A solitary hyperfunctioning thyroid nodule harboring thyroid carcinoma: review of the literature

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Mirfakhraee, Sasan; Mathews, Dana; Peng, Lan; Woodruff, Stacey; Zigman, Jeffrey M

2013-01-01

Hyperfunctioning nodules of the thyroid are thought to only rarely harbor thyroid cancer, and thus are infrequently biopsied. Here, we present the case of a patient with a hyperfunctioning thyroid nodule harboring thyroid carcinoma and, using MEDLINE literature searches, set out to determine the prevalence of and characteristics of malignant ?hot? nodules as a group. Historical, biochemical and radiologic characteristics of the case subjects and their nodules were compared to those in cases o...

Evaluation of steroid laboratory tests and adrenal gland imaging with radiocholesterol in the aetiological diagnosis of Cushing's syndrome

International Nuclear Information System (INIS)

Barbarino, A.; De Marinis, L.; Liberale, I.; Menini, E.

1979-01-01

Basal values of the urinary excretion of 17-oxogenic steroids and serum levels of cortisol were not satisfactory in the differentiation of 'suspected' subjects from patients with true Cushing's syndrome. With a RIA method for serum cortisol determination, the overnight dexamethasone suppression test provided the most reliable single test in establishing adrenocortical hyperfunction. Thirty-five normal subjects, fifty-nine obese patients, thirteen 'suspected' patients and thirteen patients with disease states other than Cushing's syndrome had suppressed values below 4.0 μg/100 ml. None of the ten patients with Cushing's syndrome had a cortisol concentration less than 16.3 μg/100ml. Adrenal gland scintigraphy after radiocholesterol injection is a more valuable tool than the metyrapone test and the high-dose dexamethasone suppression test in the localization and differential diagnosis of adrenocortical lesions causing Cushing's syndrome. It obviates the need for angiographic procedure in the localization of adenomas. It is a reliable technique for identifying functioning adrenal remnants. Therefore a schedule is proposed for studying patients with suspected adrenocortical hyperfunction. (author)

Vocal Hyperfunction in Parents of Children With Attention Deficit Hyperactivity Disorder.

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Teresa, Garcia-Real; Díaz-Román, Tomás M

2016-05-01

The objective of this study was to evaluate the presence of habits and symptoms of vocal hyperfunction in the parents of children with attention deficit hyperactivity disorder (ADHD). Parents of 24 children with ADHD and 30 children of a control group completed a specific questionnaire to detect the hyperfunctional use of the voice (excessive talking, excessive loudness, talking too fast, and shouting), hoarseness, vocal fatigue, mental and physical fatigue, and the degree of parental concern for the vocal health of their child. Parents of children with ADHD spoke more often, faster, and stronger than the parents of the control group; in addition, they also used a louder volume than they usually used when they spoke to their children. The parents manifested more vocal, mental, and physical fatigue than the parents of the control group. There was a significant correlation between the "concern" for the vocal health of their children with respect to vocal symptoms of the children, the habits of vocal hyperfunctioning, and the symptoms suffered by the parents. These results suggest that the parents of children with ADHD change their vocal attitude when communicating with their children. Most likely, the increased concern of parents with ADHD children and their respective level of stress lead to hyperfunctional vocal usage. This subsequently leads to symptoms of vocal, physical, and mental fatigue at the end of the day. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Hyperfunction solutions of the zero rest mass equations and representations of LIE groups

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Dunne, E.G.

1984-01-01

Recently, hyperfunctions have arisen in an essential way in separate results in mathematical physics and in representation theory. In the setting of the twistor program, Wells, with others, has extended the Penrose transform to hyperfunction solutions of the zero rest mass equations, showing that the fundamental isomorphisms hold for this larger space. Meanwhile, Schmid has shown the existence of a canonical globalization of a Harish-Chandra module, V, to a representation of the group. This maximal globalization may be realized as the completion of V in a locally convex vector space in the hyperfunction topology. This thesis shows that the former is a particular case of the latter where the globalization can be done by hand. This explicit globalization is then carried out for a more general case of the Radon transform on homogeneous spaces

Canine hyperadrenocorticism due to adrenocortical neoplasia: pretreatment evaluation of 41 dogs

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Reusch, C.E.; Feldman, E.C.

1991-01-01

This retrospective study identifies parameters that might separate dogs with hyperadrenocorticism caused by adrenocortical tumors from dogs with pituitary-dependent hyperadrenocorticism. Further, an attempt was made to identify factors that could separate dogs with adrenocortical adenomas from dogs with carcinomas. The records of 41 dogs with hyperadrenocorticism caused by adrenocortical neoplasia were reviewed. The history, physical examination, urinalysis, hemogram (CBC), chemistry profile adrenocorticotrophic hormone (ACTH) stimulation and low dose dexamethasone test results were typical of the nonspecific diagnosis of hyperadrenocorticism. The preceding information on the 41 dogs with adrenocortical tumors was compared with that from 44 previously diagnosed pituitary-dependent hyperadrenocorticoid dogs. There was no parameter which aided in separating these two groups of dogs. Thirty dogs with adrenocortical tumors were tested with a high-dose dexamethasone test and none had suppressed plasma cortisol concentrations 8 hours after IV administration of 0.1 mg/kg of dexamethasone. In 29 of the 41 adrenal tumor dogs, plasma endogenous ACTH was not detectable on at least one measurement (less than 20 pg/ml). The remaining 12 dogs from this group had nondiagnostic concentrations (20-45 pg/ml). Thirteen of 22 dogs (59%) with adrenocortical carcinomas had adrenal masses identified on abdominal radiographs and seven of 13 dogs (54%) with adrenocortical adenomas had radiographically visible adrenal masses. Thirteen of 17 adrenocortical carcinomas (76%) and five of eight adenomas (62%) were identified with ultrasonography. Radiographs of the thorax and ultrasonography of the abdomen identified most of the dogs (8 of 11) with metastatic lesions

Diagnosis of bilateral adrenocortical hemorrhage by computed tomography

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Liu, L.; Haskin, M.E.; Rose, L.I.; Bemis, C.E.

1982-01-01

Adrenocortical hemorrhage has been diagnosed on the basis of the clinical presentation and response to steroids or autopsy findings. Prompt recognition of the disease has been difficult because of its similarity to other disorders. We report the diagnosis of a bilateral adrenocortical hemorrhage by computed tomography (CT), followed by biochemical confirmation of the diagnosis

Management of hyperfunctioning single thyroid nodules in the era of minimally invasive thyroid surgery.

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Tan, Charles; Sidhu, Stan; Sywak, Mark; Delbridge, Leigh

2009-05-01

Both surgical excision and radioiodine ablation are effective modalities in the management of hyperfunctioning thyroid nodules. Minimally invasive thyroid surgery (MITS) using the lateral mini-incision approach has previously been demonstrated to be a safe and effective technique for thyroid lobectomy. As such MITS may offer advantages as a surgical approach to hyperfunctioning thyroid nodules without the need for a long cervical incision or extensive dissection associated with formal open hemithyroidectomy. The aim of the present study was to assess the safety and efficacy of MITS for the treatment of hyperfunctioning thyroid nodules. This is a retrospective case study. Data were obtained from the University of Sydney Endocrine Surgical Unit Database from 2002 to 2007. There were 86 cases of hyperfunctioning thyroid nodules surgically removed during the study period, of which 10 (12%) were managed using the MITS approach. The ipsilateral recurrent laryngeal nerve was identified and preserved in all cases with no incidence of temporary or permanent nerve palsy. The external branch of the superior laryngeal nerve was visualized and preserved in eight cases (80%). There were no cases of postoperative bleeding. There was one clinically significant follicular thyroid carcinoma in the series (10%). In nine of 10 cases (90%) normalization of thyroid function followed surgery. MITS is a safe and effective procedure, achieving the benefits of a minimally invasive procedure with minimal morbidity. As such it now presents an attractive alternative to radioiodine ablation for the management of small hyperfunctioning thyroid nodules.

Percutaneous ethanol injection of large autonomous hyperfunctioning thyroid nodules.

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Tarantino, L; Giorgio, A; Mariniello, N; de Stefano, G; Perrotta, A; Aloisio, V; Tamasi, S; Forestieri, M C; Esposito, F; Esposito, F; Finizia, L; Voza, A

2000-01-01

To verify the effectiveness of percutaneous ethanol injection (PEI) in the treatment of large (>30-mL) hyperfunctioning thyroid nodules. Twelve patients (eight women, four men; age range, 26-76 years) with a large hyperfunctioning thyroid nodule (volume range, 33-90 mL; mean, 46.08 mL) underwent PEI treatment under ultrasonographic (US) guidance. US was used to calculate the volume of the nodules and to assess the diffusion of the ethanol in the lesions during the procedure. When incomplete necrosis of the nodule was depicted at scintigraphy performed 3 months after treatment, additional PEI sessions were performed. Four to 11 PEI sessions (mean, seven) were performed in each patient, with an injection of 3-14 mL of 99.8% ethanol per session (total amount of ethanol per patient, 30-108 mL; mean, 48.5 mL). At scintigraphy after treatment in all patients, recovery of extranodular uptake, absence of uptake in the nodule, and normalization of thyroid-stimulating hormone (thyrotropin) levels were observed. In all patients, US showed volume reductions of 30%-50% after 3 months and 40%-80% after 6-9 months. Side effects were self-limiting in all patients. During the 6-48-month follow-up, no recurrence was observed. PEI is an effective and safe technique for the treatment of large hyperfunctioning thyroid nodules.

GNAq mutations are not identified in papillary thyroid carcinomas and hyperfunctioning thyroid nodules.

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Cassol, Clarissa A; Guo, Miao; Ezzat, Shereen; Asa, Sylvia L

2010-12-01

Activating mutations of GNAq protein in a hotspot at codon 209 have been recently described in uveal melanomas. Since these neoplasms share with thyroid carcinomas a high frequency of MAP kinase pathway-activating mutations, we hypothesized whether GNAq mutations could also play a role in the development of thyroid carcinomas. Additionally, activating mutations of another subtype of G protein (GNAS1) are frequently found in hyperfunctioning thyroid adenomas, making it plausible that GNAq-activating mutations could also be found in some of these nodules. To investigate thyroid papillary carcinomas and thyroid hyperfunctioning nodules for GNAq mutations in exon 5, codon 209, a total of 32 RET/PTC, BRAF, and RAS negative thyroid papillary carcinomas and 13 hyperfunctioning thyroid nodules were evaluated. No mutations were identified. Although plausible, GNAq mutations seem not to play an important role in the development of thyroid follicular neoplasms, either benign hyperfunctioning nodules or malignant papillary carcinomas. Our results are in accordance with the literature, in which no GNAq hotspot mutations were found in thyroid papillary carcinomas, as well as in an extensive panel of other tumors. The molecular basis for MAP-kinase pathway activation in RET-PTC/BRAF/RAS negative thyroid carcinomas remains to be determined.

Outcome of radioiodine-131 therapy in hyperfunctioning thyroid nodules: a 20 years' retrospective study.

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Ceccarelli, Claudia; Bencivelli, Walter; Vitti, Paolo; Grasso, Lucia; Pinchera, Aldo

2005-03-01

To investigate the risk of hypothyroidism after radioiodine (131I) treatment for hyperfunctioning thyroid nodules. Retrospective analysis of patients treated with 131I for hyperfunctioning thyroid nodules and followed up for a maximum of 20 years. A total of 346 patients treated with 131I in the years 1975-95, for a single hyperfunctioning nodule. Hypothyroidism was defined as TSH levels > 3.7 mU/l. Kaplan-Meier survival analysis was used to analyse permanence of euthyroidism after 131I. A stepwise Cox proportional hazard model was used to identify factors influencing the progression to hypothyroidism. The cumulative incidence of hypothyroidism was 7.6% at 1 year, 28% at 5 years, 46% at 10 years and 60% at 20 years. Age (P thyroid and nodule size, thyroid status at diagnosis and degree of extranodular thyroid parenchymal suppression had no influence. In hyperthyroid patients with partial parenchymal suppression, however, previous MMI treatment was the most important prognostic factor (P hyperfunctioning nodule are hypothyroid. Factors increasing the risk of hypothyroidism are age, 131I uptake and MMI pretreatment. The prognostic value of this last factor, however, depends on the degree of suppression of the extranodular thyroid parenchyma at the scan.

Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter.

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Tonacchera, M; Agretti, P; Chiovato, L; Rosellini, V; Ceccarini, G; Perri, A; Viacava, P; Naccarato, A G; Miccoli, P; Pinchera, A; Vitti, P

2000-06-01

Toxic multinodular goiter, a heterogeneous disease producing hyperthyroidism, is frequently found in iodine-deficient areas. The pathogenesis of this common clinical entity is still unclear. The aim of the present study was to search for activating TSH receptor (TSHr) or Gs alpha mutations in areas of toxic or functionally autonomous multinodular goiters that appeared hyperfunctioning at thyroid scintiscan but did not clearly correspond to definite nodules at physical or ultrasonographic examination. Surgical tissue specimens from nine patients were carefully dissected, matching thyroid scintiscan and thyroid ultrasonography, to isolate hyperfunctioning and nonfunctioning areas even if they did not correspond to well-defined nodules. TSHr and Gs alpha mutations were searched for by direct sequencing after PCR amplification of genomic DNA. Only 2 adenomas were identified at microscopic examination, whereas the remaining 18 hyperfunctioning areas corresponded to hyperplastic nodules containing multiple aggregates of micromacrofollicules not surrounded by a capsule. Activating TSHr mutations were detected in 14 of these 20 hyperfunctioning areas, whereas no mutation was identified in nonfunctioning nodules or areas contained in the same gland. No Gs alpha mutation was found. In conclusion, activating TSHr mutations are present in the majority of nonadenomatous hyperfunctioning nodules scattered throughout the gland in patients with toxic or functionally autonomous multinodular goiter.

MicroRNAs as potential biomarkers in adrenocortical cancer: progress and challenges

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Nadia eCHERRADI

2016-01-01

Full Text Available Adrenocortical carcinoma is a rare malignancy with poor prognosis and limited therapeutic options. Over the last decade, pan-genomic analyses of genetic and epigenetic alterations and genome-wide expression profile studies allowed major advances in the understanding of the molecular genetics of adrenocortical carcinoma. Besides the well-known dysfunctional molecular pathways in adrenocortical tumors such as the IGF2 pathway, the Wnt pathway and TP53, high-throughput technologies enabled a more comprehensive genomic characterization of adrenocortical cancer. Integration of expression profile data with exome sequencing, SNP array analysis, methylation and microRNA profiling led to the identification of subgroups of malignant tumors with distinct molecular alterations and clinical outcomes. MicroRNAs post-transcriptionally silence their target gene expression either by degrading mRNA or by inhibiting translation. Although our knowledge of the contribution of deregulated microRNAs to the pathogenesis of adrenocortical carcinoma is still in its infancy, recent studies support their relevance in gene expression alterations in these tumors. Some microRNAs have been shown to carry potential diagnostic and prognostic values while others may be good candidates for therapeutic interventions. With the emergence of disease-specific blood-borne microRNAs signatures, analyses of small cohorts of patients with adrenocortical carcinoma suggest that circulating microRNAs represent promising non-invasive biomarkers of malignancy or recurrence. However, some technical challenges still remain, and most of the microRNAs reported in the literature have not yet been validated in sufficiently powered and longitudinal studies. In this review, we discuss the current knowledge regarding the deregulation of tumor-associated and circulating microRNAs in adrenocortical carcinoma patients, while emphasizing their potential significance in adrenocortical carcinoma pathogenic

Hyperfunctioning solid/trabecular follicular carcinoma of the thyroid gland.

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Giovanella, Luca; Fasolini, Fabrizio; Suriano, Sergio; Mazzucchelli, Luca

2010-01-01

A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the (99m)Tc-pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed a solid/trabecular follicular thyroid carcinoma. To the best of our knowledge, this is the first case of hyperfunctioning follicular solid/trabecular carcinoma reported in the literature. Even if a hyperfunctioning thyroid carcinoma is an extremely rare malignancy, careful management is recommended so that a malignancy will not be overlooked in the hot thyroid nodules.

Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma.

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Tonacchera, M; Chiovato, L; Pinchera, A; Agretti, P; Fiore, E; Cetani, F; Rocchi, R; Viacava, P; Miccoli, P; Vitti, P

1998-02-01

Toxic multinodular goiter is a cause of nonautoimmune hyperthyroidism and is believed to differ in its nature and pathogenesis from toxic adenoma. Gain-of-function mutations of the TSH receptor gene have been identified as a cause of toxic adenoma. The pathogenesis at the molecular level of hyperfunctioning nodules in toxic multinodular goiter has yet not been reported. Six patients with a single hot nodule within a multinodular goiter and 11 patients with toxic thyroid adenoma were enrolled in our study. At histology five hyperfunctioning nodules in multinodular goiters showed the features of adenomas, and one was identified as a hyperplastic nodule. The entire exon 10 of the TSH receptor gene was directly sequenced after PCR amplification from genomic DNA obtained from surgical specimens. Functional studies of mutated receptors were performed in COS-7 cells. Five out of 6 (83%) hyperfunctioning nodules within toxic multinodular goiters harbored a TSH receptor mutation. A TSH receptor mutation was also evident in the hyperfunctioning nodule that at histology had the features of noncapsulated hyperplastic nodule. Among toxic adenomas, 8 out of 11 (72%) nodules harbored a TSH receptor mutation. All the mutations were heterozygotic and somatic. Nonfunctioning nodules, whether adenomas or hyperplastic nodules present in association with hyperfunctioning nodules in the same multinodular goiters, had no TSH receptor mutation. All the mutations identified had constitutive activity as assessed by cAMP production after expression in COS-7 cells. Hyperfunctioning thyroid nodules in multinodular goiters recognize the same pathogenetic event (TSH receptor mutation) as toxic adenoma. Other mechanisms are implicated in the growth of nonfunctioning thyroid nodules coexistent in the same gland.

Activating thyrotropin receptor mutations in histologically heterogeneous hyperfunctioning nodules of multinodular goiter.

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Tonacchera, M; Vitti, P; Agretti, P; Giulianetti, B; Mazzi, B; Cavaliere, R; Ceccarini, G; Fiore, E; Viacava, P; Naccarato, A; Pinchera, A; Chiovato, L

1998-07-01

Activating thyrotropin (TSH) receptor mutations have been found in toxic adenomas and in hot nodules contained in toxic multinodular goiter. The typical feature of multinodular goiter is the heterogeneity in morphology and function of different follicles within the same enlarged gland. In this report we describe a patient with a huge multinodular goiter, normal free triiodothyronine (FT3) and free thyroxine (FT4) serum values, and subnormal TSH serum concentration. Thyroid scintiscan showed two hot areas corresponding to the basal and apical nodules of the left lobe. The right lobe was poorly visualized by the radioisotope. The patient underwent thyroidectomy, and histological examination of the tissue was performed. Genomic DNA was extracted from the tissue specimen and direct sequencing of the TSH receptor and Gs alpha genes was done. At histology, one hyperfunctioning nodule had the typical microscopic structure of thyroid adenomas, and the other contained multiple macrofollicular areas not confined by a capsule. In spite of this histological difference, both hyperfunctioning nodules harbored a mutation of the thyrotropin receptor (TSHr) gene: an isoleucine instead of a threonine in position 632 (T632I) in the first nodule and a methionine instead of an isoleucine in position 486 (I486M) in the second nodule. In conclusion, our findings show for the first time that gain-of-function TSHr mutations are not only present in hyperfunctioning thyroid nodules with the histological features of the true thyroid adenomas, but also in hyperfunctioning hyperplastic nodules contained in the same multinodular goiter.

Hyperfunctioning thyroid nodules in children and adolescents.

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de Luca, F; Chaussain, J L; Job, J C

1986-01-01

Eight children and adolescents, seven female and one male, aged 7.1 to 15.0 years, referred over a 12-year period for a solitary mass in an otherwise normal thyroid gland, exhibited a hyperfunctioning nodule on thyroid scintiscan. Tracer uptake in the surrounding thyroid tissue was reduced or completely suppressed, but could be restored after TSH stimulation. Only one patient had mild clinical hyperthyroidism with normal T4 but increased T3 serum levels and blunted TSH responsiveness to TRH. A similar hormonal pattern suggestive of subclinical hyperthyroidism was found in three other subjects who were clinically euthyroid. One patient initially euthyroid progressed to subclinical hyperthyroidism two years later. In the whole group a significant negative relationship was found between serum T3 level and TRH-stimulated TSH peak (r = -0.829, p less than 0.02). All the patients underwent selective surgery after a 3-month to 2-year period of follow-up. Microscopic examination was consistent with adenoma in seven patients, while in one case a well-encapsulated papillary adenocarcinoma was found. Though hyperfunctioning nodules are seldom malignant, their surgical removal must be recommended when they become thyrotoxic, exceed 3 cm or show progressive enlargement.

Management implications from routine needle biopsy of hyperfunctioning thyroid nodules.

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Walfish, P G; Strawbridge, H T; Rosen, I B

1985-12-01

To evaluate the diagnostic and treatment consequences of using a routine needle biopsy procedure on all thyroid nodules without a radioisotopic scintigraphic study, 12 patients with documented hyperfunctioning thyroid nodules were retrospectively evaluated regarding the physical and cytologic observations obtained after a fine-needle (22 to 27-gauge) aspiration biopsy (FNB) procedure. Among the seven solid lesions, features of marked cellularity and nuclear pleomorphism were present in three and moderate sheets of epithelium in four raising the suspicion of underlying malignancy, while five mixed (cystic and solid) lesions were larger than 3 cm, hemorrhagic, and recurrent, with two having detectable sheets of epithelium. Evidence for concomitant lymphocytic thyroiditis was seen in five of 12 (42%) patients, and nine had positive serum antithyroid antibody titers as well. In conclusion, total reliance on FNB without scintigraphy could lead to operations on hyperfunctioning thyroid adenomas for suspected malignancy, of whom the vast majority would be benign, and could expose some unprepared patients with thyrotoxicosis to surgical morbidity. Routine thyroid hormone suppression therapy for apparently benign inflammatory or cystic degenerative lesions could also induce hyperthyroidism in patients with hyperfunctional or autonomous (nonsuppressible) nodules. When using an initial FNB approach, the need for thyroid function studies and scintigraphy before undertaking surgery or thyroid hormone feeding, as well as the consequences of omitting such studies, should be considered.

Analysis of adrenocortical tumours morphology as regards their structure and potential malignancy

International Nuclear Information System (INIS)

Kajor, M.; Ciupinska-Kajor, M.; Dobrosz, Z.; Ziaja, J.; Krol, R.; Heitzman, M.; Cierpka, L.

2006-01-01

Introduction: A consequence of diagnosis of adrenocortical carcinoma (ACC) is introduction of pharmacological therapy, precise monitoring of the patients and in some cases re-operation. The aim of the study is to analyse morphology of adrenocortical tumours as regards their malignancy by use of criteria proposed by Weiss. Material and methods: 110 adrenocortical tumours in 107 patients were analysed (M 27.1%, F 72.9%; age 32 to 77 years, mean 55.2 ± 9.7). Conn syndrome was diagnosed in 16 patients (14.9%), Cushing syndrome in 12 (11.2%), and virilisation in 3 (2.8%). In 76 patients (71.0%) biochemical tests did not reveal hormonal hyperactivity of the tumour. Results: In routine histopathological examination ACC was diagnosed in 6 tumours (5.4%), adrenocortical adenoma (ACA) in 92 (83.6%) and adrenocortical hyperplasia in 12 (10.9%). Nuclear grade III or IV was observed in 8 tumours (7.3%), mitotic rate > 5/50 high power fields in 6 (5.4%), atypical mitoses in 5 (4.5%), clear cells constituting < 25% of the tumour in 10 (9.1%), diffuse architecture in 8 (7.3%), necrosis in 16 (14.5%), veins infiltration in 4 (3.6%), sinusoids infiltration in 7 (6.3%), and tumour capsule infiltration in 5 (4.5%). Among ACC tumours 4 - 9 features of malignancy were present, among ACA - 0 - 3 features. Statistical analysis revealed correlation between number of criteria proposed by Weiss and maximal tumour size (p < 0.05). Conclusion: The structure and cell arrangement in adrenocortical adenoma are heterogeneous. Application of criteria proposed by Weiss in histopathological examination of adrenocortical tumours can be useful in differentiating adrenocortical adenoma from carcinoma. (author)

Hyperfunctioning Solid/Trabecular Follicular Carcinoma of the Thyroid Gland

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Luca Giovanella

2010-01-01

Full Text Available A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the 99mTc-pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed a solid/trabecular follicular thyroid carcinoma. To the best of our knowledge, this is the first case of hyperfunctioning follicular solid/trabecular carcinoma reported in the literature. Even if a hyperfunctioning thyroid carcinoma is an extremely rare malignancy, careful management is recommended so that a malignancy will not be overlooked in the hot thyroid nodules.

Two novel mutations in the sixth transmembrane segment of the thyrotropin receptor gene causing hyperfunctioning thyroid nodules.

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Gozu, Hulya; Avsar, Melike; Bircan, Rifat; Claus, Maren; Sahin, Serap; Sezgin, Ozlem; Deyneli, Oguzhan; Paschke, Ralf; Cirakoglu, Beyazit; Akalin, Sema

2005-04-01

Autonomously functioning thyroid nodules (AFTNs) can present as hyperfunctioning adenomas or toxic multinodular goiters. In the last decade, a large number of activating mutations have been identified in the thyrotropin receptor (TSHR) gene in autonomously functioning thyroid nodules. Most have been situated close to, or within the sixth transmembrane segment and third intracellular loop of the TSHR where the receptor interacts with the Gs protein. In this study we describe two novel mutations in the sixth transmembrane segment of the TSHR causing hyperfunctioning thyroid nodules. Genomic DNAs were isolated from four hyperfunctioning thyroid nodules, normal tissues and peripheral leukocytes of two patients with toxic multinodular goiter. After amplifying the related regions, TSHR and G(s)alpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. Functional studies were done by site-directed mutagenesis and transfection of a mutant construct into COS-7 cells. We identified two novel TSHR mutations in two hyperfunctioning thyroid nodules: Phe631Val in the first patient and Iso630Met in the second patient. Both mutant receptors display an increase in constitutive stimulation of basal cyclic adenosine monophosphate (cAMP) levels compared to the wild-type receptor. This confirms that these mutant receptors cause hyperfunctioning thyroid nodules.

Maternal-child adrenocortical attunement in early childhood: continuity and change.

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Hibel, Leah C; Granger, Douglas A; Blair, Clancy; Finegood, Eric D

2015-01-01

This study evaluated continuity and change in maternal-child hypothalamic-pituitary-adrenal axis attunement in early childhood. Participants were drawn from a prospective study of 1,292 mother-child dyads, which were racially diverse, predominantly low-income, and non-urban. Child focused stress tasks designed to elicit anger, fear, and frustration were administered during early infancy, later infancy, and toddlerhood. Mothers' and children's saliva samples (later assayed for cortisol) were collected before and after the tasks. The strength of mother-child adrenocortical attunement was conserved across infancy and toddlerhood. The magnitude of maternal-child adrenocortical attunement decreased in response to the child-focused stress tasks. Maternal sensitivity and the child's task-related emotional reactivity moderated adrenocortical attunement across the task, with greater maternal sensitivity during a free-play, and lower levels of child emotional reactivity during the stress tasks, stabilizing attunement from pre- to post-task levels. The findings advance our understanding of individual differences in the social regulation of adrenocortical activity in early childhood. © 2014 Wiley Periodicals, Inc.

Percutaneous ethanol injection of hyperfunctioning thyroid nodules: long-term follow-up in 125 patients.

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Tarantino, Luciano; Francica, Giampiero; Sordelli, Ignazio; Sperlongano, Pasquale; Parmeggiani, Domenico; Ripa, Carmine; Parmeggiani, Umberto

2008-03-01

The purpose of this study was to assess the long-term efficacy of percutaneous ethanol injection (PEI) for the treatment of hyperfunctioning thyroid nodules. One hundred twenty-five patients (88 women, 37 men; age range, 17-76 years; mean age, 53 years) with 127 hyperfunctioning thyroid nodules (volume, 1.2-90 mL; mean, 10.3 mL) were treated with PEI. There were 1-11 PEI sessions per patient (average, 3.9) performed, with injection of 1-14 mL of ethanol per session (total injected ethanol per patient, 3-108 mL; mean, 14.0 mL). Efficacy of the treatment was assessed with color Doppler sonography; scintigraphy; and free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) assays. Follow-up (9-144 months; median, 60 months) was performed with TSH and color Doppler sonography every 2 months for 6 months and every 6 months thereafter. Three (2.4%) of 125 patients refused completion of PEI therapy because of pain. Results are reported in 122 patients with 124 nodules. All 122 patients showed posttreatment normal levels of FT3, FT4, and TSH. A complete cure (absent uptake in the nodule and recovery of normal uptake in the thyroid parenchyma) was obtained in 113 (93%) of 122 patients-115 (92.7%) of 124 treated nodules. Residual hyperfunctioning nodular tissue along with decreased thyroid parenchyma uptake (partial cure) was present in nine patients accounting for nine (7.3%) of 124 nodules. Rates of complete cure after PEI were: overall nodules, 115 (92.7%) of 124; nodules nodules > 10 to nodules > 30 to nodules > 60 mL, three (100%) of three. The overall rate of major complications (transient laryngeal nerve damage, two patients; abscess and hematoma, one patient each) was four (3.2%) of 125 patients. Follow-up examinations showed marked shrinkage of 112 treated nodules ranging from 50% to 90% of the pretreatment volume (mean, 66%) and new growth of hyperfunctioning tissue in four patients at color Doppler sonography and scintigraphy at 12

Isolation of rat adrenocortical mitochondria

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Solinas, Paola [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Fujioka, Hisashi [Electron Microscopy Facility, Department of Pharmacology, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Tandler, Bernard [Department of Biological Sciences, School of Dental Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Hoppel, Charles L., E-mail: charles.hoppel@case.edu [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States)

2012-10-12

Highlights: Black-Right-Pointing-Pointer A method for isolation of adrenocortical mitochondria from the adrenal gland of rats is described. Black-Right-Pointing-Pointer The purified isolated mitochondria show excellent morphological integrity. Black-Right-Pointing-Pointer The properties of oxidative phosphorylation are excellent. Black-Right-Pointing-Pointer The method increases the opportunity of direct analysis of adrenal mitochondria from small animals. -- Abstract: This report describes a relatively simple and reliable method for isolating adrenocortical mitochondria from rats in good, reasonably pure yield. These organelles, which heretofore have been unobtainable in isolated form from small laboratory animals, are now readily accessible. A high degree of mitochondrial purity is shown by the electron micrographs, as well as the structural integrity of each mitochondrion. That these organelles have retained their functional integrity is shown by their high respiratory control ratios. In general, the biochemical performance of these adrenal cortical mitochondria closely mirrors that of typical hepatic or cardiac mitochondria.

Effect of acupuncture on adrenocortical hormone production in rabbits with a central lesion

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Liao, Y.Y.; Seto, K.; Saitoh, H.; Kawakami, M.

A study was made of adrenocortical hormone production under electroacupuncture stimulation of the Tsu-San-Li locus in rabbits with a lesion in the fornix, stria terminalis, ventromedial nucleus or arcuate nucleus. In rabbits with a lesion in the stria terminalis or ventromedial nucleus, electroacupuncture stimulation of Tsu-San-Li resulted in no increase in phase 1 but an increase in phase 2 of adrenocortical hormone production. In rabbits with a lesion in the fornix or arcuate nucleus electroacupuncture stimulation of Tsu-San-Li was followed by increased adrenocortical hormone production in the both phases. These results show that the stria terminalis and the ventromedial nucleus play a major role in the augmentation of adrenocortical hormone production by electroacupuncture stimulation of Tsu-San-Li.

