part to the presence of fragments that are soluble in 4% trichloroacetic acid. These fragments are derived from both the amino- and carboxyl-terminal regions of the hormone. The hormonal fractions precipitated with trichloroacetic acid were further purified by gel filtration and ion-exchange chromatography. At the final ion-exchange purification step, some preparations of the hormone eluted in multiple fractions. When the various components were characterized separately by immunoassay, amino acid composition, enzymic cleavage and partial sequence analysis, they were found to be closely comparable, although the most acidic fraction contained a blocked terminal amino group. Extraction of a number of batches of tissue permitted revision of the amino acid composition of human parathyroid hormone. Biosynthetic studies with labelled amino acids confirmed the absence of tyrosine and the presence of phenylalanine and threonine and localized these residues to definite regions of the molecule.

  7. Experimental induction of parathyroid adenomas in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Wynford-Thomas, V.; Wynford-Thomas, D.; Williams, E.D.

    1983-01-01

    Neonatal inbred Wistar albino rats were given either 5 or 10 microCi radioiodine (/sup 131/I) within 24 hours of birth. After weaning, animals were placed on diets high, normal, or deficient in vitamin D3 (cholecalciferol) for periods up to 2 years. In animals aged 12 months and older, adenomas were found in 0 of 67 unirradiated controls, in 22 of 67 given 5 microCi /sup 131/I, and in 25 of 67 given to microCi /sup 131/I. The incidence of tumors in irradiated animals was highest (55%) in those on a low-vitamin D diet and lowest (20%) in those on a high-vitamin D diet. Plasma calcium levels were significantly increased by the high-vitamin D diet, but the low-vitamin D diet did not lead to any significant decrease as compared to the calcium levels of the normal vitamin D diet group. Small but significant calcium increases were found in tumor-bearing animals. These findings indicate that parathyroid tumors in the rat can be induced by radiation and that their incidence is strongly influenced by dietary vitamin D content. The possibility that metabolites of vitamin D3 may influence parathyroid growth and tumor formation directly is discussed.

  8. Experimental induction of parathyroid adenomas in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Wynford-Thomas, V.; Wynford-Thomas, D.; Williams, E.D.

    1983-01-01

    Neonatal inbred Wistar albino rats were given either 5 or 10 mCi radioiodine (/sup 131/I) within 24 hours of birth. After weaning, animals were placed on diets high, normal, or deficient in vitamin D3 (cholecalciferol) for periods up to 2 years. In animals aged 12 months and older, adenomas were found in 0 of 67 unirradiated controls, in 22 of 67 given 5 mCi /sup 131/I, and in 25 of 67 given 10 mCi /sup 131/I. The incidence of tumors in irradiated animals was highest (55%) in those on a low-vitamin D diet and lowest (20%) in those on a high-vitamin D diet. Plasma calcium levels were significantly increased by the high-vitamin D diet, but the low-vitamin D diet did not lead to any significant decrease as compared to the calcium levels of the normal vitamin D diet group. Small but significant calcium increases were found in tumor-bearing animals. These findings indicate that parathyroid tumors in the rat can be induced by radiation and that their incidence is strongly influenced by dietary vitamin D content. The possibility that metabolites of vitamin D3 may influence parathyroid growth and tumor formation directly is discussed.

  9. Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement

    Science.gov (United States)

    Rubin, Mishaela R.; Bilezikian, John P.

    2013-01-01

    Objective Hypoparathyroidism is a disorder in which parathyroid hormone is deficient in the circulation due most often to immunological destruction of the parathyroids or to their surgical removal. The objective of this work was to define the abnormalities in skeletal microstructure as well as to establish the potential efficacy of PTH(1-84) replacement in this disorder. Subjects and methods Standard histomorphometric and μCT analyses were performed on iliac crest bone biopsies obtained from patients with hypoparathyroidism. Participants were treated with PTH(1-84) for two years. Results Bone density was increased and skeletal features reflected the low turnover state with greater BV/TV, Tb. Wi and Ct. Wi as well as suppressed MS and BFR/BS as compared to controls. With PTH(1-84), bone turnover and bone mineral density increased in the lumbar spine. Requirements for calcium and vitamin D fell while serum and urinary calcium concentrations did not change. Conclusion Abnormal microstructure of the skeleton in hypoparathyroidism reflects the absence of PTH. Replacement therapy with PTH has the potential to correct these abnormalities as well as to reduce the requirements for calcium and vitamin D. PMID:20485912

  10. A mathematical/physiological model of parathyroid hormone secretion in response to blood-ionized calcium lowering in vivo

    DEFF Research Database (Denmark)

    Momsen, G; Schwarz, P

    1997-01-01

    The aim of the present study was to test a mathematical model of the biochemical processes in the parathyroid glands responsible for the secretion of parathyroid hormone resulting from extracellular calcium reduction. A double exponential curve described the parathyroid hormone secretion induced...... plasma and the rate of cellular production/secretion was observed. This could be interpreted as an adaptation of the parathyroid gland's ability to produce parathyroid hormone depending on the average demand from the body....... by rapid lowering of blood-ionized calcium in humans with normal as well as abnormal parathyroid tissue. Our data show that it was possible to establish a simple mathematical model of the parathyroid hormone response to blood-ionized calcium lowering, sufficient to fit experimental data obtained from...

  11. Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism

    Science.gov (United States)

    Komaba, Hirotaka; Nakanishi, Shohei; Fujimori, Akira; Tanaka, Motoko; Shin, Jeongsoo; Shibuya, Koji; Nishioka, Masato; Hasegawa, Hirohito; Kurosawa, Takeshi

    2010-01-01

    Background and objectives: Cinacalcet is effective in reducing serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. However, it has not been proven whether parathyroid gland size predicts response to therapy and whether cinacalcet is capable of inducing a reduction in parathyroid volume. Design, setting, participants, & measurements: This 52-week, multicenter, open-label study enrolled hemodialysis patients with moderate to severe secondary hyperparathyroidism (intact PTH >300 pg/ml). Doses of cinacalcet were adjusted between 25 and 100 mg to achieve intact PTH 30% reduction from baseline (88 versus 78%), but this was not statistically significant. Cinacalcet therapy also resulted in a significant reduction in parathyroid gland volume regardless of pretreatment size, which was in sharp contrast to historical controls (n = 87) where parathyroid gland volume progressively increased with traditional therapy alone. Conclusions: Cinacalcet effectively decreases serum PTH levels and concomitantly reduces parathyroid gland volume, even in patients with marked parathyroid hyperplasia. PMID:20798251

  12. Assessment of parathyroid glands in hemodialysis patients by using color Doppler sonography.

    Science.gov (United States)

    Ozcan, Umit Aksoy; Oktay, Ilay

    2009-11-01

    The aim of this study was to assess the role of color and spectral Doppler ultrasound (CDU) in the evaluation of enlarged parathyroid glands in hemodialysis patients with secondary hyperparathyroidism. Fourteen hemodialysis patients with elevated intact parathyroid hormone (iPTH) levels were evaluated prospectively with CDU. The volume of each observed parathyroid gland and the spectral CDU data (velocities, resistance and pulsatility indices, systolic to diastolic ratio, and flow volume output (FVO)) were noted. The biochemical data (iPTH, calcium, phosphate levels), and CDU results were analyzed with the Spearman correlation test. Two patients were excluded, and 27 enlarged parathyroid glands were observed in 12 patients. The mean total volume of enlarged parathyroid glands per patient was 1.95 cm(3) (0.06-5.5 cm(3)). Arterial supply was demonstrated in 78% (21/27) of enlarged parathyroid glands. Mean total FVO of enlarged glands per patient was 238.5 ml/min (620-0 ml/min) and mean iPTH level was 1,477 pg/ml (643-3,132 pg/ml). The positive correlations of total volume (p = 0.022), iPTH (p = 0.024), and FVO (p = 0.022) were statistically significant. In secondary hyperparathyroidism, total volume of the visualized enlarged parathyroid glands and the total of FVOs per patient are positively correlated with iPTH levels which may help clinical management and follow-up of end-stage renal disease patients.

  13. Spontaneous proliferative and neoplastic lesions in thyroid and parathyroid glands of nondomestic felids.

    Science.gov (United States)

    Pope, Jenny P; Steeil, James; Ramsay, Edward C; Reel, Danielle; Newman, Shelley J

    2017-01-01

    Based on microscopic and immunohistochemical characterization, we documented spontaneous proliferative and neoplastic lesions in the thyroid and parathyroid glands of nondomestic felids. Ten animals (4 leopards, 3 tigers, and 3 cougars), all with a previous diagnosis of thyroid neoplasia were identified from the University of Tennessee College of Veterinary Medicine database. The mean age of affected animals was 15.9 y. Twelve neoplasms were identified; 2 animals had 2 concurrent neoplasms. After immunohistochemical characterization using a panel of chromogranin A, thyroglobulin, and calcitonin, 7 of the former thyroid neoplasms were diagnosed as thyroid adenomas, 1 was diagnosed as a thyroid carcinoma, and 4 were diagnosed as parathyroid adenomas. No thyroid medullary neoplasms (C-cell tumors) were diagnosed in the current study. Most of the diagnosed neoplasms were benign (11 of 12), and metastasis was not documented in the single carcinoma. Only 2 animals were suspected to have functional neoplasms (1 thyroid adenoma and 1 parathyroid adenoma), based on associated tissue lesions or serum biochemistry. Other documented lesions in the thyroid and parathyroid glands included thyroid nodular hyperplasia ( n = 7), parathyroid hyperplasia associated with chronic renal disease ( n = 2), a thyroid abscess, and a branchial cyst. Parathyroid adenomas were more commonly diagnosed than expected in comparison with domestic cats. We demonstrated that an immunohistochemistry panel for thyroglobulin, calcitonin, and chromogranin A can be used to differentiate neoplasms of thyroid from parathyroid origin in nondomestic felids.

  14. Location, number and morphology of parathyroid glands: results from a large anatomical series.

    Science.gov (United States)

    Lappas, Dimitrios; Noussios, George; Anagnostis, Panagiotis; Adamidou, Fotini; Chatzigeorgiou, Antonios; Skandalakis, Panagiotis

    2012-09-01

    Surgical management of parathyroid gland disease may sometimes be difficult, due mainly to the surgeon's failure to successfully detect parathyroids in unusual locations. The records of 942 cadavers (574 men and 368 women) who underwent autopsy in the Department of Forensic Medicine in Athens during the period 1988-2009 were reviewed. In total, 3,796 parathyroid glands were resected and histologically verified. Parathyroid glands varied in number. In 47 cases (5 %), one supernumerary (fifth) parathyroid was found, while in 19 cases (2 %) three parathyroid glands found. Superior glands were larger than inferior ones. However, there was no significant difference between the genders with respect to gland size. In 324 (8.5 %) out of 3,796, the glands were detected in an ectopic location: 7 (0.2 %) in the thyroid parenchyma, 79 (2 %) in different sites in the neck and 238 (6.3 %) in the mediastinum, 152 (4.1 %) of which were found in the upper and 86 (2.2 %) in the lower mediastinum. Significant anatomical variations of normal parathyroid glands may exist regarding number and location-knowledge that is essential for their successful identification and surgical management.

  15. Intrathyroidal Parathyroid Carcinoma: Report of an Unusual Case and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Lizette Vila Duckworth

    2013-01-01

    Full Text Available Intrathyroidal parathyroid carcinoma is an exceedingly rare cause of primary hyperparathyroidism. A 51-year-old African American female presented with goiter, hyperparathyroidism, and symptomatic hypercalcemia. Sestamibi scan revealed diffuse activity within an enlarged thyroid gland with uptake in the right thyroid lobe suggestive of hyperfunctioning parathyroid tissue. The patient underwent thyroidectomy and parathyroidectomy. At exploration, a 2.0 cm nodule in the usual location of the right inferior parathyroid was sent for intraoperative frozen consultation, which revealed only ectopic thyroid tissue. No parathyroid glands were identified grossly on the external aspect of the thyroid. Interestingly, postoperative parathyroid hormone levels normalized after removal of the thyroid gland. Examination of the thyroidectomy specimen revealed a 1.4 cm parathyroid nodule located within the parenchyma of the right superior thyroid, with capsular and vascular invasion and local infiltration into surrounding thyroid tissue. We present only the eighth reported case of intrathyroidal parathyroid carcinoma and review the literature.

  16. Endogenous parathyroid hormone-related protein compensates for the absence of parathyroid hormone in promoting bone accrual in vivo in a model of bone marrow ablation.

    Science.gov (United States)

    Zhu, Qi; Zhou, Xichao; Zhu, Min; Wang, Qian; Goltzman, David; Karaplis, Andrew; Miao, Dengshun

    2013-09-01

    To assess the effect of hypoparathyroidism on osteogenesis and bone turnover in vivo, bone marrow ablation (BMXs) were performed in tibias of 8-week-old wild-type and parathyroid hormone-null (PTH(-/-)) mice and newly formed bone tissue was analyzed from 5 days to 3 weeks after BMX. At 1 week after BMX, trabecular bone volume, osteoblast numbers, alkaline phosphatase-positive areas, type I collagen-positive areas, PTH receptor-positive areas, calcium sensing receptor-positive areas, and expression of bone formation-related genes were all decreased significantly in the diaphyseal regions of bones of PTH(-/-) mice compared to wild-type mice. In contrast, by 2 weeks after BMX, all parameters related to osteoblastic bone accrual were increased significantly in PTH(-/-) mice. At 5 days after BMX, active tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts had appeared in wild-type mice but were undetectable in PTH(-/-) mice, Both the ratio of mRNA levels of receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) and TRAP-positive osteoclast surface were still reduced in PTH(-/-) mice at 1 week but were increased by 2 weeks after BMX. The expression levels of parathyroid hormone-related protein (PTHrP) at both mRNA and protein levels were upregulated significantly at 1 week and more dramatically at 2 weeks after BMX in PTH(-/-) mice. To determine whether the increased newly formed bones in PTH(-/-) mice at 2 weeks after BMX resulted from the compensatory action of PTHrP, PTH(-/-) PTHrP(+/-) mice were generated and newly formed bone tissue was compared in these mice with PTH(-/-) and wild-type mice at 2 weeks after BMX. All parameters related to osteoblastic bone formation and osteoclastic bone resorption were reduced significantly in PTH(-/-) PTHrP(+/-) mice compared to PTH(-/-) mice. These results demonstrate that PTH deficiency itself impairs osteogenesis, osteoclastogenesis, and osteoclastic bone resorption, whereas subsequent upregulation of PTHr

  17. Lesion localization in patients with hyperparathyroidism using double-phase Tc-99m MIBI parathyroid scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jung Woo; Ryu, Jin Sook; Kim, Jae Seung; Moon, Dae Hyuk; Hong, Seung Mo; Gong, Gyung Yub; Hong, Suk Joon; Lee, Hee Kyung [College of Medicine, Ulsan Univ., Seoul (Korea, Republic of)

    1999-02-01

    This study was performed to evaluate the diagnostic usefulness of double-phase Tc-99m MIBI parathyroid scintigraphy with single photon emission computed tomography (SPECT) in patients with hyperparathyroidism. We also evaluated the relationship between Tc-99m MIBI uptake and oxyphil cell contents in parathyroid glands. The subjects were 28 parathyroid glands of 10 patients who underwent Tc-99m MIBI parathyroid scintigraphy and parathyroidectomy for clinically suspected hyperparathyroidism. Early and delayed pinhole images were obtained at 15 minutes and 2 hours after injection of Tc-99m MIBI, and SPECT images were followed. The weight and oxyphil cell contents of parathyroid tissue were obtained from pathologic specimen, and the scintigraphic findings were compared with histopathology. In surgical histopathology, 6 parathyroid adenomas and 9 parathyroid hyperplasias were confirmed. The sensitivity, specificity, and positive predictive value of early and delayed images were 46.7% (7/15), 76.9% (10/13), 70% (7/10) and 66.7% (10/15), 92.3% (12/13), 90.9% (10/11), respectively. SPECT image detected an additional small hyperplasia. The sensitivity, specificity, and positive predictive value of combined interpretation of early and delayed images with SPECT were 73.3% (11/15), 100% (13/13), 100% (11/11). The sensitivity was 100% (6/6) for adenoma, whereas that was 55.5% (5/9) for hyperplasia. Both adenomas and hyperplasias showed significantly increased oxyphil cell contents compared with normal parathyroid glands (p<0.0001), but the oxyphil cell content and weight were not significantly different between adenomas and hyperplasias. Double-phase Tc-99m MIBI parathyroid scintigraphy with SPECT is useful for lesion localization in patients with hyperparathyroidism. Although both adenoma and hyperplasia have increased oxyphil cell content, the sensitivity is high in adenoma, but low in hyperplasia.

  18. Let-7 and MicroRNA-148 Regulate Parathyroid Hormone Levels in Secondary Hyperparathyroidism.

    Science.gov (United States)

    Shilo, Vitali; Mor-Yosef Levi, Irit; Abel, Roy; Mihailović, Aleksandra; Wasserman, Gilad; Naveh-Many, Tally; Ben-Dov, Iddo Z

    2017-03-15

    Secondary hyperparathyroidism commonly complicates CKD and associates with morbidity and mortality. We profiled microRNA (miRNA) in parathyroid glands from experimental hyperparathyroidism models and patients receiving dialysis and studied the function of specific miRNAs. miRNA deep-sequencing showed that human and rodent parathyroids share similar profiles. Parathyroids from uremic and normal rats segregated on the basis of their miRNA expression profiles, and a similar finding was observed in humans. We identified parathyroid miRNAs that were dysregulated in experimental hyperparathyroidism, including miR-29, miR-21, miR-148, miR-30, and miR-141 (upregulated); and miR-10, miR-125, and miR-25 (downregulated). Inhibition of the abundant let-7 family increased parathyroid hormone (PTH) secretion in normal and uremic rats, as well as in mouse parathyroid organ cultures. Conversely, inhibition of the upregulated miR-148 family prevented the increase in serum PTH level in uremic rats and decreased levels of secreted PTH in parathyroid cultures. The evolutionary conservation of abundant miRNAs in normal parathyroid glands and the regulation of these miRNAs in secondary hyperparathyroidism indicates their importance for parathyroid function and the development of hyperparathyroidism. Specifically, let-7 and miR-148 antagonism modified PTH secretion in vivo and in vitro, implying roles for these specific miRNAs. These findings may be utilized for therapeutic interventions aimed at altering PTH expression in diseases such as osteoporosis and secondary hyperparathyroidism.

  19. Technetium-99m tetrofosmin parathyroid imaging in patients with primary hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Hiromatsu, Yuji; Ishibashi, Masatoshi; Nishida, Hidemi; Okuda, Seiya; Miyake, Ikuyo [Kurume Univ., Fukuoka (Japan). School of Medicine

    2000-02-01

    To confirm the clinical significance of {sup 99m}Tc-tetrofosmin imaging for the localization of hyperfunctioning parathyroid glands in patients with primary hyperparathyroidism. All patients were imaged with {sup 99m}Tc-tetrofosmin at 10 minutes and 2 hours after radiotracer injection, and with ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI). The parathyroid/ thyroid uptake ratio of {sup 99m}Tc-tetrofosmin (P/T uptake ratio) was calculated. Twenty patients with primary hyperparathyroidism were referred to our clinic, underwent surgical neck exploration or mediastinotomy and were diagnosed as having parathyroid adenoma. These patients were investigated for the preoperative localization by {sup 99m}Tc-tetrofosmin scintigraphy. {sup 99m}Tc-tetrofosmin imaging demonstrated focal uptake in 19 out of 20 patients with parathyroid adenoma. Two of the lesions were ectopic. US identified 17 parathyroid glands. CT and MRI initially detected 17 parathyroid glands. However, two additional parathyroid glands were localized on repeated CT and MRI in tandem with the results of the {sup 99m}Tc-tetrofosmin imaging. Thus, the sensitivity and specificity of tetrofosmin imaging were 95% (19/20) and 95% (19/20); US, 85% (17/20) and 94% (16/17); initial CT, 85% (17/20) and 94% (16/17); and initial MRI, 88% (17/20) and 94% (16/17), respectively. The P/T uptake ratio at 2 hours after tetrofosmin injection was correlated with the serum concentration of intact parathyroid hormone (PTH) (rs=0.47, p<0.05) and the resected tumor weight (rs=0.53, p<0.05). {sup 99m}Tc-tetrofosmin scintigraphy is useful for localization of parathyroid adenoma. Tetrofosmin uptake depends on the tumor weight and serum intact PTH levels. (author)

  20. Parathyroid scintigraphy findings in chronic kidney disease patients with recurrent hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Hindie, Elif [Universite Paris 7, Nuclear Medicine, Hopital Saint Louis, Paris (France); Hopital Saint-Louis, Service de Medecine Nucleaire, Paris (France); Zanotti-Fregonara, Paolo; Keller, Isabelle [Universite Paris VI, Nuclear Medicine, Hopital Saint Antoine, Paris (France); Just, Pierre-Alexandre; Toubert, Marie-Elisabeth; Moretti, Jean-Luc [Universite Paris 7, Nuclear Medicine, Hopital Saint Louis, Paris (France); Sarfati, Emile [Universite Paris 7, Endocrine Surgery, Hopital Saint Louis, Paris (France); Melliere, Didier [Universite Paris XII, Endocrine Surgery, Hopital Henri Mondor, Creteil (France); Jeanguillaume, Christian [Universite d' Angers, Centre Paul Papin, Angers (France); Urena-Torres, Pablo [Clinique du Landy, Service de Nephrologie-Dialyse, Saint Ouen (France)

    2010-03-15

    Parathyroidectomy (PTX), either subtotal or total with forearm autografting, is a well-established treatment for refractory renal hyperparathyroidism (RHPT). However, 20-30% of patients develop persistent or recurrent disease. Obtaining accurate localization before reoperation is difficult. The study group comprised 21 consecutive adult patients (18 undergoing haemodialysis and 3 with a renal graft) imaged using {sup 99m}Tc-sestamibi/{sup 123}I subtraction scintigraphy. Of the 21 patients, 12 had undergone one previous PTX and the other 9 between two and four parathyroid operations. All patients had symptoms and signs of severe RHPT. The mean serum PTH level was 1,142 pg/ml. {sup 99m}Tc-Sestamibi and {sup 123}I images were recorded simultaneously. Imaging views comprised a planar view of the neck and mediastinum, followed by a magnified pinhole view over the thyroid bed area. If parathyroid ectopy was detected, SPECT or SPECT-CT was performed. The forearm was imaged in case of autograft. Parathyroid scintigraphy was negative in one patient and positive in the other 20 (sensitivity 95.2%). One patient had uptake corresponding to two unresected parathyroid glands. Recurrence at the site of the partially resected gland or autograft was seen in 11 patients. However, six of them had a second {sup 99m}Tc-sestamibi focus corresponding to a supernumerary parathyroid gland. Seven other patients had a supernumerary parathyroid gland as the sole cause of relapse. Three of the supernumerary glands showed major ectopy (intrathyroidal, low mediastinal, undescended within the vagus nerve). One patient had parathyromatosis with multiple parathyroid nodules scattered over the left side of the neck. Reoperation was possible in 13 patients, with no false-positive findings. Many patients referred with the hypothesis of hyperplasia of a subtotally resected parathyroid gland or autograft were found to harbour a supernumerary parathyroid gland missed at the initial surgery. (orig.)

  1. Switch from calcitriol to paricalcitol in secondary hyperparathyroidism of hemodialysis patients: Responsiveness is related to parathyroid gland size.

    Science.gov (United States)

    Vulpio, Carlo; Maresca, Giulia; Distasio, Enrico; Cacaci, Silvia; Panocchia, Nicola; Luciani, Giovanna; Bossola, Maurizio

    2011-01-01

    Paricalcitol is more effective than calcitriol in hemodialysis patients (HD) with secondary hyperparathyroidism (SHPT), but it is not effective in some of them. We have investigated the relationship between paricalcitol responsiveness and parathyroid gland (PTG) size. Thirty HD with SHPT treated previously with calcitriol for at least 6 months were switched to paricalcitol (1:4 conversion ratio). Parathyroid gland number and size (maximum longitudinal diameter [MLD] of largest PTG) was measured by ultrasonography. Patients were divided into 2 groups: group A (MLD ≤9.0 mm [17 HD]); and group B (MLD >9.0 mm [13 HD]). They were defined responder if both the last 2 monthly determinations of inhibit parathyroid hormone (iPTH) were within the target (<300 pg/mL) according to National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommendations. Twenty-six and 20 HD completed 6-month and 12-month paricalcitol therapy, respectively. After 6 months of paricalcitol treatment, 23.5% HD of group A and 7.7% of group B were responders. At 12 months, 41.2 % of group A and 7.7% of group B were responders. Throughout paricalcitol therapy, serum calcium and phosphorus concentrations slightly increased in all HD but more significantly in group B. The baseline iPTH and MLD of the largest PTG were significantly correlated with final iPTH levels. Paricalcitol is more effective than calcitriol in SHPT, but the responsiveness to paricalcitol and hypercalcemia are related to PTG size. The measurement of MLD by ultrasonography may be useful for predicting responsiveness to paricalcitol, avoiding an unnecessary and expensive therapy. © 2011 The Authors. Hemodialysis International © 2011 International Society for Hemodialysis.

  2. Association between long-term efficacy of cinacalcet and parathyroid gland volume in haemodialysis patients with secondary hyperparathyroidism.

    Science.gov (United States)

    Tanaka, Motoko; Nakanishi, Shohei; Komaba, Hirotaka; Itoh, Kazuko; Matsushita, Kazutaka; Fukagawa, Masafumi

    2008-08-01

    Purpose. Secondary hyperparathyroidism with nodular hyperplasia is resistant to medical therapies. Cinacalcet is an effective treatment for severe secondary hyperparathyroidism. This multicentre retrospective study was designed to determine the long-term efficacy of cinacalcet in patients with nodular hyperplasia, the advanced type of parathyroid hyperplasia. Subjects and methods. The study subjects were 20 haemodialysis patients with secondary hyperparathyroidism. Patients with ultrasonographically confirmed large parathyroid glands (volume >0.5 cm(3)) were considered to have nodular hyperplasia (n = 8). Cinacalcet was started at the dose of 25 mg/day and titrated up to 100 mg/day to achieve the target intact-parathyroid hormone (iPTH) level of <250 pg/ml. Serum iPTH, corrected calcium, serum phosphorus, calcium × phosphorus product were measured and compared over the 48-week period of treatment with cinacalcet in all 20 patients and over 120 weeks in 6 of the patients (2 with nodular hyperplasia and 4 with non-nodular hyperplasia). We also examined the achievement rate of K/DOQI guideline treatment targets. The dosages of vitamin D preparation, sevelamer hydrochloride and calcium- containing phosphate binder were adjusted for the above target values. Results. iPTH levels were significantly lower at 48 weeks in both groups. However, corrected calcium levels, serum phosphorus levels and calcium phosphorus products were within the target values in the non-nodular hyperplasia group (n = 12), while the target value could not be achieved in the nodular hyperplasia group. In the long-term follow-up group, the levels of iPTH, corrected calcium, serum phosphorus and calcium × phosphorus products were significantly higher in nodular hyperplasia than in non-nodular hyperplasia. Conclusion. Our study suggests that cinacalcet lacks long-term efficacy in nodular hyperplasia, especially for controlling serum calcium and phosphorus levels.

  3. Association between long-term efficacy of cinacalcet and parathyroid gland volume in haemodialysis patients with secondary hyperparathyroidism

    Science.gov (United States)

    Tanaka, Motoko; Nakanishi, Shohei; Komaba, Hirotaka; Itoh, Kazuko; Matsushita, Kazutaka; Fukagawa, Masafumi

    2008-01-01

    Purpose. Secondary hyperparathyroidism with nodular hyperplasia is resistant to medical therapies. Cinacalcet is an effective treatment for severe secondary hyperparathyroidism. This multicentre retrospective study was designed to determine the long-term efficacy of cinacalcet in patients with nodular hyperplasia, the advanced type of parathyroid hyperplasia. Subjects and methods. The study subjects were 20 haemodialysis patients with secondary hyperparathyroidism. Patients with ultrasonographically confirmed large parathyroid glands (volume >0.5 cm3) were considered to have nodular hyperplasia (n = 8). Cinacalcet was started at the dose of 25 mg/day and titrated up to 100 mg/day to achieve the target intact-parathyroid hormone (iPTH) level of <250 pg/ml. Serum iPTH, corrected calcium, serum phosphorus, calcium × phosphorus product were measured and compared over the 48-week period of treatment with cinacalcet in all 20 patients and over 120 weeks in 6 of the patients (2 with nodular hyperplasia and 4 with non-nodular hyperplasia). We also examined the achievement rate of K/DOQI guideline treatment targets. The dosages of vitamin D preparation, sevelamer hydrochloride and calcium- containing phosphate binder were adjusted for the above target values. Results. iPTH levels were significantly lower at 48 weeks in both groups. However, corrected calcium levels, serum phosphorus levels and calcium phosphorus products were within the target values in the non-nodular hyperplasia group (n = 12), while the target value could not be achieved in the nodular hyperplasia group. In the long-term follow-up group, the levels of iPTH, corrected calcium, serum phosphorus and calcium × phosphorus products were significantly higher in nodular hyperplasia than in non-nodular hyperplasia. Conclusion. Our study suggests that cinacalcet lacks long-term efficacy in nodular hyperplasia, especially for controlling serum calcium and phosphorus levels. PMID:25983974

  4. Preoperative localization of hyperfunctioning parathyroid glands with 4D-CT

    DEFF Research Database (Denmark)

    Lundstroem, Anke Katrin; Trolle, Waldemar; Soerensen, Christian Hjort

    2016-01-01

    the diagnostic value of four-dimensional computed tomography (4D-CT) as a preoperative imaging tool in relation to the localization of pathologic parathyroid glands in patients with pHPT and negative sestamibi scans. This study included 43 consecutive patients with pHPT referred for parathyroidectomy...... available as references for the accuracy of this imaging tool. Hyperfunctioning parathyroid glands were found in 40 patients. 4D-CT identified 32 solitary hyperfunctioning parathyroid glands located on the correct side of the neck (PPV 76 %) and 21 located within the correct quadrant (PPV 49 %). Unilateral...