A Computerized Tomography Study of Vocal Tract Setting in Hyperfunctional Dysphonia and in Belting.

Science.gov (United States)

Saldias, Marcelo; Guzman, Marco; Miranda, Gonzalo; Laukkanen, Anne-Maria

2018-04-03

Vocal tract setting in hyperfunctional patients is characterized by a high larynx and narrowing of the epilaryngeal and pharyngeal region. Similar observations have been made for various singing styles, eg, belting. The voice quality in belting has been described to be loud, speech like, and high pitched. It is also often described as sounding "pressed" or "tense". The above mentioned has led to the hypothesis that belting may be strenuous to the vocal folds. However, singers and teachers of belting do not regard belting as particularly strenuous. This study investigates possible similarities and differences between hyperfunctional voice production and belting. This study concerns vocal tract setting. Four male patients with hyperfunctional dysphonia and one male contemporary commercial music singer were registered with computerized tomography while phonating on [a:] in their habitual speaking pitch. Additionally, the singer used the pitch G4 in belting. The scannings were studied in sagittal and transversal dimensions by measuring lengths, widths, and areas. Various similarities were found between belting and hyperfunction: high vertical larynx position, small hypopharyngeal width, and epilaryngeal outlet. On the other hand, belting differed from dysphonia (in addition to higher pitch) by a wider lip and jaw opening, and larger volumes of the oral cavity. Belting takes advantage of "megaphone shape" of the vocal tract. Future studies should focus on modeling and simulation to address sound energy transfer. Also, they should consider aerodynamic variables and vocal fold vibration to evaluate the "price of decibels" in these phonation types. Copyright © 2018. Published by Elsevier Inc.

Mouse Models Recapitulating Human Adrenocortical Tumors: What is lacking?

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Felicia Leccia

2016-07-01

Full Text Available Adrenal cortex tumors are divided into benign forms such as primary hyperplasias and adrenocortical adenomas (ACAs, and malignant forms or adrenocortical carcinomas (ACCs. Primary hyperplasias are rare causes of ACTH-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely functional, i.e producing steroids. When functional, adenomas result in endocrine disorders such as Cushing’s syndrome (hypercortisolism or Conn’s syndrome (hyperaldosteronism. In contrast, ACCs are extremely rare but highly aggressive tumors that may also lead to hypersecreting syndromes. Genetic analyses of patients with sporadic or familial forms of adrenocortical tumors led to the identification of potentially causative genes, most of them being involved in PKA, Wnt/β-catenin and P53 signaling pathways. Development of mouse models is a crucial step to firmly establish the functional significance of candidate genes, to dissect mechanisms leading to tumors and endocrine disorders and in fine to provide in vivo tools for therapeutic screens. In this article we will provide an overview on the existing mouse models (xenografted and genetically engineered of adrenocortical tumors by focusing on the role of PKA and Wnt/β-catenin pathways in this context. We will discuss the advantages and limitations of models that have been developed heretofore and we will point out necessary improvements in the development of next generation mouse models of adrenal diseases.

Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

International Nuclear Information System (INIS)

Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

2011-01-01

Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

Localizing diagnosis of hyperfunctional parathyroid glands using 99mTc-methoxyisobutylisonitrile (MIBI)

International Nuclear Information System (INIS)

Katagiri, Makoto; Yokobayashi, Tsuneo; Fukunaga, Masao; Harada, Tanekazu.

1995-01-01

In this study, we investigated the detectability of hyperfunctional parathyroid gland(s) by subtraction scintigraphy using 99m Tc-methoxyisobutylisonitrile and 99m Tc-pertechnetate (MIBI-Tc), and compared the findings with those obtained by conventional subtraction scintigraphy using 201 Tl-Cl and 99m Tc-pertechnetate (Tl-Tc), ultrasonography (US) and computed tomography (CT). The subjects were 6 patients with primary hyperparathyroidism (PHP) with a single adenoma and 13 with renal hyperparathyroidism (RHP) with hyperplasia receiving chronic maintenance hemodialysis. All of the patients underwent surgery, and the number and location of the abnormal parathyroid glands were confirmed. The numbers of resected parathyroid glands were 6 in the PHP group and 52 in the RHP group. In the PHP group, the detectability of hyperfunctional parathyroid glands with MIBI-Tc, Tl-Tc, US and CT was 83.3%, 100%, 83.3% and 83.3%, respectively. In the RHP group, on the other hand, these values were lower than those in the PHP group: 51.9%, 44.2%, 57.7% and 56.3%, respectively. No statistically significant differences were observed among the diagnostic tools in either group. As 99m Tc-MIBI has many physiological advantages over 201 Tl-Cl as a radiotracer, this radionuclide is expected to become useful for the detection of hyperfunctional parathyroid glands. (author)

Expression of adenylyl cyclase types III and VI in human hyperfunctioning thyroid nodules.

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Celano, M; Arturi, F; Presta, I; Bruno, R; Scarpelli, D; Calvagno, M G; Cristofaro, C; Bulotta, S; Giannasio, P; Sacco, R; Filetti, S; Russo, D

2003-05-30

Hyperfunctioning thyroid nodules are characterized by the presence of spontaneous somatic mutations responsible for constitutive activation of the cAMP pathway. However, alterations affecting other elements of the cAMP signaling system may counteract the effects of the mutations. In this study, the expression of the adenylyl cyclase (AC) types III and VI was investigated by Western blot in 18 hyperfunctioning thyroid nodules; in 12 samples, we also assessed the presence of TSH receptor (TSHR) or gsp mutations and levels of AC VI and III mRNA. We found that the expression of nodular AC VI (but not AC III) was significantly lower (85.1% of normal, P=0.014) than the expression of both adenylyl cycles types of perinodular tissue from the same patients. Slightly, but not significant differences were detected in nodules with or without mutations and AC protein levels generally showed correlation with the levels of the transcripts detected by RT-PCR. In addition, AC III and AC VI expression levels within a given nodule were characterized by a significant positive correlation. These findings indicate that a diminished expression of AC type VI may be part of the mechanisms occurring in the hyperfunctioning nodules, independently of the presence of TSHR or gsp mutations, which influence the resulting phenotype.

Primary pigmented nodular adrenocortical disease

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Marie T Manipadam

2011-01-01

Full Text Available Primary pigmented nodular adrenocortical disease (PPNAD is a rare cause of ACTH-independent Cushing′s syndrome and has characteristic gross and microscopic pathologic findings. We report a case of PPNAD in a 15-year-old boy, which was not associated with Carney′s complex. Bilateral adrenalectomy is the treatment of choice.

Feminizing Adrenocortical Carcinoma Without Gynecomastia

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Farida Chentli1*,

2017-07-01

Full Text Available Malignant feminizing adrenocortical tumors are exceedingly rare. Their main presentation is gynecomastia. In these estrogen secreting tumors (with or without other adrenocortical hormones lack of gynecomastia is exceptional as in our case. A 44-year-old man presented with abdominal pain. Radiological assessment revealed a tumor measuring 120 × 95 mm in the retroperitoneal area with numerous metastases. Pathological examination pleaded for an adrenal origin with a Weiss’s score of 5. Six months later, the tumor relapsed, and he had a second surgery and was sent for hormone assessment. Clinical examination showed a skinny man with severe fatigue. He had no Cushingoid features. Gynecomastia and galactorrhea were absent. Penile length, testicular volume, and body hair growth were normal. Several cutaneous nodules were present. Biological assessment showed high morning plasma cortisol, which failed to be suppressed by treatment with 2 mg dexamethasone. Plasma estradiol and 17OH progesterone levels were high, but his testosterone levels were low. Radiological exploration showed numerous metastases: pleural, pulmonary, retroperitoneal, and abdominal. He was treated with classical chemotherapy, but he died four months after diagnosis.

Feminizing adrenocortical carcinoma with distant metastases: can surgery be considered?

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Alessandro Fancellu

2014-07-01

Full Text Available Functioning adrenocortical carcinomas are rare diseases with dismal prognosis. A 41-year-old man presenting with gynecomastia had a giant feminizing adrenocortical carcinoma at stage IV. Although surgical resection was controversial, we removed the primary tumor to reduce the mass effects. He lived for 12 months with an acceptable quality of life. Gynecomastia may be the first sign of feminizing adrenal malignancies. Surgery may ameliorate the quality of life in selected patients with metastatic disease.

A Case of Cushing's Syndrome with Multiple Adrenocortical Adenomas Composed of Compact Cells and Clear Cells.

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Asakawa, Masahiro; Yoshimoto, Takanobu; Ota, Mitsutane; Numasawa, Mitsuyuki; Sasahara, Yuriko; Takeuchi, Takato; Nakano, Yujiro; Oohara, Norihiko; Murakami, Masanori; Bouchi, Ryotaro; Minami, Isao; Tsuchiya, Kyoichiro; Hashimoto, Koshi; Izumiyama, Hajime; Kawamura, Naoko; Kihara, Kazunori; Negi, Mariko; Akashi, Takumi; Eishi, Yoshinobu; Sasano, Hironobu; Ogawa, Yoshihiro

2016-06-01

A 58-year-old woman was referred to our hospital for Cushingoid features and diagnosed as adrenal Cushing's syndrome due to a right adrenocortical mass (60 × 55 mm). The mass was composed of three different tumors; the first one was homogeneously lipid-poor neoplasm measuring 20 × 13 mm located at the most dorsal region, the second one was heterogeneous and lipid-rich tumor containing multiple foci of calcification measuring 50 × 32 mm located at the central region, and the last one was heterogeneous harboring dilated and tortuous vessels and lipid-poor one measuring 35 × 18 mm at the most ventral region of the adrenal gland. A right adrenalectomy was subsequently performed by open surgery. Macroscopic and microscopic analyses revealed that all three tumors were adrenocortical adenomas; the first one represents a pigmented adrenocortical adenoma, the second one adrenocortical adenoma associated with degeneration, and the third one adrenocortical adenoma harboring extensive degeneration. Immunohistochemical analysis of the steroidogenic enzymes also revealed that all of the tumors had the capacity of synthesizing cortisol. This is a very rare case of Cushing's syndrome caused by multiple adrenocortical adenomas including a pigmented adenoma. Immunohistochemical analysis of steroidogenic enzymes contributed to understanding of steroidogenesis in each of these three different adrenocortical adenomas in this case.

Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid.

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Rossi, E D; Raffaelli, M; Mule', A; Miraglia, A; Lombardi, C P; Vecchio, F M; Fadda, G

2006-06-01

The histological diagnosis is critical for the postsurgical management and follow-up of thyroid malignancies. The differential diagnosis between papillary carcinoma and hyperfunctioning lesions, either with papillary hyperplasia or with a follicular architecture, can create real diagnostic difficulty. The aim of this study was to evaluate the expression of several antibodies considered to be markers of malignancy in malignant and hyperfunctioning thyroid neoplasms and to include the most effective of them in a diagnostic panel. One hundred resected thyroid nodules--58 hyperfunctioning benign lesions and 42 papillary carcinomas (14 follicular variant, 14 macrofollicular variant and 14 classic type)--were immunohistochemically studied for HBME-1, galectin-3, cytokeratin (CK) 19 and RET-proto-oncogene. HBME-1 and galectin-3 showed 92.8% and 89% sensitivity, respectively, and their coexpression was present in 36 out of 42 papillary carcinomas (85.7%) and absent in non-malignant lesions. Their association increased sensitivity to 94.7% and the diagnostic accuracy to 97.9% and involved the highest number of cases (95%) in comparison with two other panels including, respectively, three (HBME-1, galectin-3, CK19) and all four antibodies. An immunohistochemical panel consisting of HBME-1 and galectin-3 can make a correct distinction between malignant and hyperfunctioning thyroid neoplasms with high diagnostic accuracy.

Treatment of hyperfunctioning thyroid nodules by percutaneous ethanol injection

OpenAIRE

Larijani, Bagher; Pajouhi, Mohammad; Ghanaati, Hossein; Bastanhagh, Mohammad-Hassan; Abbasvandi, Fereshteh; Firooznia, Kazem; Shirzad, Mahmood; Amini, Mohammad-Reza; Sarai, Maryam; Abbasvandi, Nasreen; Baradar-Jalili, Reza

2002-01-01

Abstract Background Autonomous thyroid nodules can be treated by a variety of methods. We assessed the efficacy of percutaneous ethanol injection in treating autonomous thyroid nodules. Methods 35 patients diagnosed by technetium-99 scanning with hyperfunctioning nodules and suppressed sensitive TSH (sTSH) were given sterile ethanol injections under ultrasound guidance. 29 patients had clinical and biochemical hyperthyroidism. The other 6 had sub-clinical hyperthyroidism with suppressed sTSH ...

Characterization of differential gene expression in adrenocortical tumors harboring beta-catenin (CTNNB1) mutations.

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Durand, Julien; Lampron, Antoine; Mazzuco, Tania L; Chapman, Audrey; Bourdeau, Isabelle

2011-07-01

Mutations of β-catenin gene (CTNNB1) are frequent in adrenocortical adenomas (AA) and adrenocortical carcinomas (ACC). However, the target genes of β-catenin have not yet been identified in adrenocortical tumors. Our objective was to identify genes deregulated in adrenocortical tumors harboring CTNNB1 genetic alterations and nuclear accumulation of β-catenin. Microarray analysis identified a dataset of genes that were differently expressed between AA with CTNNB1 mutations and wild-type (WT) tumors. Within this dataset, the expression profiles of five genes were validated by real time-PCR (RT-PCR) in a cohort of 34 adrenocortical tissues (six AA and one ACC with CTNNB1 mutations, 13 AA and four ACC with WT CTNNB1, and 10 normal adrenal glands) and two human ACC cell lines. We then studied the effects of suppressing β-catenin transcriptional activity with the T-cell factor/β-catenin inhibitors PKF115-584 and PNU74654 on gene expression in H295R and SW13 cells. RT-PCR analysis confirmed the overexpression of ISM1, RALBP1, and PDE2A and the down-regulation of PHYHIP in five of six AA harboring CTNNB1 mutations compared with WT AA (n = 13) and normal adrenal glands (n = 10). RALBP1 and PDE2A overexpression was also confirmed at the protein level by Western blotting analysis in mutated tumors. ENC1 was specifically overexpressed in three of three AA harboring CTNNB1 point mutations. mRNA expression and protein levels of RALBP1, PDE2A, and ENC1 were decreased in a dose-dependent manner in H295R cells after treatment with PKF115-584 or PNU74654. This study identified candidate genes deregulated in CTNNB1-mutated adrenocortical tumors that may lead to a better understanding of the role of the Wnt-β-catenin pathway in adrenocortical tumorigenesis.

Transcription factor GATA-4 is a marker of anaplasia in adrenocortical neoplasms of the domestic ferret (Mustela putorius furo).

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Peterson, R A; Kiupel, M; Bielinska, M; Kiiveri, S; Heikinheimo, M; Capen, C C; Wilson, D B

2004-07-01

Adrenocortical neoplasms are a common cause of morbidity in neutered ferrets. Recently we showed that gonadectomized DBA/2J mice develop adrenocortical tumors that express transcription factor GATA-4. Therefore, we screened archival specimens of adrenocortical neoplasms from neutered ferrets to determine whether GATA-4 could be used as a tumor marker in this species. Nuclear immunoreactivity for GATA-4 was evident in 19/22 (86%) of ferret adrenocortical carcinomas and was prominent in areas exhibiting myxoid differentiation. Normal adrenocortical cells lacked GATA-4 expression. Two other markers of adrenocortical tumors in gonadectomized mice, inhibin-alpha and luteinizing hormone receptor, were coexpressed with GATA-4 in some of the ferret tumors. No GATA-4 expression was observed in three cases of nodular hyperplasia, but patches of anaplastic cells expressing GATA-4 were evident in 7/14 (50%) of tumors classified as adenomas. We conclude that GATA-4 can function as a marker of anaplasia in ferret adrenocortical tumors.

Evaluation of proliferation potential in thyroid normo-/hypofunctioning and hyperfunctioning nodules.

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Cornianu, Marioara; Stan, V; Lazăr, Elena; Dema, Alis; Golu, Ioana; Tăban, Sorina; Vlad, Mihaela; Faur, Alexandra; Vărcuş, F; Babău, F

2011-01-01

Thyroid follicular adenomas (FA) and adenomatous thyroid nodules (AN) - lesions that are frequently found in areas with iodine deficiency, can be normo-/hypofunctioning (scintigraphically cold - SCN) or hyperfunctioning (scintigraphically hot - SHN) nodules. Evaluation of proliferation potential in thyroid nodules on tissue samples obtained at surgery from euthyroid patients clinically diagnosed with SCN and from patients with thyroid hyperfunction and SHN. We investigated the proliferation activity estimated by assessing PCNA and Ki-67 proliferation markers in 20 SCN (eight FA and 12 AN) and 16 toxic nodules (six hyperfunctioning FA and 10 toxic multinodular goiters), on formalin-fixed and paraffin-embedded tissue samples, 4-5 μm thick; we used the immunohistochemical technique in LSAB system (DAB visualization) with anti-PCNA (PC10) and anti-Ki-67 (MIB-1) monoclonal antibodies. For each case, we calculated the proliferation index PI-PCNA and PI-Ki-67. The dates were statistically evaluated using the t-unpaired test. We observed a higher PI-PCNA in thyroid nodules than in the normal surrounding thyroid tissue, with statistically significant values for FA (14.3% vs. 3.8%; pnodules vs. surrounding thyroid tissue was 1.64% vs. 1.10% in FA (p0.05). We also noted: (1) significantly higher PI-PCNA values (p 0.05); (2) increased proliferation rate (pthyroid nodules with aspects of lymphocytic thyroiditis (LT) (PI-Ki-67 was 1.21%) as compared to nodules without LT (PI-Ki-67 was 0.12%); (3) a mean PI-PCNA of 8.5% and PI-Ki-67 of 4.61% in toxic thyroid nodules (TTN) vs. 3.01% and 1.5% in normal surrounding thyroid, respectively. The clinical expression of SCN is the consequence of increased thyrocyte proliferation in the nodules; the increased proliferative potential of TTN thyrocytes is a common feature of nodules, independent of their histopathological characteristics.

Clinical results of the use of mitotane for adrenocortical carcinoma

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Kasperlik-Zaluska A.A.

2000-01-01

Full Text Available Mitotane (o,p'-DDD acts mainly as an inhibitor of intramitochondrial pregnenolone and cortisol synthesis. Its adrenolytic effect depends on metabolic activation due to conversion to o,p'-DDA and o,p'-DDE. The drug has been used for 40 years in the treatment of adrenocortical carcinoma, mainly its regional and metastatic stage, as an adjuvant to surgical resection of the tumor. In the medical literature there are controversial opinions about its efficacy for the treatment of adrenocortical carcinoma. In our experience, mitotane administered immediately after surgery appeared to be much more efficient than when administered later. We have administered this drug in all cases of microscopically confirmed adrenocortical carcinoma, irrespectively of stage at the time of surgery, for fear of a false too optimistic classification. In our series of 82 patients with adrenocortical carcinoma, 59 patients have been treated with mitotane, 32 of them immediately after surgery, and 27 with a delay of 2 to 24 months. Today there are 18 survivors in the group of patients treated with mitotane soon after the operation and only 6 survivors in the group receiving mitotane with a delay. All patients were simultaneously given replacement therapy. Undesired effects of mitotane administration included increased aminotransferase and alkaline phosphatase activity, decreased white cell, platelet or red cell number, and myasthenia. Furthermore, we used mitotane with good results in Cushing's syndrome of non-malignant origin as pre-treatment before surgery or in long-term treatment for patients with poor tolerance of other adrenal inhibitors.

Pathogenesis of canine cortisol-secreting adrenocortical tumors

NARCIS (Netherlands)

Kool, Miriam

2015-01-01

In dogs, hypercortisolism is one of the most frequently observed endocrine disorders, with an estimated incidence of about 1-2 cases per 1000 dogs per year. Approximately 15% of these cases is due to a cortisol-secreting adrenocortical tumor (AT). Cortisol-secreting ATs are characterized by

Pediatric adrenocortical neoplasms: can imaging reliably discriminate adenomas from carcinomas?

International Nuclear Information System (INIS)

Flynt, Kelsey A.; Dillman, Jonathan R.; Smith, Ethan A.; Strouse, Peter J.; Davenport, Matthew S.; Caoili, Elaine M.; Else, Tobias

2015-01-01

There is a paucity of literature describing and comparing the imaging features of adrenocortical adenomas and carcinomas in children and adolescents. To document the CT and MRI features of adrenocortical neoplasms in a pediatric population and to determine whether imaging findings (other than metastatic disease) can distinguish adenomas from carcinomas. We searched institutional medical records to identify pediatric patients with adrenocortical neoplasms. Pre-treatment CT and MRI examinations were reviewed by two radiologists in consensus, and pertinent imaging findings were documented. We also recorded relevant histopathological, demographic, clinical follow-up and survival data. We used the Student's t-test and Wilcoxon rank sum test to compare parametric and nonparametric continuous data, and the Fisher exact test to compare proportions. We used receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performances of tumor diameter and volume for discriminating carcinoma from adenoma. A P-value ≤0.05 was considered statistically significant. Among the adrenocortical lesions, 9 were adenomas, 15 were carcinomas, and 1 was of uncertain malignant potential. There were no differences in mean age, gender or sidedness between adenomas and carcinomas. Carcinomas were significantly larger than adenomas based on mean estimated volume (581 ml, range 16-2,101 vs. 54 ml, range 3-197 ml; P-value = 0.003; ROC area under the curve = 0.92) and mean maximum transverse plane diameter (9.9 cm, range 3.0-14.9 vs. 4.4 cm, range 1.9-8.2 cm; P-value = 0.0001; ROC area under the curve = 0.92). Carcinomas also were more heterogeneous than adenomas on post-contrast imaging (13/14 vs. 2/9; odds ratio [OR] = 45.5; P-value = 0.001). Six of 13 carcinomas and 1 of 8 adenomas contained calcification at CT (OR = 6.0; P-value = 0.17). Seven of 15 children with carcinomas exhibited metastatic disease at diagnosis, and three had inferior vena cava invasion. Median

Pediatric adrenocortical neoplasms: can imaging reliably discriminate adenomas from carcinomas?

Energy Technology Data Exchange (ETDEWEB)

Flynt, Kelsey A.; Dillman, Jonathan R.; Smith, Ethan A.; Strouse, Peter J. [University of Michigan Health System, Section of Pediatric Radiology, C. S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Davenport, Matthew S.; Caoili, Elaine M. [University of Michigan Health System, Division of Abdominal Imaging, Department of Radiology, Ann Arbor, MI (United States); Else, Tobias [University of Michigan Health System, Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, Ann Arbor, MI (United States)

2015-08-15

There is a paucity of literature describing and comparing the imaging features of adrenocortical adenomas and carcinomas in children and adolescents. To document the CT and MRI features of adrenocortical neoplasms in a pediatric population and to determine whether imaging findings (other than metastatic disease) can distinguish adenomas from carcinomas. We searched institutional medical records to identify pediatric patients with adrenocortical neoplasms. Pre-treatment CT and MRI examinations were reviewed by two radiologists in consensus, and pertinent imaging findings were documented. We also recorded relevant histopathological, demographic, clinical follow-up and survival data. We used the Student's t-test and Wilcoxon rank sum test to compare parametric and nonparametric continuous data, and the Fisher exact test to compare proportions. We used receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performances of tumor diameter and volume for discriminating carcinoma from adenoma. A P-value ≤0.05 was considered statistically significant. Among the adrenocortical lesions, 9 were adenomas, 15 were carcinomas, and 1 was of uncertain malignant potential. There were no differences in mean age, gender or sidedness between adenomas and carcinomas. Carcinomas were significantly larger than adenomas based on mean estimated volume (581 ml, range 16-2,101 vs. 54 ml, range 3-197 ml; P-value = 0.003; ROC area under the curve = 0.92) and mean maximum transverse plane diameter (9.9 cm, range 3.0-14.9 vs. 4.4 cm, range 1.9-8.2 cm; P-value = 0.0001; ROC area under the curve = 0.92). Carcinomas also were more heterogeneous than adenomas on post-contrast imaging (13/14 vs. 2/9; odds ratio [OR] = 45.5; P-value = 0.001). Six of 13 carcinomas and 1 of 8 adenomas contained calcification at CT (OR = 6.0; P-value = 0.17). Seven of 15 children with carcinomas exhibited metastatic disease at diagnosis, and three had inferior vena cava invasion. Median

Marital Conflict Predicts Mother-to-Infant Adrenocortical Transmission.

Science.gov (United States)

Hibel, Leah C; Mercado, Evelyn

2017-12-21

Employing an experimental design, mother-to-infant transmission of stress was examined. Mothers (N = 117) were randomized to either have a positive or conflictual discussion with their marital partners, after which infants (age = 6 months) participated in a fear and frustration task. Saliva samples were collected to assess maternal cortisol responses to the discussion and infant cortisol responses to the challenge task. Results indicate maternal cortisol reactivity and recovery to the conflict (but not positive) discussion predicted infant cortisol reactivity to the infant challenge. Mothers' positive affect during the discussion buffered, and intrusion during the free-play potentiated, mother-to-infant adrenocortical transmission. These findings advance our understanding of the social and contextual regulation of adrenocortical activity in early childhood. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

A black adrenocortical adenoma causing Cushing's syndrome not imaged by radiocholesterol scintigraphy

International Nuclear Information System (INIS)

Reschini, E.; Baldini, M.; Cantalamessa, L.

1990-01-01

In a 33-year-old female patient with left adrenal tumour and Cushing's syndrome, adrenocortical scintigraphy with radiocholesterol did not image the tumour nor the suppressed contralateral gland. Histology showed a black adrenocortical adenoma composed only of compact cells; there was no evidence of malignancy. This demonstrates that non-visualization of the adrenal glands in a patient with Cushing's syndrome is not invariably due to adrenal carcinoma. The literature on black adrenal adenomas causing Cushing's syndrome is reviewed. (orig.)

Hyperfunctioning metastatic follicular thyroid carcinoma in Pendred's syndrome

International Nuclear Information System (INIS)

Abs, R.; Verhelst, J.; Schoofs, E.; De Somer, E.

1991-01-01

A 66-year-old woman with Pendred's syndrome underwent a partial thyroidectomy when she was 17 years old. At the age of 52 years, she had a second thyroid operation because of hyperthyroidism due to a toxic multinodular goiter with a mediastinal extension consisting of several separate nodules. Five years later a hyperfunctioning metastatic follicular carcinoma was diagnosed histologically. After treatment with radioactive iodine, the patient was well. To the authors' knowledge, this is the first description of a metastatic follicular thyroid carcinoma in Pendred's syndrome and the first report of hyperthyroidism occurring after malignant degeneration of a dyshormonogenetic goiter

Adrenocortical function in hospitalised patients with active ...

African Journals Online (AJOL)

2006-05-17

May 17, 2006 ... Tuberculosis (TB) is a major cause of morbidity and mortality in sub-Sah aran Africa, ... To assess whether adrenocortical function was compromised in patients with active tuberculosis. (TB) during the first 5 days of ..... Hernandez-Pando R, de la Luz Streber M, Orozco H, et al. Emergent immunoregulatory.

Hyper-functioning Thyroid Nodule with Scintigraphic Owl's Eye Appearance

International Nuclear Information System (INIS)

Al-Kordi, R.S.; Elgazzar, A.H.

2006-01-01

Hyper-functioning thyroid nodules may produce various scintigraphic appearances on thyroid scans. Autonomously hyper functioning thyroid nodules invariably demonstrate degenerative changes. These changes may give rise to central or less commonly peripheral photopenic areas on a thyroid scan within otherwise a hot nodule. In this report we present a case of hyper functioning autonomous nodule with peripheral degeneration and residual central functioning tissue giving the appearance of an owl's eye. Although rare, this pattern can be seen in a variety of benign and malignant thyroid conditions. (author)

High-density lipoprotein is a potential growth factor for adrenocortical cells

International Nuclear Information System (INIS)

Murao, Koji; Imachi, Hitomi; Cao, Wenming; Yu, Xiao; Li, Junhua; Yoshida, Kazuya; Ahmed, Rania A.M.; Matsumoto, Kensuke; Nishiuchi, Takamasa; Wong, Norman C.W.; Ishida, Toshihiko

2006-01-01

The entry of cholesterol contained within high-density lipoprotein (HDL) into adrenocortical cells is mediated by a human homologue of SR-BI, CD36, and LIMPII Analogous-1 (CLA-1) and thus augmenting their growth. To address the role of CLA-1, we created a mutant mCLA that lacked the C-terminal tail. HDL CE selective uptake by cells carrying the mCLA-1 receptor was fully active and equivalent to those transfected with full-length CLA-1 (fCLA-1). Expression of mCLA inhibited the proliferation of an adrenocortical cell line and the incorporation of [ 3 H]thymidine into the cells. This effect was sensitive to wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). Our transcriptional studies revealed that the inhibitory action of mCLA required the transcriptional factor AP-1 and the effect of HDL on AP-1 activation was also abrogated by wortmannin. These findings raise the possibility that the inhibitors of the effects of HDL may be of therapeutic value for adrenocortical tumor

Dysfunctional or hyperfunctional? The amygdala in posttraumatic stress disorder is the bull in the evolutionary China shop.

Science.gov (United States)

Diamond, David M; Zoladz, Phillip R

2016-06-01

Our motivation in writing this Review arose not only from the great value in contributing to this special issue of the Journal of Neuroscience Research but also from the desire to express our opinion that the description of the amygdala as "dysfunctional" in posttraumatic stress disorder (PTSD) might not be appropriate. We acknowledge that excessive activation of the amygdala contributes to the cluster of PTSD symptoms, including hypervigilance, intrusive memories, and impaired sleep, that underlies the devastating mental and physical outcomes in trauma victims. The issue that we address is whether the symptoms of PTSD represent an impaired (dysfunctional) or sensitized (hyperfunctional) amygdala status. We propose that the amygdala in PTSD is hyperfunctional rather than dysfunctional in recognition of the fact that the individual has already survived one life-threatening attack and that another may be forthcoming. We therefore consider PTSD to be a state in which the amygdala is functioning optimally if the goal is to ensure a person's survival. The misery caused by a hyperfunctional amygdala in PTSD is the cost of inheriting an evolutionarily primitive mechanism that considers survival more important than the quality of one's life. © 2015 Wiley Periodicals, Inc.

Adrenocortical zonation, renewal, and remodeling

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Marjut ePihlajoki

2015-03-01

Full Text Available The adrenal cortex is divided into concentric zones. In humans the major cortical zones are the zona glomerulosa, zona fasciculata, and zona reticularis. The adrenal cortex is a dynamic organ in which senescent cells are replaced by newly differentiated ones. This constant renewal facilitates organ remodeling in response to physiological demand for steroids. Cortical zones can reversibly expand, contract, or alter their biochemical profiles to accommodate needs. Pools of stem/progenitor cells in the adrenal capsule, subcapsular region, and juxtamedullary region can differentiate to repopulate or expand zones. Some of these pools appear to be activated only during specific developmental windows or in response to extreme physiological demand. Senescent cells can also be replenished through direct lineage conversion; for example, cells in the zona glomerulosa can transform into cells of the zona fasciculata. Adrenocortical cell differentiation, renewal, and function are regulated by a variety of endocrine/paracrine factors including adrenocorticotropin, angiotensin II, insulin-related growth hormones, luteinizing hormone, activin, and inhibin. Additionally, zonation and regeneration of the adrenal cortex are controlled by developmental signaling pathways, such as the sonic hedgehog, delta-like homologue 1, fibroblast growth factor, and WNT/β-catenin pathways. The mechanisms involved in adrenocortical remodeling are complex and redundant so as to fulfill the offsetting goals of organ homeostasis and stress adaptation.