  5. Nonfunctional Metastatic Parathyroid Carcinoma in the Setting of Multiple Endocrine Neoplasia Type 2A Syndrome

    Directory of Open Access Journals (Sweden)

    María Posada-González

    2014-01-01

    Full Text Available Parathyroid carcinoma is a very rare malignancy. It has been associated with hyperparathyroidism-jaw tumour syndrome, familial isolated primary hyperparathyroidism, and multiple endocrine neoplasia type 1 (MEN-1 and 2A (MEN-2A syndromes. We report a 54-year-old man with a MEN-2A which presents with a nonfunctional metastatic parathyroid carcinoma and a pheochromocytoma in the absence of medullary thyroid carcinoma. Only a few cases of parathyroid carcinoma have been reported in the literature associated with this syndrome.

  6. Primary hyperparathyroidism due to an intrathyroidal parathyroid adenoma associated with chronic lymphocytic thyroiditis.

    Science.gov (United States)

    Cating-Cabral, Monica Therese; Cabungcal, Arsenio Claro; Villafuerte, Cesar Vincent; Añel-Quimpo, Joselynna

    2012-06-08

    This is a case of a 44-year-old woman with an anterior neck mass and hypothyroidism who presented with an incidental finding of an elevated serum calcium level and was found to have primary hyperparathyroidism and osteoporosis. During surgical exploration no parathyroid adenoma was found, although a nodule was palpated within the right thyroid lobe. Examination of the excised right thyroid lobe revealed an intrathyroidal parathyroid adenoma and chronic lymphocytic thyroiditis. After surgery, she did not develop severe hypocalcaemia and this was attributed to preoperative treatment with pamidronate. In the months following surgery, parathyroid hormone remained undetectable.

  7. Increased protein kinase A type Iα regulatory subunit expression in parathyroid gland adenomas of patients with primary hyperparathyroidism.

    Science.gov (United States)

    Hibi, Yatsuka; Kambe, Fukushi; Imai, Tsuneo; Ogawa, Kimio; Shimizu, Yoshimi; Shibata, Masahiro; Kagawa, Chikara; Mizuno, Yutaka; Ito, Asako; Iwase, Katsumi

    2013-01-01

    Protein kinase A (PKA) regulatory subunit type Iα (RIα) is a major regulatory subunit that functions as an inhibitor of PKA kinase activity. We have previously demonstrated that elevated RIα expression is associated with diffuse-to-nodular transformation of hyperplasia in parathyroid glands of renal hyperparathyroidism. The aim of the current study was to determine whether or not RIα expression is increased in adenomas of primary hyperparathyroidism (PHPT), because monoclonal proliferation has been demonstrated in both adenomas and nodular hyperplasia. Surgical specimens comprising 22 adenomas and 11 normal glands, obtained from 22 patients with PHPT, were analyzed. Western blot and immunohistochemical analyses were employed to evaluate RIα expression. PKA activities were determined in several adenomas highly expressing RIα. RIα expression was also separately evaluated in chief and oxyphilic cells using the "Allred score" system. Expression of proliferating cell nuclear antigen (PCNA), a proliferation marker, was also immunohistochemically examined. Western blot analysis revealed that 5 out of 8 adenomas highly expressed RIα, compared with normal glands. PKA activity in adenomas was significantly less than in normal glands. Immunohistochemical analysis further demonstrated high expression of RIα in 20 out of 22 adenomas. In adenomas, the greater RIα expression and more PCNA positive cells were observed in both chief and oxyphilic cells. The present study suggested that high RIα expression could contribute to monoclonal proliferation of parathyroid cells by impairing the cAMP/PKA signaling pathway.

  8. Parathyroid hormone pulsatility:physiological and clinical aspects

    Institute of Scientific and Technical Information of China (English)

    Silvia Chiavistelli; Andrea Giustina; Gherardo Mazziotti

    2015-01-01

    Parathyroid hormone (PTH) secretion is characterized by an ultradian rhythm with tonic and pulsatile components. In healthy subjects, the majority of PTH is secreted in tonic fashion, whereas approximately 30%is secreted in low-amplitude and high-frequency bursts occurring every 10–20 min, superimposed on tonic secretion. Changes in the ultradian PTH secretion were shown to occur in patients with primary and secondary osteoporosis, with skeletal effects depending on the reciprocal modifications of pulsatile and tonic components. Indeed, pathophysiology of spontaneous PTH secretion remains an area potentially suitable to be explored, particularly in those conditions such as secondary forms of osteoporosis, in which conventional biochemical and densitometric parameters may not always give reliable diagnostic and therapeutic indications. This review will highlight the literature data supporting the hypothesis that changes of ultradian PTH secretion may be correlated with skeletal fragility in primary and secondary osteoporosis.

  9. Compliance and persistence with treatment with parathyroid hormone for osteoporosis

    DEFF Research Database (Denmark)

    Thorsteinsson, Anne-Luise; Vestergaard, Peter; Eiken, Pia

    2015-01-01

    UNLABELLED: Medical intervention is important in the treatment of osteoporosis, and compliance with medical treatment is essential for an optimal outcome. Based on Danish national registers, we found that compliance with parathyroid hormone (PTH) treatment is high and associated with marital status......, working status, and type of PTH treatment. PURPOSE: Compliance and persistence are essential for an optimal outcome during medical treatment of osteoporosis. We aimed to evaluate compliance and persistence with treatment with PTH in daily clinical practice in Danish patients and to describe factors...... affecting compliance. METHODS: Register-based nationwide cohort study on all patients in Denmark initiates PTH or analogue treatment for osteoporosis in 2003-2010 (n = 4281). PTH drugs included were the PTH analogue teriparatide(1-34) and recombinant human PTH (rhPTH(1-84)). Compliance with treatment...

  10. Parathyroid carcinoma masquerading as morning sickness in pregnancy.

    Science.gov (United States)

    Panchani, Roopal; Varma, Tarun; Goyal, Ashutosh; Tripathi, Sudhir

    2013-10-01

    Incidence of primary hyperparathyroidism (PHP) in pregnancy is 8/100,000 population/year with less than 200 cases reported. Physiological changes associated with pregnancy make a diagnosis of PHP difficult and 80% are asymptomatic. High index of suspicion is required as physiological hypocalcemia related to hemodilution, increased glomerular filtration rate resulting in maternal hypercalciuria and gestational hypoalbuminemia can mask hypercalcemia of PHP. Maternal and fetal complication rates are high. Early recognition followed by appropriate management and treatment significantly reduces complications. Here, we present a rare case of parathyroid carcinoma in pregnancy and highlight the difficulties in diagnosis given the non-specific symptoms related to hypercalcemia. We have also discussed the management of PHP during the pregnancy. PHP is a preventable cause of fetal and maternal morbidity and mortality.

  11. Parathyroid carcinoma masquerading as morning sickness in pregnancy

    Directory of Open Access Journals (Sweden)

    Roopal Panchani

    2013-01-01

    Full Text Available Incidence of primary hyperparathyroidism (PHP in pregnancy is 8/100,000 population/year with less than 200 cases reported. Physiological changes associated with pregnancy make a diagnosis of PHP difficult and 80% are asymptomatic. High index of suspicion is required as physiological hypocalcemia related to hemodilution, increased glomerular filtration rate resulting in maternal hypercalciuria and gestational hypoalbuminemia can mask hypercalcemia of PHP. Maternal and fetal complication rates are high. Early recognition followed by appropriate management and treatment significantly reduces complications. Here, we present a rare case of parathyroid carcinoma in pregnancy and highlight the difficulties in diagnosis given the non-specific symptoms related to hypercalcemia. We have also discussed the management of PHP during the pregnancy. PHP is a preventable cause of fetal and maternal morbidity and mortality.

  12. Parathyroid hormone related protein (PTHrP) in tumor progression.

    Science.gov (United States)

    Kremer, Richard; Li, Jiarong; Camirand, Anne; Karaplis, Andrew C

    2011-01-01

    Parathyroid hormone-related protein (PTHrP) is widely expressed in fetal and adult tissues and is a key regulator for cellular calcium transport and smooth muscle cell contractility, as well as a crucial control factor in cell proliferation, development and differentiation. PTHrP stimulates or inhibits apoptosis in an autocrine/paracrine and intracrine fashion, and is particularly important for hair follicle and bone development, mammary epithelial development and tooth eruption. PTHrP's dysregulated expression has traditionally been associated with oncogenic pathologies as the major causative agent of malignancy-associated hypercalcemia, but recent evidence revealed a driving role in skeletal metastasis progression. Here, we demonstrate that PTHrP is also closely involved in breast cancer initiation, growth and metastasis through mechanisms separate from its bone turnover action, and we suggest that PTHrP as a facilitator of oncogenes would be a novel target for therapeutic purposes.

  13. Parathyroid hormone dependent T cell proliferation in uremic rats

    DEFF Research Database (Denmark)

    Lewin, E; Ladefoged, Jens; Brandi, L

    1993-01-01

    Chronic renal failure (CRF) is combined with an impairment of the immune system. The T cell may be a target for the action of parathyroid hormone (PTH). Rats with CRF have high blood levels of PTH. Therefore, the present investigation examined some aspects of the T cell function in both normal...... and CRF rats before and after parathyroidectomy and after an isogenic kidney transplantation. The T cell proliferative response to phytohemagglutinin (PHA) stimulation was significantly higher in peripheral blood mononuclear cell (PBMC) cultures obtained from CRF rats than from normal rats. After...... parathyroidectomy the T cells of normal as well as of uremic rats could still be significantly stimulated by PHA, but now no significant difference was seen. When CRF was reversed after an isogenic kidney transplantation and PTH reversed to levels in the normal range, the T cell proliferative response to PHA...

  14. HISTOLOGICAL SEXUAL DIFFERENCES IN ADULT HUMAN PARATHYROID GLANDS

    Directory of Open Access Journals (Sweden)

    Fating Anita

    2014-07-01

    Full Text Available CONTEXT (BACKGROUND: Increasing problems of calcium deficiency with physiological conditions like pregnancy, lactation etc. it becomes the need of time to focus attention towards these glands as one of the essential entity. Hence we have undertaken this study to have an idea about normal variation in the gland as per sex. AIMS: To reveal sexual differences in adult human parathyroid glands. METHODS AND MATERIAL: Parathyroid glands from 25 autopsied cases of 20 to 59 years were studied after staining with Hematoxylin & Eosin, Masson’s Trichrome & Reticulin stains. STATISTICAL ANALYSIS: Data is analyzed on statistical software intercooled STATA version 8.0. Data was presented in mean± standard deviation & categorical variables were expressed in percentages. Comparison of oxyphil scores in male & female was done by unpaired‘t’ test. P < 0.05 was taken as statistical significance. RESULTS: Stroma composed of short often branching reticular fibres along with blood vessels and fat cells. By statistical examination the amount of fat was more in case of females than in males of same age groups. Oxyphil cells being less numerous than chief cells were distinguished by their dark eosinophilic, granular cytoplasm and were arranged mostly in closely packed groups without interstitial fat in between the cells. Oxyphil cells also found as placed singly among chief cells. It was also observed as continuous masses or anastomosing columns. As compared with males oxyphil cells are more in females. CONCLUSIONS: By statistical analysis 1 Percentage of stromal fat in case of females was slightly greater than in males of same age group. 2 The score of oxyphil cells in females was double to more than triple as compared to male score of same age group. 3 This study is clinically important as hormonal changes occurs early in females than in males and it is in favor of providing supplementary calcium with D3 along with minimal dose of estrogen as age advances in

  15. Contrast Agent Ultrasonography before and after HIFU Treatment of Parathyroid Glands

    Science.gov (United States)

    Kovatcheva, Roussanka; Arnaud, Françoise; Lacoste, François

    2010-03-01

    OBJECTIVES: To observe changes in the parathyroid tissue treated by extracorporeal HIFU. MATERIAL AND METHODS: 5 patients were treated for primary hyperparathyroidism by thermally ablating enlarged parathyroid glands using an external HIFU applicator. The treated glands were visualized with B-Mode and contrast enhanced ultrasonography (CEUS) before, 1 week and 4 weeks post HIFU. Serum iPTH, calcium, and phosphorus levels were monitored before and after the treatment. RESULTS: The initial results showed a correlation between contrast agent uptake of treated parathyroid tissue, the reduction of volume of the gland and the decrease of iPTH levels. CONCLUSIONS These results show it is possible to use CEUS to monitor the thermal ablation of parathyroid glands.

  16. PRELIMINARY APPLICATION OF COLOR DOPPLER FLOW IMAGING IN THE LOCALIZATION OF PARATHYROID ADENOMAS

    Institute of Scientific and Technical Information of China (English)

    张缙熙; 李建初

    1994-01-01

    From December 1991 to April 1993,we performed color Doppler flow imaging(CDFI) in 11 patients with parathyroid adenoma,and all cases were confirmed by toperation and pathology.In all the parathyroid adenomas,vessels were clearly revealed at the periphery of the upper pole and /or anterior periphery,where arterial signals were elicited.These arteries had branches into the adenomas and originated from inferior thyroid arteries on the same side in most cases.The internal flow signals were increased markedly as compared to normal thyroid,and high-velocity arterial signals were detected.Because of the thyroid's rich blood supply and landmark peripheral vessels.CDFI can distinguish parathyroid foci from thyroid nodules,lymph nodes,and normal tissues and provide a sound basis for the diagnosis of small parathyroid foci.

  17. Epigenetic Methylation of Parathyroid CaR and VDR Promoters in Experimental Secondary Hyperparathyroidism

    DEFF Research Database (Denmark)

    Hofman-Bang, Jacob; Gravesen, Eva; Olgaard, Klaus

    2012-01-01

    R in parathyroid cultures decreases rapidly. Methylation of promoter regions is often detected during epigenetic downregulation of gene expression. Therefore, using an experimental rat model, we examined changes in methylation levels of parathyroid CaR and VDR promoters in vivo and in vitro. Methods. Uremia...... was induced by 5/6 nephrectomy. Melting temperature profiling of CaR and VDR PCR products after bisulfite treatment of genomic DNA from rat parathyroids was performed. Real-time PCR measured expression of PTH, CaR, VDR, and klotho genes in vitro. Results. Parathyroids from uremic rats had similar low levels...... of methylation in vivo and in vitro. In culture, a significant downregulation of CaR, VDR, and klotho within two hours of incubation was observed, while housekeeping genes remained stable for 24 hours. Conclusion. In uremic s-HPT and in vitro, no overall changes in methylation levels in the promoter regions...

  18. Modulation of experimental renal dysfunction of hereditary fructose intolerance by circulating parathyroid hormone.

    Science.gov (United States)

    Morris, R C; McSherry, E; Sebastian, A

    1971-01-01

    In a woman with hereditary fructose intolerance and intact parathyroid function, the experimental administration of fructose at different dosage schedules invariably induced the dose-dependent, complex dysfunction of the proximal renal tubule now recognized as characteristic. But in a woman with hereditary fructose intolerance and hypoparathyroidism given similar amounts of fructose, the experimental dysfunction was strikingly attenuated or nondemonstrable unless or until fructose and parathyroid hormone were administered in sustained combination. Thereupon, a renal dysfunction of characteristic type and severity occurred invariably and almost immediately. Thus, the concentration of circulating parathyroid hormone can modulate the functional expression of the experimental renal disorder. This effect of parathyroid hormone, which appears to involve more than simple physiologic summation, may have important clinical implications.

  19. New clinical guidelines for selective direct injection therapy of the parathyroid glands in chronic dialysis patients.

    Science.gov (United States)

    Onoda, Noritaka; Fukagawa, Masafumi; Tominaga, Yoshihiro; Kitaoka, Masafumi; Akizawa, Tadao; Koiwa, Fumihiko; Kakuta, Takatoshi; Kurokawa, Kiyoshi

    2008-08-01

    In 2000, the Japanese Society for Parathyroid Intervention issued the 'Guidelines for percutaneous ethanol injection therapy of the parathyroid glands in chronic dialysis patients'. Since then, the concept of 'selective PEIT' has been well accepted and the number of patients treated by this method in Japan has increased. Recently, it has been reported that the effect of PEIT differs depending on the degree of nodular hyperplasia. Several new drugs have become available since 2000, and active vitamin D and its analogue have also been used for direct injection into the parathyroids. We present the new 'Guidelines for selective direct injection therapy of the parathyroid glands in chronic dialysis patients', a revised version of the 2000 Guidelines. We believe that these new guidelines are useful for selecting direct injection therapy in patients with advanced secondary hyperparathyroidism.

  20. Pathologic Fracture of the Femur in Brown Tumor Induced in Parathyroid Carcinoma: A Case Report

    Science.gov (United States)

    Park, Sang-Hyun; Kwon, Yong-Uk; Park, Jun-Ho

    2016-01-01

    Brown tumor refers to a change of skeletones that develops as a complication of hyperparathyroidism. As osteoclast is activated to stimulate reabsorption and fibrosis of bone, it causes a cystic change of the bone. Parathyroid carcinoma is being reported as a tumor that induces primary hyperparathyroidism. It causes excessive secretion of the parathyroid hormone and increases the blood parathyroid hormone and calcium. Bone deformation due to brown tumor is known to be naturally recovered through the treatment for hyperparathyroidism. However, there is no clearly defined treatment for lesions that can induce pathological fractures developing in lower extremities. We experienced a case where brown tumor developed in the proximal femur of a 57-year-old female patient due to parathyroid carcinoma. In this case, spontaneous fracture occurred without any trauma, and it was cured by performing intramedullary nailing fixation and parathyroidectomy. We report the treatment results along with a literature review. PMID:27777921

  1. Age-related changes of the ultrastrucure in the parathyroid gland of the golden hamster.

    Science.gov (United States)

    Utsumi, Michiya; Moriguchi, Keiichi; Kato, Akiko; Maeda, Hatsuhiko; Ohno, Norikazu

    2014-01-01

    We qualitatively and quantitatively investigated the parathyroid glands of golden hamsters aged 6, 12, 18, 24 and 30 months. Percent area of rER in the parathyroid gland in golden hamsters at 24 months of age was significantly higher when compared to 6 and 12 months of age, and the percent area at 30 months of age was significantly higher when compared to 12 months of age, but there were no significant differences between 24 and 30 months of age. Percent area of the Golgi apparatus at 24 and 30 months of age was significantly higher when compared to 6, 12 and 18 months of age. Ultrastructurally, we believe that in the parathyroid gland of the golden hamster, synthesis and release of parathyroid hormone increase gradually from 6 to 24months of age and are maintained from 24 to 30 months of age.

  2. Histomorphological study of the parathyroid gland in female Kuttanad ducks (Anas platyrhynchos domesticus

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    Firdous Ahmad Dar

    2013-11-01

    Full Text Available Aim: The present work was targeted to form the baseline data of normal morphological and histological picture of parathyroid gland in female Kuttanad ducks.Materials and Methods: A Histomorphological study of the parathyroid gland was carried out in twelve adult female Kuttanad ducks (Anas platyrhynchos domesticus of 20 weeks of age. Birds reared semintensively were procured from Kerala Veterinary and Animal Sciences University Poultry and Duck Farm and sacrificed humanely. Glands were collected and gross parameters were recorded. The glands were fixed in 10 percent neutral buffered formalin. The small sized glands were processed as such by routine histological methods, paraffin blocks were prepared and sectioned to a thickness of 5µ. The tissues were stained by Haematoxylin and Eosin (H&E for routine histological studies and Gomori's rapid one step trichrome method for connective tissue fibres. Micrometric parameters were recorded using ocular micrometer. Results: Parathyroid glands in Kuttanad ducks lay just caudal to the division of the innominate artery into the subclavian and common carotid arteries. Parathyroids were oval to spherical in shape, yellow in colour and smaller than thyroid gland of the representative sides. The arterial blood supply was from common carotid artery and blood from gland was drained directly into jugular vein. Although it lied close to the thyroid, thymus and ultimobranchial gland, parathyroid tissue did not merge to any of the above mentioned three glands. Parenchyma was composed irregular anatomizing cords of cells supplied by connective tissue stroma penetrated by blood capillaries. Parenchyma was predominantly made of lightly stained cell, the chief cell. The nuclei were round and contain one or two nucleoli. Oxyphil cells present in parathyroid glands of other mammals were not seen in the present study. Conclusion: Histomorphological features or characteristics of Parathyroid gland in Kuttanad duck were

  3. Parathyroid scintigraphy in chronic renal failure; Exploration scintigraphique des glandes parathyroides au cours de l`insuffisance renale

    Energy Technology Data Exchange (ETDEWEB)

    Baulieu, J.L.; Houlier, S.; Baulieu, F.; Rousseau, C. [Hopital Bretonneau, 37 - Tours (France)

    1995-12-31

    The performances of the scintigraphic localization of parathyroid adenoma have improved with the use of technetium-99m radiolabeled tracers and the development of thyroid subtraction methods. By using methoxy--isobutyl-isonitrile (MIB) alone in two phases, sensitivity and specificity are respectively O.85 and 0.92. The interest of scintigraphy compared with ultrasonography is specially marked in the situations encountered in patients with renal failure: hyperplasia, multiple or ectopic adenoma, association with thyroid nodules. However, the localisation of adenoma remains more difficult in renal failure than in primary hyperthyroidism. Scintigraphy seems to be essential for localizing adenoma and eventually hyperplasia, before surgery in patients in bad conditions or before a second operation. (authors). 26 refs., 3 figs., 2 tabs.

  4. Water Clear Cell Adenoma of the Parathyroid Gland: A Forgotten Cause of Primary Hyperparathyroidism.

    Science.gov (United States)

    El Hussein, Siba; Poppiti, Robert

    2017-08-01

    Water clear cell adenoma of the parathyroid gland is a rare neoplasm composed of large clear cells with foamy cytoplasm and mild nuclear pleomorphism, compressing the residual nonneoplastic parathyroid tissue. The differential diagnosis includes a variety of neoplasms with clear cell features. In this article, we provide an overview of the entity with a historical perspective, in order to help pathologists in distinguishing it from other neoplasms in their daily practice.

  5. Failure of fragmented parathyroid gland autotransplantation to prevent permanent hypoparathyroidism after total thyroidectomy.

    Science.gov (United States)

    Lorente-Poch, Leyre; Sancho, Juan; Muñoz, Jose Luis; Gallego-Otaegui, Lander; Martínez-Ruiz, Carlos; Sitges-Serra, Antonio

    2017-03-01

    Parathyroid autotransplantation during total thyroidectomy leads to higher rates of postoperative hypocalcaemia. It has been argued, however, that it prevents permanent hypoparathyroidism. The impact of autografted normal parathyroid gland fragments on long-term parathyroid status has not been assessed properly. To clarify this, the short- and long-term parathyroid function was assessed in patients with three glands remaining in situ after total thyroidectomy, in whom the fourth gland was either autotransplanted (Tx) or accidentally resected (AR). Consecutive patients (n = 669) undergoing first-time total thyroidectomy were prospectively studied recording the number of parathyroid glands remaining in situ: PGRIS =4-(glands autografted + glands in the specimen). The study was focused on the subgroup of 186 patients with three parathyroid glands remaining in situ as a result of either accidental resection (AR, n = 76) or autotransplantation into the sternocleidomastoid muscle (Tx, n = 110). Prevalence of postoperative hypocalcaemia, protracted, and permanent hypoparathyroidism were compared between the two groups. Demographic, disease-related, laboratory, and surgical variables were recorded. All patients were followed for at least 1 year. Both groups were comparable in terms of disease and extent of surgery. Mean postoperative serum calcium was the same (AR: 1.97 ± 0.2 vs Tx: 1.97 ± 0.22 mmol/L). Rates of protracted (AR: 24% vs Tx: 25.5%) and permanent hypoparathyroidism (AR: 5.3% vs Tx: 7.3%) were similar in both groups. The prevalence of parathyroid failure syndromes after total thyroidectomy was similar whether a parathyroid gland was inadvertently excised or autotransplanted. Autotransplantation did not influence the permanent hypoparathyroidism rate.

  6. Dynein light chain binding to a 3′-untranslated sequence mediates parathyroid hormone mRNA association with microtubules

    Science.gov (United States)

    Epstein, Eyal; Sela-Brown, Alin; Ringel, Israel; Kilav, Rachel; King, Stephen M.; Benashski, Sharon E.; Yisraeli, Joel K.; Silver, Justin; Naveh-Many, Tally

    2000-01-01

    The 3′-untranslated region (UTR) of mRNAs binds proteins that determine mRNA stability and localization. The 3′-UTR of parathyroid hormone (PTH) mRNA specifically binds cytoplasmic proteins. We screened an expression library for proteins that bind the PTH mRNA 3′-UTR, and the sequence of 1 clone was identical to that of the dynein light chain LC8, a component of the dynein complexes that translocate cytoplasmic components along microtubules. Recombinant LC8 binds PTH mRNA 3′-UTR, as shown by RNA electrophoretic mobility shift assay. We showed that PTH mRNA colocalizes with microtubules in the parathyroid gland, as well as with a purified microtubule preparation from calf brain, and that this association was mediated by LC8. To our knowledge, this is the first report of a dynein complex protein binding an mRNA. The dynein complex may be the motor that is responsible for transporting mRNAs to specific locations in the cytoplasm and for the consequent is asymmetric distribution of translated proteins in the cell. PMID:10683380

  7. Concurrence of primary hyperparathyroidism and metastatic breast carcinoma affected a parathyroid gland.

    Science.gov (United States)

    Lee, Sang Hee; Kim, Bo Hyun; Bae, Min Jung; Yi, Yang Seon; Kim, Won Jin; Jeon, Yun Kyung; Kim, Sang Soo; Kim, Yong Ki; Kim, In Joo

    2013-08-01

    Involvement of the parathyroid glands by metastatic tumor is rare. Breast is 1 of the primary sites in metastatic cancers. We introduce a rare case of metastatic breast carcinoma affecting a parathyroid gland, which was clinically combined with parathyroid gland hyperplasia. A 65-year-old woman was referred due to hypercalcemia and constipation. The patient had a history of left breast carcinoma. She was admitted to the hospital because of the recent discovery of hypercalcemia and elevation of PTH. A Tc99m-sestamibi scan showed retained uptake in the right thyroid and in the lower pole of the left thyroid gland. Aspiration biopsy results revealed that the nodule in the posterior portion of the right thyroid was metastatic breast cancer and the nodule in the left thyroid gland was the hyperplastic parathyroid gland. This case illustrates that hyperparathyroidism caused by parathyroid hyperplasia was concurrent with metastatic breast cancer to a parathyroid gland without disseminated systemic metastasis. Although this case is very uncommon and it is not clear whether there is a relationship between breast cancer and primary hyperparathyroidism, that possibility should always be considered as the cause of hypercalcemia in patients with breast cancer.

  8. Effects of a 2X gravity environment on the ultrastructure of the gerbil parathyroid gland

    Science.gov (United States)

    Sannes, P. L.; Hayes, T. G.

    1975-01-01

    A number of studies concerning the effects of hypergravity on bone have shown increases in bone mass or bone dimensions. Correlative studies, which could provide clues to the mechanism for such a response, have been lacking. The purpose of the present study was to evaluate the ultrastructure of parathyroid glands of Mongolian gerbils exposed to a continuous 2 X gravity force for 60 d. It was found that the experimental animals had parathyroid glands which had a greater percentage of chief cells in the active stage of their secretory cycle when compared with control animals. This result was interpreted to indicate an increase in parathyroid gland secretory activity and, hence, an increase in parathyroid hormone release. It was suggested that increased parathyroid secretory activity was necessary to maintain serum calcium levels of hypergravity animals within normal limits. Cellular forms resembling water clear cells and highly compact, degenerating cells were described in experimental animals but not in controls. Areas suggestive of cellular dissolution and disorganization were also reported in experimental parathyroids.

  9. Cancer of ectopic parathyroid gland presentation of the disease with a case report.

    Science.gov (United States)

    Pesovic, Jovan P; Milosevic, Bojan Z; Canovic, Dragan S; Cvetkovic, Aleksandar M; Milosavljevic, Milos Z; Jevdjic, Jasna D; Pavlovic, Mladen D; Petrovic, Marko D

    2013-01-01

    Tc-99m-methoxyisobutylisonitril (MIBI) scintigraphy is localizing diagnostic methods that is used for detection of sicken parathyroid gland (PT). The use of this method for PT diseases diagnosis makes surgical treatment of a patient more successful. This is a report about the patient who was surgically treated for primary hyperparathyroidism caused by hyperplasia of parathyroid glands and cancer of ectopic parathyroid gland. He was operated in two acts. The first surgical intervention was performed without preoperative diagnostics of Tc-99m-MIBI scintigraphy, while the second surgical intervention was preceded by Tc-99m-MIBI scintigraphy which clearly showed the existence of tumor in the back mediastinum (ectopic parathyroid gland). Pathophysiological analysis of the extirpated parathyroid gland showed the case of ectopic parathyroid gland cancer. The use of Tc-99m-MIBI scintigraphy as a localizing method before the first surgical intervention could have saved the patient from the second one and from risks it could have caused, as well.