Clinical management and outcomes in patients with hyperfunctioning distant metastases from differentiated thyroid cancer after total thyroidectomy and radioactive iodine therapy.

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Qiu, Zhong-Ling; Shen, Chen-Tian; Luo, Quan-Yong

2015-02-01

Hyperfunctioning distant metastasis (HFDM) from differentiated thyroid cancer (DTC) is a rare entity. This study aimed to assess the outcomes of DTC patients presenting with HFDM after total thyroidectomy and radioactive iodine therapy. A total of 5367 DTC patients treated with (131)I after total thyroidectomy were analyzed retrospectively from January 1991 to June 2013. Therapeutic efficacy was evaluated based on changes in serum thyroglobulin (Tg) and anatomical imaging changes in metastatic lesions. The relationships between survival time and several variables were assessed by univariate and multivariate analyses using the Kaplan-Meier method and Cox's proportional hazards model respectively. Thirty-eight patients with HFDM from DTC were diagnosed, including four with hyperthyroidism, four with subclinical hyperthyroidism, and three with subclinical hypothyroidism. The remaining 27 were euthyroid. Of 25 patients with lung metastases, 84% (21/25) showed disappearance or shrinkage of lung nodules; of 24 patients with bone metastases, 66.67% (16/24) exhibited no obvious imaging changes in metastatic bone lesions after (131)I therapy. Serum Tg decreased significantly in 81.58% (31/38) and increased in 18.42% (7/38) after (131)I therapy. The 10-year survival rate of DTC patients with HFDM was 65.79% (25/38). Multivariate analyses identified age at occurrence of distant metastases (thyroid cancer (PTC; p=0.032, NA, and 0.043) as independent predictors of survival. The response of hyperfunctioning lung metastases to (131)I treatment was better than that of non-hyperfunctioning lung metastases in DTC, while hyperfunctioning bone metastases responded similarly compared to non-hyperfunctioning bone metastases. Patients younger than 45 years at occurrence of distant metastases, those with only lung metastases, and patients with PTC had better prognoses.

Cushing Syndrome in a 6-Month-Old Infant due to Adrenocortical Tumor

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Volmar KeithE

2009-09-01

Full Text Available Cushing syndrome is rare in infancy and usually due to an adrenocortical tumor (ACT. We report an infant with Cushing syndrome due to adrenocortical carcinoma. The patient presented at six months of age with a three-month history of growth failure, rapid weight gain, acne, and irritability. Physical examination showed obesity, hypertension, and Cushingoid features. Biochemical evaluation showed very high serum cortisol, mildly elevated testosterone, and suppressed ACTH. Abdominal MRI revealed a heterogeneous right adrenal mass extending into the inferior vena cava. Evaluation for metastases was negative. The tumor was removed surgically en bloc. Pathologic examination demonstrated low mitotic rate, but capsular and vascular invasion. She received no adjuvant therapy. Her linear growth has improved and Cushingoid features resolved. Hormonal markers and quarterly PET scans have been negative for recurrence 24 months postoperatively. In conclusion, adrenocortical neoplasms in children are rare, but should be considered in the differential diagnosis of Cushing syndrome.

Adrenocortical oncocytic neoplasm presenting with Cushing's syndrome: a case report

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Kabayegit Ozlem

2008-07-01

Full Text Available Abstract Introduction Oncocytic neoplasms occur in several organs and are most commonly found in the thyroid, kidneys and salivary glands. Oncocytic neoplasms of the adrenal cortex are extremely rare and are usually non-functioning. Case presentation We report the case of an adrenocortical oncocytic neoplasm with uncertain malignant potential in a 31-year-old man with Cushing's syndrome. The patient had been operated on following diagnosis of a 7 cm adrenal mass. Following surgery, the Cushing's syndrome resolved. The patient is still alive with no metastases one year after the surgery. Conclusion Adrenocortical oncocytic neoplasms must be considered in the differential diagnosis of both functioning and non-functioning adrenal masses.

Adrenocortical carcinoma, an unusual cause of secondary hypertension.

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Veron Esquivel, Daniel; Batiz, Fernando; Farias Vega, Alfonso; Carrillo Gonzalez, Perla A

2016-12-07

We present the case of a female patient aged 39 years who was admitted to our hospital due to hypertension, severe hypokalaemia and metabolic alkalosis; physical examination was remarkable for plethoric moon face, centripetal obesity and bilateral lower extremity oedema. She was admitted for intravenous potassium replacement and further assessment of hypertension and associated clinical findings. Laboratory testing showed increased levels of aldosterone, renin, cortisol, testosterone and androstenedione. An abdominal CT revealed a large mass in the right adrenal gland with hepatic involvement. The patient was started on antihypertensive medications and underwent laparoscopic surgery for mass and liver biopsy. The pathological diagnosis was adrenocortical carcinoma with liver metastasis. Hyperaldosteronism is a cause of secondary hypertension and its diagnosis is usually benign. Adrenocortical carcinoma is a rare condition and aldosterone secreting tumours are even rarer; associated hypertension usually improves after tumour resection, but with the presence of metastasis, blood pressure control is difficult. 2016 BMJ Publishing Group Ltd.

Hyperfunctioning papillary thyroid carcinoma: A case report with literature review

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Abdulwahid M. Salih; F.H. Kakamad; Han Nihad

2016-01-01

Introduction: Thyroid malignant tumors are rarely associated with hyperfunctioning thyroid. The incidence of this co-incidence is highly variable. Here we report a rare case of papillary thyroid cancer associated with hyperthyroidism with brief literature review. Case report: A 40-year-old male, presented with palpitation, excess sweating and weight loss for one month duration. There was asymmetrical swelling of the neck, more on right side, mobile. Free T3: 11.09 pmol/L, free T4: 34.41 pm...

Non-invasive measurement of adrenocortical activity in a ...

African Journals Online (AJOL)

Measuring physiological stress reactions through the quantification of plasma cortisol often involves physical restraint, which acts as a stressor itself. Here, we present the validation of a non-invasive method for assessing adrenocortical activity as an indicator of stress in the bat-eared fox (Otocyon megalotis). By conducting ...

Advanced diagnostic approaches and current medical management of insulinomas and adrenocortical disease in ferrets (Mustela putorius furo).

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Chen, Sue

2010-09-01

Endocrine neoplasia is the most common tumor type in domestic ferrets, especially in middle-aged to older ferrets. Islet cell tumors and adrenocortical tumors constitute the major types of endocrine neoplasms. Insulinoma is a tumor that produces and releases excessive amounts of insulin. Evaluation of fasted blood glucose levels provides a quick diagnostic assessment for the detection of insulinomas. Use of glucocorticoids, diazoxide, and diet modification are some of the medical treatment options for insulinomas. Adrenocortical neoplasia in ferrets usually overproduces one or more sex hormones. Sex hormones which can result in progressive alopecia, vulvar swelling in females, and prostagomegaly in males. Abdominal ultrasonography and sex hormone assays can be used to diagnose adrenocortical neoplasms. Drugs such as leuprolide acetate, deslorelin acetate, and the hormone melatonin can be used to treat adrenocortical neoplasms in ferrets when surgery is not an option. Copyright 2010 Elsevier Inc. All rights reserved.

[Autonomy and malignancy of thyroid glad tumors. A critical analysis of the literature on the existence of hyperfunctioning follicular and papillary thyroid gland carcinomas].

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Schröder, S; Marthaler, B

1996-09-01

Data in the literature communicated in 63 publications were evaluated in which scintigraphically warm or hot nodules were described as identical to a follicular or papillary carcinoma diagnosed based on histology of the resection specimen, thus suggesting autonomous hyperfunction of a malignant thyroid neoplasia. In the majority of cases, this assumption could not be accepted, or only within strict limits. In these patients, it appeared more likely that the carcinoma was located adjacent to or within a benign hyperfunctioning thyroid area or that large masses of a thyroid carcinoma had only simulated the picture of a hyperfunctioning nodule by suppression of endogenous TSH and thus of the residual parenchyma's function. In other cases, the diagnosis of a hyperfunctioning thyroid carcinoma had to be doubted or rejected owing to the lack of plausibility of the documented morphological findings. At the end of the literature survey, only 10 case descriptions unequivocally verified that, though very rarely, a papillary or follicular thyroid carcinoma may manifest itself as a solitary warm or hot thyroid nodule. Such a scintigraphical finding thus cannot be regarded as proof of benignancy of a given thyroid tumour.

Morphological changes in the pituitary-adrenocortical axis in natives of La Paz

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Gosney, John; Heath, Donald; Williams, David; Rios-Dalenz, Jaime

1991-03-01

Increased activity of the hypothalamic-pituitary-adrenocortical axis is part of the response to the stress of initial exposure to hypoxia, but there is evidence to suggest that it persists after homeostatic stability has been regained and acclimatization achieved. The adrenal glands of five lifelong residents of La Paz, Bolivia, who had lived at altitudes in the range 3600 3800 m, were significantly larger than those in age-matched controls from sea level (15.3g vs 10.4g; Ppituitary glands of the highlanders were not significantly different in size from those of the controls (0.67 g vs 0.51 g), but contained larger populations of corticotrophs expressed in terms of the total cell population of their anterior lobes (25.6% vs 19.4%; P<0.001). In conjunction with other studies of this endocrine axis in man and animals exposed to a hypoxic environment, these data suggest that greater amounts of adrenocorticotrophic hormone (ACTH) are required to maintain normal adrenocortical function under such circumstances, probably as a result of hypoxic inhibition of adrenocortical sensitivity to stimulation. Physiological hyperplasia of the adrenal cortex may be common in people living at high altitude.

Adrenocortical carcinoma with extension to the inferior vena cava and right atrium: 20-month-old girl with TP53 mutation

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Terry L. Levin, MD

2015-01-01

Full Text Available A 20-month-old female presented with respiratory distress and a right adrenal mass extending into the inferior vena cava and right atrium. The mass was initially thought to be neuroblastoma. Pathology later revealed adrenocortical carcinoma. Inferior vena cava extension is far more common in adrenocortical carcinoma than neuroblastoma, and its presence should prompt clinical and laboratory evaluation for an adrenocortical tumor. The genetic findings in TP53 associated with this disease are discussed.

Hyperfunctioning papillary thyroid carcinoma: A case report with literature review.

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Salih, Abdulwahid M; Kakamad, F H; Nihad, Han

2016-01-01

Thyroid malignant tumors are rarely associated with hyperfunctioning thyroid. The incidence of this co-incidence is highly variable. Here we report a rare case of papillary thyroid cancer associated with hyperthyroidism with brief literature review. A 40-year-old male, presented with palpitation, excess sweating and weight loss for one month duration. There was asymmetrical swelling of the neck, more on right side, mobile. Free T3: 11.09pmol/L, free T4: 34.41pmol/L, TFT: less than 0.005mIU/ml, Neck ultrasound showed features of background thyroiditis. Left lobe contained 9×7×5mm nodule with irregular outline and multiple dots of calcification, other nodules are of the same features. Under ultrasound guide, fine needle aspiration cytology showed features of papillary carcinoma. After preparation, total thyrodectomy done and the result of histopathological examination confirmed papillary thyroid carcinoma. The patient was put on 0.2mg thyroxine daily. Literature review has showed an increasing number of papers reporting the association of high level of thyroid function tests and thyroid malignancy. The cause of high level of TH in thyroid malignancy is thought to be due to an active mutation of the gene of TH receptor. Niepomniszcze and colleagues found that a combination of TSH receptor mutations and Ki-RAS was the main etiological factor for hyperfunction of the thyroid malignancy. Although the coexistence of them is rare, thyroid malignancy should be put in the differential diagnosis of hyperthyroid goiter. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Nationwide analysis of adrenocortical carcinoma reveals higher perioperative morbidity in functional tumors.

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Parikh, Punam P; Rubio, Gustavo A; Farra, Josefina C; Lew, John I

2017-08-25

Current adrenalectomy outcomes for functional adrenocortical carcinoma (ACC) remain unclear. This study examines nationwide in-hospital post-adrenalectomy outcomes for ACC. A retrospective analysis of the Nationwide Inpatient Sample database (2006-2011) to identify unilateral adrenalectomy patients for functional or nonfunctional ACC was performed. Patient demographics, comorbidities and postoperative outcomes were evaluated by t-test, Chi-square and multivariate regression. Of 2199 patients who underwent adrenalectomy, 87% had nonfunctional and 13% had functional ACC (86% hypercortisolism, 16% hyperaldosteronism, 4% hyperandrogenism). Functional ACC patients had significantly more comorbidities, and experienced certain postoperative complications more frequently including wound issues, adrenocortical insufficiency and acute kidney injury with longer hospital stay compared to nonfunctional ACC (P analysis, functional ACC was an independent prognosticator for wound complications (28.1, 95%CI 4.59-176.6). Patients with functional ACC manifest significant comorbidities with certain in-hospital complications. Such high-risk patients require appropriate preoperative medical optimization prior to adrenalectomy. Patients with functional adrenocortical carcinoma (ACC) have significant preoperative comorbidities and experience higher rates of certain postoperative complications including wound complications, hematoma formation, adrenal insufficiency, pulmonary embolism and acute kidney injury. Functional ACC patients also necessitate longer hospitalizations. These patients should undergo appropriate preoperative counseling in preparation for adrenalectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

Hyperfunction Thyroid Nodules: Their Risk for Becoming or Being Associated with Thyroid Cancers

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Lee, Eun Sun; Kim, Ji-hoon; Na, Dong Gyu; Paeng, Jin Chul; Min, Hye Sook; Choi, Seung Hong; Sohn, Chul Ho; Chang, Ki-Hyun

2013-01-01

Objective To retrospectively evaluate the risk of thyroid cancer in patients with hyperfunctioning thyroid nodules through ultrasonographic-pathologic analysis. Materials and Methods Institutional review board approval was obtained and informed consent was waived. From 2003 to 2007, 107 patients consecutively presented with hot spots on thyroid scans and low serum thyroid-stimulating hormone levels. Among them, 32 patients who had undergone thyroid ultrasonography were analyzed in this study....

Global gene expression response to telomerase in bovine adrenocortical cells

International Nuclear Information System (INIS)

Perrault, Steven D.; Hornsby, Peter J.; Betts, Dean H.

2005-01-01

The infinite proliferative capability of most immortalized cells is dependent upon the presence of the enzyme telomerase and its ability to maintain telomere length and structure. However, telomerase may be involved in a greater system than telomere length regulation, as recent evidence has shown it capable of increasing wound healing in vivo, and improving cellular proliferation rate and survival from apoptosis in vitro. Here, we describe the global gene expression response to ectopic telomerase expression in an in vitro bovine adrenocortical cell model. Telomerase-immortalized cells showed an increased ability for proliferation and survival in minimal essential medium above cells transgenic for GFP. cDNA microarray analyses revealed an altered cell state indicative of increased adrenocortical cell proliferation regulated by the IGF2 pathway and alterations in members of the TGF-B family. As well, we identified alterations in genes associated with development and wound healing that support a model that high telomerase expression induces a highly adaptable, progenitor-like state

Hyperfunctioning metastatic follicular thyroid carcinoma in Pendred's syndrome

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Abs, R.; Verhelst, J.; Schoofs, E.; De Somer, E. (University Hospital, Antwerp (Belgium))

1991-04-15

A 66-year-old woman with Pendred's syndrome underwent a partial thyroidectomy when she was 17 years old. At the age of 52 years, she had a second thyroid operation because of hyperthyroidism due to a toxic multinodular goiter with a mediastinal extension consisting of several separate nodules. Five years later a hyperfunctioning metastatic follicular carcinoma was diagnosed histologically. After treatment with radioactive iodine, the patient was well. To the authors' knowledge, this is the first description of a metastatic follicular thyroid carcinoma in Pendred's syndrome and the first report of hyperthyroidism occurring after malignant degeneration of a dyshormonogenetic goiter.