  10. Derivation of Parathyroid Gland Cells and Their Progenitors fromInduced Pluripotent Stem Cells (iPSCs) for Personalized Therapy

    Science.gov (United States)

    2016-09-01

    Award Number: W81XWH-15-1-0261 TITLE: Derivation of Parathyroid Gland Cells and Their Progenitors from Induced Pluripotent Stem Cells (iPSCs) for...REPORT TYPE Annual 3. DATES COVERED 1 Aug 2015 - 31 Jul 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Derivation of Parathyroid Gland Cells and... parathyroid gland (PTG) dysfunction and a disruption of calcium homeostasis and metabolism. Hypoparathyroidism is particularly devastating and is becoming

  11. Full length parathyroid hormone (1–84 in the treatment of osteoporosis in postmenopausal women

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    Esteban Jódar-Gimeno

    2007-04-01

    Full Text Available Esteban Jódar-GimenoEndocrinology and Metabolism Service, University Hospital “12 de Octubre”, Madrid, Spain. Associate Professor of Medicine Universidad Complutense, Madrid, SpainObjective: To review the pharmacological properties and the available clinical data of full length parathyroid hormone (PTH in post-menopausal osteoporosis.Sources: A MEDLINE search was completed, together with a review of information obtained from the manufacturer and from the medicine regulatory agencies.Study and data selection: Studies were selected according to relevance and availability. Relevant information (design, objectives, patients’ characteristics, outcomes, adverse events, dosing, etc was analyzed.Results: Different studies have shown that, when administered intermittently as a subcutaneous injection in the abdomen, PTH increases bone mineral density (BMD and prevents vertebral fractures. On completion of PTH therapy (up to 24 months, there is evidence that sequential treatment with alendronate is associated with a therapeutic benefit in terms of increase in BMD. Further trials are necessary to determine long-term safety and the role of PTH in combination with other treatments for osteoporosis and the effect of repeated cycles of PTH followed by an anti-catabolic agent. There are currently no completed comparative trials with other osteoporosis treatments.Conclusions: Full length PTH, given intermittently as an abdominal subcutaneous injection, appears to be a safe and efficacious treatment option for high risk osteoporosis. More data are needed to determine its specific role in osteoporosis treatment.Keywords: postmenopausal osteoporosis, anabolic therapy, PTH (1–84

  12. ROLE OF 99Tcm-SESTAMIBI DUAL-PHASE PARATHYROID SCINTIGRAPHY IN PREOPERATIVE LOCALIZATION IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To evaluate the application of 99Tcm-sestamibi dual-phase parathyroid scintigraphy in the preoperative localization in patients with primary hyperparathyroidism and to compare the diagnostic efficacy of various imaging modalities. Methods Ninety-two consecutive patients, diagnosed as hyperparathyroidism and presented with hypercalcaemia as the predominant symptom, were included. All the patients underwent dual-phase parathyroid scintigraphy using 99Tcm-sestamibi and parathyroid ultrasound scan. Among them, 48 patients underwent parathyroid computed tomography (CT). All patients were referred for parathyroidectomy. Results 99Tcm-sestamibi dual-phase parathyroid scintigraphy revealed the diagnostic sensitivity of 76.5%, 80%, 75% and 33.3% for the subgroup of single adenomas, multiple adenomas, ectopic parathyroid and parathyroid hyperplasia respectively. The specificity was 100% for all leisons. 99Tcm-sestamibi dual-phase parathyroid scintigraphy was proved to be superior to the other imaging modalities (ultrasound and CT) in terms of the preoperative diagnostic accuracy. The lesion weight was found to be an underlying factor leading to the false negative result. Conclusion 99Tcm-sestamibi dual-phase parathyroid scintigraphy was found to have higher diagnostic accuracy in comparison with other imaging modalities and is recommended preoperatively in order to reduce the sugery time and unnecessary neck exploration.

  13. Gastrin induces parathyroid hormone-like hormone expression in gastric parietal cells.

    Science.gov (United States)

    Al Menhali, Asma; Keeley, Theresa M; Demitrack, Elise S; Samuelson, Linda C

    2017-06-01

    Parietal cells play a fundamental role in stomach maintenance, not only by creating a pathogen-free environment through the production of gastric acid, but also by secreting growth factors important for homeostasis of the gastric epithelium. The gastrointestinal hormone gastrin is known to be a central regulator of both parietal cell function and gastric epithelial cell proliferation and differentiation. Our previous gene expression profiling studies of mouse stomach identified parathyroid hormone-like hormone (PTHLH) as a potential gastrin-regulated gastric growth factor. Although PTHLH is commonly overexpressed in gastric tumors, its normal expression, function, and regulation in the stomach are poorly understood. In this study we used pharmacologic and genetic mouse models as well as human gastric cancer cell lines to determine the cellular localization and regulation of this growth factor by the hormone gastrin. Analysis of Pthlh(LacZ/+) knock-in reporter mice localized Pthlh expression to parietal cells in the gastric corpus. Regulation by gastrin was demonstrated by increased Pthlh mRNA abundance after acute gastrin treatment in wild-type mice and reduced expression in gastrin-deficient mice. PTHLH transcripts were also observed in normal human stomach as well as in human gastric cancer cell lines. Gastrin treatment of AGS-E gastric cancer cells induced a rapid and robust increase in numerous PTHLH mRNA isoforms. This induction was largely due to increased transcriptional initiation, although analysis of mRNA half-life showed that gastrin treatment also extended the half-life of PTHLH mRNA, suggesting that gastrin regulates expression by both transcriptional and posttranscriptional mechanisms.NEW & NOTEWORTHY We show that the growth factor parathyroid hormone-like hormone (PTHLH) is expressed in acid-secreting parietal cells of the mouse stomach. We define the specific PTHLH mRNA isoforms expressed in human stomach and in human gastric cancer cell lines and

  14. In situ preservation of the inferior parathyroid gland during central neck dissection for papillary thyroid carcinoma.

    Science.gov (United States)

    Wang, J B; Wu, K; Shi, L H; Sun, Y Y; Li, F B; Xie, L

    2017-10-01

    Postoperative hypocalcaemia due to dysfunction of the parathyroid glands is the most common complication after total thyroidectomy plus central neck dissection (CND). There is a lack of surgical techniques described to help preserve the inferior parathyroid gland in situ during CND. The objective of this study was to introduce the 'TBP layer' (layer of thymus-blood vessel-inferior parathyroid gland) concept for preserving the inferior parathyroid gland in situ during CND, and to evaluate its effectiveness. The study group included patients with primary papillary thyroid cancer who underwent total thyroidectomy with CND using the new surgical concept between January and December 2014. The control group included sex- and age-matched patients who underwent conventional total thyroidectomy with CND between January 2012 and December 2013. The proportion of inferior parathyroid glands preserved in situ and postoperative hypoparathyroidism rates in the two groups were compared. There were 181 patients in the study group and 306 in the control group. There were no significant differences between the groups in tumour size, multifocality, extrathyroidal extension, and number of harvested and metastatic central lymph nodes. The rate of inferior parathyroid gland preservation in situ was significantly improved from 37·9 to 76·3 per cent on the left side (P < 0·001), and from 52·0 to 77·9 per cent on the right side (P < 0·001), in the study group compared with the control group. The incidence of transient hypoparathyroidism decreased significantly from 35·0 to 7·2 per cent (P < 0·001). Applying the proposed surgical concept improved the rate of inferior parathyroid gland preservation in situ and decreased the incidence of transient postoperative hypoparathyroidism. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  15. Preoperative parathyroid gland localization with technetium-99m sestamibi in secondary hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Pons, F.; Vidal-Sicart, S.; Fuster, D.; Herranz, R. [Department of Nuclear Medicine, Hospital Clinic, University of Barcelona (Spain); Torregrosa, J.V. [Unit of Renal Transplant, Hospital Clinic, Barcelona (Spain); Sabater, L.; Fernandez-Cruz, L. [Department of Surgery, Hospital Clinic, Barcelona (Spain)

    1997-12-01

    Technetium-99m sestamibi scintigraphy has become a valuable tool in locating parathyroid glands in patients with primary hyperparathyroidism. The aim of this study was to evaluate its usefulness in secondary hyperparathyroidism. Twenty patients were injected intravenously with 740 MBq of {sup 99m}Tc-sestamibi and images were obtained at 15 min and 2 h post injection. All patients underwent parathyroid ultrasonography (US) as well as bilateral surgical neck exploration and 64 parathyroid glands were removed. US revealed at least one enlarged gland in 15/20 patients (75%), while {sup 99m}Tc-sestamibi scintigraphy showed focal areas of increased uptake in at least one gland in 17/20 patients (85%). When imaging results for all glands were evaluated according to surgical results, sensitivity was 54% for parathyroid scintigraphy and 41% for US, and specificity was 89% for both imaging techniques. There was a discrepancy between the two imaging modalities in 28 glands (35%). The mean surgical weight of US-positive glands (1492{+-}1436 mg) was significantly higher than that of US-negative glands (775{+-}703 mg) (P<0.05). However, there were no significant differences in weight between sestamibi-positive and sestamibi-negative glands. When only sestamibi-positive glands were considered, a positive correlation between uptake and weight was found (r=0.4, P<0.05). In conclusion, parathyroid US and {sup 99m}Tc-sestamibi scintigraphy are complementary imaging techniques in the preoperative localization of abnormal parathyroid glands in patients with secondary hyperparathyroidism. The limited sensitivity of the techniques means that patients will still require bilateral neck exploration; therefore routine preoperative parathyroid scanning in renal patients is not justified. (orig.) With 3 figs., 2 tabs., 22 refs.

  16. Video-assisted mediastinoscopy (VAM for surgical resection of ectopic parathyroid adenoma

    Directory of Open Access Journals (Sweden)

    Lansdown Mark

    2007-10-01

    Full Text Available Abstract Background Ectopic mediastinal parathyroid adenomas or hyperplasia account for up to 25% of primary hyperparathyroidism (HPT. Two percent of them are not accessible by standard cervical surgical approaches. Surgical resection has traditionally been performed via median sternotomy or thoracotomy and more recently, via video assisted thoracoscopic surgery (VATS. We present our experience with the novel use of Video-Assisted Mediastinoscopy (VAM for resection of ectopic mediastinal parathyroid glands. Case presentation 4 patients underwent VAM for removal of an ectopic intramediastinal parathyroid gland. All of them had at least one previous unsuccessful neck exploration. In all cases histology confirmed complete resection of ectopic parathyroid glands (3 parathyroid adenomas and one parathyroid hyperplasia. Two of the patients required a partial sternal split to facilitate exploration. Conclusion The cervical approach for resection of ectopic parathyroid adenomas is frequently unsuccessful. Previously, the standard surgical approach in such cases was sternotomy and exploration of the mediastinum. Recently, a number of less invasive modalities have been introduced. We found that VAM has several advantages. It has a short theatre time does not require a complex anaesthetic and is performed with the patient in classic supine position utilising often a previous cervical scar with good cosmetic results. It offers a short hospital stay; it is cost effective with minimal use of fancy and pricy consumables with a comfortable incision and no violation of the pleural space. Additionally the use of digital Video imaging has increased the sensitivity of the mediastinoscopy and has added safety and confidence in performing a detailed mediastinal exploration with an additional great training value as well.

  17. Prevalence of Secondary Hyper Parathyroidism in Hemodialysis Patients

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    F Behzad

    2007-04-01

    Full Text Available Introduction: Osteodystrophy is one of the long term complications of chronic renal failure and is expressed in two forms;low turn over and high turn over. It is an important cause of morbidity in patients with renal failure and if diagnosed and managed properly, many problems of these patients can be resolved. In this study we evaluated the prevalence of hyperparathyroidism in hemodialysis patients and its correlation with different factors. Methods: This study was an analytic, observational study that was done by the cross- sectional method. We formatted a questionnaire for hemodialysis patients who were enrolled in the study over a period of 6 months. Fasting blood samples (5-10c.c were drawn to measure levels of PTH(parathyroid hormone ,calcium, phosphorous and alkaline phosphatase. Skull and wrist X-rays were also taken and the radiologist evaluated them with regards to hyperparathyroidism. Results: In the 80 patients studied, prevalence of hyperparathyroidism was 45% (36 patients. 44 patients were diabetics. Among different factors, hyperparathyroidism did not correlate with frequency and duration of dialysis, age, sex ,familial history, diabetes, hypertension , bone pains, muscle weakness, purities and level of calcium and phosphorous. But there was a significant relationship between hyperparathyroidism and alkaline phosphatase levels and radiological findings. Conclusion: We can use alkaline phosphatase levels and/or radiographic changes for evaluation of renal osteodystrophy in hemodialysis patients and prevent complications by early diagnosis and proper management.

  18. Parathyroid hormone mediates hematopoietic cell expansion through interleukin-6.

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    Flavia Q Pirih

    Full Text Available Parathyroid hormone (PTH stimulates hematopoietic cells through mechanisms of action that remain elusive. Interleukin-6 (IL-6 is upregulated by PTH and stimulates hematopoiesis. The purpose of this investigation was to identify actions of PTH and IL-6 in hematopoietic cell expansion. Bone marrow cultures from C57B6 mice were treated with fms-like tyrosine kinase-3 ligand (Flt-3L, PTH, Flt-3L plus PTH, or vehicle control. Flt-3L alone increased adherent and non-adherent cells. PTH did not directly impact hematopoietic or osteoclastic cells but acted in concert with Flt-3L to further increase cell numbers. Flt-3L alone stimulated proliferation, while PTH combined with Flt-3L decreased apoptosis. Flt-3L increased blasts early in culture, and later increased CD45(+ and CD11b(+ cells. In parallel experiments, IL-6 acted additively with Flt-3L to increase cell numbers and IL-6-deficient bone marrow cultures (compared to wildtype controls but failed to amplify in response to Flt-3L and PTH, suggesting that IL-6 mediated the PTH effect. In vivo, PTH increased Lin(- Sca-1(+c-Kit(+ (LSK hematopoietic progenitor cells after PTH treatment in wildtype mice, but failed to increase LSKs in IL-6-deficient mice. In conclusion, PTH acts with Flt-3L to maintain hematopoietic cells by limiting apoptosis. IL-6 is a critical mediator of bone marrow cell expansion and is responsible for PTH actions in hematopoietic cell expansion.

  19. Sustained cyclic AMP production by parathyroid hormone receptor endocytosis.

    Science.gov (United States)

    Ferrandon, Sébastien; Feinstein, Timothy N; Castro, Marian; Wang, Bin; Bouley, Richard; Potts, John T; Gardella, Thomas J; Vilardaga, Jean-Pierre

    2009-10-01

    Cell signaling mediated by the G protein-coupled parathyroid hormone receptor type 1 (PTHR) is fundamental to bone and kidney physiology. It has been unclear how the two ligand systems--PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine--can effectively operate with only one receptor and trigger different durations of the cAMP responses. Here we analyze the ligand response by measuring the kinetics of activation and deactivation for each individual reaction step along the PTHR signaling cascade. We found that during the time frame of G protein coupling and cAMP production, PTHrP(1-36) action was restricted to the cell surface, whereas PTH(1-34) had moved to internalized compartments where it remained associated with the PTHR and Galpha(s), potentially as a persistent and active ternary complex. Such marked differences suggest a mechanism by which PTH and PTHrP induce differential responses, and these results indicate that the central tenet that cAMP production originates exclusively at the cell membrane must be revised.

  20. Parathyroid Hormone-Related Protein Analogs as Osteoporosis Therapies.

    Science.gov (United States)

    Esbrit, Pedro; Herrera, Sabina; Portal-Núñez, Sergio; Nogués, Xavier; Díez-Pérez, Adolfo

    2016-04-01

    The only bone anabolic agent currently available for osteoporosis treatment is parathyroid hormone (PTH)-either its N-terminal 1-34 fragment or the whole molecule of 1-84 aminoacids-whose intermittent administration stimulates new bone formation by targeting osteoblastogenesis and osteoblast survival. PTH-related protein (PTHrP) is an abundant factor in bone which shows N-terminal homology with PTH and thus exhibits high affinity for the same PTH type 1 receptor in osteoblasts. Therefore, it is not surprising that intermittently administered N-terminal PTHrP peptides induce bone anabolism in animals and humans. Furthermore, the C-terminal region of PTHrP also elicits osteogenic features in vitro in osteoblastic cells and in various animal models of osteoporosis. In this review, we discuss the current concepts about the cellular and molecular mechanisms whereby PTHrP may induce anabolic actions in bone. Pre-clinical studies and clinical data using N-terminal PTHrP analogs are also summarized, pointing to PTHrP as a promising alternative to current bone anabolic therapies.

  1. Parathyroid hormone intermittent administration promotes delay on rat incisor eruption.

    Science.gov (United States)

    Silva, M A D; Vasconcelos, D F P; Marques, M R; Barros, S P

    2016-09-01

    This study evaluated the influence of parathyroid hormone (PTH) (1-34) intermittent administration on rat eruption rates of lower incisors under normo, hyper and hypofunctional conditions, Sharpey fibers insertion, and alveolar bone formation. Wistar male rats received PTH (1-34) three times a week during the entire experimental period, 31days. Control animals received the same concentration of the vehicle solution during the same period. Three injections of alizarin were also performed. The experiment evaluated the eruptive rate, the alveolar bone formation and also the morphology, and the area density of Sharpey fibers. After the sacrifice, the mandibles were dissected and samples were prepared for fluorescence and scanning electron microscopy observations. PTH-treated animals showed significantly reduced eruption rates in all different functional conditions. Analysis evidenced that PTH-treated rats present an increase in bone formation and area density of the Sharpey fibers. We concluded that the PTH (1-34) intermittent administration reduced the eruptive process rates, through bone formation enhancement and increase in the area density of Sharpey fibers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Parathyroid hormone is not an inhibitor of lipoprotein lipase activity.

    Science.gov (United States)

    Arnadottir, M; Nilsson-Ehle, P

    1994-01-01

    The reduced lipoprotein lipase (LPL) activities in uraemia are reflected by increased serum triglyceride concentrations and reduced HDL cholesterol concentrations. Both hyperparathyroidism and circulating inhibitor(s) of LPL have been associated with the disturbances of lipid metabolism in uraemia. The aim of the present study was to investigate if parathyroid hormone (PTH) had an inhibitory effect on LPL activity. Plasma post-heparin LPL activities, plasma LPL inhibitory activities, serum PTHintact and serum PTHC-terminal concentrations were analysed in 20 patients on haemodialysis and 20 healthy controls. The effects of purified, human PTHintact and a carboxyterminal fragment of PTH (PTH39-84) on LPL activities in post-heparin plasma from healthy individuals and on the enzyme activity of purified, bovine milk LPL, activated with apolipoprotein CII, were studied. Patients had significantly higher plasma LPL inhibitory activities than controls, but there was no correlation between plasma LPL inhibitory activities and serum PTH concentrations. Neither PTHintact nor PTH39-84 had a significant effect on LPL activities in vitro. Thus there was no evidence of a direct inhibition of LPL activity by PTH under the present in-vivo or in-vitro conditions.

  3. The thyroid hormone, parathyroid hormone and vitamin D associated hypertension

    Directory of Open Access Journals (Sweden)

    Sandeep Chopra

    2011-01-01

    Full Text Available Thyroid disorders and primary hyperparathyroidism have been known to be associated with increases in blood pressure. The hypertension related to hypothyroidism is a result of increased peripheral resistance, changes in renal hemodynamics, hormonal changes and obesity. Treatment of hypothyroidism with levo-thyroxine replacement causes a decrease in blood pressure and an overall decline in cardiovascular risk. High blood pressure has also been noted in patients with subclinical hypothyroidism. Hyperthyroidism, on the other hand, is associated with systolic hypertension resulting from an expansion of the circulating blood volume and increase in stroke volume. Increased serum calcium levels associated with a primary increase in parathyroid hormone levels have been also associated with high blood pressure recordings. The mechanism for this is not clear but the theories include an increase in the activity of the renin-angiotensin-aldosterone system and vasoconstriction. Treatment of primary hyperparathyroidism by surgery results in a decline in blood pressure and a decrease in the plasma renin activity. Finally, this review also looks at more recent evidence linking hypovitaminosis D with cardiovascular risk factors, particularly hypertension, and the postulated mechanisms linking the two.

  4. Results of the Dynamic Cohort Study of Parathyroid Gland Function in Patients with Secondary Hyperparathyroidism

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    N.V. Karlovich

    2014-03-01

    Full Text Available In 92 patients with end-stage chronic kidney disease we have evaluated serum levels of parathyroid hormone (PTH, vitamin D3, indicators of phosphorus and calcium metabolism and markers of bone metabolism: at baseline and at the end of dynamic follow-up period lasting from 6 to 24 months. In the whole group the mean PTH level and incidence of secondary hyperparathyroidism (SHPT have not changed significantly. Phosphorus levels decreased significantly, but did not reach the target level, indicating the lack of patients’ adherence to medical recommendations on hyperphosphatemia correction. It was found that the persistence of high levels of PTH during follow-up is determined by high baseline levels of PTH, alkaline phosphatase, osteocalcin and beta-cross-laps, as well as the young age of the patients. Persistence of hypercalcemia and hyperphosphatemia has the greatest impact on SHPT aggravation. The findings allow us to conclude that in patients with stable parameters of phosphorus and calcium metabolism, with the absence of correction for calcium and phosphorus metabolism or use of diet in combination with calcium and vitamin D3 preparations, the measurement of PTH once a year in most cases is enough to control its levels.

  5. Serum intact parathyroid hormone levels in cats with chronic kidney disease

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    Luciano H. Giovaninni

    2013-02-01

    Full Text Available Chronic kidney disease (CKD is frequently observed in cats and it is characterized as a multisystemic illness, caused by several underlying metabolic changes, and secondary renal hyperparathyroidism (SRHPT is relatively common; usually it is associated with the progression of renal disease and poor prognosis. This study aimed at determining the frequency of SRHPT, and discussing possible mechanisms that could contribute to the development of SRHPT in cats at different stages of CKD through the evaluation of calcium and phosphorus metabolism, as well as acid-base status. Forty owned cats with CKD were included and divided into three groups, according to the stages of the disease, classified according to the International Renal Interest Society (IRIS as Stage II (n=12, Stage III (n=22 and Stage IV (n=6. Control group was composed of 21 clinically healthy cats. Increased serum intact parathyroid hormone (iPTH concentrations were observed in most CKD cats in all stages, and mainly in Stage IV, which hyperphosphatemia and ionized hypocalcemia were detected and associated to the cause for the development of SRHPT. In Stages II and III, however, ionized hypercalcemia was noticed suggesting that the development of SRHPT might be associated with other factors, and metabolic acidosis could be involved to the increase of serum ionized calcium. Therefore, causes for the development of SRHPT seem to be multifactorial and they must be further investigated, mainly in the early stages of CKD in cats, as hyperphosphatemia and ionized hypocalcemia could not be the only factors involved.

  6. Intraoperative parathyroid hormone assay in patients with Graves' disease for prediction of postoperative tetany.

    Science.gov (United States)

    Moriyama, Taiki; Yamashita, Hiroyuki; Noguchi, Shiro; Takamatsu, Yuji; Ogawa, Takahiro; Watanabe, Shin; Uchino, Shinya; Ohshima, Akira; Kuroki, Syoji; Tanaka, Masao

    2005-10-01

    We measured intraoperative parathyroid hormone (IOPTH) levels before and after thyroidectomy in a large group of patients to test whether changes in IOPTH can predict postoperative tetany. Subjects were 111 consecutive patients (94 females and 17 males) with Graves' disease undergoing subtotal thyroidectomy. Blood samples for IOPTH assay were obtained after anesthesia (basal) and following skin closure (postoperative). Data were compared between patients who developed tetany (n = 9) and those who did not (n = 102). There was no significant difference in sex, age, period of antithyroid drug administration, or the weight of the thyroid between the two groups. The preoperative serum calcium level was significantly lower (p tetany group than in the non-tetany group. The IOPTH level was significantly lower (p tetany group than in the non-tetany group. A decrease in IOPTH of more than 70% was shown to be 78% sensitive, 94% specific, and 93% accurate, and it has 78% positive predictive value and 94% negative predictive value for the development of tetany. Our study shows that a postoperative decrease of IOPTH level is the most predictive of postoperative tetany of the clinical risk factors investigated. We recommend IOPTH measurement as an adjunct to postoperative management of patients with Graves' disease to assist in preventing hypocalcemia and determining the earliest time for safe discharge.

  7. Nonlinear dynamics in pulsatile secretion of parathyroid hormone in normal human subjects

    Science.gov (United States)

    Prank, Klaus; Harms, Heio; Brabant, Georg; Hesch, Rolf-Dieter; Dämmig, Matthias; Mitschke, Fedor

    1995-03-01

    In many biological systems, information is transferred by hormonal ligands, and it is assumed that these hormonal signals encode developmental and regulatory programs in mammalian organisms. In contrast to the dogma of endocrine homeostasis, it could be shown that the biological information in hormonal networks is not only present as a constant hormone concentration in the circulation pool. Recently, it has become apparent that hormone pulses contribute to this hormonal pool, which modulates the responsiveness of receptors within the cell membrane by regulation of the receptor synthesis, movement within the membrane layer, coupling to signal transduction proteins and internalization. Phase space analysis of dynamic parathyroid hormone (PTH) secretion allowed the definition of a (in comparison to normal subjects) relatively quiet ``low dynamic'' secretory pattern in osteoporosis, and a ``high dynamic'' state in hyperparathyroidism. We now investigate whether this pulsatile secretion of PTH in healthy men exhibits characteristics of nonlinear determinism. Our findings suggest that this is conceivable, although on the basis of presently available data and techniques, no proof can be established. Nevertheless, pulsatile secretion of PTH might be a first example of nonlinear deterministic dynamics in an apparently irregular hormonal rhythm in human physiology.

  8. Detection of parathyroid hormone using an electrochemical impedance biosensor based on PAMAM dendrimers.

    Science.gov (United States)

    Özcan, Hakkı Mevlüt; Sezgintürk, Mustafa Kemal

    2015-01-01

    This paper presents a novel hormone-based impedimetric biosensor to determine parathyroid hormone (PTH) level in serum for diagnosis and monitoring treatment of hyperparathyroidism, hypoparathyroidism and thyroid cancer. The interaction between PTH and the biosensor was investigated by an electrochemical method. The biosensor was based on the gold electrode modified by 12-mercapto dodecanoic (12MDDA). Antiparathyroid hormone (anti-PTH) was covalently immobilized on to poly amidoamine dendrimer (PAMAM) which was bound to a 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide (EDC/NHS) couple, self-assembled monolayer structure from one of the other NH2 sites. The immobilization of anti-PTH was monitored by electrochemical impedance spectroscopy, cyclic voltammetry and scanning electron microscope techniques. After the optimization studies of immobilization materials such as 12MDDA, EDC-NHS, PAMAM, and glutaraldehyde, the performance of the biosensor was investigated in terms of linearity, sensitivity, repeatability, and reproducibility. PTH was detected within a linear range of 10-60 fg/mL. Finally the described biosensor was used to monitor PTH levels in artificial serum samples.

  9. Regional responsiveness of the tibia to intermittent administration of parathyroid hormone as affected by skeletal unloading

    Science.gov (United States)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Tanner, S.; Curren, T.; Morey-Holton, E.

    1997-01-01

    To determine whether the acute inhibition of bone formation and deficit in bone mineral induced by skeletal unloading can be prevented, we studied the effects of intermittent parathyroid hormone (PTH) administration (8 micrograms/100 g/day) on growing rats submitted to 8 days of skeletal unloading. Loss of weight bearing decreased periosteal bone formation by 34 and 51% at the tibiofibular junction and tibial midshaft, respectively, and reduced the normal gain in tibial mass by 35%. Treatment with PTH of normally loaded and unloaded animals increased mRNA for osteocalcin (+58 and +148%, respectively), cancellous bone volume in the proximal tibia (+41 and +42%, respectively), and bone formation at the tibiofibular junction (+27 and +27%, respectively). Formation was also stimulated at the midshaft in unloaded (+47%, p < 0.05), but not loaded animals (-3%, NS). Although cancellous bone volume was preserved in PTH-treated, unloaded animals, PTH did not restore periosteal bone formation to normal nor prevent the deficit in overall tibial mass induced by unloading. We conclude that the effects of PTH on bone formation are region specific and load dependent. PTH can prevent the decrease in cancellous bone volume and reduce the decrement in cortical bone formation induced by loss of weight bearing.

  10. Parathyroid hormone levels 1 hour after thyroidectomy: an early predictor of postoperative hypocalcemia.

    Science.gov (United States)

    AlQahtani, Awad; Parsyan, Armen; Payne, Richard; Tabah, Roger

    2014-08-01

    Parathyroid dysfunction leading to symptomatic hypocalcemia is not uncommon following a total or completion thyroidectomy and is often associated with significant patient morbidity and a prolonged hospital stay. A simple, reliable indicator to identify patients at risk would permit earlier pharmacologic prophylaxis to avoid these adverse outcomes. We examined the role of intact parathormone (PTH) levels 1 hour after surgery as a predictor of post-thyroidectomy hypocalcemia. We prospectively reviewed the cases of consecutive patients undergoing total or completion thyroidectomy. Ionized calcium (Ca(2+)) and intact PTH levels were measured preoperatively and at 1-, 6- and 24-hour intervals postoperatively. The specificity, sensitivity, negative and positive predictive values of the 1-hour PTH serum levels (PTH-1) in predicting 24-hour post-thyroidectomy hypocalcemia and eucalcemia were determined. We reviewed the cases of 149 patients. Biochemical hypocalcaemia (Ca(2+) sensitivity, specificity, positive and negative predictive values of a low PTH-1 were 89%, 100%, 97% and 100%, respectively. We found that PTH-1 levels were predictive of symptomatic hypocalcemia 24 hours after thyroidectomy. Routine use of this assay should be considered, as it could prompt the early administration of calcitriol in patients at risk of hypocalcemia and allow for the safe and timely discharge of patients expected to remain eucalcemic.

  11. Restoration of parathyroid function after change of phosphate binder from calcium carbonate to lanthanum carbonate in hemodialysis patients with suppressed serum parathyroid hormone.

    Science.gov (United States)

    Inaba, Masaaki; Okuno, Senji; Nagayama, Harumi; Yamada, Shinsuke; Ishimura, Eiji; Imanishi, Yasuo; Shoji, Shigeichi

    2015-03-01

    Control of phosphate is the most critical in the treatment of chronic kidney disease with mineral and bone disorder (CKD-MBD). Because calcium-containing phosphate binder to CKD patients is known to induce adynamic bone disease with ectopic calcification by increasing calcium load, we examined the effect of lanthanum carbonate (LaC), a non-calcium containing phosphate binder, to restore bone turnover in 27 hemodialysis patients with suppressed parathyroid function (serum intact parathyroid hormone [iPTH] ≦ 150 pg/mL). At the initiation of LaC administration, the dose of calcium-containing phosphate binder calcium carbonate (CaC) was withdrawn or reduced based on serum phosphate. After initiation of LaC administration, serum calcium and phosphate decreased significantly by 4 weeks, whereas whole PTH and iPTH increased. A significant and positive correlation between decreases of serum calcium, but not phosphate, with increases of whole PTH and iPTH, suggested that the decline in serum calcium with reduction of calcium load by LaC might increase parathyroid function. Serum bone resorption markers, such as serum tartrate-resistant acid phosphatase 5b, and N-telopeptide of type I collagen increased significantly by 4 weeks after LaC administration, which was followed by increases of serum bone formation markers including serum bone alkaline phosphatase, intact procollagen N-propeptide, and osteocalcin. Therefore, it was suggested that LaC attenuated CaC-induced suppression of parathyroid function and bone turnover by decreasing calcium load. In conclusion, replacement of CaC with LaC, either partially or totally, could increase parathyroid function and resultant bone turnover in hemodialysis patients with serum iPTH ≦ 150 pg/mL.

  12. Scaffold-free parathyroid tissue engineering using tonsil-derived mesenchymal stem cells.

    Science.gov (United States)

    Park, Yoon Shin; Hwang, Ji-Young; Jun, Yesl; Jin, Yoon Mi; Kim, Gyungah; Kim, Ha Yeong; Kim, Han Su; Lee, Sang-Hoon; Jo, Inho

    2016-04-15

    To restore damaged parathyroid function, parathyroid tissue engineering is the best option. Previously, we reported that differentiated tonsil-derived mesenchymal stem cells (dTMSC) restore in vivo parathyroid function, but only if they are embedded in a scaffold. Because of the limited biocompatibility of Matrigel, however, here we developed a more clinically applicable, scaffold-free parathyroid regeneration system. Scaffold-free dTMSC spheroids were engineered in concave microwell plates made of polydimethylsiloxane in control culture medium for the first 7days and differentiation medium (containing activin A and sonic hedgehog) for next 7days. The size of dTMSC spheroids showed a gradual and significant decrease up to day 5, whereafter it decreased much less. Cells in dTMSC spheroids were highly viable (>80%). They expressed high levels of intact parathyroid hormone (iPTH), the parathyroid secretory protein 1, and cell adhesion molecule, N-cadherin. Furthermore, dTMSC spheroids-implanted parathyroidectomized (PTX) rats revealed higher survival rates (50%) over a 3-month period with physiological levels of both serum iPTH (57.7-128.2pg/mL) and ionized calcium (0.70-1.15mmol/L), compared with PTX rats treated with either vehicle or undifferentiated TMSC spheroids. This is the first report of a scaffold-free, human stem cell-based parathyroid tissue engineering and represents a more clinically feasible strategy for hypoparathyroidism treatment than those requiring scaffolds. Herein, we have for the first time developed a scaffold-free parathyroid tissue spheroids using differentiated tonsil-derived mesenchymal stem cells (dTMSC) to restore in vivo parathyroid cell functions. This new strategy is effective, even for long periods (3months), and is thus likely to be more feasible in clinic for hypoparathyroidism treatment. Development of TMSC spheroids may also provide a convenient and efficient scaffold-free platform for researchers investigating conditions

  13. Preoperative localization of hyperfunctioning parathyroid glands with 4D-CT.

    Science.gov (United States)

    Lundstroem, Anke Katrin; Trolle, Waldemar; Soerensen, Christian Hjort; Myschetzky, Peter Sand

    2016-05-01

    Primary hyperparathyroidism (pHPT) is almost exclusively the result of a solitary parathyroid adenoma. In most cases, the affected gland can be surgically removed, but precise preoperative imaging is essential for adenoma localization prior to surgical intervention. In this study, we evaluated the diagnostic value of four-dimensional computed tomography (4D-CT) as a preoperative imaging tool in relation to the localization of pathologic parathyroid glands in patients with pHPT and negative sestamibi scans. This study included 43 consecutive patients with pHPT referred for parathyroidectomy at the Department of Head and Neck Surgery of Copenhagen University Hospital Rigshospitalet in 2011 and 2012. All patients had a 4D-CT performed prior to parathyroidectomy. CT localization of the suspected adenoma was correlated to the actual surgical findings and subsequent histological diagnosis was also available as references for the accuracy of this imaging tool. Hyperfunctioning parathyroid glands were found in 40 patients. 4D-CT identified 32 solitary hyperfunctioning parathyroid glands located on the correct side of the neck (PPV 76 %) and 21 located within the correct quadrant (PPV 49 %). Unilateral resection was performed in 72 % of patients due to the localization findings of preoperative imaging. 4D-CT can, therefore, be considered an effective method for the preoperative localization of parathyroid adenomas and is an important tool in surgical intervention for patients referred to parathyroidectomy.

  14. Renal cell carcinoma metastasis to the parathyroid gland: A very rare occurrence.

    Science.gov (United States)

    Ofo, Enyinnaya; Mandavia, Rishi; Jeannon, Jean-Pierre; Odell, Edward; Simo, Ricard

    2014-01-01

    Metastases to the parathyroid gland are very uncommon. Although renal cell carcinoma metastasis to the head and neck region is well recognised, with a predilection for unpredictable metastasis to unusual sites such as the thyroid gland, nose, paranasal sinuses, and cranial bones, there are no reports of parathyroid gland involvement. We describe an unusual case of renal cell carcinoma metastasis to a parathyroid gland in a 69-year-old male who had been treated 8 years previously for a pT3b N0 M1 clear cell carcinoma of the right kidney with a right nephrectomy, and interferon immunotherapy for 18 months. The patient had originally presented to the plastic surgeons with a rapidly enlarging 3cm superficial lesion on the ventral aspect of the left forearm, which was excised with histology revealing metastatic renal (clear) cell carcinoma. Renal cell carcinoma has a reputation for unpredictable patterns of metastasis, and our case highlights this, with the first description in the literature of parathyroid gland metastasis. Despite the poor prognosis associated with metastatic renal cell carcinoma, our patient is still alive 10 years following original presentation, despite having metastasis to two different extra-renal sites and a shortened course of initial adjuvant systemic therapy. In parathyroid gland metastasis, metastectomy can offer excellent local long term local control. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Risk of parathyroid adenomas in patients with thyrotoxicosis exposed to radioactive iodine

    Energy Technology Data Exchange (ETDEWEB)

    Rasmuson, Torgny; Tavelin, Bjoern [Umeaa Univ. (Sweden). Dept. of Radiation Sciences, Oncology

    2006-12-15

    External ionizing radiation is a risk factor for primary hyperparathyroidism. Whether exposure to radioactive iodine contributes to the risk of primary hyperparathyroidism is unknown. Patients with thyrotoxicosis are often treated with radioactive iodine and its accumulation in the thyroid gland exposes the adjacent parathyroid glands to radioactivity. Six thousand and eighty two patients with thyrotoxicosis were identified from medical records. In a randomly selected subcohort we assessed the frequency of treatment with radioactive iodine to be 86%. The number of patient-years at risk was 77-118. Patients with parathyroid adenomas were recruited from the Swedish Cancer Registry. Eleven patients with parathyroid adenomas following the diagnosis of thyrotoxicosis were identified. The standard incidence ratio (SIR) compared to the reference population of 900,000 was 1.14. The median age at exposure was 59 years and the latency period between diagnosis of thyrotoxicosis and parathyroid adenoma was 7.4 years (range <1-19 years). This study does not indicate that patients with thyrotoxicosis treated with radioactive iodine in adult age have increased risk of developing parathyroid adenoma.

  16. Non-functioning parathyroid adenoma: a rare differential diagnosis for vocal-cord paralysis.

    Science.gov (United States)

    Kamali, D; Sharpe, A; Nagarajan, S; Elsaify, W

    2016-07-01

    Introduction Adenomas of the parathyroid gland typically present with symptoms of hyperparathyroidism, manifested by fatigue, bone pain, abdominal pain, weakness, dyspepsia, nephrolithiasis and skeletal bone disease. Here, we describe, for the first time, a case of a non-functioning benign tumour of the parathyroid gland presenting as vocal-cord paralysis. Case History A 49-year-old male presented with a 10-week history of dysphonia and the feeling of having 'something stuck in my throat'. History-taking elicited no other associated symptoms. Flexible nasal endoscopy demonstrated paralysis of the left vocal cord. Computed tomography of the neck revealed a cystic lesion, 18mm in diameter adjacent to the oesophagus. After more rigorous tests, a neck exploration, left hemithyroidectomy, excision of the left paratracheal mass and level-VI neck dissection was undertaken, without incident to the patient or surgical team. Histology was consistent with a parathyroid adenoma. Conclusions This case emphasises the importance of including adenomatous disease of the parathyroid gland in the differential diagnosis despite normal parathyroid status as a cause of vocal cord palsy.

  17. A mathematical/physiological model of parathyroid hormone secretion in response to blood-ionized calcium lowering in vivo

    DEFF Research Database (Denmark)

    Momsen, G; Schwarz, P

    1997-01-01

    patients with abnormal and normal parathyroid tissue. The fitted parameters showed no significant differences between patients with insulin-dependent diabetes mellitus and controls. In primary hyperparathyroidism, the parathyroid hormone production and steady-state transport across the cell membrane were...

  18. Influence of prolactin administration on the ultimobranchial body and parathyroid glands of the freshwater snake, Natrix piscator.

    Science.gov (United States)

    Srivastav, A K; Rani, L; Sasayama, Y

    1994-05-01

    The effects of ovine prolactin (10 I.U./100 g body wt) on the ultimobranchial body and parathyroid glands were investigated in Natrix piscator for 15 days. The ultimobranchial body of the prolactin treated specimens depicts signs of increased activity whereas the parathyroid glands exhibit reduced activity.

  19. Parathyroid hormone-related protein and glucocorticoid receptor beta are regulated by cortisol in the kidney of male mice.

    Science.gov (United States)

    Yoo, Yeong-Min; Baek, Myung-Gi; Jung, Eui-Man; Yang, Hyun; Choi, Kyung-Chul; Yu, Frank H; Jeung, Eui-Bae

    2011-10-24

    Parathyroid hormone-related protein (PTHrP) is a peptide growth factor produced in a wide range of tissues from brain and parathyroid, to kidney and uterus. The purpose of this study was to determine whether the adrenal cortical hormones, hydrocortisone (cortisol), modulate PTHrP expression and glucocorticoid receptor (GR)β in mice kidney. Changes in PTHrP gene expression were determined by real-time PCR and its protein level was examined by Western blot analysis. In addition, expression of renal PTHrP protein was localized by immunohistochemistry. Effects of RU486 on the expression levels of GRα/β or PTHrP gene in the kidneys were analyzed by Western blot analysis. We found that renal expression levels of PTHrP mRNA were higher in males than in females up to 9weeks of age. Using immunohistochemistry, we observed higher levels of PTHrP expression within the cortex than in the medulla in both male and female mice, and this expression was localized in the epithelial cells of the renal proximal tubules. Treatment of 4-week-old mice with aldosterone and cortisol for three days showed larger increases in both PTHrP mRNA and protein levels in males compared with females. The expression of GRβ in male, but not female, kidneys was significantly upregulated after treatment with cortisol, but not after treatment with aldosterone. Inhibition of glucocorticoid signaling by pre-treatment with a GR antagonist prior to cortisol administration largely abolished this cortisol-dependent increase in PTHrP and GRβ expressions. These results suggest that PTHrP expression and GRβ in the kidneys of male mice may be regulated by cortisol. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Aortopulmonary window parathyroid gland causing primary hyperparathyroidism in men type 1 syndrome.

    Science.gov (United States)

    Tonelli, Francesco; Biagini, Carlo; Giudici, Francesco; Cioppi, Federica; Brandi, Maria Luisa

    2016-01-01

    Primary hyperparathyroidism (HPT) is the most common endocrinopathy in Multiple Endocrine Neoplasia type 1 (MEN1) syndrome. Supernumerary and/or ectopic parathyroid glands, potentially causes of persistent or recurrent HPT after surgery, have been previously described. However, this is the first ever described case of ectopic parathyroid gland localized in the aortopulmunary window causing HPT in MEN1. After a consistent concordant pre-operative imaging assessment the patient, a 16 years old male affected by a severe hypercalcemia, underwent surgery. The parathyroid was found very deeply near the tracheal bifurcation, hidden by the aortic arch itself and for this reason not visible at the beginning of the dissection but only after being identified by palpation for its typical consistence. The intraoperative PTH decreased at normal level 10 min after removal of the ectopic gland. The patient remained with normal value of calcemia and PTH during the 10 months of follow-up.

  1. Localisation of the neuropeptide PACAP and its receptors in the rat parathyroid and thyroid glands

    DEFF Research Database (Denmark)

    Fahrenkrug, Jan; Hannibal, Jens

    2011-01-01

    PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2). Here we examined the localisation and nature of PACAP-immunoreactive nerves in the rat thyroid and parathyroid glands and defined...... the distribution of PAC(1), VPAC(1) and VPAC(2) receptor mRNA's. In the parathyroid gland a large number of nerve fibres displaying PACAP-immunoreactivity were distributed beneath the capsule, around blood vessels and close to glandular cells. Most of the PACAP-nerves were sensory, since they co-stored CGRP...... (calcitonin-gene-related peptide) and were sensitive to capsaicin-treatment. mRNA's for PAC(1) and VPAC(2) receptors occurred in the parathyroid gland, mainly located in the glandular cells. In the thyroid gland PACAP-immunoreactive nerve fibres were associated with blood vessels, thyroid follicles...

  2. An analysis of preoperative localization of parathyroid glands in hyperparathyroidism associated with thyroid diseases

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, Makoto; Inoue, Kazuaki [Fujimi-kogen Hospital, Nagano (Japan); Itoh, Atsuko

    1996-05-01

    Recently hyperparathyroidism associated with some thyroid diseases, especially nonmedually thyroid carcinoma has been payed attention to. In this study we analyzed 12 cases of hyperparathyroidism (6 cases independent of thyroid diseases and 6 cases associated with thyroid diseases) and estimated the affect of association with thyroid diseases on the preoperative localization of the parathyroid glands. The results of preoperative localization of the parathyroid glands in cases independent of thyroid diseases were relatively satisfactory. On the other hand, the preoperative localization in cases associated with thyroid diseases came to false result in about half of them. It was far from satisfactory. Association of thyroid diseases strongly affected the preoperative localization of the parathyroid glands in hyperparathyroidism. Conventional imaging such as ultrasonography, CT, MRI and {sup 201}Tl-{sup 99m}TC subtraction scintigraphy alone were not satisfactory. Now {sup 99m}Tc-MIBI scintigraphy is expected to be one of reliable imaging methods for progress in the preoperative localization. (author)

  3. Parathyroid Adenoma Located on Anterior Mediastinum and Hungry Bone Syndrome ; Case Report

    Directory of Open Access Journals (Sweden)

    Ali Celik

    2013-10-01

    Full Text Available   Anterior mediastinum is a rare localization for ectopic parathyroid adenoma. This localization seen about 1-2 % in the patient that looked for primary  ypherparathyroidism etiology. On a 33 - years old male patient who had searched for primary   perparathyroidism etiology, an anterior mediastinal lesion which referred to be an ectopic parathyroid adenoma was detected via Tc-99m MIBI. After, total mass excision was performed via sternotomy, pathologic examination reported as parathyroid adenoma. In early postoperative period, hungry bone syndrome was occured. After treatment, the patient whose clinic and laboratory results was normal discharged uneventful. The ectopic paratroid adenomas and their surgical  options and postoperative management has reviewed with literature knowladge  due to this case.

  4. The calcium-sensing receptor and the parathyroid: past, present, future

    Directory of Open Access Journals (Sweden)

    Arthur David Conigrave

    2016-12-01

    Full Text Available Parathyroid hormone (PTH defends the extracellular fluid from hypocalcemia and has powerful and well-documented actions on the skeleton and renal tubular system. To achieve a satisfactory stable plasma calcium level, the secretion of PTH, and the resulting serum PTH level, is titrated carefully to the prevailing plasma ionized Ca2+ concentration via a Ca2+ sensing mechanism that mediates feedback inhibition of PTH secretion. Herein, I consider the properties of the parathyroid Ca2+ sensing mechanism, the identity of the Ca2+ sensor, the intracellular biochemical mechanisms that it controls, the manner of its integration with other components of the PTH secretion control mechanism, and its modulation by other nutrients. Together the well established, recently elucidated, and yet-to-be discovered elements of the story constitute the past, present, and future of the parathyroid and its calcium-sensing receptor (CaSR.

  5. Ectopic paraesophageal mediastinal parathyroid adenoma, a rare cause of acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Koutarelos Dimitrios

    2004-11-01

    Full Text Available Abstract Background The manifestation of primary hyperparathyroidism with acute pancreatitis is a rare event. Ectopic paraesophageal parathyroid adenomas account for about 5%–10% of primary hyperparathyroidism and surgical resection results in cure of the disease. Case presentation A 71-year-old woman was presented with acute pancreatitis and hypercalcaemia. During the investigation of hypercalcemia, a paraesophageal ectopic parathyroid mass was detected by computerized tomography (CT scan and 99mTc sestamibi scintigraphy. The tumor was resected via a cervical collar incision and calcium and parathormone tumor levels returned to normal within 48 hours. Conclusions Acute pancreatitis associated with hypercalcaemia should pose the suspicion of primary hyperparathyroidism. Accurate preoperative localization of an ectopic parathyroid adenoma, by using the combination of 99mTc sestamibi scintigraphy and CT scan of the neck and chest allows successful surgical treatment.

  6. Role of the metabolism of parathyroid hormone. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Teitelbaum, Anne P. [Univ. of Rochester, NY (United States)

    1978-01-01

    The heterogeneity of parathyroid hormone (PTH) in plasma has prompted investigations of the metabolism of PTH and its relationship to hormone action. The time course of tissue distribution and metabolism of electrolytically iodinated PTH (E-PTH) previously shown to retain biological activity was compared with that of inactive PTH iodinated with Chloramine-T (CT-PTH). Labeled PTH (0.4 μg) was injected in the saphenous veins of anesthetized rats which were sacrificed at 1, 3, 5, 10, and 20 min. Tissue extracts from kidney, liver, and serum were chromatographed to separate intact PTH from its metabolites. In the kidney, the initial rate of degradation of E-PTH was greater than that of CT-PTH. The difference in initial rates of metabolism may be due, in part, to receptor-specific hydrolysis on peritubular cell membranes which selectively act on biologically active PTH molecules. PTH-responsive adenyl cyclase activity in isolated kidney cortex plasma membranes was measured and PTH metabolism was monitored simultaneously. When degradation was completely blocked by histone f3 (1 mg/ml), adenyl cyclase activity was significantly increased over control. In addition, when adenyl cyclase activity was negligible, the rate of PTH degradation by the membranes was not significantly diminished. Consistent with the in vivo data was the observation that E-PTH is metabolized by these membranes at a greater rate than CT-PTH. The data demonstrate the existence of a receptor-specific metabolism at sites which are independent of PTH receptor mediated adenyl cyclase activity.

  7. The Neuroendocrine Functions of the Parathyroid Hormone 2 Receptor

    Directory of Open Access Journals (Sweden)

    Arpad eDobolyi

    2012-10-01

    Full Text Available The G-protein coupled parathyroid hormone 2 receptor (PTH2R is concentrated in endocrine and limbic regions in the forebrain. Its endogenous ligand,tuberoinfundibular peptide of 39 residues (TIP39, is synthesized in only 2 brain regions, within the posterior thalamus and the lateral pons. TIP39-expressing neurons have a widespread projection pattern, which matches the PTH2R distribution in the brain. Neuroendocrine centers including the preoptic area, the periventricular, paraventricular, and arcuate nuclei contain the highest density of PTH2R-positive networks. The administration of TIP39 and an antagonist of the PTH2R as well as the investigation of mice that lack functional TIP39 and PTH2R revealed the involvement of the PTH2R in a variety of neural and neuroendocrine functions. TIP39 acting via the PTH2R modulates several aspects of the stress response. It evokes corticosterone release by activating corticotropin-releasing hormone-containing neurons in the hypothalamic paraventricular nucleus. Block of TIP39 signaling elevates the anxiety state of animals and their fear response, and increases stress-induced analgesia. TIP39 has also been suggested to affect the release of additional pituitary hormones including arginine vasopressin and growth hormone. A role of the TIP39-PTH2R system in thermoregulation was also identified. TIP39 may play a role in maintaining body temperature in a cold environment via descending excitatory pathways from the preoptic area. Anatomical and functional studies also implicated the TIP39-PTH2R system in nociceptive information processing. Finally, TIP39 induced in postpartum dams may play a role in the release of prolactin during lactation. Potential mechanisms leading to the activation of TIP39 neurons and how they influence the neuroendocrine system are also described. The unique TIP39-PTH2R neuromodulator system provides the possibility for developing drugs with a novel mechanism of action to control

  8. Parathyroid hormone-related protein promotes epithelial-mesenchymal transition.

    Science.gov (United States)

    Ardura, Juan Antonio; Rayego-Mateos, Sandra; Rámila, David; Ruiz-Ortega, Marta; Esbrit, Pedro

    2010-02-01

    Epithelial-mesenchymal transition (EMT) is an important process that contributes to renal fibrogenesis. TGF-beta1 and EGF stimulate EMT. Recent studies suggested that parathyroid hormone-related protein (PTHrP) promotes fibrogenesis in the damaged kidney, apparently dependent on its interaction with vascular endothelial growth factor (VEGF), but whether it also interacts with TGF-beta and EGF to modulate EMT is unknown. Here, PTHrP(1-36) increased TGF-beta1 in cultured tubuloepithelial cells and TGF-beta blockade inhibited PTHrP-induced EMT-related changes, including upregulation of alpha-smooth muscle actin and integrin-linked kinase, nuclear translocation of Snail, and downregulation of E-cadherin and zonula occludens-1. PTHrP(1-36) also induced EGF receptor (EGFR) activation; inhibition of protein kinase C and metalloproteases abrogated this activation. Inhibition of EGFR activation abolished these EMT-related changes, the activation of ERK1/2, and upregulation of TGF-beta1 and VEGF by PTHrP(1-36). Moreover, inhibition of ERK1/2 blocked EMT induced by either PTHrP(1-36), TGF-beta1, EGF, or VEGF. In vivo, obstruction of mouse kidneys led to changes consistent with EMT and upregulation of TGF-beta1 mRNA, p-EGFR protein, and PTHrP. Taken together, these data suggest that PTHrP, TGF-beta, EGF, and VEGF might cooperate through activation of ERK1/2 to induce EMT in renal tubuloepithelial cells.

  9. Parathyroid Hormone–Related Protein Promotes Epithelial–Mesenchymal Transition

    Science.gov (United States)

    Ardura, Juan Antonio; Rayego-Mateos, Sandra; Rámila, David; Ruiz-Ortega, Marta

    2010-01-01

    Epithelial–mesenchymal transition (EMT) is an important process that contributes to renal fibrogenesis. TGF-β1 and EGF stimulate EMT. Recent studies suggested that parathyroid hormone–related protein (PTHrP) promotes fibrogenesis in the damaged kidney, apparently dependent on its interaction with vascular endothelial growth factor (VEGF), but whether it also interacts with TGF-β and EGF to modulate EMT is unknown. Here, PTHrP(1-36) increased TGF-β1 in cultured tubuloepithelial cells and TGF-β blockade inhibited PTHrP-induced EMT-related changes, including upregulation of α-smooth muscle actin and integrin-linked kinase, nuclear translocation of Snail, and downregulation of E-cadherin and zonula occludens-1. PTHrP(1-36) also induced EGF receptor (EGFR) activation; inhibition of protein kinase C and metalloproteases abrogated this activation. Inhibition of EGFR activation abolished these EMT-related changes, the activation of ERK1/2, and upregulation of TGF-β1 and VEGF by PTHrP(1-36). Moreover, inhibition of ERK1/2 blocked EMT induced by either PTHrP(1-36), TGF-β1, EGF, or VEGF. In vivo, obstruction of mouse kidneys led to changes consistent with EMT and upregulation of TGF-β1 mRNA, p-EGFR protein, and PTHrP. Taken together, these data suggest that PTHrP, TGF-β, EGF, and VEGF might cooperate through activation of ERK1/2 to induce EMT in renal tubuloepithelial cells. PMID:19959711

  10. Correlation between serum parathyroid hormone levels and coronary artery calcification in patients without renal failure.

    Science.gov (United States)

    Wu, Gang-Yong; Xu, Bai-Da; Wu, Ting; Wang, Xiao-Ying; Wang, Tian-Xiao; Zhang, Xiao; Wang, Xiao; Xia, Yang; Zong, Gang-Jun

    2016-11-01

    The aim of the present study was to investigate the correlation between serum parathyroid hormone (PTH) levels and coronary artery calcification (CAC) in patients without renal failure, as well as to determine independent risk factors of CAC score (CACS). A total of 157 patients who underwent coronary computed tomography angiographic examination at the 101th Hospital of the People's Liberation Army between December 2013 and February 2015 were retrospectively evaluated. The correlation between PTH levels and CACS was determined using a Pearson correlation analysis. A receiver operating characteristic (ROC) curve was drawn to determine the best cutoff PTH level for prediction of CAC. The independent association between serum PTH levels and CAC was analyzed by using a logistic regression analysis model with the response variable Be binary class. The results revealed that PTH levels in patients in the CAC group were significantly higher than those of patients in the non-calcification group. PTH levels were positively correlated with CACS (r=0.288, PCAC, with a sensitivity of 80.88%, specificity of 60.67% and an area under the curve of 0.761. After including predictive factors for CAC (gender, age, smoking status, diabetes, hypertension, hyperlipidemia, body mass index, glomerular filtration rate and calcium, phosphorus, calcium-phosphorus product, magnesium, PTH, total cholesterol, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol and C-reactive protein levels), the odds ratio of the serum PTH levels regarding the prediction of CAC was 1.050 (95% confidence interval, 1.027-1.074; PCAC in patients without renal failure and may thus be used as a reliable predictor of CAC.

  11. Parathyroid gland anatomical distribution and relation to anthropometric and demographic parameters: a cadaveric study.

    Science.gov (United States)

    Hojaij, Flávio; Vanderlei, Felipe; Plopper, Caio; Rodrigues, Consuelo Junqueira; Jácomo, Alfredo; Cernea, Claudio; Oliveira, Leonardo; Marchi, Luis; Brandão, Lenine

    2011-12-01

    Parathyroid glands play an important role in controlling calcium levels, which influence muscular contraction and neurotransmission. The number of variants, localization and ectopic positions make these glands tricky during surgical exploration. Detailed anatomical knowledge of these glands is fundamental to avoid postsurgical hypoparathyroidism, such as failures during thyroidectomy and parathyroid procedures. The purposes of this work were to study and report practical knowledge for surgeons in order to localize the glands. Dissections were performed on 56 cadavers. Gland identity was confirmed by histological study. Also, mediastinal tissue and the carotid sheath were treated with Carnoy's solution to identify ectopic glands. The thyroid gland was divided and sliced to identify parathyroid glands in the parenchymal and subcapsular space. Four or more parathyroid glands were found in 89.3% of the studied specimens. Mean gland weight was 33.1 mg, and its mean measurements were 6.7 × 3.9 × 2.0 mm. In more than 90% of the cases there was a correlation with the inferior laryngeal nerve and the parathyroid glands: the upper glands were located in medial positions, and the lower ones were found to be located laterally. In 42.8% of cases at least one ectopic gland was observed. The main ectopic regions were the mediastinum and thymus (19.6%), thyroid subcapsular space (12.5%) and thyroid parenchyma (5.4%). Quantity, gland characteristics and location were not influenced by anthropometric and demographic parameters. Here we show the high incidence of parathyroid glands positioned at "abnormal" locations, and as a controversial topic in endocrine surgery, this matter must be continuously studied and reported in the literature.

  12. Double-phase Tc-99m tetrofosmin parathyroid scan in hyperparathyroidism: comparison with ultrasonography

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    Kim, In Soo; Kim, Sang Yoon [Daegu Fatima Hospital, Daegu (Korea, Republic of); Zeon, Seok Kil; Won, Kyoung Sook [School of Medicine, Keimyung University, Daegu (Korea, Republic of)

    2004-07-01

    This study was performed to evaluate the utility of double-phase Tc-99m Tetrofosmin(TF) parathyroid scan in the detection of pathologic lesions of primary hyperparathyroidism, and comparison with the ultrasonography(US). The double phase TF parathyroid scan of the anterior neck including upper mediastinum with 800 MBq TF were acquired at ten minutes (early phase) and at two hours (delayed phase) after radiopharmaceutical injection, in 24 consecutive patients under the clinical impression of primary hyperparathyroidism and hypercalcaemia. The images were evaluated for abnormal focal areas of increased tracer localization in the anterior neck and superior mediastinum in early phase, and visualization of parathyroid gland radioactivity after wash-out of the thyroid gland radioactivity in delayed phase. US of the anterior neck including upper mediastinum was performed by a diagnostic radiologist in 24 consecutive patients, within one week before or after the scan. The findings of double phase TF parathyroid scan and US were compared with the pathologic results. Ten of 24 patients were surgically explored and pathologic results showed eight adenomas and two hyperplasia. The double phase TF parathyroid scan showed positive findings in seven patients of eight adenomas and one patient of two hyperplasia patients. US image showed positive findings in six patients of eight adenomas and no positive findings of two hyperplasia. The sensitivity of the double phase TF scan for detection of the causes of the primary hyperparathyroidism was 80% and US was 60%. The double phase Tc-99m Tetrofosmin parathyroid scan showed higher sensitivity in detection of the pathologic lesions of primary hyperparathyroidism than ultrasonography.