Nuclear imaging for the Cushing's syndrome etiological diagnosis

International Nuclear Information System (INIS)

Nocaudie, M.

2000-01-01

Etiologic diagnosing of a Cushing's syndrome relies upon the probabilities of the various causes of the pathologies. It takes advantage of the hormonal determinations to establish the mechanism of the hyper-secretion and of the radiological examination to detect morphological abnormalities. The scinti-scans are useful at this time only, to locate hyper-functioning tissue, to guide its resection and to suggest alternative option, either pharmaceutical or radio-metabolic. In the ACTH-independent Cushing's syndrome, noriodocholesterol scintigraphy can indicate that the adrenocortical hyper-functioning is unilateral or that it is bilateral. In the ACTH-dependent Cushing's syndrome, the current somatostatin radio-analogs have not proven their efficiency in pituitary ACTH-producing tumours but they are useful in the diagnosis and the management of bronchial carcinoids as of other neuro-endocrine tumors with the para-neoplastic Cushing's syndrome. (author)

Follicular variant of papillary carcinoma presenting as a hyperfunctioning thyroid nodule.

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Gabalec, Filip; Svilias, Ioannis; Plasilova, Ivana; Hovorkova, Eva; Ryska, Aler; Horacek, Jiri

2014-03-01

In this study, we describe a case of papillary carcinoma in a 15-year-old girl who presented with a hyperfunctioning (hot) thyroid nodule and discuss it in the context of current management guidelines for patients with thyroid nodules. In adults, hot nodules rarely require cytologic or histologic evaluation, and hyperthyroidism is often treated with radioiodine (131I). However, in children and adolescents, the malignancy rate for nodules (both cold and hot) is higher and surgery is often necessary. Surgery may serve as a therapy, as well as a diagnostic tool, to treat hot nodules in children and adolescents.

Papillary thyroid carcinoma in an autonomous hyperfunctioning thyroid nodule: case report and review of the literature.

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Tfayli, Hala M; Teot, Lisa A; Indyk, Justin A; Witchel, Selma Feldman

2010-09-01

Whereas thyroid nodules are less common among children than among adults, the anxiety generated by the finding of a thyroid nodule is high because 20% of nodules found in children contain thyroid cancer. Discovery of a nodule in the context of hyperthyroidism is usually comforting due to the presumption that the nodule represents a benign toxic adenoma. An 11-year-old girl presented with heavy menses, fatigue, and a right thyroid mass. Laboratory evaluation revealed elevated triiodothyronine and undetectable thyroid-stimulating hormone. Thyroid ultrasonography revealed a 3.5 cm nonhomogenous nodule, and scintigraphy was consistent with an autonomous hyper-functioning nodule. Fine-needle aspiration biopsy could not rule out malignancy, and patient underwent right hemithyroidectomy and isthmusectomy. Pathology was consistent with papillary thyroid carcinoma. We report the discovery of papillary thyroid carcinoma in an autonomously hyperfunctioning nodule in an 11-year-old girl. Detection of an autonomously functioning thyroid nodule in children and adolescents does not exclude the possibility of thyroid carcinoma and warrants careful evaluation and appropriate therapy.

Radioiodine therapy of hyperfunctioning thyroid nodules: usefulness of an implemented dose calculation algorithm allowing reduction of radioiodine amount.

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Schiavo, M; Bagnara, M C; Pomposelli, E; Altrinetti, V; Calamia, I; Camerieri, L; Giusti, M; Pesce, G; Reitano, C; Bagnasco, M; Caputo, M

2013-09-01

Radioiodine is a common option for treatment of hyperfunctioning thyroid nodules. Due to the expected selective radioiodine uptake by adenoma, relatively high "fixed" activities are often used. Alternatively, the activity is individually calculated upon the prescription of a fixed value of target absorbed dose. We evaluated the use of an algorithm for personalized radioiodine activity calculation, which allows as a rule the administration of lower radioiodine activities. Seventy-five patients with single hyperfunctioning thyroid nodule eligible for 131I treatment were studied. The activities of 131I to be administered were estimated by the method described by Traino et al. and developed for Graves'disease, assuming selective and homogeneous 131I uptake by adenoma. The method takes into account 131I uptake and its effective half-life, target (adenoma) volume and its expected volume reduction during treatment. A comparison with the activities calculated by other dosimetric protocols, and the "fixed" activity method was performed. 131I uptake was measured by external counting, thyroid nodule volume by ultrasonography, thyroid hormones and TSH by ELISA. Remission of hyperthyroidism was observed in all but one patient; volume reduction of adenoma was closely similar to that assumed by our model. Effective half-life was highly variable in different patients, and critically affected dose calculation. The administered activities were clearly lower with respect to "fixed" activities and other protocols' prescription. The proposed algorithm proved to be effective also for single hyperfunctioning thyroid nodule treatment and allowed a significant reduction of administered 131I activities, without loss of clinical efficacy.

Thyroid hyperfunctioning adenomas with and without Gsp/TSH receptor mutations show similar clinical features.

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Arturi, F; Capula, C; Chiefari, E; Filetti, S; Russo, D

1998-01-01

Activating mutations of Gs alpha protein (gsp) and TSH receptor (TSH-R) identified in autonomously hyperfunctioning thyroid adenomas have been proposed as the primary event responsible for this disease. Since mutations have not been detected in 100% (ranging from less than 10% to 90%) of the patients, we evaluated whether the presence of gsp and TSH-R mutations cause differences in the clinical and biochemical parameters of the affected patients. Fifteen consecutive patients (11 women and 4 men) with autonomously hyperfunctioning thyroid adenomas who underwent thyroidectomy, previously examined for the presence of gsp or TSH-R mutations, were investigated. In all of the patients we examined plasma free T3, free T4, TSH levels and ultrasound volume of the nodules. The patients with mutations in gsp or TSH-R were similar to the patients without mutations for clinical presentation, sex distribution and mean age. Furthermore, basal serum FT3, TSH and tumor volume in the patients with mutations were not significantly different from the group without mutations. Our preliminary data demonstrate that no significant differences are present in the two groups of patients examined, suggesting that factors other than gsp or TSH-R mutations play a role in the clinical presentation of the disease.

Hyperfunctioning thyroid cancer: a five-year follow-up.

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Azevedo, Monalisa Ferreira; Casulari, Luiz Augusto

2010-02-01

Differentiated thyroid cancer rarely occurs in association with hyperfunctioning nodules. We describe a case of a 47-year-old woman who developed symptoms of hyperthyroidism associated with a palpable thyroid nodule. Thyroid scintigraphy showed an autonomous nodule, and fine-needle aspiration biopsy was suggestive of papillary carcinoma. Laboratorial findings were consistent with the diagnosis of hyperthyroidism. The patient underwent thyroidectomy and a papillary carcinoma of 3.0 x 3.0 x 2.0 cm, follicular variant, was described by histological examination. The surrounding thyroid tissue was normal. Postoperatively, the patient received 100 mCi of (131)I, and whole body scans detected only residual uptake. No evidence of metastasis was detected during five years of follow-up. Hot thyroid nodules rarely harbor malignancies, and this case illustrated that, when a carcinoma occurs the prognosis seems to be very good with no evidence of metastatic dissemination during a long-term follow-up.

Blood Transfusion and Survival for Resected Adrenocortical Carcinoma: A Study from the United States Adrenocortical Carcinoma Group.

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Poorman, Caroline E; Postlewait, Lauren M; Ethun, Cecilia G; Tran, Thuy B; Prescott, Jason D; Pawlik, Timothy M; Wang, Tracy S; Glenn, Jason; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E; Keplinger, Kara; Fields, Ryan C; Jin, Linda X; Weber, Sharon M; Salem, Ahmed; Sicklick, Jason K; Gad, Shady; Yopp, Adam C; Mansour, John C; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C; Kiernan, Colleen M; Votanopoulos, Konstantinos I; Levine, Edward A; Staley, Charles A; Poultsides, George A; Maithel, Shishir K

2017-07-01

Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of these, 57 patients (38.3%) received perioperative transfusions. Compared to nontransfused patients, transfused patients more commonly had stage 4 disease (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P Transfusion was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs 91.0 months, P transfusion, stage IV, hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS. On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95% confidence interval (CI) =1.0-2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7-5.9, P transfusion HR = 2.0, 95% CI = 1.1-3.8, P = 0.02; stage 4 HR = 6.2, 95% CI = 3.1-12.4, P 2 units of packed red blood cells in median RFS (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63). Perioperative transfusion is associated with earlier recurrence and decreased survival after curative-intent resection of ACC. Strategies and protocols to minimize blood transfusion should be developed and followed.

DNA methylation is an independent prognostic marker of survival in adrenocortical cancer

NARCIS (Netherlands)

Jouinot, Anne; Assie, Guillaume; Libe, Rossella; Fassnacht, Martin; Papathomas, Thomas; Barreau, Olivia; De La Villeon, Bruno; Faillot, Simon; Hamzaoui, Nadim; Neou, Mario; Perlemoine, Karine; Rene-Corail, Fernande; Rodriguez, Stephanie; Sibony, Mathilde; Tissier, Frederique; Dousset, Bertrand; Sbiera, Silviu; Ronchi, Cristina; Kroiss, Matthias; Korpershoek, Esther; De Krijger, Ronald; Waldmann, Jens; Bartsch, Detlef K.; Quinkler, Marcus; Haissaguerre, Magalie; Tabarin, Antoine; Chabre, Olivier; Sturm, Nathalie; Luconi, Michaela; Mantero, Franco; Mannelli, Massimo; Cohen, Regis; Kerlan, Veronique; Touraine, Philippe; Barrande, Gaelle; Groussin, Lionel; Bertagna, Xavier; Baudin, Eric; Amar, Laurence; Beuschlein, Felix; Clauser, Eric; Coste, Joel; Bertherat, Jerome

2017-01-01

Context: Adrenocortical cancer (ACC) is an aggressive tumor with a heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival. Objective:

Differential expression of microRNA-675, microRNA-139-3p and microRNA-335 in benign and malignant adrenocortical tumours

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Helwig, J; Bertram, S; Sheu, S Y; Suttorp, A C; Seggewiß, J; Willscher, E; Walz, M K; Worm, K; Schmid, K W

2011-01-01

Background For the clinical management of adrenocortical neoplasms it is crucial to correctly distinguish between benign and malignant tumours. Even histomorphologically based scoring systems do not allow precise separation in single lesions, thus novel parameters are desired which offer a more accurate differentiation. The tremendous potential of microRNAs (miRNAs) as diagnostic biomarkers in surgical pathology has recently been shown in a broad variety of tumours. Methods In order to elucidate the diagnostic impact of miRNA expression in adrenocortical neoplasms, a cohort of 20 adrenocortical specimens including normal adrenal tissue (n=4), adrenocortical adenomas (ACAs) (n=9), adrenocortical carcinomas (ACCs) (n=4) and metastases (n=3) was analysed using TaqMan low density arrays to identify specific miRNA profiles in order to distinguish between benign and malignant adrenocortical lesions. Results were validated in a validation cohort (n=16). Results Concerning the differential diagnosis of ACAs and ACCs, 159 out of 667 miRNAs were up- and 89 were down-regulated in ACAs. Using real-time PCR analysis of three of the most significantly expressed single key miRNAs allowed separation of ACAs from ACCs. ACCs exhibited significantly lower levels of miR-139-3p (up to 8.49-fold, p<0.001), miR-675 (up to 23.25-fold, p<0.001) and miR-335 (up to 5.25-fold, p<0.001). A validation cohort of 16 specimen with known Weiss score showed up-regulation of miR-335 and miR-675 in the majority of cases with probable malignant course, although overlapping values exist. Conclusion miRNA profiling of miR-675 and miR-335 helps in discriminating ACCs from ACAs. miRNA analysis may indicate malignant behaviour in cases with indeterminate malignant potential. PMID:21471143

APE/Ref-1 is increased in nuclear fractions of human thyroid hyperfunctioning nodules.

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Russo, D; Celano, M; Bulotta, S; Bruno, R; Arturi, F; Giannasio, P; Filetti, S; Damante, G; Tell, G

2002-08-30

Apurinic/apyrimidinic endonuclease APE/Ref-1 is a multifunctional protein provided with DNA repair, transcription-factor regulation and anti-apoptotic activities. We have previously reported that, in thyroid cells, TSH regulates both the synthesis and nuclear translocation of APE/Ref-1. We have also shown that nuclear levels of this protein are reduced both in thyroid carcinoma tissues and cell lines. In the present study, APE/Ref-1 expression and cellular localization were analysed by Western blot in hyperfunctioning thyroid nodules from patients with toxic adenoma and/or toxic multinodular goiter. The total content of APE/Ref-1 protein was increased in the majority of the hyperfunctioning tissues with respect to normal adjacent tissue. There was also an increase in the nuclear levels of APE/Ref-1, suggesting enhanced cytoplasm-to-nucleus translocation of the protein in addition to its increased rate of synthesis. These results demonstrate that the phenomenon of nuclear translocation of APE/Ref-1 hypothesized on the basis of cell culture experiments does actually occur in vivo. Together with previous observations in thyroid carcinomas and tumoral cell lines, our findings suggest a two-stage model of APE/Ref-1 behaviour during malignant thyrocyte transformation: an early stage characterized by simple hyperplasia and upregulation of APE/Ref-1 in the nuclear compartment of the cell and a later stage in which nuclear levels of the protein drop to below-normal levels as the cell becomes progressively undifferentiated.

Imaging Findings of Pelvic Tumor Thrombosis Extending from Sacral Bone Metastasis of Adrenocortical Carcinoma

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Kenichiro Ishida

2012-01-01

Full Text Available We report the imaging findings of a patient with adrenocortical carcinoma who showed pelvic tumor thrombosis extending from sacral bone metastasis. Contrast-enhanced computed tomography demonstrated extensive intraluminal filling defects in the pelvic veins. A lytic lesion in the sacrum was also noted and continuity between the sacral lesion and the filling defect in the branch of pelvic veins was indicated. The filling defects showed increased uptake on positron emission tomography with 18F-fluorodeoxyglucose and single-photon emission computed tomography with 131I-iodomethylnorcholesterol, and fusion images with computed tomography aided the localization of the increased uptake areas. Multimodality imaging may be beneficial for the characterization and localization of lesions in patients suspected of having metastatic adrenocortical carcinoma.

PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues

Science.gov (United States)

Felizola, Saulo J. A.; Nakamura, Yasuhiro; Ono, Yoshikiyo; Kitamura, Kanako; Kikuchi, Kumi; Onodera, Yoshiaki; Ise, Kazue; Takase, Kei; Sugawara, Akira; Hattangady, Namita; Rainey, William E.; Satoh, Fumitoshi; Sasano, Hironobu

2014-01-01

Purkinje cell protein 4 (PCP4) is a calmodulin (CaM) binding protein that accelerates calcium association and dissociation with CaM. It has been previously detected in aldosterone-producing adenomas (APA) but details on its expression and function in adrenocortical tissues have remained unknown. Therefore, we performed the immunohistochemical analysis of PCP4 in the following tissues: normal adrenal (NA; n=15), APA (n=15), cortisol producing adenomas (CPA; n=15) and idiopathic hyperaldosteronism cases (IHA; n=5). APA samples (n=45) were also submitted to quantitative RT-PCR (qPCR) of PCP4, CYP11B1, and CYP11B2, as well as DNA sequencing for KCNJ5 mutations. Transient transfection analysis using PCP4 siRNA was also performed in H295R adrenocortical carcinoma cells, following ELISA analysis, and CYP11B2 luciferase assays were also performed after PCP4 vector transfection in order to study the regulation of PCP4 protein expression. In our findings, PCP4 immunoreactivity was predominantly detected in APA and in the zona glomerulosa (ZG) of NA and IHA. In APA, the mRNA levels of PCP4 were significantly correlated with those of CYP11B2 (P<0.0001) and were significantly higher in cases with KCNJ5 mutation than wild-type (P=0.005). Following PCP4 vector transfection, CYP11B2 luciferase reporter activity was significantly higher than controls in the presence of angiotensin-II. Knockdown of PCP4 resulted in a significant decrease in CYP11B2 mRNA levels (P=0.012) and aldosterone production (P=0.011). Our results indicate that PCP4 is a regulator of aldosterone production in normal, hyperplastic and neoplastic human adrenocortical cells. PMID:24403568

Acoustic and capacity analysis of voice academic teachers with diagnosed hyperfunctional dysphonia by using DiagnoScope Specialist software.