  13. Parathyroid ultrasonography and bone metabolic profile of patients on dialysis with hyperparathyroidism

    Science.gov (United States)

    Ribeiro, Cláudia; Penido, Maria Goretti Moreira Guimarães; Guimarães, Milena Maria Moreira; Tavares, Marcelo de Sousa; Souza, Bruno das Neves; Leite, Anderson Ferreira; de Deus, Leonardo Martins Caldeira; Machado, Lucas José de Campos

    2016-01-01

    AIM To evaluate the parathyroid ultrasonography and define parameters that can predict poor response to treatment in patients with secondary hyperparathyroidism due to renal failure. METHODS This cohort study evaluated 85 patients with chronic kidney disease stage V with parathyroid hormone levels above 800 pg/mL. All patients underwent ultrasonography of the parathyroids and the following parameters were analyzed: Demographic characteristics (etiology of chronic kidney disease, gender, age, dialysis vintage, vascular access, use of vitamin D), laboratory (calcium, phosphorus, parathyroid hormone, alkaline phosphatase, bone alkaline phosphatase), and the occurrence of bone changes, cardiovascular events and death. The χ2 test were used to compare proportions or the Fisher exact test for small sample frequencies. Student t-test was used to detect differences between the two groups regarding continuous variables. RESULTS Fifty-three patients (66.4%) had parathyroid nodules with higher levels of parathyroid hormone, calcium and phosphorus. Sixteen patients underwent parathyroidectomy and had higher levels of phosphorus and calcium × phosphorus product (P = 0.03 and P = 0.006, respectively). They also had lower mortality (32% vs 68%, P = 0.01) and lower incidence of cardiovascular or cerebrovascular events (27% vs 73%, P = 0.02). Calcium × phosphorus product above 55 mg2/dL2 [RR 1.48 (1.06, 2.08), P = 0.03], presence of vascular calcification [1.33 (1.01, 1.76), P = 0.015] and previous occurrence of vascular events [RR 2.25 (1.27, 3.98), P < 0.001] were risk factors for mortality in this population. There was no association between the occurrence of nodules and mortality. CONCLUSION The identification of nodules at ultrasonography strengthens the indication for parathyroidectomy in patients with secondary hyperparathyroidism due to renal failure. PMID:27648407

  14. Causes of discordant or negative ultrasound of parathyroid glands in treatment naïve patients with primary hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Chandramohan, Anuradha, E-mail: anuradhachandramohan@gmail.com [Department of Radiology, Christian Medical College, Vellore, Tamil Nadu 632004 (India); Sathyakumar, Kirthi, E-mail: kirthi86s@yahoo.com [Department of Radiology, Christian Medical College, Vellore, Tamil Nadu 632004 (India); Irodi, Aparna, E-mail: aparnashyam@gmail.com [Department of Radiology, Christian Medical College, Vellore, Tamil Nadu 632004 (India); Abraham, Deepak, E-mail: abrahamdt@gmail.com [Department of Endocrine Surgery, Christian Medical College, Vellore, Tamil Nadu 632004 (India); Paul, M.J., E-mail: mjpaul@cmcvellore.ac.in [Department of Endocrine Surgery, Christian Medical College, Vellore, Tamil Nadu 632004 (India)

    2012-12-15

    Objectives: To describe causes of discordant or negative parathyroid ultrasound and to assess factors influencing them. Materials and methods: Retrospective review of patients who underwent parathyroidectomy between 2000 and 2012 was done. Imaging findings were compared with operative findings and pathology to identify discrepant (n = 60; 32 negative, 28 incorrect) parathyroid ultrasounds. Results: Fifty (83.3%) patients had parathyroid adenoma, of which 10 (16.6%) were ectopic and three were double adenomas; 8 (13.3%) had multigland hyperplasia and two had parathyroid carcinoma. Discrepant reports were due to incorrect localisation in 8 (13.3%); difficulty in differentiating thyroid from parathyroid lesion in 12 (20%); large and small size in two and three patients, respectively; overcall in 5 (8.3%) and satisfaction of search in 7 (11.7%) patients. There was significant correlation between presence of multi-nodular goitre and incorrect reports (χ{sup 2} = 4.112, p = 0.04). Experience of ultrasound operators performing initial and second look ultrasound was significantly different (p < 0.0001). Second look ultrasound was concordant with surgical findings in 39(65%) patients; 21 (66%) patients with initially negative ultrasound and four out of five extra-mediastinal ectopic lesions. Ten patients with negative initial ultrasound had elongated parathyroid lesion. Scintigraphy was concordant in 44 (73.3%) patients and nine were ectopic. Conclusion: Second look ultrasound performed by experienced operator for negative or discordant initial ultrasound of parathyroid is a useful strategy which will improve the accuracy of parathyroid ultrasound. Being able to differentiate thyroid from parathyroid lesion is a factor which will influence performance of parathyroid ultrasound.

  15. Development and prevention of morphologic and ultrastructural changes in uremia-induced hyperplastic parathyroid gland.

    Science.gov (United States)

    Shiizaki, Kazuhiro; Hatamura, Ikuji; Mato, Masao; Nakazawa, Eiko; Saji, Fumie; Onishi, Akira; Ogura, Manabu; Watanabe, Yuko; Kusano, Eiji

    2011-10-01

    The detailed ultrastructural changes of uremia-induced hyperplastic parathyroid gland and the effects of current medical treatments for secondary hyperparathyroidism were investigated. Marked enlargement of parathyroid cell with accumulation of mitochondria and lipids and a significant increase in the thickness of the pericapillary area with increased fibrosis and appearance of fibroblast like cells were noted in the hyperplastic gland caused by uremia and phosphate retention. These ultrastructural changes and biochemical findings indicating hyperparathyroidism were significantly suppressed by all of the treatment using phosphate restriction, calcitriol, and cinacalcet. The characteristic ultrastructural changes, including the morphologic evidence of nodule formation, were indicated.

  16. Turn-on switch in parathyroid hormone receptor by a two-step parathyroid hormone binding mechanism.

    Science.gov (United States)

    Castro, Marián; Nikolaev, Viacheslav O; Palm, Dieter; Lohse, Martin J; Vilardaga, Jean-Pierre

    2005-11-01

    Parathyroid hormone (PTH) and its related receptor (PTHR) are essential regulators of calcium homeostasis and bone physiology. PTH activates PTHR by interacting with a ligand-binding site localized within the N-terminal extracellular domain (the N-domain) and the domain comprising the seven transmembrane helices and the connecting extracellular loops (the J-domain). PTH binding triggers a conformational switch in the receptor, leading to receptor activation and subsequent cellular responses. The process of receptor activation occurs rapidly, within approximately 1 s, but the binding event preceding receptor activation is not understood. By recording FRET between tetramethyl-rhodamine in PTH(1-34) and GFP in the N-domain of the receptor, we measured the binding event in real time in living cells. We show that the association time course between PTH(1-34) and PTHR involves a two-step binding process where the agonist initially binds the receptor with a fast time constant (tau approximately 140 ms) and then with slower kinetics (tau approximately 1 s). The fast and slow phases were assigned to hormone association to the receptor N- and J domains, respectively. Our data indicate that the slow binding step to the J-domain coincides with a conformational switch in the receptor, also monitored by FRET between the enhanced cyan fluorescent protein and the enhanced yellow fluorescent protein in the PTHR sensor, PTHR enhanced cyan fluorescent protein/enhanced yellow fluorescent protein (PTHR(CFP/YFP)). These data suggest that the conformational change that switches the receptor into its active state proceeds in a sequential manner, with the first rapid binding step event preceding receptor activation by PTH(1-34).

  17. Vitamin D3 differentially regulates parathyroid hormone/parathyroid hormone-related peptide receptor expression in bone and cartilage.

    Science.gov (United States)

    Amizuka, N; Kwan, M Y; Goltzman, D; Ozawa, H; White, J H

    1999-02-01

    Transcription of the mouse parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTHR) gene is controlled by promoters P1 and P2. We performed transcript-specific in situ hybridization and found that P2 is the predominant promoter controlling PTHR gene expression in bone and cartilage. Treatment with 1alpha, 25-dihydroxyvitamin D3 (D3) in vivo specifically downregulated P2-specific transcripts in osteoblasts, but not in chondrocytes, under conditions where it enhanced bone resorption. Treatment of the osteoblastic cell line MC3T3-E1 with D3 in vitro reduced expression of both P2-specific transcripts and PTHR protein. This effect was not blocked by cycloheximide, indicating that D3 inhibits PTHR expression by downregulating transcription of the P2 promoter. A similar inhibitory effect of D3 was not observed in the chondrocytic cell line CFK2. Gene-transfer experiments showed that P2, but not P1, is active in both MC3T3-E1 and CFK2 cells, and that D3 specifically inhibited P2 promoter activity in MC3T3-E1, but not in CFK2 cells. Inhibition of P2 activity by D3 required promoter sequences lying more that 1.6 kb upstream of the P2 transcription start site. Thus, the P2 promoter controls PTHR gene expression in both osteoblasts and chondrocytes. D3 downregulates PTHR gene transcription in a cell-specific manner by inhibiting P2 promoter activity in osteoblasts, but not in chondrocytes.

  18. Parathyroid scintigraphy protocols in Finland in 2010. Results of the query and current status

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    Tunninen, V. [The Dept. of Nuclear Medicine, Satakunta Central Hospital, Pori (Finland); Kauppinen, T. [HUS Helsinki Medical Imaging Centre, Helsinki Univ. Hospital (Finland); Eskola, H. [The Dept. of Biomedical Engineering, Tampere Univ. of Technology (Finland); Koskinen, M.O. [Medical Imaging Centre, Tampere Univ. Hospital (Finland)

    2010-07-01

    The goal of this study was to describe current clinical parathyroid scintigraphy (PS) protocols in Finland. Methods: All departments of nuclear medicine in Finland were contacted, and instructions regarding PS were requested. Results: Instructions regarding PS were received from all of the departments that perform PS (n = 19). Seven hundred and sixty-nine PS studies were performed in 2009 (between 7 and 209 per hospital). Three methods of PS were used. The dual-phase method with {sup 99m}Tc-sestamibi is used in seven hospitals, the dual-tracer method with {sup 123}I/{sup 99m}Tc-sestamibi in eleven, and {sup 99m}TcO{sub 4}/{sup 99m}Tc-sestamibi in one hospital. The activities of {sup 99m}Tc-sestamibi, {sup 123}I and {sup 99m}TcO{sub 4} were 150-800 MBq, 10-30 MBq and 50 MBq, respectively. The anterior image with parallel-hole collimators, the anterior image with pinhole collimator, the oblique angles with pinhole collimator, SPECT and hybrid CT with SPECT were acquired in 84%, 26%, 16%, 63%, and 42% of the hospitals, respectively. Because the imaging techniques were combined, one to four acquisitions were performed per patient. Scatter and attenuation correction were used in five protocols. A correction for crosstalk of {sup 123}I and {sup 99m}Tc gamma energies was not used, but the amount of crosstalk was decreased by using narrow or asymmetric energy windows in all dual isotope protocols. Conclusion: 19 hospitals used 18 different study protocols. Thus, significant variability exists in the current practice of PS in Finland. The protocols should be tested with known phantoms to determine any differences in sensitivities for detecting small active structures. Further studies with phantoms are needed to determine the optimal imaging techniques. The results of these phantom studies will provide guidelines for proposing national recommendations for PS. (orig.)

  19. Bone-targeting parathyroid hormone conjugates outperform unmodified PTH in the anabolic treatment of osteoporosis in rats.

    Science.gov (United States)

    Yang, Yang; Aghazadeh-Habashi, Ali; Panahifar, Arash; Wu, Yuchin; Bhandari, Krishna H; Doschak, Michael R

    2017-08-01

    Synthetic parathyroid hormone (PTH) is clinically indicated for the treatment of osteoporosis, through its anabolic effects on parathyroid hormone receptors (PTHRs), located on osteoblast cells. However, the bioavailability of PTH for bone cells is restricted by the short half-life of PTH and the widespread distribution of PTHRs in non-skeletal tissues. To impart affinity for mineralized bone surfaces, bisphosphonate (BP)-mediated PTH analogues were synthesized, characterized, and evaluated in vitro and in vivo. The successful synthesis of PTH-PEG-BP was identified on MALDI-ToF mass spectra; bone-targeting potential was evaluated by hydroxyapatite binding test; and receptor bioactivity was assessed in UMR-106 (rat osteosarcoma) cells that constitutively express PTHRs. Therapeutic efficacy was evaluated using ovariectomized rats that remained untreated for 8 weeks to allow development of osteopenia. Those rats then received daily subcutaneous injections of PTH-PEG-BP, thiol-BP vehicle, or unmodified PTH, and compared to sham-operated healthy rats at 0, 4, 8, 12, and 16 weeks. In vivo micro-CT was conducted on the proximal tibial metaphysis to measure microstructural bone parameters, and new bone formation was detected using dynamic labeling. Bone strength was assessed using three-point bending mechanical testing. Our study determined that PTH-PEG-BP conjugates significantly enhanced PTH targeting to the bone matrix while retaining full PTH bioactivity. Moreover, PTH-PEG-BP conjugates significantly increased trabecular bone quality, anabolic bone formation, and improved bone strength over systemically administered PTH alone. We highlight the promise of a novel class of bone-targeting anabolic compound for the treatment of osteoporosis and related bone disorders.

  20. Response to an oral calcium load in nephrolithiasis patients with fluctuating parathyroid hormone and ionized calcium levels

    Directory of Open Access Journals (Sweden)

    Gomes S.A.

    2004-01-01

    Full Text Available the response to an oral calcium load test was assessed in 17 hypercalciuric nephrolithiasis patients who presented elevated parathyroid hormone (PTH irrespective of the ionized calcium (sCa2+ levels. Blood samples were collected at baseline (0 min and at 60 and 180 min after 1 g calcium load for serum PTH, total calcium, sCa2+, and 1.25(OH2D3 determinations. According to the sCa2+ level at baseline, patients were classified as normocalcemic (N = 9 or hypercalcemic (N = 8. Six healthy subjects were also evaluated as controls. Bone mineral density was reduced in 14/17 patients. In the normocalcemic group, mean PTH levels at 0, 60 and 180 min (95 ± 76, 56 ± 40, 57 ± 45 pg/ml, respectively did not differ from the hypercalcemic group (130 ± 75, 68 ± 35, 80 ± 33 pg/ml but were significantly higher compared to healthy subjects despite a similar elevation in sCa2+ after 60 and 180 min vs baseline in all 3 groups. Mean total calcium and 1.25(OH2D3 were similar in the 3 groups. Additionally, we observed that 5 of 9 normocalcemic patients presented a significantly higher concentration-time curve for serum PTH (AUC0',60',180' than the other 4 patients and the healthy subjects, suggesting a primary parathyroid dysfunction. These data suggest that the individual response to an oral calcium load test may be a valuable dynamic tool to disclose a subtle primary hyperparathyroidism in patients with high PTH and fluctuating sCa2+ levels, avoiding repeated measurements of both parameters.

  1. Response to an oral calcium load in nephrolithiasis patients with fluctuating parathyroid hormone and ionized calcium levels

    Directory of Open Access Journals (Sweden)

    S.A. Gomes

    2004-09-01

    Full Text Available the response to an oral calcium load test was assessed in 17 hypercalciuric nephrolithiasis patients who presented elevated parathyroid hormone (PTH irrespective of the ionized calcium (sCa2+ levels. Blood samples were collected at baseline (0 min and at 60 and 180 min after 1 g calcium load for serum PTH, total calcium, sCa2+, and 1.25(OH2D3 determinations. According to the sCa2+ level at baseline, patients were classified as normocalcemic (N = 9 or hypercalcemic (N = 8. Six healthy subjects were also evaluated as controls. Bone mineral density was reduced in 14/17 patients. In the normocalcemic group, mean PTH levels at 0, 60 and 180 min (95 ± 76, 56 ± 40, 57 ± 45 pg/ml, respectively did not differ from the hypercalcemic group (130 ± 75, 68 ± 35, 80 ± 33 pg/ml but were significantly higher compared to healthy subjects despite a similar elevation in sCa2+ after 60 and 180 min vs baseline in all 3 groups. Mean total calcium and 1.25(OH2D3 were similar in the 3 groups. Additionally, we observed that 5 of 9 normocalcemic patients presented a significantly higher concentration-time curve for serum PTH (AUC0',60',180' than the other 4 patients and the healthy subjects, suggesting a primary parathyroid dysfunction. These data suggest that the individual response to an oral calcium load test may be a valuable dynamic tool to disclose a subtle primary hyperparathyroidism in patients with high PTH and fluctuating sCa2+ levels, avoiding repeated measurements of both parameters.

  2. Localization of parathyroid hormone-related protein in the preimplantation mouse embryo is associated with events of blastocyst hatching.

    Science.gov (United States)

    Erbach, Gregory T; Biggers, John D; Manning, Peter C; Nowak, Romana A

    2013-08-01

    To determine the pattern of expression of parathyroid hormone-related protein (PTHrP) and its receptor, parathyroid hormone receptor 1 (PTHR1), in mouse embryos in different stages of preimplantation development. Embryos were cultured from the pronuclear zygote stage and harvested as 2-cell, 4-cell and 8-cell embryos, morulae and blastocysts. RT-PCR was carried out on mRNAs of these and of trophoblast outgrowths for detection of PTHrP and PTHR1. Whole mounted embryos intact or stripped of zonae pellucidae were immunofluorescently stained for PTHrP and PTH receptor and observed with confocal microscopy. PTHrP mRNA was present in the pronuclear zygote, not present in 2-cell, 4-cell and uncompacted 8-cell embryos, present in the 8-cell compacting embryo, and not detected in 16-cell morulae or blastocysts. The mRNA was present in trophoblasts growing on fibronectin beds. mRNA for PTHR1 was detected in the pronuclear zygote, then undetected until the compacted 8-cell stage and thereafter. PTH receptor protein was observed in 2-cell embryos, morulae and in the inner cell mass and trophectoderm of blastocysts. PTHrP was observed dispersed in the cytoplasm of 2-cell, 4-cell and uncompacted 8-cell embryos, and in distinct foci near the nuclei of morulae. In blastocysts, PTHrP appeared on the apical surface of only trophoblast cells which had extruded from the zona pellucida. Fully hatched blastocysts expressed the protein on the apical side of all trophoblasts. When morulae were prematurely stripped of their zonae, PTHrP was observed on the embryos' outer surface. PTHrP protein is expressed throughout early embryo development, and its receptor PTHR1 is expressed from the morula stage. Embryo hatching is associated with translocation of PTHrP to the apical plasma membrane of trophoblasts. PTHrP may thus have autocrine effects on the developing blastocyst.

  3. MOLECULAR MODELS OF PARATHYROID METABOLISM BY CARBOXYLESTERASES: DIFFERENTIAL EFFECTS DUE TO STEREOCHEMISTRY.

    Science.gov (United States)

    PARATHYROIDS ARE A CHEMICAL CLASS OF WIDELY USED INSECTICIDES, & AT LEAST 16 CHEMICALS IN THIS CLASS ARE REGISTERED FOR USE IN THE US. IN ORDER TO EXTRAPOLATE THE KNOWLEDGE FROM RODENTS TO HUMANS, PHYSIOLOGICALLY-BASED PHARMACOKINETIC (pbpk) MODELS ARE CURRENTLY BEING DEVELOPED.

  4. Relationship of the recurrent laryngeal nerve to the superior parathyroid gland during thyroidectomy.

    Science.gov (United States)

    Persky, Michael; Fang, Y; Myssiorek, D

    2014-03-25

    Design: The relationship of the recurrent laryngeal nerve to the superior parathyroid gland during consecutive thyroidectomies was prospectively evaluated. When one structure was noted, careful dissection was performed to locate the other structure, to preserve their natural anatomical relationship. Patients: In total, 103 consecutive thyroid lobectomies were performed on 73 patients. The distance from the superior parathyroid gland to the recurrent laryngeal nerve was recorded. Results: In 88 cases (88.9 per cent), the superior parathyroid gland was identified within 5 mm of the recurrent laryngeal nerve. In 62 cases (62.6 per cent), the gland was within 1 mm of the recurrent laryngeal nerve. The height of the thyroid lobe was positively associated with the distance between the two structures (p = 0.001), as was the incidence of cancer (p = 0.033). The incidence of recurrent laryngeal nerve paresis was less than 4 per cent. Conclusion: In most cases, the recurrent laryngeal nerve was found in close proximity to the superior parathyroid gland. In a thyroid gland with a large height, or in a cancerous lobe, this relationship is less reliable.

  5. Five to 10 years follow-up after total parathyroidectomy and autotransplantation of parathyroid tissue

    DEFF Research Database (Denmark)

    Knudsen, L; Brandi, L; Daugaard, H

    1996-01-01

    The aim of the present study was to assess the long-term function of autotransplanted parathyroid tissue in patients with chronic renal disease. We examined the medical records of a consecutive series of 21 patients with chronic renal failure, who had undergone total parathyroidectomy with autotr...

  6. Critical Role of Activating Transcription Factor 4 in the Anabolic Actions of Parathyroid Hormone in Bone

    NARCIS (Netherlands)

    Yu, Shibing; Franceschi, Renny T.; Luo, Min; Fan, Jie; Jiang, Di; Cao, Huiling; Kwon, Tae-Geon; Lai, Yumei; Zhang, Jian; Patrene, Kenneth; Hankenson, Kurt; Roodman, G. David; Xiao, Guozhi

    2009-01-01

    Parathyroid hormone (PTH) is a potent anabolic agent for the treatment of osteoporosis. However, its mechanism of action in osteoblast and bone is not well understood. In this study, we show that the anabolic actions of PTH in bone are severely impaired in both growing and adult ovariectomized mice

  7. Bilateral synchronous parathyroids cancer and femoral neck fracture as the complications of tertiary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    A F Romanchishen

    2013-12-01

    Full Text Available In the paper has presented the first in Russia observation of bilateral synchronous parathyroids cancer in patient with urolithiasis complicated by chronic pyelonephritis, renal insufficiency with tertiary hyperparathyroidism and femoral neck fracture. During observation of the patient in our hospital were found hyperparathyroid osteodystrophy, medial right femoral neck fracture, very high level of parathormone (1969,0 pg/ml, tumorous of right (16,0 × 17,0 mm and left (23,0 × 17,0 mm parathyroid glands located behind of inferior thyroid poles during ultrasound research. Surgical exploration has found bilateral whitish parathyroid tumorous with invasion to right recurrent laryngeal nerve. Were performed right hemithyroidectomy, left thyroid lobe resection and central neck dissections. Parathormone level has decreased to 3.5 times (up to 582 pg/ml. 20 minutes later after bilateral inferior parathyroidectomies. The regular hemodialysis was restore and six months later was successfully undertaken the hip prosthetics. Two year later after the surgery signs of parathyroid cancer relapses were no found.

  8. Diagnostic performance of computed tomography for parathyroid adenoma localization; a systematic review and meta-analysis

    NARCIS (Netherlands)

    Kluijfhout, Wouter; Pasternak, Jesse D.; Beninato, Toni; Drake, Frederick Thurston; Gosnell, Jessica E.; Shen, Wen T.; Duh, Quan Yang; Allen, Isabel E.; Vriens, Menno|info:eu-repo/dai/nl/236443461; de Keizer, Bart|info:eu-repo/dai/nl/271625112; Hope, Thomas A.; Suh, Insoo

    2017-01-01

    Abstract purpose To perform a systematic review and meta-analysis of the sensitivity and positive predictive value (PPV) of CT for preoperative parathyroid localization in patients with primary hyperparathyroidism (pHPT), and subsequently compare the different protocols and their performance in diff

  9. Sarcoidosis-related hypercalcaemia due to production of parathyroid hormone-related peptide

    NARCIS (Netherlands)

    van Raalte, Daniel H; Goorden, Susan M; Kemper, Evelien A; Brosens, Lodewijk A A; ten Kate, Reinier W

    2015-01-01

    Hypercalcaemia is frequently observed in patients with sarcoidosis. This is classically attributed to ectopic production of 1,25 dihydroxy vitamin D by sarcoid granulomas. We present a case of sarcoidosis-related hypercalcaemia with normal vitamin D levels. In this patient, production of parathyroid

  10. Parathyroid hormone-related protein regulates tumor-relevant genes in breast cancer cells.

    NARCIS (Netherlands)

    Dittmer, A.; Vetter, M.; Schunke, D.; Span, P.N.; Sweep, C.G.J.; Thomssen, C.; Dittmer, J.

    2006-01-01

    The effect of endogenous parathyroid hormone-related protein (PTHrP) on gene expression in breast cancer cells was studied. We suppressed PTHrP expression in MDA-MB-231 cells by RNA interference and analyzed changes in gene expression by microarray analysis. More than 200 genes showed altered

  11. Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans

    DEFF Research Database (Denmark)

    Aslan, Derya; Dahl Andersen, Mille; Gede, Lene Bjerring;

    2012-01-01

    Intermittent low-dose treatment with parathyroid hormone (PTH) analogues has become widely used in the treatment of severe osteoporosis. During normal physiological conditions, PTH stimulates both bone formation and resorption, and in patients with primary hyperparathyroidism, bone loss is frequent...

  12. Coordinated control of renal Ca(2+) transport proteins by parathyroid hormone.

    NARCIS (Netherlands)

    Abel, M. van; Hoenderop, J.G.J.; Kemp, J.W.C.M. van der; Friedlaender, M.M.; Leeuwen, J.P.P.M. van; Bindels, R.J.M.

    2005-01-01

    BACKGROUND: The kidney is one of the affected organs involved in the clinical symptoms of parathyroid hormone (PTH)-related disorders, like primary hyperparathyroidism and familial hypocalciuric hypercalcemia. The molecular mechanism(s) underlying alterations in renal Ca(2+) handling in these disord

  13. Greater seasonal cycling of 25-hydroxyvitamin D is associated with increased parathyroid hormone and bone resorption

    NARCIS (Netherlands)

    Darling, A L; Hart, K H; Gibbs, M A; Gossiel, F; Kantermann, T; Horton, K; Johnsen, S; Berry, J L; Skene, D J; Eastell, R; Vieth, R; Lanham-New, S A

    2014-01-01

    SUMMARY: This analysis assessed whether seasonal change in 25-hydroxyvitamin D concentration was associated with bone resorption, as evidenced by serum parathyroid hormone and C-terminal telopeptide concentrations. The main finding was that increased seasonal fluctuation in 25-hydroxyvitamin D was a

  14. Modern Surgical Management of Familial and Sporadic Parathyroid and Adrenal Disorders

    NARCIS (Netherlands)

    Scholten, A.

    2013-01-01

    Primary hyperparathyroidism (pHPT) is a common disease of the parathyroid glands. Multiple endocrine neoplasia (MEN) 1-related pHPT is most often caused by multiglandular disease and can best be treated with subtotal parathyroidectomy (3-3½ glands) and bilateral transcervical thymectomy to lower the

  15. Modern Surgical Management of Familial and Sporadic Parathyroid and Adrenal Disorders

    NARCIS (Netherlands)

    Scholten, A.

    2013-01-01

    Primary hyperparathyroidism (pHPT) is a common disease of the parathyroid glands. Multiple endocrine neoplasia (MEN) 1-related pHPT is most often caused by multiglandular disease and can best be treated with subtotal parathyroidectomy (3-3½ glands) and bilateral transcervical thymectomy to lower the

  16. Fine-Needle Aspiration Cytology of Parathyroid Carcinoma Mimic Hürthle Cell Thyroid Neoplasm

    Directory of Open Access Journals (Sweden)

    Chutintorn Sriphrapradang

    2014-01-01

    Full Text Available Background. Fine-needle aspiration (FNA can cause misdiagnosis of cytomorphological findings between parathyroid and thyroid lesions. Case Presentation. A 31-year-old man presented with a palpable neck mass on the right thyroid lobe. FNA cytology was reported as intrathyroidal lymphoid hyperplasia. After 5 years, repeated FNA was done on the enlarged nodule with result of Hürthle cell lesion. Prior to right lobectomy, laboratories revealed elevated serum calcium and parathyroid hormone (PTH. Careful history taking revealed chronic knee pain and ossifying fibroma at the maxilla. Ultrasonography showed a 2.8 cm mass inferior to right thyroid lobe. Pathology from en bloc resection was parathyroid carcinoma and immunohistochemical study revealed positivity for PTH. Genetic analysis found somatic mutation of CDC73 gene in exon1 (c.70delG which caused premature stop codon in amino acid 26 (p.Glu24Lysfs2*. The final diagnosis was hyperparathyroidism-jaw tumor syndrome. Conclusions. FNA cytology of parathyroid can mimic thyroid lesion. It is important to consider and correlate the entire information from clinical history, laboratory, imaging, and FNA.

  17. A threshold for low-protein-diet-induced elevations in parathyroid hormone

    DEFF Research Database (Denmark)

    Kerstetter, J E; Svastisalee, C M; Caseria, D M;

    2000-01-01

    We reported previously that lowering dietary protein intake in young healthy women to 0.7 g/kg depressed intestinal calcium absorption and was accompanied by elevations in parathyroid hormone (PTH). Moderate amounts of dietary protein (1.0 g/kg) did not appear to perturb calcium homeostasis....

  18. Cinacalcet for hypercalcemia caused by pulmonary squamous cell carcinoma producing parathyroid hormone-related Peptide

    NARCIS (Netherlands)

    Bech, A.; Smolders, K.; Telting, D.; Boer, H. de

    2012-01-01

    BACKGROUND: Current treatments for hypercalcemia caused by lung cell carcinomas producing parathyroid hormone-related peptide (PTH-rp) have limited efficacy, probably because of their lack of effect on PTH-rp secretion. In this case study we explored the efficacy of the calcimimetic cinacalcet as su

  19. The use of cinacalcet in pregnancy to treat a complex case of parathyroid carcinoma

    Science.gov (United States)

    Bailey, M; Chahal, H; Raja, O; Bhat, R; Gayle, C; Grossman, A B; Druce, M R

    2014-01-01

    Summary We present the case of a patient with metastatic parathyroid carcinoma whose hypercalcaemia was medically managed through two pregnancies. The diagnosis was made when the patient presented with chronic knee pain and radiological findings consistent with a brown tumour, at the age of 30. Her corrected calcium and parathyroid hormone (PTH) levels were significantly elevated. Following localisation studies, a right parathyroidectomy was performed with histology revealing parathyroid carcinoma, adherent to thyroid tissue. Aged 33, following biochemical recurrence of disease, the patient underwent a second operation. A subsequent CT and FDG–PET revealed bibasal pulmonary metastases. Aged 35, the patient was referred to our unit for treatment of persistent hypercalcaemia. The focus of treatment at this time was debulking metastatic disease using radiofrequency ablation. Despite advice to the contrary, the patient conceived twice while taking cinacalcet. Even though there are limited available data regarding the use of cinacalcet in pregnancy, both pregnancies continued to term with the delivery of healthy infants, using intensive medical management for persistent hypercalcaemia. Learning points Parathyroid carcinoma is a rare cause of primary hyperparathyroidism.Hypercalcaemia during pregnancy can result in significant complications for both the mother and the foetus.The use of high-dose cinacalcet in pregnancy has been shown, in this case, to aid in the management of resistant hypercalcaemia without teratogenicity. PMID:25298882

  20. Impact of the parathyroid scintigraphy with MIBI -{sup 99m}Tc in the detection of an infra-centimetric parathyroid adenoma; Impact de la scintigraphie parathyroidienne au MIBI-99mTc dans la detection d'un adenome parathyroidien infracentimetrique

    Energy Technology Data Exchange (ETDEWEB)

    Ben Ali, K.; Mortazavi-Jhanno, N.; Burg; Rouzet, F.; Lebtahi, R.; Le Guludec, D. [Service de medecine nucleaire, hopital Bichat, AP-HP, Paris, (France); Leghzali, H.; Besse, H.; Stievenart, J.L. [service de medecine nucleaire, hopital Beaujon, AP-HP, Paris, (France)

    2009-05-15

    The objective is to enlighten the contribution of the parathyroid scintigraphy with MIBI-{sup 99m}Tc in the detection of infra-centimetric parathyroid adenomas. Conclusions: the small low intense visible centres with a single time of scintigraphy can correspond to adenomas. The association parathyroid scintigraphy with MIBI-{sup 99m}Tc to a cervical echography contributes to raise the sensitivity in the detection of parathyroid infra-centimetric adenomas. (N.C.)

  1. Parathyroid hormone related-protein promotes epithelial-to-mesenchymal transition in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Weg M Ongkeko

    Full Text Available Parathyroid hormone-related protein (PTHrP possesses a variety of physiological and developmental functions and is also known to facilitate the progression of many common cancers, notably their skeletal invasion, primarily by increasing bone resorption. The purpose of this study was to determine whether PTHrP could promote epithelial-to-mesenchymal transition (EMT, a process implicated in cancer stem cells that is critically involved in cancer invasion and metastasis. EMT was observed in DU 145 prostate cancer cells stably overexpressing either the 1-141 or 1-173 isoform of PTHrP, where there was upregulation of Snail and vimentin and downregulation of E-cadherin relative to parental DU 145. By contrast, the opposite effect was observed in PC-3 prostate cancer cells where high levels of PTHrP were knocked-down via lentiviral siRNA transduction. Increased tumor progression was observed in PTHrP-overexpressing DU 145 cells while decreased progression was observed in PTHrP-knockdown PC-3 cells. PTHrP-overexpressing DU 145 formed larger tumors when implanted orthoptopically into nude mice and in one case resulted in spinal metastasis, an effect not observed among mice injected with parental DU 145 cells. PTHrP-overexpressing DU 145 cells also caused significant bone destruction when injected into the tibiae of nude mice, while parental DU 145 cells caused little to no destruction of bone. Together, these results suggest that PTHrP may work through EMT to promote an aggressive and metastatic phenotype in prostate cancer, a pathway of importance in cancer stem cells. Thus, continued efforts to elucidate the pathways involved in PTHrP-induced EMT as well as to develop ways to specifically target PTHrP signaling may lead to more effective therapies for prostate cancer.

  2. Temporal relationship between vitamin D status and parathyroid hormone in the United States.

    Directory of Open Access Journals (Sweden)

    Martin H Kroll

    Full Text Available Interpretation of parathyroid hormone (iPTH requires knowledge of vitamin D status that is influenced by season.Characterize the temporal relationship between 25-hydroxyvitamin D3 levels [25(OHD3] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D2 [25(OHD2] levels with PTH levels and total 25(OHD levels.We retrospectively determined population weekly-mean concentrations of unpaired [25(OHD2 and 25(OHD3] and iPTH using 3.8 million laboratory results of adults. The 25(OHD3 and iPTH distributions were normalized and the means fit with a sinusoidal function for both gender and latitudes: North >40, Central 32-40 and South 65 pg/mL. The percentage of patients deficient in 25(OHD3 seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OHD2 had higher PTH levels and 57% of the samples with a total 25(OHD > 50 ng/mL had detectable 25(OHD2.25(OHD3 and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D2 treated patients; 25(OHD3, being higher in the summer and lower in the winter months, with iPTH showing the reverse pattern. A large percentage of the tested population showed vitamin D deficiency and secondary hyperparathyroidism. These observations held across three latitudinal regions, both genders, multiple-years, and in the presence or absence of detectable 25(OHD2, and thus are applicable for patient care.

  3. Systemic but no local effects of combined zoledronate and parathyroid hormone treatment in experimental autoimmune arthritis.

    Directory of Open Access Journals (Sweden)

    Kresten Krarup Keller

    Full Text Available INTRODUCTION: Local bone erosions and osteoporosis in rheumatoid arthritis (RA are the result of a more pronounced bone resorption than bone formation. Present treatment strategies for RA inhibit inflammation, but do not directly target bone erosions. The aim of the study was in experimental arthritis to investigate the juxtaarticular and systemic effects of simultaneous osteoclast inhibition with zoledronate (ZLN and osteoblast stimulation with parathyroid hormone (PTH. METHODS: Arthritis was induced in 36 SKG mice. The mice were randomized to three treatment groups and an untreated group: ZLN, PTH, PTH+ZLN, and untreated. Arthritis score and ankle width measurements were performed. Histological sections were cut from the right hind paw, and design-based stereological estimators were used to quantify histological variables of bone volume and bone formation and resorption. The femora were DXA- and μCT-scanned, and the bone strength was determined at the femoral neck and mid-diaphysis. RESULTS: Locally, we found no differences in arthritis score or ankle width throughout the study. Similarly, none of the treatments inhibited bone erosions or stimulated bone formation in the paw. Systemically, all treatments improved bone mineral density, strength of the femoral neck and mid-diaphysis, and μCT parameters of both cortical and trabecular bone. In addition, there was an additive effect of combination treatment compared with single treatments for most trabecular parameters including bone mineral density and bone volume fraction. CONCLUSIONS: No local effect on bone was found by the combined action of inhibiting bone resorption and stimulating bone formation. However, a clear systemic effect of the combination treatment was demonstrated.

  4. Activated effects of parathyroid hormone-related protein on human hepatic stellate cells.

    Directory of Open Access Journals (Sweden)

    Fen-Fen Liang

    Full Text Available BACKGROUND & AIMS: After years of experiments and clinical studies, parathyroid hormone-related protein(PTHrP has been shown to be a bone formation promoter that elicits rapid effects with limited adverse reaction. Recently, PTHrP was reported to promote fibrosis in rat kidney in conjunction with transforming growth factor-beta1 (TGF-β1, which is also a fibrosis promoter in liver. However, the effect of PTHrP in liver has not been determined. In this study, the promoting actions of PTHrP were first investigated in human normal hepatic stellate cells (HSC and LX-2 cell lines. METHODS: TGF-β1, alpha-smooth muscle actin (α-SMA, matrix metalloproteinase 2 (MMP-2, and collagen I mRNA were quantified by real-time polymerase chain reaction (PCR after HSCs or LX-2 cells were treated with PTHrP(1-36 or TGF-β1. Protein levels were also assessed by western-blot analysis. Alpha-SMA were also detected by immunofluorescence, and TGF-β1 secretion was measured with enzyme-linked immunosorbent assay (ELISA of HSC cell culture media. RESULTS: In cultured human HSCs, mRNA and protein levels of α-SMA, collagen I, MMP-2, and TGF-β1 were increased by PTHrP treatment. A similar increasing pattern was also observed in LX-2 cells. Moreover, PTHrP significantly increased TGF-β1 secretion in cultured media from HSCs. CONCLUSIONS: PTHrP activated HSCs and promoted the fibrosis process in LX-2 cells. These procedures were probably mediated via TGF-β1, highlighting the potential effects of PTHrP in the liver.

  5. Parathyroid hormone-related protein (PTHrP) inhibits mitochondrial-dependent apoptosis through CK2.

    Science.gov (United States)

    Okoumassoun, Liliane Eustache; Russo, Caterina; Denizeau, Francine; Averill-Bates, Diana; Henderson, Janet E

    2007-09-01

    Over the past decade, parathyroid hormone-related protein (PTHrP) has been identified as a key survival factor for cells subjected to apoptotic stimuli. Its anti-apoptotic activity has been attributed to nuclear accumulation of the intact protein, or a synthetic peptide corresponding to its nuclear targeting sequence (NTS), which promotes rapid exit of nutrient deprived cells from the cell cycle. Intracellular PTHrP also inhibited apoptosis by blocking tumor necrosis factor alpha (TNFalpha)-induced apoptosis by blocking signaling from the "death receptor" and preventing damage to the mitochondrial membrane. In both cases, the anti-apoptotic activity was significantly reduced in the presence of a nuclear deficient form of PTHrP with a (88)K/E K/E.K/I(91) mutation in the NTS. The current work was undertaken to determine the mechanism by which nuclear PTHrP blocked mitochondrial-mediated apoptosis. Using sub-cellular fractionation and functional assays we showed that pre-treatment of HEK293 cells with exogenous NTS peptide before inducing apoptosis with TNFalpha was as effective as expression of the full-length protein in inhibiting apoptosis. Inhibition of apoptosis was associated with increased expression of protein kinase casein kinase 2 (CK2) and in sustained CK2 accumulation and activity in the nuclear fraction. In primary chondrogenic cells harvested from the limb buds of PTHrP(+/-) and PTHrP(-/-) embryonic mice, there was a dose-dependent decrease in CK2 expression and activity that correlated with increased susceptibility to apoptosis. Taken together the results indicate that nuclear accumulation of PTHrP effectively inhibits mitochondrial-mediated apoptosis through regulation of the expression, activity, and sub-cellular trafficking of CK2.

  6. Activated effects of parathyroid hormone-related protein on human hepatic stellate cells.

    Science.gov (United States)

    Liang, Fen-Fen; Liu, Cui-Ping; Li, Li-Xuan; Xue, Min-Min; Xie, Fang; Guo, Yu; Bai, Lan

    2013-01-01

    After years of experiments and clinical studies, parathyroid hormone-related protein(PTHrP) has been shown to be a bone formation promoter that elicits rapid effects with limited adverse reaction. Recently, PTHrP was reported to promote fibrosis in rat kidney in conjunction with transforming growth factor-beta1 (TGF-β1), which is also a fibrosis promoter in liver. However, the effect of PTHrP in liver has not been determined. In this study, the promoting actions of PTHrP were first investigated in human normal hepatic stellate cells (HSC) and LX-2 cell lines. TGF-β1, alpha-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and collagen I mRNA were quantified by real-time polymerase chain reaction (PCR) after HSCs or LX-2 cells were treated with PTHrP(1-36) or TGF-β1. Protein levels were also assessed by western-blot analysis. Alpha-SMA were also detected by immunofluorescence, and TGF-β1 secretion was measured with enzyme-linked immunosorbent assay (ELISA) of HSC cell culture media. In cultured human HSCs, mRNA and protein levels of α-SMA, collagen I, MMP-2, and TGF-β1 were increased by PTHrP treatment. A similar increasing pattern was also observed in LX-2 cells. Moreover, PTHrP significantly increased TGF-β1 secretion in cultured media from HSCs. PTHrP activated HSCs and promoted the fibrosis process in LX-2 cells. These procedures were probably mediated via TGF-β1, highlighting the potential effects of PTHrP in the liver.

  7. Parathyroid hormone related-protein promotes epithelial-to-mesenchymal transition in prostate cancer.

    Science.gov (United States)

    Ongkeko, Weg M; Burton, Doug; Kiang, Alan; Abhold, Eric; Kuo, Selena Z; Rahimy, Elham; Yang, Meng; Hoffman, Robert M; Wang-Rodriguez, Jessica; Deftos, Leonard J

    2014-01-01

    Parathyroid hormone-related protein (PTHrP) possesses a variety of physiological and developmental functions and is also known to facilitate the progression of many common cancers, notably their skeletal invasion, primarily by increasing bone resorption. The purpose of this study was to determine whether PTHrP could promote epithelial-to-mesenchymal transition (EMT), a process implicated in cancer stem cells that is critically involved in cancer invasion and metastasis. EMT was observed in DU 145 prostate cancer cells stably overexpressing either the 1-141 or 1-173 isoform of PTHrP, where there was upregulation of Snail and vimentin and downregulation of E-cadherin relative to parental DU 145. By contrast, the opposite effect was observed in PC-3 prostate cancer cells where high levels of PTHrP were knocked-down via lentiviral siRNA transduction. Increased tumor progression was observed in PTHrP-overexpressing DU 145 cells while decreased progression was observed in PTHrP-knockdown PC-3 cells. PTHrP-overexpressing DU 145 formed larger tumors when implanted orthoptopically into nude mice and in one case resulted in spinal metastasis, an effect not observed among mice injected with parental DU 145 cells. PTHrP-overexpressing DU 145 cells also caused significant bone destruction when injected into the tibiae of nude mice, while parental DU 145 cells caused little to no destruction of bone. Together, these results suggest that PTHrP may work through EMT to promote an aggressive and metastatic phenotype in prostate cancer, a pathway of importance in cancer stem cells. Thus, continued efforts to elucidate the pathways involved in PTHrP-induced EMT as well as to develop ways to specifically target PTHrP signaling may lead to more effective therapies for prostate cancer.

  8. Distribution and regulation of the 25-hydroxyvitamin D3 1α-hydroxylase in human parathyroid glands.

    Science.gov (United States)

    Ritter, Cynthia S; Haughey, Bruce H; Armbrecht, Harvey J; Brown, Alex J

    2012-05-01

    Parathyroid glands express the 25-hydroxyvitamin D(3) 1α-hydroxylase (1αOHase). 1,25-dihydroxyvitamin D(3) (calcitriol) synthesized by extrarenal tissues generally does not enter the circulation, but plays an autocrine/paracrine role specific to the cell type, and is regulated by the needs of that particular cell. While the role of calcitriol produced in the parathyroid glands presumably is to suppress PTH and cell growth, its regulation in this cell type has not been defined. In the present study, we found that regulation of the human parathyroid 1αOHase differs from the renal enzyme in that it is induced by FGF-23 and extracellular calcium. Hyperplastic parathyroid glands from patients with chronic kidney failure normally display a heterogeneous cellularity. We found that the 1αOHase is expressed at much higher levels in oxyphil cells than in chief cells in these patients. Recent findings indicate that oxyphil cell content is increased by treatment with calcium receptor activators (calcimimetics). Here, we demonstrate that the calcimimetic cinacalcet increases the expression of 1αOHase in human parathyroid cultures. Additionally, we found that the 1αOHase in human parathyroid cultures is functionally active, as evidenced by the ability of the enzyme to 1-hydroxylate 25(OH)D(3) in parathyroid monolayers. Calcium, as well as cinacalcet, also induced expression of the degradation enzyme 24-hydroxylase, indicating the presence of a negative feedback system in the parathyroid cells. Therefore, local production of 1αOHase suggests an autocrine/paracrine role in regulating parathyroid function and may mediate, in part, the suppression of PTH by calcium and FGF-23.

  9. Heterogeneous expression of SNARE proteins SNAP-23, SNAP-25, Syntaxin1 and VAMP in human parathyroid tissue.

    Science.gov (United States)

    Lu, Ming; Forsberg, Lars; Höög, Anders; Juhlin, Christofer C; Vukojević, Vladana; Larsson, Catharina; Conigrave, Arthur D; Delbridge, Leigh W; Gill, Anthony; Bark, Christina; Farnebo, Lars-Ove; Bränström, Robert

    2008-06-11

    In regulated exocytosis synaptosomal-associated protein of 25kDa (SNAP-25) is one of the key-players in the formation of SNARE (soluble N-ethylmaleimide-sensitive fusion attachment protein receptor) complex and membrane fusion. SNARE proteins are essentially expressed in neurons, neuroendocrine and endocrine cells. Whether parathyroid cells express these proteins is not known. In this study, we have examined the expression of the SNARE protein SNAP-25 and its cellular homologue SNAP-23, as well as syntaxin1 and VAMP (vesicle-associated membrane protein) in samples of normal parathyroid tissue, chief cell adenoma, and parathyroid carcinoma, using immunohistochemistry and Western blot analysis. SNAP-23 and VAMP were evenly expressed in all studied parathyroid tissues using immunohistochemistry and/or Western blot analysis. SNAP-25 (and Syntaxin1) was not expressed in normal parathyroid tissue, but in approximately 20% of chief cell adenomas, and in approximately 45% of parathyroid carcinoma samples. It is likely that the SNARE proteins SNAP-23 and VAMP play a role in the stimulus-secretion coupling and exocytosis of parathyroid hormone as these proteins were expressed in all of the parathyroid samples we studied. In particular, preferential expression of SNAP-23 rather than SNAP-25 provides an explanation of the high level of PTH secretion that occurs under conditions of low cytoplasmic free Ca(2+) concentration (around 0.1micromol/l). SNAP-25 (and Syntaxin1) appears to be a tumour-specific protein(s) in parathyroid tissues since its expression was restricted to pathological tissues.

  10. Effect of tumor volume on the enhancement pattern of parathyroid adenoma on parathyroid four-dimensional CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Kyoung [Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of); Dongguk University Ilsan Hospital, Department of Radiology, Goyang-si (Korea, Republic of); Yun, Tae Jin; Kim, Ji-hoon; Kang, Koung Mi; Choi, Seung Hong; Sohn, Chul-Ho [Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of); Seoul National University Hospital, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Lee, Kyu Eun; Kim, Su-jin [Seoul National University Hospital, Department of Surgery, Seoul (Korea, Republic of); Won, Jae-Kyung [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of)

    2016-05-15

    The purpose of this study is to assess the effect of tumor volume on the enhancement pattern of parathyroid adenoma (PTA) on four-dimensional computed tomography (4D-CT). We analyzed the enhancement patterns of PTA on four-phase 4D-CT in 44 patients. Dependency of the changes of Hounsfield unit values (ΔHU) on the tumor volumes and clinical characteristics was evaluated using linear regression analyses. In addition, an unpaired t test was used to compare ΔHU of PTAs between PTA volume ≥1 cm{sup 3} and <1 cm{sup 3}, thyroid gland, and lymph node. PTA volume based on CT was the strongest factor on the ΔHU{sub Pre} {sub to} {sub Arterial} and ΔHU{sub Arterial} {sub to} {sub Venous} and ΔHU{sub Arterial} {sub to} {sub Delayed} (R {sup 2} = 0.34, 0.25, and 0.32, respectively, P < 0.001 for both). PTA ≥1 cm {sup 3} had statistically significant greater enhancement between the unenhanced phase and the arterial phase than PTA <1 cm {sup 3} (mean values ± standard deviations (SDs) of ΔHU{sub Pre} {sub to} {sub Arterial}, 102.7 ± 33.7 and 57.5 ± 28.8, respectively, P < 0.001). PTA ≥1 cm {sup 3} showed an early washout pattern on the venous phase, whereas PTA <1 cm {sup 3} showed a progressive enhancement pattern on the venous phase (mean values ± SDs of ΔHU{sub Arterial} {sub to} {sub Venous}, -13.2 ± 31.6 and 14.4 ± 32.7, respectively; P = 0.009). The enhancement pattern of PTA on 4D-CT is variable with respect to PTA volume based on CT. Therefore, the enhancement pattern of PTA on 4D-CT requires careful interpretation concerning the tumor volume, especially in cases of PTA <1 cm {sup 3}. (orig.)

  11. Characterization of parathyroid hormone/parathyroid hormone-related protein receptor and signaling in hypercalcemic Walker 256 tumor cells.

    Science.gov (United States)

    Esbrit, P; Benítez-Verguizas, J; de Miguel, F; Valín, A; García-Ocaña, A

    2000-07-01

    Parathyroid hormone (PTH)-related protein (PTHrP) is the main factor responsible for humoral hypercalcemia of malignancy. Both PTH and PTHrP bind to the common type I PTH/PTHrP receptor (PTHR), thereby activating phospholipase C and adenylate cyclase through various G proteins, in bone and renal cells. However, various normal and transformed cell types, including hypercalcemic Walker 256 (W256) tumor cells, do not produce cAMP after PTHrP stimulation. We characterized the PTHrP receptor and the signaling mechanism upon its activation in the latter cells. Scatchard analysis of PTHrP-binding data in W256 tumor cells revealed the presence of high affinity binding sites with an apparent K(d) of 17 nM, and a density of 90 000 sites/cell. In addition, W256 tumor cells immunostained with an anti-PTHR antibody, recognizing its extracellular domain. Furthermore, reverse transcription followed by PCR, using primers amplifying two different regions in the PTHR cDNA corresponding to the N- and C-terminal domains, yielded products from W256 tumor cell RNA which were identical to the corresponding products obtained from rat kidney RNA. Consistent with our previous findings on cAMP production, 1 microM PTHrP(1-34), in contrast to 10 microg/ml cholera toxin or 1 microM isoproterenol, failed to affect protein kinase A activity in W256 tumor cells. However, in these cells we found a functional PTHR coupling to G(alpha)(q/11), whose presence was demonstrated in these tumor cell membranes by Western blot analysis. Our findings indicate that W256 tumor cells express the PTHR, which seems to be coupled to G(alpha)(q/11). Taken together with previous data, these results support the hypothesis that a switch from the cAMP pathway to the phospholipase C-intracellular calcium pathway, associated with PTHR activation, occurs in malignant cells.

  12. Intraoperative detection of parathyroid gland perfusion during endocrine surgeries (Conference Presentation)

    Science.gov (United States)

    Mannoh, Emmanuel; Thomas, Giju; Solorzano, Carmen C.; Mahadevan-Jansen, Anita

    2017-02-01

    As many as 80,000 patients a year in the US undergo thyroidectomies or parathyroidectomies for diseased glands. About 21% of these surgeries result in disruption of blood supply to health parathyroid glands, which, if unaddressed, may result in long-term hypocalcemia. Surgeons need to know as soon as possible whether or not the blood supply to a parathyroid gland has been disrupted, as this informs their decision on whether or not to excise and reimplant the gland. There is a non-trivial failure rate involved in this transplantation process, and in the absence of an objective gold-standard surgeons often rely on subjective visual inspection in making this decision. Here we present Laser Speckle Imaging as a real-time objective method to assess parathyroid viability. Our device consists of a 785 nm laser source and a near-infrared camera with a zoom lens, positioned above the surgical field with an articulated arm. With the laser diffusing light onto the tissue, the camera acquires images which are processed in real-time and displayed on a monitor. These speckle contrast images are then averaged and the relative difference in speckle contrast between the parathyroid gland and surrounding thyroid tissue is calculated and correlated with the surgeon's assessment of viability. Preliminary findings from in vivo measurement of 9 diseased glands show 100% agreement with the surgeon when taking a greater than 5% relative difference to indicate devascularization. This device has the potential to be used as an intraoperative tool for assessing parathyroid viability.

  13. Parathyroid adenoma apoplexy as a temporary solution of primary hyperparathyroidism: a case report

    Directory of Open Access Journals (Sweden)

    Pereira Francisco A

    2007-11-01

    Full Text Available Abstract Introduction The natural history of patients with spontaneous parathyroid necrosis is unknown. In this case report we describe the clinical course, laboratory, radiographic, bone densitometry tests, parathyroid ultrasonography and scintigraphy examinations of a patient performed over a period of eight years after she first presented with a sudden episode of spontaneous resolution of primary hyperparathyroidism (PHPT. Case presentation A 24-year-old woman with a clinical history and laboratory and radiographic tests compatible with PHPT suffered a sudden episode of cervical pain and presented with clinical evidence of hypocalcemia. Biopsy of a cervical nodule revealed necrotic material compatible with ischemia of the parathyroid. The follow-up of the patient presented four distinct phases: the first, which lasted two years, was compatible with a period of bone hunger during which it was necessary to introduce calcitriol and calcium carbonate. During this period, the patient showed bone mass gain. The second phase was characterized by normalization of calcium and parathyroid hormone levels and its end was difficult to define. During the third phase there was a recurrence of hypercalcemia associated with elevated parathyroid hormone (PTH levels and loss of bone mass. The last phase corresponded to the interval after parathyroidectomy, which was characterized by normalization of serum levels of calcium and PTH, as well as bone mass gain. Conclusion This case report indicates that spontaneous resolution of PHPT by adenoma necrosis is potentially temporary. Thus, in cases in which a conservative approach is chosen, clinical and laboratory follow-up is indispensable. Bone mass measurement is a useful tool in the follow-up of these cases. However, this option exposes the patient to a potential roller-coaster ride of bone mass gain and loss, whose long term consequences are still unknown.

  14. Parathyroid gland autotransplantation after total thyroidectomy in surgical management of hypopharyngeal and laryngeal carcinomas: A case series

    Directory of Open Access Journals (Sweden)

    Abd Elmaksoud M. Abd Elmaksoud

    2015-06-01

    Conclusions: Parathyroid gland autotranplantation is a simple safe technique with high success rate in preventing persistent hypoparathyroidism after total thyroidectomy in surgical management of advanced hypopharyngeal and laryngeal carcinomas.

  15. Needle in a haystack-parathyroid gland in a 10-day old infant: a case report and literature review.

    Science.gov (United States)

    Ismail, Adel; Abbas, Tariq O; Al-Khalaf, Fawziya

    2011-01-01

    Neonatal severe primary hyperparathyroidism (NSPHT) is a rare autosomal recessive disorder of calcium homeostasis. It presents shortly after birth and is characterized by striking hyperparathyroidism, marked hypercalcemia, and hyperparathyroid bone disease. It is caused by mutations of the calcium-sensing receptor (CASR), the ionized calcium sensor for the parathyroid cells, the parafollicular thyroid C cells, and the kidney epithelium, as well as cells in bone and intestine. Without early intervention, which frequently requires surgical removal of the hyperplastic parathyroids, the patients often succumb to complications of hypercalcemia and respiratory failure. Finding the parathyroid gland in small neonates is not an easy task. Here we report on a patient with neonatal hyperparathyroidism who was treated by total parathyroidectomy and discuss the various ways of helping to find the parathyroid glands during surgery at this young age.

  16. Relationship Between Aldosterone and Parathyroid Hormone, and the Effect of Angiotensin and Aldosterone Inhibition on Bone Health

    DEFF Research Database (Denmark)

    L.S., Bislev; T., Sikjaer; L., Rolighed

    2015-01-01

    Emerging evidence suggests a stimulating effect of parathyroid hormone (PTH) on the reninnullangiotensinnullaldosterone system (RAAS). In primary hyperparathyroidism, chronic-elevated PTH levels seem to stimulate the RAAS which may explain the increased risk of cardiovascular disease (CVD). In ad...

  17. Serum phosphorus reduction in dialysis patients treated with cinacalcet for secondary hyperparathyroidism results mainly from parathyroid hormone reduction

    DEFF Research Database (Denmark)

    Zitt, Emanuel; Fouque, Denis; Jacobson, Stefan H

    2013-01-01

    The calcimimetic cinacalcet lowers parathyroid hormone (PTH), calcium (Ca) and phosphorus (P) in dialysis patients with secondary hyperparathyroidism (SHPT). We explored serum P changes in dialysis patients treated with cinacalcet, while controlling for vitamin D sterol and phosphate binder (PB...

  18. Cinacalcet reduces plasma intact parathyroid hormone, serum phosphate and calcium levels in patients with secondary hyperparathyroidism irrespective of its severity.

    LENUS (Irish Health Repository)

    2011-09-01

    To evaluate the relationship between the severity of secondary hyperparathyroidism (SHPT) - defined in terms of baseline plasma intact parathyroid hormone (iPTH) level - and the magnitude of response to cinacalcet.

  19. A prospective cohort study of novel functional types of parathyroid glands in thyroidectomy: In situ preservation or auto-transplantation?