Science.gov (United States)

Zielińska-Bliźniewska, Hanna; Pietkiewicz, Piotr; Miłoński, Jarosław; Urbaniak, Joanna; Olszewski, Jurek

2013-01-01

The aim of the study was to assess the acoustic and capacity analyses of voice in academic teachers with hyperfunctional dysphonia using DiagnoScope Specialist software. The study covered 46 female academic teachers aged 34-48 years. The women were diagnosed with hyperfunctional dysphonia (with absence of organic pathologies). Having obtained the informed consent, a primary medical history was taken, videolaryngoscopic and stroboscopic examinations were performed and diagnostic voice acoustic and capacity analyses were carried out using DiagnoScope Specialist software. The acoustic analysis carried out of academic teachers with diagnosed hyperfunctional dysphonia showed enhancement in the following parameters: fundamental frequency (FO) by 1.2%; relative average perturbation (Jitter by 100.0% and RAP by 81.8%); relative amplitude perturbation quotient (APQ) by 2.9%; non-harmonic to harmonic ratio (U2H) by 16.0%; and noise to harmonic ratio (NHR) by 13.4%. A decrease of 2.5% from normal values was noted in relative amplitude perturbation (Shimmer). Formant frequencies also showed reduction (F1 by 10.7%, F2 by 5.1%, F3 by 2.2%, and F4 by 3.5%). The harmonic perturbation quotient (HPQ) was 0.8% lower and the residual harmonic perturbation quotient (RHPQ) 16.8% lower, with the residual to harmonic (R2H) decreasing by 35.1 per cent; the sub-harmonic to harmonic (S2H) by 2.4%; and the Yanagihara coefficient by 20.2%. The capacity analysis with the DiagnoScope Specialist software showed figures significantly lower than normal values of the following parameters: phonation time, true phonation time, phonation break coefficients, vocal capacity coefficient and mean vocal capacity. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Clinical application of SPECT in adrenal imaging with iodine-131 6 beta-iodomethyl-19-norcholesterol

International Nuclear Information System (INIS)

Ishimura, J.; Kawanaka, M.; Fukuchi, M.

1989-01-01

Forty-one patients with or without adrenocortical disorders were studied to evaluate the clinical usefulness of SPECT in adrenal imaging with I-131 Adosterol. In the SPECT images from this study, all glands with either normally functioning or hyperfunctioning adrenal cortices could be detected, while those glands with hypofunctioning adrenal cortices could not be detected. Particularly in transaxial and sagittal slices, the adrenal gland was identified posteriorly and was clearly distinguished from the gallbladder. In preliminary results using SPECT by a standard method, uptake in 68 detectable glands ranged from 1.7% to 4.9% in four glands with Cushing's syndrome, from 1.1% to 1.3% in seven glands with primary aldosteronism, and were distributed below 1.0% in the remaining glands with normally functioning adrenal cortices. These data show that it is possible to evaluate the adrenocortical functioning status simply by analyzing the SPECT images of the adrenal

Experience by the use of /sup 131/I-19-iodocholesterol

Energy Technology Data Exchange (ETDEWEB)

Kinoshita, H; Tsuru, Y; Inazuki, S; Fujimoto, S; Futagawa, S [Nagasaki Univ. (Japan). School of Medicine

1975-01-01

Clinical application of /sup 131/I-iodocholesterol to adrenal scintigraphy of the total 50 times was made in 36 patients suggestive of adrenal disease. The index and ratio of bilateral adrenal alands were calculated by ROI processing on the computer scintigram, which was assumed useful for diagnosis of adrenocortical hypofunction as well as its hyperfunction as formerly said. Adrenal scintigraphy with /sup 131/I-iodocholesterol is routine examination which should be positively applied to patients with adrenal cortex disease, because its exposure dose is as small as it matters little except for repeating frequently.

Plurihormonal Cosecretion by a Case of Adrenocortical Oncocytic Neoplasm

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J. J. Corrales

2016-01-01

Full Text Available Adrenocortical oncocytic neoplasms (oncocytomas are extremely rare; only approximately 159 cases have been described so far. The majority are nonfunctional and benign. We describe an unusual case of a functional oncocytoma secreting an excess of glucocorticoids (cortisol and androgens (androstenedione and DHEAS, a pattern of plurihormonal cosecretion previously not reported in men, presenting with endocrine manifestations of Cushing’s syndrome. The neoplasm was considered to be of uncertain malignant potential (borderline according to the Lin-Weiss-Bisceglia criteria.

A Late Onset of Adrenocortical Cancer Assosiated with Beckwith-Wiedemann Syndrome

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N S Kuznetsov

2014-06-01

Full Text Available Beckwith-Wiedemann syndrome (BWS is a genetic overgrowth disorder involving a predisposition to tumor development. The common features of Beckwith-Wiedemann syndrome include omphalocele, macroglos- sia and macrosomia. The increased risk for neoplasia is concentrated in the first eight years of life. However, this case presents a late onset of adrenocortical cancer assosiated with Beckwith-Wiedemann syndrome.

Increased adrenocortical response to adrenocorticotropic hormone (ACTH) in sport horses with equine glandular gastric disease (EGGD).

Science.gov (United States)

Scheidegger, M D; Gerber, V; Bruckmaier, R M; van der Kolk, J H; Burger, D; Ramseyer, A

2017-10-01

This study tested the hypothesis that adrenocortical function would be altered in horses with equine gastric ulcer syndrome (EGUS). Twenty-six sport horses competing at national or international levels in eventing (n=15) or endurance (n=11) were subjected to a gastroscopic examination and an adrenocorticotropic hormone (ACTH) stimulation test. Salivary cortisol concentrations were measured before (baseline) and after (30, 60, 90, 120 and 150min) IV ACTH injection (1μg/kg bodyweight). Within EGUS, two distinct diseases, equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD), can be distinguished. ESGD was diagnosed in 8/11 (73%; 95% confidence intervals [95%CI], 43-92%) endurance horses and 5/15 (33%; 95% CI, 14-58%) eventing horses. EGGD was observed in 9/11 (82%; 95% CI, 53-96%) endurance horses and 9/15 (60%; 95% CI, 35-81%) eventing horses. The presence or severity of ESGD was unrelated to the presence or severity of EGGD. ACTH stimulation induced a larger increase in cortisol concentration in horses with moderate EGGD than in horses with mild EGGD. Cortisol concentration during the entire sampling period (total increase in cortisol concentration during the entire sampling period [dAUC], 31.1±6.4ng/mL) and the highest measured concentration at a single time point (maximal increase in cortisol concentration [dMAX], 10.3±2.3ng/mL) were increased (P=0.005 and P=0.038, respectively), indicating that horses with glandular gastric disease exhibited increased adrenocortical responses to ACTH stimulation. These results suggest that EGGD might be associated with an enhanced adrenocortical sensitivity. Further investigations are warranted to confirm the association between adrenocortical sensitivity and EGGD and to elucidate the pathophysiological mechanisms involved. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Relations between Bullying Exposures in Middle Childhood, Anxiety, and Adrenocortical Activity

Science.gov (United States)

Carney, JoLynn V.; Hazler, Richard J.; Oh, Insoo; Hibel, Leah C.; Granger, Douglas A.

2010-01-01

This exploratory study investigated how exposure to bullying at school in middle childhood is associated with student anxiety levels and adrenocortical activity at a time preceding lunch when anxiety about potential bullying would potentially be higher. Ninety-one sixth-grade students (55 female and 36 male) reported being exposed one or more…

Virilizing Adrenocortical Carcinoma Advancing to Central Precocious Puberty after Surgery

OpenAIRE

Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

2015-01-01

Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was...

Adrenocortical neoplasia: Evolving concepts in tumorigenesis with an emphasis on adrenal cortical carcinoma variants

NARCIS (Netherlands)

R.R. de Krijger (Ronald); T.G. Papathomas (Thomas)

2012-01-01

textabstractAdrenocortical carcinoma (ACC) is a rare, heterogeneous malignancy with a poor prognosis. According to WHO classification 2004, ACC variants include oncocytic ACCs, myxoid ACCs and ACCs with sarcomatous areas. Herein, we provide a comprehensive review of these rare subtypes of

Adrenal scintigraphy with 131I-19-iodocholesterol in the diagnosis of Cushing's syndrome associated with adrenal tumor

International Nuclear Information System (INIS)

Barliev, G.B.

1979-01-01

Seven patients with Cushing's syndrome secondary to adrenocortial tumors were studied using 131 I-19-iodocholesterol. The diagnoses of all cases were verified histologically. In three cases with adenoma the uptake of the tracer was in the tumor only, while the two patients with adrenocortical carcinoma failed to show adrenal accumulation of the labelled compound. In two patients there was a hyperplasia-like scintigraphic pattern, while the stimulation and suppression biochemical tests suggested adrenal tumor. One of these cases was verified as a mixed form (adenoma plus hyperplasia), and the tumor bearing gland was significantly larger on the scan which helped the preoperative localization. In the other case, verified as bilateral multiple adrenocortical adenomas, the autonomus function of both adrenals was proved by dexamethasone suppression scanning. It seems reasonable to use the latter as an adjunctive diagnostic procedure in patients where there is a discrepancy between the standard scintiscan and the biochemical indexes of adrenal hyperfunction. (orig.) 891 MG/orig. 892 MBE [de

Clinical application of SPECT in adrenal imaging with iodine-131 6 beta-iodomethyl-19-norcholesterol

Energy Technology Data Exchange (ETDEWEB)

Ishimura, J.; Kawanaka, M.; Fukuchi, M.

1989-04-01

Forty-one patients with or without adrenocortical disorders were studied to evaluate the clinical usefulness of SPECT in adrenal imaging with I-131 Adosterol. In the SPECT images from this study, all glands with either normally functioning or hyperfunctioning adrenal cortices could be detected, while those glands with hypofunctioning adrenal cortices could not be detected. Particularly in transaxial and sagittal slices, the adrenal gland was identified posteriorly and was clearly distinguished from the gallbladder. In preliminary results using SPECT by a standard method, uptake in 68 detectable glands ranged from 1.7% to 4.9% in four glands with Cushing's syndrome, from 1.1% to 1.3% in seven glands with primary aldosteronism, and were distributed below 1.0% in the remaining glands with normally functioning adrenal cortices. These data show that it is possible to evaluate the adrenocortical functioning status simply by analyzing the SPECT images of the adrenal.

Long-term Results after CT-Guided Percutaneous Ethanol Ablation for the Treatment of Hyperfunctioning Adrenal Disorders

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Nathan Elie Frenk

Full Text Available OBJECTIVES: To evaluate the safety and long-term efficacy of computed tomography-guided percutaneous ethanol ablation for benign primary and secondary hyperfunctioning adrenal disorders. METHOD: We retrospectively evaluated the long-term results of nine patients treated with computed tomography-guided percutaneous ethanol ablation: eight subjects who presented with primary adrenal disorders, such as pheochromocytoma, primary macronodular adrenal hyperplasia and aldosterone-producing adenoma, and one subject with Cushing disease refractory to conventional treatment. Eleven sessions were performed for the nine patients. The patient data were reviewed for the clinical outcome and procedure-related complications over ten years. RESULTS: Patients with aldosterone-producing adenoma had clinical improvement: symptoms recurred in one case 96 months after ethanol ablation, and the other patient was still in remission 110 months later. All patients with pheochromocytoma had clinical improvement but were eventually submitted to surgery for complete remission. No significant clinical improvement was seen in patients with hypercortisolism due to primary macronodular adrenal hyperplasia or Cushing disease. Major complications were seen in five of the eleven procedures and included cardiovascular instability and myocardial infarction. Minor complications attributed to sedation were seen in two patients. CONCLUSION: Computed tomography-guided ethanol ablation does not appear to be suitable for the long-term treatment of hyperfunctioning adrenal disorders and is not without risks.

Biosynthesis of Various Steroids in vitro by Isolated Adrenal Cells in Primary Aldosteronism, Cushing's Syndrome, and Adrenogenital Syndrome due to Adrenocortical Adenoma

OpenAIRE

MIZUNO, SHIGERU; FUNAHASHI, HIROOMI

1981-01-01

To a further understanding of the role of steroid hormones in adrenal disorders, we have prepared free cell system of adrenal cells, using adrenal tissues that had been removed by operation from (i) cases of Cushing's syndrome due to adrenocortical adenoma or adrenocortical hyperplasia, (ii) a case of primary aldosteronism, and (iii) a patient with virilizing adrenal tumor. Twelve important steroid hormones were measured, such as pregnenolone, cortisol and aldosterone, which were produced by ...

Adrenocortical function and reserve in children treated for acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Pawlaczyk, B.; Malecka, E.H.; Krause, W.

1993-01-01

Serum cortisol and 17 OHS, 17 KS and DHA levels in 24-hour urine were determined in 30 children (22 girls and boys) 0.5 to 4 years after completion of therapy (radio- and chemotherapy) for acute lymphoblastic leukemia (ALL). Serum cortisol after Syncthen (adrenocortical reserve) was determined in 15 girls and 4 boys. The results show that therapy for ALL depresses glucocorticosteroid synthesis; however, it does not disturb the adrenal reserve or androgenesis. (author)

Treatment with docetaxel and cisplatin in advanced adrenocortical carcinoma, a phase II study

DEFF Research Database (Denmark)

Urup, Thomas; Pawlak, W Z; Petersen, P M

2013-01-01

Adrenocortical carcinoma (ACC) is a rare disease with a poor response to chemotherapy. Cisplatin is the most widely investigated drug in the treatment of ACC and in vitro studies have indicated activity of taxanes. The objectives of this study were to evaluate the efficacy and toxicity of cisplatin...... combined with docetaxel as first-line treatment of advanced ACC....

Cushing's Syndrome caused by pigmented adrenocortical micro nodular dysplasia - A familial case

Energy Technology Data Exchange (ETDEWEB)

Gomez-Segovia, I; Gallowitsch, H J; Kresnik, E; Kumnig, G; Mikosch, P; Lind, P [Dept.of Nuclear Medicine and Endocrinology, LKH Klagenfurt (Austria)

2002-09-01

Introduction: We present a Case of Cushing's syndrome (CS) in a 16 year old male adolescent. Adrenocortical micro nodular dysplasia is a rare cause of CS. It mostly develops in the first two decades of life. In pathogenesis a stimulatory effect of circulating Immunoglobulins on adrenal steroidogenesis has been postulated. Familial cases have been reported in relation to Carney's Syndrome. We report the clinical case at first diagnosis and preoperative follow up of 1 year prior to treatment. The leading symptoms were severe bilateral (fibrotic) gynaecomastia, weight gain and growth retardation, without hypertension,but osteoporosis, secondary hypogonadism and glucose intolerance. Laboratory findings and the results of functional tests were diagnostic for CS. In addition LDH (I-131 Isotopes), CK, Lipoproteins, GPT, Androstendion, Prolactin were elevated. MRI abdomen revealed a slight enlargement of the adrenals, and suspected a bilateral micro nodular dysplasia. Iodo-cholesterol-scan under dexamethason suppression showed a diffuse bilateral Iodo-cholesterol uptake confirming the autonomous production of cortisol bilateral in the adrenals.Whole body bone scan showed a diffuse reduced diphosphonate uptake in the skeleton and the growth plates. The bone mineral density was significantly reduced.Radiologically osteoporosis was overt. The rapid increase of free urinary cortisol excretion/24h within one year of observation led to a total bilateral adrenalectomy. Postoperative 5 year follow up examinations. Documentation of the outcome and recovery of clinical signs,symptoms and laboratory findings, discussion about the most appropriate long-term substitution therapy. Familial anamnesis:affected family member was the father (micro nodular bilateral adrenocortical dysplasia), the aunt (pararenal incidentaloma, histologically lipoma) and a cousin (micro nodular adrenocortical dysplasia). Sequential analysis of the menin gene from the patient was negative.The detection of

Cushing's Syndrome caused by pigmented adrenocortical micro nodular dysplasia - A familial case

International Nuclear Information System (INIS)

Gomez-Segovia, I.; Gallowitsch, H.J.; Kresnik, E.; Kumnig, G.; Mikosch, P.; Lind, P.