    Science.gov (United States)

    Cui, Qiuxia; Li, Zhihua; Kong, Deguang; Wang, Kun; Wu, Gaosong

    2016-12-01

    The best method of preventing hypoparathyroidism after thyroidectomy is to keep parathyroid glands in situ. However, hypoparathyroidism still regularly occurs with the existing parathyroid classification system, and the incidence of permanent hypoparathyroidism has not been reduced. We created a novel system for classifying parathyroid glands that can guide parathyroid preservation in thyroidectomy.We prospectively observed parathyroid glands using the new system in 218 neck surgeries, compared with 132 under the traditional system from January 2014 to September 2015 at a single clinic center. Briefly, we classified parathyroid glands as follows: Type A, no dependency on the thyroid; B1, partial blood supply from the thyroid but retains adequate blood supply after removal of the thyroid; B2, partial blood supply from the thyroid and becomes devascularized after the removal of the thyroid; B3, blood supply mostly from the thyroid; and C, blood supply completely dependent on the thyroid. The classifications were used to decide between in situ preservation or auto-transplantation.The most common type of parathyroid gland was type B1 (53.77%), followed by type A (20.89%), which are the perfect categories for in situ preservation. Type B2 (17.52%) and type B3 (1.21%) have a chance to be kept in situ. For type C (6.61%), in situ preservation is impossible. When in-situ preservation is ruled out, parathyroid auto-transplantation is an alternative, with partial or total gland tissue, depending on the classification and the surgeon's discretion. Among the patients who were classified under the new system, 43.6% presented with transient hypoparathyroidism (symptoms lasting ≤6 months) after surgery, versus 42.4% in the old system, which was not a significant difference. However, permanent hypothyroidism (symptoms lasting >6 months) was not detected in the applied group, but in 3.0% of patients in the nonapplied group (P = 0.01).Our novel functional nomenclature system

  20. Modifications of transaxillary approach in endoscopic da Vinci-assisted thyroid and parathyroid gland surgery.

    Science.gov (United States)

    Al Kadah, Basel; Piccoli, Micaela; Mullineris, Barbara; Colli, Giovanni; Janssen, Martin; Siemer, Stephan; Schick, Bernhard

    2015-03-01

    Endoscopic surgery for treatment of thyroid and parathyroid pathologies is increasingly gaining attention. The da Vinci system has already been widely used in different fields of medicine and quite recently in thyroid and parathyroid surgery. Herein, we report about modifications of the transaxillary approach in endoscopic surgery of thyroid and parathyroid gland pathologies using the da Vinci system. 16 patients suffering from struma nodosa in 14 cases and parathyroid adenomas in two cases were treated using the da Vinci system at the ENT Department of Homburg/Saar University and in cooperation with the Department of General Surgery in New Sant'Agostino Hospital, Modena/Italy. Two different retractors, endoscopic preparation of the access and three different incision modalities were used. The endoscopic preparation of the access allowed us to have a better view during preparation and reduced surgical time compared to the use of a headlamp. To introduce the da Vinci instruments at the end of the access preparation, the skin incisions were over the axilla with one incision in eight patients, two incisions in four patients and three incisions in a further four patients. The two and three skin incisions modality allowed introduction of the da Vinci instruments without arm conflicts. The use of a new retractor (Modena retractor) compared to a self-developed retractor made it easier during the endoscopic preparation of the access and the reposition of the retractor. The scar was hidden in the axilla and independent of the incisions selected, the cosmetic findings were judged by the patients to be excellent. The neurovascular structures such as inferior laryngeal nerve, superior laryngeal nerve and vessels, as well as the different pathologies, were clearly 3D visualized in all 16 cases. No paralysis of the vocal cord was observed. All patients had a benign pathology in their histological examination. The endoscopic surgery of the thyroid and parathyroid gland can be

  1. Correlation analysis of high precision blood flow imaging in secondary parathyroid function in maintenance hemodialysis patients

    Institute of Scientific and Technical Information of China (English)

    Wen-Ze Du; Le Chen; Xiao-Yun Wu

    2016-01-01

    Objective:To investigate the value of high precision blood flow imaging (Fine-Flow) in secondary parathyroid function (SHPT) in patients with maintenance hemodialysis (MHD). Methods: A total of 95 MHD patients with SHPT in our hospital from January 2015 to June 2016 were selected as the research object. According to the Fine-Flow examination of parathyroid gland, 73 cases were divided into display group, 22 cases were not shown; Display group according to the hyperplasia of parathyroid diameter were divided into 1.5 cm group of 17 cases; display group according to the blood flow into the rich group of 41 cases, not rich group of 32 cases; according to whether calcification were divided into calcification group of 43 cases, non calcified group of 30 cases. CDFI was used for the anterior region of neck transverse and longitudinal scanning, check the thyroid and around the dorsal lobes.The size, echo, lesion number and blood flow were measured, parathyroid hormone (PTH), serum calcium (Ca), phosphorus (P), and calculate the Ca and P product (Ca×P) were measured.Results: PTH and Ca of the display group were significantly higher than that of the non display group, and differences in P and Ca×P were not statistically significant; Parathyroid diameter >1.5 cm PTH levels were significantly higher than the other three groups, diameter 1-1.5 cm group and >1.5 cm group Ca, diameter Ca×P was higher than that in group <5 cm and 0.5-1.0 cm group, difference in P of four groups was not statistical significant; group PTH, P, abundant blood flow Ca×P were not significantly higher than the rich group, difference in P of two groups was no statistical significance; group Ca was significantly higher than that of calcification calcification group, differences in PTH, P, Ca×P of the two groups were not statistically significant.Conclusions:MHD patients with SHPT, parathyroid Fine-Flow display rate is high, and has the characteristic performance. Its operation is simple, non

  2. Correlation between blood pressure and vitamin D, parathyroid hormone, calcium, and phosphorus in sedentary postmenopausal women

    Directory of Open Access Journals (Sweden)

    Bakhtyar Tartibian

    2016-11-01

    Full Text Available Background: Hypertension is one of the major risk factors for cardiovascular disease. The studies show that factors such as vitamin D, parathyroid hormone, calcium and phosphorus are involved in the regulation of blood pressure. The purpose of this study was to investigate the relationship between blood pressure with vitamin D, parathyroid hormone, calcium, and phosphorus in sedentary postmenopausal women. Methods: This investigation is in the form of a descriptive correlational study that was performed in September 2015. The statistical population was all healthy and sedentary postmenopausal women 50-70 years old in Urmia city, Iran. Fifty-four sedentary postmenopausal women were selected as subjects and voluntarily and bona fide participated in this study. General and anthropometric characteristics of height, weight, and body mass index (BMI in subjects were measured by wall-meter with an accuracy of one millimeter, digital scale with precision of 100 g (Beurer, Germany, and dual emission X-ray absorptiometry (DXA (Hologic, USA machines, respectively. Diastolic and systolic blood pressure was measured by indicator machine. Serum levels of vitamin D, parathyroid hormone, calcium, and phosphorus were measured by ELISA and Auto-analyzer (BT 1500, Biotecnica, Italy machines, respectively. Results: The mean general, anthropometric, and physiological/laboratory variables of subjects were: age 54 yr, height 156 cm; weight 72 kg; BMI 29 kg/m2; systolic and diastolic blood pressure 76.20 and 110.70, respectively; vitamin D 25.22 ng/ml, parathyroid hormone 33.29 ng/ml, calcium 9.44 ng/ml, and phosphorus 3.26 ng/ml. Moreover, results showed that there was no significant relationship between systolic and diastolic blood pressure and vitamin D (P>0.581 and P>0.619, respectively. There was no significant relationship between systolic and diastolic blood pressure and parathyroid hormone (P>0.623 and P>0.341, respectively. There was no significant

  3. Relationship Between Aldosterone and Parathyroid Hormone, and the Effect of Angiotensin and Aldosterone Inhibition on Bone Health

    DEFF Research Database (Denmark)

    L.S., Bislev; T., Sikjaer; L., Rolighed

    2015-01-01

    Emerging evidence suggests a stimulating effect of parathyroid hormone (PTH) on the reninnullangiotensinnullaldosterone system (RAAS). In primary hyperparathyroidism, chronic-elevated PTH levels seem to stimulate the RAAS which may explain the increased risk of cardiovascular disease (CVD...... hyperparathyroidism due to increased renal calcium excretion. Moreover, the angiotensin II receptor is expressed by human parathyroid tissue, and angiotensin may therefore directly stimulates PTH secretion. An increased bone loss is found in patients with hyperaldosteronism. The angiotensin II receptor seems main...

  4. Thyroid, parathyroid, and salivary gland evaluations in patients exposed to multiple fluoroscopic examinations during tuberculosis therapy: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, M.M.; Boice, J.D. Jr.; Ames, D.B.; Rosenstein, M.

    1988-02-01

    The prevalence of thyroid, parathyroid, and salivary abnormalities was determined in 91 women who received an average of 112 fluoroscopic chest examinations during pneumothorax treatment for tuberculosis more than 40 yr previously and in 72 women treated for tuberculosis by other modalities. Thyroid abnormalities were determined by physical examination, scintiscans, and measurements of serum free T4 index, TSH, and thyroid microsomal antibodies. Thyroid nodules were diagnosed in 7.7% of the exposed and 4.2% of the comparison group (prevalence ratio, 1.8; 90% confidence interval 0.6-5.7). Autoimmune thyroid disease was diagnosed in 15.2% of the exposed and 6.9% of the comparison group (prevalence ratio, 2.2; 95% confidence interval, 0.8-6.2). No salivary tumors were detected. Two exposed women and 1 comparison woman had primary hyperparathyroidism. Although absorbed dose to the thyroid could not be precisely determined, approximately 60 rads would be expected to yield the observed excess of thyroid nodules. While the prevalence ratios were not significantly increased in the exposed group, the results suggest that susceptibility of the thyroid to nodules from cumulative radiation doses of this magnitude could be increased even when the doses are accumulated over years and that such x-ray exposure of the thyroid gland may predispose the patient to the development of autoimmune disease.

  5. Fine-needle aspiration with measurement of parathyroid hormone levels in thyroidectomy%甲状腺术中应用抽吸组织测定甲状旁腺激素的临床意义

    Institute of Scientific and Technical Information of China (English)

    黄海燕; 李浩; 林少建; 邓维叶; 李秋梨; 陈艳峰; 杨安奎; 张诠; 郭朱明

    2013-01-01

    Objective Hypoparathyroidism is one of the most serious complications of thyroidectomy.It is important to identify the parathyroid glands during thyroidectomy.In order to find an economic,simple and less traumatic way to identify the parathyroid glands and testify its feasibility,fineneedle aspiration of suspected parathyroid tissue was used to measure the parathyroid hormone (PTH) levels during the surgical procedure.Methods From Nov.2011 to Apr.2012,50 patients were recruited for thyroid surgery in the Sun Yat-sen University Cancer Centre.During surgery,fine-needle aspiration of suspected tissues,including parathyroid gland,thyroid gland,muscle,fat tissue,and lymph node,was performed,the PTH levels were measured.In addition,the tissues above-mentioned were taken to pathological examination.Statistical processing was adopted to determine the sensitivity and specificity of intraoperative fine-needle aspiration with measurement of PTH level in finding the pathology of the parathyroid gland.Results There were 237 tissues from 50 patients in total,and 45 of them were certified as the parathyroid glands by pathology.Intra-operative PTH (ioPTH) of the tissues in forty-four cases were higher than 600 ng/L,ioPTH of the tissues in one case was lower than 600 ng/L,and it was 160 ng/L.The highest ioPTH in other cases was 537.7 ng/L.The sensitivity was 97.8%.The specificity was 100%.The difference between the sensitivity and the specificity of two groups was not statistically significant,and P > 0.05.The level of PTH of parathyroid gland were much higher than other tissues,and P < 0.001.Conclusions The level of ioPTH of parathyroid gland were far higher than thyroid,muscle,fat,lymph node.It is an economic,fast and less traumatic way to identify the parathyroid gland by using the fine-needle aspiration of the parathyroid tissue with measurement of PTH levels.The sensitivity and the specificity are high.It can be used in the thyroidectomy to identify the parathyroid

  6. Relationship between the dimension of parathyroid glands estimated by ultrasonography and the hyperplastic pattern in patients with renal hyperparathyroidism.

    Science.gov (United States)

    Matsuoka, Susumu; Tominaga, Yoshihiro; Sato, Tetsuhiko; Uno, Nobuaki; Hiramitu, Takahisa; Goto, Norihiko; Nagasaka, Takaharu; Uchida, Kazuharu

    2008-10-01

    In renal hyperparathyroidism (HPT), the parathyroid glands initially proliferate diffusely and polyclonally, and are then transformed to monoclonal nodular hyperplasia with aggressive growth potential. In this study we evaluated the relationship between the maximal dimension of parathyroid glands estimated by ultrasonography (US) and the hyperplastic pattern of parathyroid glands in patients with renal HPT. Between October 1999 and December 2006, 141 patients who underwent total parathyroidectomy (PTx) with forearm autograft in our department were enrolled in this study. In these patients 308 parathyroid glands were detected by US before PTx. The largest dimension of the gland estimated preoperatively by US was correlated closely with its measurement at surgery (R2 was 0.31, P parathyroid hyperplasia and the glandular diameter when we defined 8 mm as the maximal diameter estimated by US as a cut-off value. As a result of receiver operating characteristic analyses, using these criteria the US technique could predict nodular hyperplasia with a high sensitivity (78.9%) and specificity (78.7%). Parathyroid glands that are enlarged by more than 8 mm in the largest dimension estimated by US may represent glands with nodular hyperplasia.

  7. Localization of abnormal parathyroid gland(s) using thallium-201/iodine-123 subtraction scintigraphy in patients with primary hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Picard, D.; D' Amour, P.; Carrier, L.; Chartrand, R.; Poisson, R.

    1987-01-01

    Tl-201/I-123 subtraction scintigraphy was performed in 17 patients with clinical symptoms and biochemical measurements suggestive of primary hyperparathyroidism. Nineteen abnormal sites were identified. These results were correlated with PTH measurements and surgical findings. Three sites were considered unrelated to the parathyroid glands, two corresponding to palpable thyroid nodules and one to muscle uptake of unknown origin. One scintigram did not reveal either of two abnormal glands while two others were considered falsely positive in view of surgical failure. Fourteen sites corresponded to abnormal parathyroid gland at surgery; five glands, weighing more than 2000 mg, could be correctly located on the Tl-201 scintigraphy prior to the subtraction procedure; six glands, weighing between 500 and 2000 mg, were easily localized after the subtraction procedure; three glands, weighing between 180 and 200 mg, were correctly localized after further manipulation of the subtraction procedure. In a patient with parathyroid hyperplasia, one gland, weighing 150 mg, was not located and another was not found upon surgery. Overall sensitivity was 87.5%. A positive correlation between PTH levels, tumor weight, and ease of detection on scintigraphy was found. This correlation was particularly useful in excluding large abnormal uptake related to thyroid disorder or artifact. The results suggest that Tl-201/I-123 parathyroid scintigraphy could become an alternative to Tl-201/Tc-99m parathyroid scintigraphy, with possibly improved detection of low weight abnormal parathyroid glands.

  8. Parathyroid gland autotransplantation after total thyroidectomy in surgical management of hypopharyngeal and laryngeal carcinomas: A case series.

    Science.gov (United States)

    Abd Elmaksoud, Abd Elmaksoud M; Farahat, Iman G; Kamel, Mahmoud M

    2015-06-01

    Total thyroidectomy is indicated in most cases with postcricoid carcinoma, circumferential hypopharyngeal carcinoma and in advanced laryngeal carcinoma. Persistent hypoparathyroidism is a frequent complication after total thyroidectomy which is difficult to manage unlike hypothyroidism. This study was to assess the feasibility of parathyroid gland autotranplantation after total thyroidectomy in advanced carcinomas and their effectiveness in preventing persistent hypoparathyroidism. This study included 26 patients with hypopharyngeal and laryngeal carcinoma presented to National Cancer Institute, Cairo University. Total thyroidectomy and total parathyroid gland excision were performed as a part of adequate oncologic surgical procedure. The parathyroid glands were identified, resected and stored in iced saline. Histological confirmation was necessary before implantation into separated muscle pockets in the anterior forearm muscles. Regular samples were drawn to assess serum parathormone and calcium levels. All patients experienced hypocalcaemia within 1-5 days after operation. Only one patient experienced parathyroid graft failure while the remaining patients were normocalcemic during follow up after surgery, indicating functioning parathyroid grafts. Parathyroid gland autotranplantation is a simple safe technique with high success rate in preventing persistent hypoparathyroidism after total thyroidectomy in surgical management of advanced hypopharyngeal and laryngeal carcinomas.

  9. Incidence and prognosis of parathyroid gland carcinoma: a population-based study in The Netherlands estimating the preoperative diagnosis.

    Science.gov (United States)

    Schaapveld, Michael; Jorna, Francisca H; Aben, Katja K H; Haak, Harm R; Plukker, John T M; Links, Thera P

    2011-11-01

    Parathyroid carcinoma is a rare malignancy and generally is diagnosed after surgery for primary hyperparathyroidism. Lack of a preoperative diagnosis and ill-considered surgical planning with its impact on survival are ill-described. In a retrospective population-based cohort study the clinical features, treatment, recurrences, and survival of 41 parathyroid cancer patients are reported and compared with characteristics of patients with primary hyperparathyroidism. Patients with parathyroid carcinoma had significantly higher serum parathyroid hormone and calcium levels compared with patients with primary hyperparathyroidism. Nineteen patients (46%) had a palpable neck mass. A parathyroid hormone level more than 3 times the upper normal limits was suspicious and levels more than 10 times carried a positive predictive value of 84% for carcinoma. Ten-year recurrence-free and disease-specific survival rates were 71% and 79%, respectively. Parathyroid hormone levels of more than 3 times upper normal limits, palpable neck mass, and profound hypercalcemia are suspicious signs of carcinoma necessitating surgical exploration by an experienced surgeon. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Study on Identification of Parathyroid Surgery%甲状旁腺术中辨认的研究

    Institute of Scientific and Technical Information of China (English)

    吴孟闱

    2014-01-01

    Identifing the parathyroid gland intraoperatively is important to protect parathyroid. Because of the similarity between the parathyroid, fat tissue, lymph node and the nodules, it is dif icult to identify the parathyroid without assistance in the surgery. So far, two types of basic approaches have been developed to assist Identifing parathyroid in the surgery, including Methylene blue, BB5-G1, 5-ALA, 99Tcm-MIBI to label the parathyroid and lymphatic tracer to label the lymph node. These approaches wil be discussed in detail in this review.%在甲状腺全切及淋巴结清扫术中准确辨认甲状旁腺是保护甲状旁腺、避免误切的关键。目前术中定位甲状旁腺主要有两种基本思路,一是利用亚甲蓝、抗甲状旁腺抗体BB5-G1耦合Cibacron Blue、5-ALA、99Tcm-MIBI联合酌探头特异性地标记甲状旁腺,另一种思路是用纳米碳等淋巴示踪剂标记出甲状腺的引流淋巴结,从而负染色地标记出甲状旁腺。本文对这些方法分类叙述。

  11. Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors.

    Science.gov (United States)

    Mingione, Alessandra; Verdelli, Chiara; Terranegra, Annalisa; Soldati, Laura; Corbetta, Sabrina

    2015-01-01

    Parathyroid tumors are almost invariably associated with parathormone (PTH) hypersecretion resulting in primary (PHPT) or secondary (SHPT) hyperparathyroidism. PHPT is the third most common endocrine disorder with a prevalence of 1-2% in post-menopausal women; SHPT is a major complication of chronic kidney failure, the prevalence of which is increasing. The calciumsensing receptor (CASR) is the key molecule regulating PTH synthesis and release from the parathyroid cells in response to changes in extracellular calcium concentrations. A potent calcimimetic, cinacalcet, has been developed in the last ten years and made available for medical treatment of both PHPT and SHPT. Cinacalcet has been demonstrated to be effective in inhibiting PTH secretion, though the drug fails to normalize PTH release, both in PHPT and SHPT patients with different degrees of disease severity, including patients with parathyroid carcinomas and with MEN1-related parathyroid tumors. Here we reviewed the molecular aspects of CASR target therapy and the effect of the CASR gene single nucleotide polymorphisms. Clinical data concerning the efficacy and safety of cinacalcet in controlling hyperparathyroidism are reported, focusing on the treatment of the different types of parathyroid tumors. Finally, limits of this target therapy are analyzed, pointing out the lack of efficacy in improving kidney and bone morbidities in PHPT and cardiovascular diseases in SHPT. Though cinacalcet is a target therapeutic option for parathyroid tumors, further approaches are warranted to fully control these metabolic disorders and the underlying tumors.

  12. Vitamin D receptor and PCNA expression in severe parathyroid hyperplasia of uremic patients

    Institute of Scientific and Technical Information of China (English)

    王笑云; 孙彬; 周富华; 胡建明; 俞香宝; 彭韬

    2001-01-01

    目的研究维生素D受体(VDR)在继发性甲旁亢(SHPT)患者甲状旁腺(PT)中的表达,探讨严重继发性甲旁亢患者对钙三醇抵抗的机制以及与PT增生的关系。 方法7例严重SHPT病人的PT19枚,正常人6枚,用免疫组化ABC法检测细胞增殖核抗原(PCNA)、维生 素D受体表达,计算阳性细胞率。 结果SHPT组PT总重比正常人增加16.1倍,PCNA表达明显增加,分别为(6.35±3.36)‰和(1.73± 1.31)‰(P<0.001)。结节性增生区(NH)增加更为显著(P<0.001),PCNA表达与腺体重量呈正相关(r= 0.58,P<0.01)。SHPT组VDR阳性率(40.28±13.13)%比对照组(83.79±3.77)%明显减少(P<0.001)。 结节性较弥漫性增生减少更显著,为(27.14±4.12)%和(49.84±7.33)%(P<0.001)。VDR表达与腺体 重量、PCNA阳性率均呈负相关(r=-0.46,P<0.05与r=-0.75,P<0.001)。 结论SHPT甲旁腺VDR表达明显减少,结节性较弥漫性增生更甚,与PCNA阳性率呈负相关。提示严重 SHPT患者PT细胞VDR明显减少可能是导致对钙三醇抵抗的重要原因,且与细胞增殖有关。%Objective To clarify the role of vitamin D receptor (VDR)expression in parathyroid proliferation and resistance of parathyroid glands to 1,25(OH)2D3 with secondary hyperparathyroidism (SHPT). Methods This study used archive parathyroid with 7 uremic patients. The expression of proliferation cell nuclear antigen (PCNA) and VDR was evaluated in nineteen-surgically excised parathyroid tissues, including 11 diffuse hyperplasia (DH-type) and 8 nodular hyperplasia (NH-type) of parathyroid glands, by immunohistochemistry (avidin-biotin complex method). Results The weight of parathyroid in SHPT was remarkably increased by 16.1 times. The numbers of parathyroid cells were increased by 1.86 times. The rate of PCNA was remarkably increased in parathyroid hyperplasia with SHPT compared with that in control group [(6.35±3.36)‰ vs (1.73±1.31)‰, P<0.001]. The number of

  13. Methylene blue and parathyroid adenoma localization: Three new cases of a rare cutaneous complication.

    Science.gov (United States)

    Lieberman, Elliot D; Thambi, Rakhi; Pytynia, Kristen B

    2016-02-01

    Methylene blue has been safely used for the localization of parathyroid glands during parathyroidectomy, and only a few adverse effects have been documented. Methylene blue administration as a cause of pulse-oximetry-related skin injury is extremely rare. We describe 2 such cases in patients who developed a blister on the second digit at the pulse oximetry site after an uncomplicated excision of a parathyroid adenoma. In another case, a patient became bradycardic intraoperatively; she was successfully resuscitated, but she incurred a second-degree burn at the pulse oximetry site. In all 3 cases, the burns resolved with local wound care. We publish this report to alert surgeons and anesthesiologists to the risk of skin complications with the use of high-dose intraoperative methylene blue.

  14. 甲状旁腺移植现状%Current staus in parathyroid transplantation

    Institute of Scientific and Technical Information of China (English)

    涂刚; 罗浩军; 姚榛祥

    2008-01-01

    甲状旁腺(parathyroid glands,PTG)分泌的甲状旁腺激素(parathyroid hormone,PTH)在调节体内钙、磷代谢,稳定钙、磷浓度,维持神经、肌肉稳定性方面起着决定性作用。甲状腺手术特别是二次手术时造成PTG损伤、PTG的炎症、肿瘤以及遗传缺陷均可引起PTH分泌不足或活性降低,从而导致PTG功能低下症(hypoparathyroidism,HPT),表现为血钙降低,神经、肌肉的应激性显著增高,手足抽搐,甚至喉与膈肌痉挛而危及生命。

  15. PRIMARY HYPERPARATHYROIDISM AT THE BACKGROUND OF PARATHYROID GLAND HYPERPLASIA. PECULIARITIES AND DIFFICULTIES OF DIAGNOSTICS

    Directory of Open Access Journals (Sweden)

    L. P. Yakovleva

    2015-01-01

    Full Text Available The article uses a clinical case of primary hyperparathyroidism in young patient with hyperplastic parathyroid gland localization in tissues of thyroid gland as an example to study the matters of cytological, histological, clinical and laboratory diagnostics of such pathology. It provides a literature reference on the difficulties of establishing a cytological and histological diagnoses, sets out the peculiarities of morphological pattern, discusses the tactical matters of primary hyperparathyroidism management, indications for surgical treatment and case follow-up of patients.

  16. Adult onset pseudohypoparathyroidism type-1b with normal phosphaturic response to exogenous parathyroid hormone

    Directory of Open Access Journals (Sweden)

    Sandeep Kharb

    2011-01-01

    Full Text Available Pseudohypoparathyroidism type-1b is a hereditary disorder of clinical hypoparathyroidism without AHO phenotype, characterized by blunted nephrogenous cyclic-AMP (cAMP response to exogenous parathyroid hormone (PTH. Here we report a young adult presenting with hypocalcemic tetany with raised PTH levels. His urinary cAMP response to exogenous PTH (recombinant 1-34 was blunted; however, phosphaturic response was normal.

  17. A Naturally Occurring Isoform Inhibits Parathyroid Hormone Receptor Trafficking and Signaling

    OpenAIRE

    Alonso, Ver?nica; Ardura, Juan A; WANG Bin; Sneddon, W Bruce; Peter A Friedman

    2010-01-01

    Parathyroid hormone (PTH) regulates calcium homeostasis and bone remodeling through its cognitive receptor (PTHR). We describe here a PTHR isoform harboring an in-frame 42-bp deletion of exon 14 (?e14-PTHR) that encodes transmembrane domain 7. ?e14-PTHR was detected in human kidney and buccal epithelial cells. We characterized its topology, cellular localization, and signaling, as well as its interactions with PTHR. The C-terminus of the ?e14-PTHR is extracellular, and cell surface expression...

  18. Parathyroid hormone-related protein and regulation of cell survival in the kidney.

    Science.gov (United States)

    Kramann, Rafael; Schneider, Rebekka K

    2013-05-01

    Parathyroid hormone-related protein (PTHrP) is a pleiotropic factor with multiple physiological functions in morphogenesis, cell proliferation, differentiation, apoptosis, and calcium homeostasis. In the kidney, PTHrP is known to be expressed abundantly and to be upregulated in various experimental nephropathies, showing growth-modulatory and proinflammatory properties. Ardura et al. demonstrate a possible link between PTHrP-induced Runx2 expression and an antiapoptotic effect in tubular epithelial cells.

  19. Development of a C-terminal-region-specific radioimmunoassay of parathyroid hormone-related protein

    Energy Technology Data Exchange (ETDEWEB)

    Kasahara, Hiroyuki; Tsuchiya, Masumi; Adachi, Ryoji; Horikawa, Shuji; Tanaka, Shuichi; Tachibana, Seiji (Daiichi Radioisotope Labs. Ltd., Tokyo (Japan))

    1992-04-01

    Few data are published regarding the molecular forms or concentrations of circulating and urinary parathyroid hormone-related protein (PTHrP) in normal subjects and patients with humoral hypercalcemia of malignancy (HHM). We have developed a C-terminal-region-specific radioimmunoassay for human PTHrP 109-141 (C-PTHrP radioimmunoassay) using a sheep antiserum immunized with a novel synthetic human PTHrP 109-141 for immunogen and a novel synthetic [Tyr[sup 108

  20. Physiological and clinical studies of calcium-regulating hormones calcitonin and parathyroid hormone-related protein

    OpenAIRE

    1997-01-01

    The present studies were performed to elucidate several physiological and clinical questions of calcitonin (CT) and parathyroid hormone-related protein (PTHrP) such as: a) Does age influence the basal and calcium-stimulated levels and circulating molecular forms of CT in healthy females? b) Are osteoporotic patients lacking circulating monomeric CT? c) How is salmon CT (sCT) absorbed and cleared during treatment of diseases? d) Is there any effect of acute physical activity ...

  1. Cinacalcet hydrochloride relieves hypercalcemia in Japanese patients with parathyroid cancer and intractable primary hyperparathyroidism.

    Science.gov (United States)

    Takeuchi, Yasuhiro; Takahashi, Shunsuke; Miura, Daishu; Katagiri, Makoto; Nakashima, Noriaki; Ohishi, Hiroko; Shimazaki, Ryutaro; Tominaga, Yoshihiro

    2016-11-21

    Pharmacological treatment of hypercalcemia is essential for patients with parathyroid carcinoma and intractable primary hyperparathyroidism (PHPT). Use of the calcimimetic cinacalcet hydrochloride (cinacalcet) is an option to treat such patients. We investigated the efficacy and safety of cinacalcet in Japanese patients with parathyroid carcinoma and intractable PHPT. Five Japanese patients with parathyroid carcinoma and two with intractable PHPT were enrolled in an open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated until the albumin-corrected serum calcium concentration decreased to 10.0 mg/dL or less or until dose escalation was considered not necessary or feasible. Serum calcium concentration at the baseline was 12.1 ± 1.3 mg/dL (mean ± standard deviation; range 10.4-14.6 mg/dL) and decreased to 10.1 ± 1.6 mg/dL (range 8.6-13.3 mg/dL) at the end of the titration phase with cinacalcet at a dosage of up to 75 mg three times a day. At the end of the titration phase, at least a 1 mg/dL reduction in serum calcium concentration from the baseline was observed in five patients (three with carcinoma and two with PHPT), and it decreased to the normocalcemic range in five patients (three with carcinoma and two with PHPT). Common adverse events were nausea and vomiting. One patient discontinued participation in the study because of an adverse event, liver disorder. Cinacalcet effectively relieved hypercalcemia in 60% of the Japanese patients with parathyroid carcinoma and might be effective in those with intractable PHPT. The drug might be tolerable and safe at a dosage of at most 75 mg three times a day.

  2. The control of calcium metabolism by parathyroid hormone, calcitonin and vitamin D

    Science.gov (United States)

    Potts, J. T., Jr.

    1976-01-01

    Advances in analysis of chemistry and physiology of parathyroid hormone, calcitonin, and Vitamin D are described along with development of techniques in radioassay methods. Emphasis is placed on assessment of normal and abnormal patterns of secretion of these hormones in specific relation to the physiological adaptations of weightlessness and space flight. Related diseases that involve perturbations in normal skeletal and calcium homeostasis are also considered.

  3. In situ parathyroid gland blood supply preservation and parathyroid autotrausplantation during total or near total thyroidectomy%原位保留甲状旁腺血供及甲状旁腺自体移植术

    Institute of Scientific and Technical Information of China (English)

    李亦工; 高明; 郑向前; 于洋; 魏松锋

    2008-01-01

    Objective To introduce the processes of vascularized parathyroid gland reservation and parathyroid autotransplantation applied in thyroidectomy. Methods In 46 cases who underwent total/near total thyroidectomy, in situ vascularized parathyroid gland reservation was performed in 24 cases,isolated parathyroid autotransplantation was performed in 5 cases, in situ vascularized parathyroid gland reservation of 1~2 parathyroid glands combined with immediately transplantation of the remaining isolated parathyroid glands were performed in 17 cases. Results Five cases suffered from transient hypocalcaemia, including 2 cases of vascularized parathyroid gland reservation and 3 cases of vascularized parathyroid gland reservation in 1~2 parathyroid glands combined with immediately transplantation of other parathyroid glands. Two cases who received parathyroid autotransplantation suffered from hypocalcaemia and received conservative treatment with activated vitamin D3 and caleium for 4 weeks or 8 weeks. Permanent hypoparathyroidism occurred in 1 case of 46 cases which undergone the total/near total thyroidectomy(2.2%). Conclusion Application of vascularized parathyroid gland reservation and parathyroid autotransplantation in total/near total thyroidectomy could reduce the incidence rate of post-operative hypoparathyroidism.%目的 介绍甲状腺肿瘤手术中保护甲状旁腺血供及甲状旁腺自体移植的方法及疗效.方法 46例全甲状腺切除或近全切除手术中,血管化甲状旁腺保留24例,单纯自体甲状旁腺移植5例,1~2枚甲状旁腺血管化保留同时其余甲状旁腺Ⅰ期自体移植17例.结果 应用此法行全甲状腺切除或近全切除患者中,有2例原位血管化保留甲状旁腺及3例血管化保留+自体甲状旁腺移植患者术后48~72 h内出现一过性低血钙,予以补钙后3 d左右恢复正常.2例单纯甲状旁腺自体移植患者术后出现低血钙,服用钙尔奇D/罗盖全4周~8周后复查血

  4. Preoperative localization of lesions of the parathyroid gland using thallium-technetium scintiscanning

    Energy Technology Data Exchange (ETDEWEB)

    Kim, D.Y.; Fine, E.J.; Silver, C.E.

    1987-09-01

    Double tracer scanning of the neck after injection of thallium-210 and technetium pertechnetate was performed upon 33 patients with biochemically proved hyperparathyroidism operated upon during the past 14 months. Operative findings were correlated with the scans. Twenty-two of 29 single lesions of the parathyroid gland were successfully localized. There were ten unsuccessful studies, including three instances in which diffuse hyperplasia was incompletely identified. In one instance of diffuse hyperplasia, the bilateral pathologic finding was diagnosed correctly. Two of three substernal lesions were demonstrated in patients who had undergone previous unsuccessful explorations. An additional substernal lesion was localized in a patient prior to initial exploration. Nineteen of 21 lesions weighing more than 300 milligrams were identified, whereas only 50 per cent of the lesions weighing less than 300 milligrams could be seen. The scans demonstrated 12 of 14 lesions with C-terminal parathyroid hormone levels of more than 900 picograms per milliliter but only 60 per cent of the lesions that produced levels of less than 900 picograms per milliliter. Thallium-technetium scanning is a useful procedure for preoperative localization of parathyroid lesions and may preclude the need for more invasive testing in previously operated upon patients.

  5. Successful preoperative diagnosis of the localization of adenoma of the parathyroid gland by scintiscan

    Energy Technology Data Exchange (ETDEWEB)

    Takei, Ko; Shirasu, Nobuhiko; Kobayashi, Katsumi; Komatsu, Hideki; Ueno, Akira; Uchiyama, Akira

    1985-02-01

    Successful preoperative diagnosis of the localization of adenoma of the parathyroid in 59-year-old female with hyperparathyroidism by means of double tracer scanning and computerized image subtraction was described. She had been suffering from recurrent urolithiasis and was referred to our clinic because of hypercalcemia and hypophosphatemia in November 1983. The level of serum calcium was 11.2 mg/dl and inorganic serum phosphorus 2.1 mg/dl. The activity of serum alkaline phosphatase was within normal limits. Urinary calcium excretion was elevated to the level of 262 mg/day under low calcium diet (300 mg/day). CT scan could not detect adenoma of the parathyroid. Double tracer scanning with S TI as chloride salt and /sup 99m/Tc as pertechnatate and computerized image subtraction showed abnormal thallium uptake about the lower portion of the right lobe of the thyroid gland. Neck exploration revealed a parathyroid adenoma, weighing 1.0 g behind the right lobe of the thyroid gland as was demonstrated by the preoperative subtracted scintiscan. Convalescence was uneventful and the level of serum calcium and urinary calcium excretion was normalized.

  6. [Surgical treatment of secondary hyperparathyroidism in chronic kidney failure. Results of total parathyroidectomy with parathyroid autotransplantation].

    Science.gov (United States)

    Courant, O; Letessier, E; Moutel, M G; Hamy, A; Paineau, J; Visset, J

    1993-01-01

    Between 1978 and 1990, 68 patients, operated on for secondary hyperparathyroidism (HPT), received a forearm intramuscular free autologous parathyroid graft (37 women and 31 men--mean age: 43 +/- 16 years). The transplantation (Wells technique) was performed in the same time as the total parathyroidectomy and the remaining parathyroid material after surgical resection was cryopreserved. The results were evaluated in term of clinical and/or radiological and/or biological response respectively 3 or 5.5 years later, depending of the realisation of a renal transplantation (n = 27) or not. Four patients were lost to follow-up and 4 died post-operatively, including a wrong diagnosis (60 patients evaluated). Mortality rate was 12% (5 cases out of 7 related to chronic renal insufficiency). In 3 patients (5%) the transplanted gland had to be removed because of recurrent HPT (1 graft hyperplasia; 2 wrong diagnosis: 1 cervical gland left over and 1 aluminium intoxication). Second cervicotomy was performed in 3 cases (5%) for remaining cervical parathyroid gland (2 cases) and false-positive Tallium-Technetium scan (1 case). Overall results were good or very good in 51 cases (85%). A review of the literature indicate that subtotal parathyroidectomy in not superior to the Wells technique and the latter remain the landmark technique in the authors' hands in order to treat secondary HPT.

  7. Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues

    Directory of Open Access Journals (Sweden)

    Persson Bengt

    2010-10-01

    Full Text Available Abstract Background We aim to propose interactions between the parathyroid hormone-2 receptor (PTH2R and its ligand the tuberoinfundibular peptide of 39 residues (TIP39 by constructing a homology model of their complex. The two related peptides parathyroid hormone (PTH and parathyroid hormone related protein (PTHrP are compared with the complex to examine their interactions. Findings In the model, the hydrophobic N-terminus of TIP39 is buried in a hydrophobic part of the central cavity between helices 3 and 7. Comparison of the peptide sequences indicates that the main discriminator between the agonistic peptides TIP39 and PTH and the inactive PTHrP is a tryptophan-phenylalanine replacement. The model indicates that the smaller phenylalanine in PTHrP does not completely occupy the binding site of the larger tryptophan residue in the other peptides. As only TIP39 causes internalisation of the receptor and the primary difference being an aspartic acid in position 7 of TIP39 that interacts with histidine 396 in the receptor, versus isoleucine/histidine residues in the related hormones, this might be a trigger interaction for the events that cause internalisation. Conclusions A model is constructed for the complex and a trigger interaction for full agonistic activation between aspartic acid 7 of TIP39 and histidine 396 in the receptor is proposed.

  8. Developmental cues for bone formation from parathyroid hormone and parathyroid hormone-related protein in an ex vivo organotypic culture system of embryonic chick femora.

    Science.gov (United States)

    Smith, Emma L; Kanczler, Janos M; Roberts, Carol A; Oreffo, Richard O C

    2012-12-01

    Enhancement and application of our understanding of skeletal developmental biology is critical to developing tissue engineering approaches to bone repair. We propose that use of the developing embryonic femur as a model to further understand skeletogenesis, and the effects of key differentiation agents, will aid our understanding of the developing bone niche and inform bone reparation. We have used a three-dimensional organotypic culture system of embryonic chick femora to investigate the effects of two key skeletal differentiation agents, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP), on bone and cartilage development, using a combination of microcomputed tomography and histological analysis to assess tissue formation and structure, and cellular behavior. Stimulation of embryonic day 11 (E11) organotypic femur cultures with PTH and PTHrP initiated osteogenesis. Bone formation was enhanced, with increased collagen I and STRO-1 expression, and cartilage was reduced, with decreased chondrocyte proliferation, collagen II expression, and glycosaminoglycan levels. This study demonstrates the successful use of organotypic chick femur cultures as a model for bone development, evidenced by the ability of exogenous bioactive molecules to differentially modulate bone and cartilage formation. The organotypic model outlined provides a tool for analyzing key temporal stages of bone and cartilage development, providing a paradigm for translation of bone development to improve scaffolds and skeletal stem cell treatments for skeletal regenerative medicine.

  9. Role of paraoxonase-1 in bone anabolic effects of parathyroid hormone in hyperlipidemic mice

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jinxiu [Department of Physiology, University of California, Los Angeles (United States); Cheng, Henry [Department of Medicine, University of California, Los Angeles (United States); Atti, Elisa [Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles (United States); Shih, Diana M. [Department of Medicine, University of California, Los Angeles (United States); Demer, Linda L. [Department of Physiology, University of California, Los Angeles (United States); Department of Medicine, University of California, Los Angeles (United States); Department of Bioengineering, University of California, Los Angeles (United States); Tintut, Yin, E-mail: ytintut@mednet.ucla.edu [Department of Medicine, University of California, Los Angeles (United States)

    2013-02-01

    Highlights: ► Anabolic effects of PTH were tested in hyperlipidemic mice overexpressing PON1. ► Expression of antioxidant regulatory genes was induced in PON1 overexpression. ► Bone resorptive activity was reduced in PON1 overexpressing hyperlipidemic mice. ► PON1 restored responsiveness to intermittent PTH in bones of hyperlipidemic mice. -- Abstract: Hyperlipidemia blunts anabolic effects of intermittent parathyroid hormone (PTH) on cortical bone, and the responsiveness to PTH are restored in part by oral administration of the antioxidant ApoA-I mimetic peptide, D-4F. To evaluate the mechanism of this rescue, hyperlipidemic mice overexpressing the high-density lipoprotein-associated antioxidant enzyme, paraoxonase 1 (Ldlr{sup −/−}PON1{sup tg}) were generated, and daily PTH injections were administered to Ldlr{sup −/−}PON1{sup tg} and to littermate Ldlr{sup −/−} mice. Expression of bone regulatory genes was determined by realtime RT-qPCR, and cortical bone parameters of the femoral bones by micro-computed tomographic analyses. PTH-treated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTH receptor (PTH1R), activating transcription factor-4 (ATF4), and osteoprotegerin (OPG) in femoral cortical bone, as well as significantly greater cortical bone mineral content, thickness, and area in femoral diaphyses compared with untreated Ldlr{sup −/−}PON1{sup tg} mice. In contrast, in control mice (Ldlr{sup −/−}) without PON1 overexpression, PTH treatment did not induce these markers. Calvarial bone of PTH-treated Ldlr{sup −/−}PON1{sup tg} mice also had significantly greater expression of osteoblastic differentiation marker genes as well as BMP-2-target and Wnt-target genes. Untreated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTHR1 than untreated Ldlr{sup −/−} mice, whereas sclerostin expression was reduced. In femoral cortical bones, expression levels of transcription factors, Fox

  10. 微囊化甲状旁腺兔-鼠移植%Xenotransplantation of microencapsulated rabbit parathyroid tissue into rars

    Institute of Scientific and Technical Information of China (English)

    王东; 翟博; 刘颖新; 武林枫

    2011-01-01

    BACKGROUND: Microsncapsulation has been widely used in various experimental studies. Microencapsulated parathyroidtransplantation has become a hot issue, but the better transplantation site and the mechanism underlying failed transplantationare urgently to be solved.OBJECTIVE: To investigate the therapeutic effects of xenotransplantation of microencapsulated parathyroid tissue on treatmentof hypoparathyroidism in Wistar rats and to determine the optimal transplantation site and the mechanism underlying (ailedtransplantation.METHODS: Wistar rat models of hypoparathyroidism were developed. At 4 weeks after model establishment, rat models wererandomly allocated to four groups: renal adipose capsules, chest stemocleidomastoid muscle, and empty microcapsule controlgroups. Microcapsuled parathyroid tissues were transplanted into renal adipose capsules and chest stemocleidomastoid musclein renal adipose capsules group and chest stemocleidomastoid muscle group respectively. Empty microcapsules withoutparathyroid were transplanted into renal adipose capsules in empty microcapsule group. Total serum calcium was measuredevery other week. In the 16th week, transplant beds were retrieved and subjected to electron microscopic examination.RESULTS AND CONCLUSION: There was no significant difference in serum calcium level between renal adipose capsule groupand chest stemocleidomastoid muscle group during 16 weeks (P> 0.05). The serum calcium level in the cheststemocieidomastoid musda group decreased between 16-20 weeks. There were many Fiber tissues surrounding themicroencapsules in the chest sternocleidomastoid muscle group. Parathyroid tissues can be protected successfully fromAhginate-Ba capsules and then survive functionally for a long time. The renal adipose capsule is the better transplantation sitethan chest stemocleidomastoid muscle.%背景:微囊化移植技术已经普遍应用于各种实验,成为解决甲状旁腺移植免疫排斥反应的热点领域,但最佳移植

  11. Preparation and in vivo evaluation of an orally available enteric-microencapsulated parathyroid hormone (1-34-deoxycholic acid nanocomplex

    Directory of Open Access Journals (Sweden)

    Hwang SR

    2016-08-01

    Full Text Available Seung Rim Hwang,1 Dong-Hyun Seo,2 Youngro Byun,3 Jin Woo Park4 1Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, 2Department of Biomedical Engineering, College of Health Science, Yonsei University, Wonju, Gangwon, 3Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, College of Pharmacy, Seoul National University, Seoul, 4Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam, Republic of Korea Abstract: The N-terminal 34-amino-acid peptide fragment of human parathyroid hormone PTH (1-34, is used clinically to treat osteoporosis; however, it is currently administered by a once-daily subcutaneous injection, resulting in poor patient compliance. We have developed enteric microcapsules containing an ionic nanocomplex between PTH (1-34 and lysine-linked deoxycholic acid (LysDOCA for the oral delivery of PTH (1-34. We measured the particle size of the PTH/LysDOCA complex and assessed its biological activity by determining the cAMP content in MC3T3-E1 cells. We also assessed its permeability across a Caco-2 cell monolayer and the bioavailability of the intrajejunally administered PTH/LysDOCA complex compared with PTH (1-34 in rats. In addition, the antiosteoporotic activity of the PTH/LysDOCA complex, encapsulated in an enteric carrier by coaxial ultrasonic atomization, was evaluated after it was orally administered to ovariectomized (OVX rats. The formation of an ionic complex between PTH (1-34 and LysDOCA produced nanoparticles of diameter 33.0±3.36 nm, and the bioactivity of the complex was comparable with that of PTH (1-34. The Caco-2 cell permeability and AUClast value of the PTH/LysDOCA (1:10 nanocomplex increased by 2.87- and 16.3-fold, respectively, compared with PTH (1-34 alone. Furthermore, the OVX rats treated with oral PTH/LysDOCA-loaded enteric microcapsules showed an

  12. Determining

    Directory of Open Access Journals (Sweden)

    Bahram Andarzian

    2015-06-01

    Full Text Available Wheat production in the south of Khuzestan, Iran is constrained by heat stress for late sowing dates. For optimization of yield, sowing at the appropriate time to fit the cultivar maturity length and growing season is critical. Crop models could be used to determine optimum sowing window for a locality. The objectives of this study were to evaluate the Cropping System Model (CSM-CERES-Wheat for its ability to simulate growth, development, grain yield of wheat in the tropical regions of Iran, and to study the impact of different sowing dates on wheat performance. The genetic coefficients of cultivar Chamran were calibrated for the CSM-CERES-Wheat model and crop model performance was evaluated with experimental data. Wheat cultivar Chamran was sown on different dates, ranging from 5 November to 9 January during 5 years of field experiments that were conducted in the Khuzestan province, Iran, under full and deficit irrigation conditions. The model was run for 8 sowing dates starting on 25 October and repeated every 10 days until 5 January using long-term historical weather data from the Ahvaz, Behbehan, Dezful and Izeh locations. The seasonal analysis program of DSSAT was used to determine the optimum sowing window for different locations as well. Evaluation with the experimental data showed that performance of the model was reasonable as indicated by fairly accurate simulation of crop phenology, biomass accumulation and grain yield against measured data. The normalized RMSE were 3%, 2%, 11.8%, and 3.4% for anthesis date, maturity date, grain yield and biomass, respectively. Optimum sowing window was different among locations. It was opened and closed on 5 November and 5 December for Ahvaz; 5 November and 15 December for Behbehan and Dezful;and 1 November and 15 December for Izeh, respectively. CERES-Wheat model could be used as a tool to evaluate the effect of sowing date on wheat performance in Khuzestan conditions. Further model evaluations

  13. Institutional experience of PTH evaluation on fine-needle washing after aspiration biopsy to locate hyperfunctioning parathyroid tissue

    Institute of Scientific and Technical Information of China (English)

    Massimo GIUSTI; Mara DOLCINO; Lara VERA; Carla GHIARA; Francesca MASSARO; Laura FAZZUOLI; Diego FERONE; Michele MUSSAP; Francesco MINUTO

    2009-01-01

    Assaying parathyroid hormone (PTH) in the washing liquid after fine-needle aspiration biopsy (FNAB) seems to be a valid approach to locate parathyroid tissue. PTH-FNAB was evaluated in 47 patients with a clinical picture of primary hyper-parathyroidism (PHP) and ultrasonography (US) suggestive of parathyroid lesion. The patients were subdivided into two groups on the basis of the absence or presence of US thyroid alterations. The result of PTH-FNAB was compared with those of cytology, scintigraphy and, in 24 patients, surgical outcome. PTH-FNAB samples with a value higher than that recorded in the serum and higher than our institutional cut-off were deemed to be probable samples of parathyroid tissue. Cytology proved diagnostic for benign thyroid lesions, non-diagnostic for thyroid lesions, hyperplastic parathyroid tissue, undetermined or malignant thyroid lesions and other lesions in 45%, 30%, 17%, 4%, and 4% of cases, respectively. In 47% of cases, PTH-FNAB indicated that the sample had been taken in parathyroid tissue. In patients without US alterations, the diagnostic accuracy of PTH-FNAB was greater than that of scintigraphy. After surgery, comparison between the results of PTH-FNAB and scintigraphy, in terms of positive predictive value (PPV), revealed the superiority of PTH-FNAB; PPV was 94% for FNAB and 71% for scintigraphy, while sen-sitivity was 83% and 69%, respectively. PTH-FNAB evaluation after FNAB appears to be more diagnostic than cytology and scintigraphy. Of all the procedures used, PTH-FNAB appears to be the method of choice when the target is US suggestive and reachable. PTH-FNAB appears to be a useful method of guiding surgical intervention.

  14. Intraoperative localization of the parathyroid glands with indocyanine green and Firefly(R) technology during BABA robotic thyroidectomy.

    Science.gov (United States)

    Yu, Hyeong Won; Chung, Joon Woo; Yi, Jin Wook; Song, Ra-Yeong; Lee, Joon-Hyop; Kwon, Hyungju; Kim, Su-Jin; Chai, Young Jun; Choi, June Young; Lee, Kyu Eun

    2017-07-01

    It is unclear whether near-infrared (NIR) light-induced indocyanine green (ICG) fluorescence can effectively identify, and thus permit the preservation of, parathyroid glands in bilateral axillo-breast approach (BABA) robotic thyroidectomy. This case-control study with a prospectively recruited consecutive series and a retrospectively selected control group assessed the usefulness of ICG with Firefly(R) technology to identify the parathyroid glands intraoperatively during BABA robotic thyroidectomy. All consecutive patients (N = 22) who were scheduled to undergo BABA robotic thyroidectomy for papillary thyroid carcinoma in December 2013-August 2015 and met the study eligibility criteria were recruited prospectively. ICG fluorescence was used with the Firefly system (NIR illuminator: 805 nm; filter: 825 nm) integrated in the da Vinci Si robot system to identify the lower parathyroid glands. Parathyroid hormone levels were recorded on postoperative days 0, 1, 2, and 14. Propensity score matching was used to identify an age-, gender-, tumor size-, and operation type-matched group of control patients who underwent BABA robotic thyroidectomy without the Firefly system. The two groups were compared in terms of parathyroid-related outcomes. ICG fluorescence-mediated identification of the parathyroid and thyroid glands required on average (range) 203 ± 89 (125-331) and 207 ± 112 (130-356) s, respectively. The mean (range) fluorescence duration in these glands was 20.8 ± 6.0 (16.6-35.8) and 20.1 ± 7.3 (15.5-33.8) min, respectively. The ICG group had a significantly lower rate of incidental parathyroidectomy than the control group (0 vs. 15.9%, P = 0.048). ICG with NIR light may feasibly and safely identify the parathyroid glands in BABA robotic thyroidectomy.

  15. Dynamic Na+-H+ Exchanger Regulatory Factor-1 Association and Dissociation Regulate Parathyroid Hormone Receptor Trafficking at Membrane Microdomains*

    Science.gov (United States)

    Ardura, Juan A.; Wang, Bin; Watkins, Simon C.; Vilardaga, Jean-Pierre; Friedman, Peter A.

    2011-01-01

    Na/H exchanger regulatory factor-1 (NHERF1) is a cytoplasmic PDZ (postsynaptic density 95/disc large/zona occludens) protein that assembles macromolecular complexes and determines the localization, trafficking, and signaling of select G protein-coupled receptors and other membrane-delimited proteins. The parathyroid hormone receptor (PTHR), which regulates mineral ion homeostasis and bone turnover, is a G protein-coupled receptor harboring a PDZ-binding motif that enables association with NHERF1 and tethering to the actin cytoskeleton. NHERF1 interactions with the PTHR modify its trafficking and signaling. Here, we characterized by live cell imaging the mechanism whereby NHERF1 coordinates the interactions of multiple proteins, as well as the fate of NHERF1 itself upon receptor activation. Upon PTHR stimulation, NHERF1 rapidly dissociates from the receptor and induces receptor aggregation in long lasting clusters that are enriched with the actin-binding protein ezrin and with clathrin. After NHERF1 dissociates from the PTHR, ezrin then directly interacts with the PTHR to stabilize the PTHR at the cell membrane. Recruitment of β-arrestins to the PTHR is delayed until NHERF1 dissociates from the receptor, which is then trafficked to clathrin for internalization. The ability of NHERF to interact dynamically with the PTHR and cognate adapter proteins regulates receptor trafficking and signaling in a spatially and temporally coordinated manner. PMID:21832055

  16. Dynamic Na+-H+ exchanger regulatory factor-1 association and dissociation regulate parathyroid hormone receptor trafficking at membrane microdomains.

    Science.gov (United States)

    Ardura, Juan A; Wang, Bin; Watkins, Simon C; Vilardaga, Jean-Pierre; Friedman, Peter A

    2011-10-07

    Na/H exchanger regulatory factor-1 (NHERF1) is a cytoplasmic PDZ (postsynaptic density 95/disc large/zona occludens) protein that assembles macromolecular complexes and determines the localization, trafficking, and signaling of select G protein-coupled receptors and other membrane-delimited proteins. The parathyroid hormone receptor (PTHR), which regulates mineral ion homeostasis and bone turnover, is a G protein-coupled receptor harboring a PDZ-binding motif that enables association with NHERF1 and tethering to the actin cytoskeleton. NHERF1 interactions with the PTHR modify its trafficking and signaling. Here, we characterized by live cell imaging the mechanism whereby NHERF1 coordinates the interactions of multiple proteins, as well as the fate of NHERF1 itself upon receptor activation. Upon PTHR stimulation, NHERF1 rapidly dissociates from the receptor and induces receptor aggregation in long lasting clusters that are enriched with the actin-binding protein ezrin and with clathrin. After NHERF1 dissociates from the PTHR, ezrin then directly interacts with the PTHR to stabilize the PTHR at the cell membrane. Recruitment of β-arrestins to the PTHR is delayed until NHERF1 dissociates from the receptor, which is then trafficked to clathrin for internalization. The ability of NHERF to interact dynamically with the PTHR and cognate adapter proteins regulates receptor trafficking and signaling in a spatially and temporally coordinated manner.

  17. Pharmacodynamic model of parathyroid hormone modulation by a negative allosteric modulator of the calcium-sensing receptor.

    Science.gov (United States)

    Abraham, Anson K; Maurer, Tristan S; Kalgutkar, Amit S; Gao, Xiang; Li, Mei; Healy, David R; Petersen, Donna N; Griffith, David A; Mager, Donald E

    2011-06-01

    In this study, a pharmacodynamic model is developed, based on calcium-parathyroid hormone (PTH) homeostasis, which describes the concentration-effect relationship of a negative allosteric modulator of the calcium-sensing receptor (CaR) in rats. Plasma concentrations of drug and PTH were determined from plasma samples obtained via serial jugular vein sampling following single subcutaneous doses of 1, 5, 45, and 150 mg/kg to male Sprague-Dawley rats (n = 5/dose). Drug pharmacokinetics was described by a one-compartment model with first-order absorption and linear elimination. Concentration-time profiles of PTH were characterized using a model in which the compound allosterically modulates Ca(+2) binding to the CaR that, in turn, modulates PTH through a precursor-pool indirect response model. Additionally, negative feedback was incorporated to account for tolerance observed at higher dose levels. Model fitting and parameter estimation were conducted using the maximum likelihood algorithm. The proposed model well characterized the data and provided compound specific estimates of the K(i) and cooperativity constant (α) of 1.47 ng/mL and 0.406, respectively. In addition, the estimated model parameters for PTH turnover were comparable to that previously reported. The final generalized model is capable of characterizing both PTH-Ca(+2) homeostasis and the pharmacokinetics and pharmacodynamics associated with the negative allosteric CaR modulator. As such, the model provides a simple platform for analysis of drugs targeting the PTH-Ca(+2) system.

  18. Hair-cycle-dependent expression of parathyroid hormone-related protein and its type I receptor: evidence for regulation at the anagen to catagen transition.

    Science.gov (United States)

    Cho, Yong Mee; Woodard, Grant L; Dunbar, Maureen; Gocken, Todd; Jimènez, Juan A; Foley, John

    2003-05-01

    The humoral hypercalcemia factor parathyroid hormone-related protein is a paracrine-signaling molecule that regulates the development of several organ systems, including the skin. In pathologic circumstances such as hypercalcemia and in development, parathyroid hormone-related protein signaling appears to be mediated by the type I parathyroid hormone/parathyroid hormone-related protein receptor. In order to clarify the role of the ligand and receptor pair in cutaneous biology, gene expression was monitored in a series of murine skin samples ranging from embryonic day 14 to 2 y with in situ hybridization and RNase protection. In all samples, high levels of parathyroid hormone-related protein transcripts were exclusively expressed in the developing and adult hair follicle but were not observed in the interfollicular epidermis. In the adult, parathyroid hormone-related protein mRNA expression was dynamically regulated as a function of the murine hair cycle in a way similar to other signaling molecules that regulate the anagen to catagen transition. PTH receptor transcripts were abundantly expressed in the developing dermis. In the adult skin, PTH receptor mRNA was markedly reduced, but again demonstrated hair-cycle-dependent expression. The dorsal skin of the keratin 14-parathyroid hormone-related protein mouse was used to evaluate the impact of overexpression of the peptide on the murine hair cycle. All types of hair were 30-40% shorter in adult keratin 14-parathyroid hormone-related protein mice as compared with wild-type littermates. This appeared to result from a premature entry into the catagen phase of the hair cycle. Finally, the relationship between parathyroid hormone-related protein signaling and other growth factors that regulate the hair cycle was examined by cross-breeding experiments employing keratin 14-parathyroid hormone-related protein mice and fibroblast growth factor-5-knockout mice. It appears that parathyroid hormone-related protein and

  19. First evidence of TRPV5 and TRPV6 channels in human parathyroid glands: possible involvement in neoplastic transformation.

    Science.gov (United States)

    Giusti, Laura; Cetani, Filomena; Da Valle, Ylenia; Pardi, Elena; Ciregia, Federica; Donadio, Elena; Gargini, Claudia; Piano, Ilaria; Borsari, Simona; Jaber, Ali; Caputo, Antonella; Basolo, Fulvio; Giannaccini, Gino; Marcocci, Claudio; Lucacchini, Antonio

    2014-10-01

    The parathyroid glands play an overall regulatory role in the systemic calcium (Ca(2+)) homeostasis. The purpose of the present study was to demonstrate the presence of the Ca(2+) channels transient receptor potential vanilloid (TRPV) 5 and TRPV6 in human parathyroid glands. Semi-quantitative and quantitative PCR was carried out to evaluate the presence of TRPV5 and TRPV6 mRNAs in sporadic parathyroid adenomas and normal parathyroid glands. Western blot and immunocytochemical assays were used to assess protein expression, cellular localization and time expression in primary cultures from human parathyroid adenoma. TRPV5 and TRPV6 transcripts were then identified both in normal and pathological tissues. Predominant immunoreactive bands were detected at 75-80 kD for both vanilloid channels. These channels co-localized with the calcium-sensing receptor (CASR) on the membrane surface, but immunoreactivity was also detected in the cytosol and around the nuclei. Our data showed that western blotting recorded an increase of protein expression of both channels in adenoma samples compared with normal glands suggesting a potential relation with the cell calcium signalling pathway and the pathological processes of these glands.

  20. Humoral hypercalcemia associated with gastric carcinoma secreting parathyroid hormone: a case report and review of the literature.

    Science.gov (United States)

    Nakajima, Koji; Tamai, Masataka; Okaniwa, Shinji; Nakamura, Yoshiyuki; Kobayashi, Mutsuhiro; Niwa, Tomohiro; Horigome, Naoto; Ito, Nobuo; Suzuki, Satoru; Nishio, Shinichi; Komatsu, Mitsuhisa

    2013-01-01

    Hypercalcemia with concomitant elevation of serum parathyroid hormone (PTH) and PTH-related protein (PTHrP) levels was found in a patient with advanced gastric carcinoma and multiple liver metastases. The most common features are hypercalcemia associated with hypersecretion of PTHrP and physiological suppression of PTH secretion in the syndrome of humoral hypercalcemia of malignancy (HHM). Although we initially made a diagnosis of primary hyperparathyroidism concomitant with HHM due to gastric cancer, diagnostic imaging studies, such as echography, CT, sestamibi scintigraphy, and autopsy findings, did not reveal evidence of any parathyroid tumors or ectopic parathyroid glands in the mediastinum. Both primary and metastatic tumor cells showed positive staining with PTH-specific antibody as well as PTHrP-specific antibody on immunohistochemical examination. PTH concentration in the cytosolic fraction of the metastatic tumor was elevated compared to that from a control patient with no calcium metabolic disorders in vitro. These findings indicated that PTH secreted ectopically by gastric cancer cells, not by parathyroid glands, caused hypercalcemia in this patient. To our knowledge, this is the first case report of PTH-secreting gastric carcinoma cells. We report the case and a review of the previous reported PTH-secreting non-parathyroid tumors along with the mechanisms of secretion.