2002-01-01

Introduction: We present a Case of Cushing's syndrome (CS) in a 16 year old male adolescent. Adrenocortical micro nodular dysplasia is a rare cause of CS. It mostly develops in the first two decades of life. In pathogenesis a stimulatory effect of circulating Immunoglobulins on adrenal steroidogenesis has been postulated. Familial cases have been reported in relation to Carney's Syndrome. We report the clinical case at first diagnosis and preoperative follow up of 1 year prior to treatment. The leading symptoms were severe bilateral (fibrotic) gynaecomastia, weight gain and growth retardation, without hypertension,but osteoporosis, secondary hypogonadism and glucose intolerance. Laboratory findings and the results of functional tests were diagnostic for CS. In addition LDH (I-131 Isotopes), CK, Lipoproteins, GPT, Androstendion, Prolactin were elevated. MRI abdomen revealed a slight enlargement of the adrenals, and suspected a bilateral micro nodular dysplasia. Iodo-cholesterol-scan under dexamethason suppression showed a diffuse bilateral Iodo-cholesterol uptake confirming the autonomous production of cortisol bilateral in the adrenals.Whole body bone scan showed a diffuse reduced diphosphonate uptake in the skeleton and the growth plates. The bone mineral density was significantly reduced.Radiologically osteoporosis was overt. The rapid increase of free urinary cortisol excretion/24h within one year of observation led to a total bilateral adrenalectomy. Postoperative 5 year follow up examinations. Documentation of the outcome and recovery of clinical signs,symptoms and laboratory findings, discussion about the most appropriate long-term substitution therapy. Familial anamnesis:affected family member was the father (micro nodular bilateral adrenocortical dysplasia), the aunt (pararenal incidentaloma, histologically lipoma) and a cousin (micro nodular adrenocortical dysplasia). Sequential analysis of the menin gene from the patient was negative.The detection of

Increased thyrotropin binding in hyperfunctioning thyroid nodules.

Science.gov (United States)

Müller-Gärtner, H W; Schneider, C; Bay, V; Tadt, A; Rehpenning, W; de Heer, K; Jessel, M

1987-08-01

The object of this study was to investigate TSH receptors in hyperfunctioning thyroid nodules (HFN). In HFN, obtained from seven patients, 125-I-TSH binding as determined by equilibrium binding analysis on particulate membrane preparations, was found to be significantly increased as compared with normal thyroid tissues (five patients; P less than 0.001). Scatchard analysis of TSH-binding revealed two kinds of binding sites for both normal thyroid tissue and HFN, and displayed significantly increased association constants of high- and low-affinity binding sites in HFN (Ka = 11.75 +/- 6.8 10(9) M-1, P less than 0.001 and Ka = 2.1 +/- 1.0 10(7) M-1, P less than 0.025; x +/- SEM) as compared with normal thyroid tissue (Ka = 0.25 +/- 0.06 10(9) M-1, Ka = 0.14 +/- 0.03 10(7) M-1; x +/- SEM). The capacity of the high-affinity binding sites in HFN was found to be decreased (1.8 +/- 1.1 pmol/mg protein, x +/- SEM) in comparison with normal thyroid tissue (4.26 +/- 1.27 pmol/mg protein; x +/- SEM). TSH-receptor autoradiography applied to cryostatic tissue sections confirmed increased TSH binding of the follicular epithelium in HFN. These data suggest that an increased affinity of TSH-receptor sites in HFN in iodine deficient areas may be an important event in thyroid autonomy.

Adrenocortical carcinoma presenting as varicocele and renal vein thrombosis: a case report

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Horne John M

2011-08-01

Full Text Available Abstract Introduction Adrenocortical carcinomas are rare aggressive tumors. Their annual incidence is approximately one to two per million among the population of the United States of America. Patients with active endocrine tumors often present with Cushing's syndrome accompanied by virilizing features. Conversely, patients with non-functioning tumors may present with symptoms related to a mass-occupying lesion, such as abdominal pain and flank pain. Although varicoceles and acute kidney injuries are common problems in medicine, they are uncommon presentations of these rare tumors and easy to miss. We report a case of a large adrenocortical carcinoma that presented as testicular pain, varicocele, and acute kidney injury secondary to renal vein thrombosis. Case presentation A 54-year-old Caucasian man with a left-sided varicocele presented to our emergency department with lower abdominal pain and a decrease in urination. Four months previously, he had noticed pain and swelling in his left groin and had been diagnosed with left-sided varicocele. For one week, he began developing left-sided abdominal pain and decreased urination frequency, so he came to our emergency department for evaluation. His physical examination revealed a hard mass occupying the entire left side of his abdomen, crossing the midline, and extending to the pelvic brim. His blood tests showed acute kidney injury and mild anemia. Computed tomography of his abdomen showed a large retroperitoneal mass on the left side, displacing the left kidney inferiorly and the spleen superiorly with thoracic epidural compression. Thrombus was also identified in his left renal vein and inferior vena cava. Computed tomography of his chest showed bilateral pulmonary nodules. A computed tomography-guided abdominal mass biopsy was performed, and the diagnosis of adrenocortical carcinoma was made on the basis of pathology and immunohistochemistry. His hormonal evaluations were normal. His kidney

The N-terminal neurotensin fragment, NT1-11, inhibits cortisol secretion by human adrenocortical cells.

Science.gov (United States)

Sicard, Flavie; Contesse, Vincent; Lefebvre, Hervé; Ait-Ali, Djida; Gras, Marjorie; Cartier, Dorthe; Decker, Annick; Chartrel, Nicolas; Anouar, Youssef; Vaudry, Hubert; Delarue, Catherine

2006-08-01

Neurotensin (NT) modulates corticosteroid secretion from the mammalian adrenal gland. The objective of this study was to investigate the possible involvement of NT in the control of cortisol secretion in the human adrenal gland. In vitro studies were conducted on cultured human adrenocortical cells. This study was conducted in a university research laboratory. Adrenal explants from patients undergoing expanded nephrectomy for kidney cancer were studied. Cortisol secretion from cultured adrenocortical cells was measured. NT1-11, the N-terminal fragment of NT, dose-dependently inhibited basal and ACTH-stimulated cortisol production by human adrenocortical cells in primary culture. In contrast, NT had no influence on cortisol output at concentrations up to 10(-6) m. HPLC and RT-PCR analyses failed to detect any significant amounts of NT and NT mRNA, respectively, in adrenal extracts. Molecular and pharmacological studies were performed to determine the type of NT receptor involved in the corticostatic effect of NT1-11. RT-PCR analysis revealed the expression of NT receptor type (NTR) 3 mRNA but not NTR1 and NTR2 mRNAs in the human adrenal tissue. However, the pharmacological profile of the adrenal NT1-11 receptor was different from that of NTR3, indicating that this receptor type is not involved in the action of NT1-11 on corticosteroidogenesis. Our results indicate that NT1-11 may act as an endocrine factor to inhibit cortisol secretion through activation of a receptor distinct from the classical NTR1, NTR2, and NTR3.

Immunoglobulins of patients with Cushing's syndrome due to pigmented adrenocortical micronodular dysplasia stimulate in vitro steroidogenesis

NARCIS (Netherlands)

Wulffraat, N. M.; Drexhage, H. A.; Wiersinga, W. M.; van der Gaag, R. D.; Jeucken, P.; Mol, J. A.

1988-01-01

The putative stimulation of adrenal steroid production by immunoglobulins (Igs) of five patients with pigmented adrenocortical micronodular dysplasia and clinical Cushing's syndrome was investigated. Ascorbate depletion, a process linked to steroid production, was measured by a cyto-chemical

Determination by R/A of plasma cortisol levels as a parameter of adrenocortical function before and after radiotherapy of gynaecological genital carcinoma

International Nuclear Information System (INIS)

Freischem, C.W.

1980-01-01

rn 20 female patients with carcinoma of the genitals, day profiles of cortisol were established and ACTH stimulation tests carried out directly after radiotherapy and 6 months later. Plasma concentrations of cortisol were determined in a RIA as parameters of the adrenocortical function. The assumption of a change in adrenocortical activity after radiotherapy of gynaecological genital carcinoma could not be validated. Instead, there was a typical diurnal rhythm of plasma cortisol, with a peak in the early morning hours and a decrease until midnight. The same applies to the ACTH stimulation tests: In all cases, plasma cortisol levels were elevated after intravenous application of ACTH. This means that the 1976 findings of Samundzham and Butsan could not be proved. Since adrenal functions were absolutely normal in the observed cases, the adynamic clinical picture of patients after radiotherapy, which is rather infrequent, cannot be explained as being due to an impaired adrenocortical function. (orig./MG) [de

Emotional and Adrenocortical Regulation in Early Adolescence: Prediction by Attachment Security and Disorganization in Infancy

Science.gov (United States)

Spangler, Gottfried; Zimmermann, Peter

2014-01-01

The aim of the present study was to examine differences in emotion expression and emotion regulation in emotion-eliciting situations in early adolescence from a bio-psycho-social perspective, specifically investigating the influence of early mother-infant attachment and attachment disorganization on behavioural and adrenocortical responses. The…

Environmental enrichment affects adrenocortical stress responses in the endangered black-footed ferret

Science.gov (United States)

Poessel, S.A.; Biggins, D.E.; Santymire, R.M.; Livieri, T.M.; Crooks, K.R.; Angeloni, L.

2011-01-01

Potential stressors of wildlife living in captivity, such as artificial living conditions and frequent human contact, may lead to a higher occurrence of disease and reduced reproductive function. One successful method used by wildlife managers to improve general well-being is the provision of environmental enrichment, which is the practice of providing animals under managed care with environmental stimuli. The black-footed ferret (Mustela nigripes) is a highly-endangered carnivore species that was rescued from extinction by removal of the last remaining individuals from the wild to begin an ex situ breeding program. Our goal was to examine the effect of environmental enrichment on adrenocortical activity in ferrets by monitoring fecal glucocorticoid metabolites (FGM). Results demonstrated that enrichment lowered FGM in juvenile male ferrets, while increasing it in adult females; enrichment had no effect on FGM in juvenile females and adult males. These results correspond with our findings that juvenile males interacted more with the enrichment items than did adult females. However, we did not detect an impact of FGM on the incidence of disease or on the ability of ferrets to become reproductive during the following breeding season. We conclude that an environmental enrichment program could benefit captive juvenile male ferrets by reducing adrenocortical activity. ?? 2011 Elsevier Inc.

[Hyperfunctioning thyroid carcinoma. Description of a case].

Science.gov (United States)

Pandolfi, C; Colecchia, M; Gianini, A

1997-09-01

Differentiated thyroid cancers account for 1% of all neoplasias but only for 2.3% of thyroid nodules. A particular condition is represented by the association with hyperthyroidism, which is found in about 7% of cases. Even more rarely may be themselves cause of thyrotoxicosis. In the present paper, the case of a 66-year old male patient, bearing a recently appeared goiter, referred to us for suspicion of lung cancer and hyperthyroid symptoms, is reported. Among appropriate investigations, the finding of high titer of thyroglobulin in the aspiration needle and cytology examination suggested that thyroid lesion was primary and not metastatic, while scintiscan with J-131 isotope showed that excess of thyroid hormones was just due to it; histological diagnosis was of papillary carcinoma. As to the pathogenesis of the neoplasma during hyperthyroidism, a causal role of thyroid stimulating auto-antibodies has been suggested in the cases associated with Graves' disease, absent in our patient, which could elicitate cancer progression in the mean time. Interestingly, activating mutation of thyroid hormone receptor (TSH-r) gene has been demonstrated in a hyperfunctioning differentiated cancer. Notwithstanding the unexpected clinical behaviour may appear very rare, molecular biology studies on aspiration biopsies (FNAB) will allow, in the future, to better define the neoplastic nature of some hot nodules. In personal opinion, this particular pathology must be attently searched both for its implications in the prognosis and therapeutic strategy and because it could be less rare than generally considered up to now.

Treatment of hyperfunctioning thyroid nodules by percutaneous ethanol injection

Directory of Open Access Journals (Sweden)

Sarai Maryam

2002-12-01

Full Text Available Abstract Background Autonomous thyroid nodules can be treated by a variety of methods. We assessed the efficacy of percutaneous ethanol injection in treating autonomous thyroid nodules. Methods 35 patients diagnosed by technetium-99 scanning with hyperfunctioning nodules and suppressed sensitive TSH (sTSH were given sterile ethanol injections under ultrasound guidance. 29 patients had clinical and biochemical hyperthyroidism. The other 6 had sub-clinical hyperthyroidism with suppressed sTSH levels (3, T4 and sTSH levels had returned to normal, or else injections could no longer be performed because significant side effects. Patients were followed up at 3, 6 and, in 15 patients, 24 months after the last injection. Results Average pre-treatment nodule volume [18.2 ± 12.7 ml] decreased to 5.7 ± 4.6 ml at 6 months follow-up [P 4 and sTSH did not change significantly between 6 months and 2 years [P > 0.05]. Ethanol injections were well tolerated by the patients, with only 2 cases of transient dysphonia. Conclusion Our findings indicate that ethanol injection is an alternative to surgery or radioactive iodine in the treatment of autonomous thyroid nodules.

Rosiglitazone induces autophagy in H295R and cell cycle deregulation in SW13 adrenocortical cancer cells

International Nuclear Information System (INIS)

Cerquetti, Lidia; Sampaoli, Camilla; Amendola, Donatella; Bucci, Barbara; Masuelli, Laura; Marchese, Rodolfo; Misiti, Silvia; De Venanzi, Agostino; Poggi, Maurizio; Toscano, Vincenzo; Stigliano, Antonio

2011-01-01

Thiazolidinediones, specific peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands, used in type-2 diabetes therapy, show favourable effects in several cancer cells. In this study we demonstrate that the growth of H295R and SW13 adrenocortical cancer cells is inhibited by rosiglitazone, a thiazolidinediones member, even though the mechanisms underlying this effect appeared to be cell-specific. Treatment with GW9662, a selective PPAR-γ-inhibitor, showed that rosiglitazone acts through both PPAR-γ-dependent and -independent mechanisms in H295R, while in SW13 cells the effect seems to be independent of PPAR-γ. H295R cells treated with rosiglitazone undergo an autophagic process, leading to morphological changes detectable by electron microscopy and an increased expression of specific proteins such as AMPKα and beclin-1. The autophagy seems to be independent of PPAR-γ activation and could be related to an increase in oxidative stress mediated by reactive oxygen species production with the disruption of the mitochondrial membrane potential, triggered by rosiglitazone. In SW13 cells, flow cytometry analysis showed an arrest in the G0/G1 phase of the cell cycle with a decrease of cyclin E and cdk2 activity, following the administration of rosiglitazone. Our data show the potential role of rosiglitazone in the therapeutic approach to adrenocortical carcinoma and indicate the molecular mechanisms at the base of its antiproliferative effects, which appear to be manifold and cell-specific in adrenocortical cancer lines.

Rosiglitazone induces autophagy in H295R and cell cycle deregulation in SW13 adrenocortical cancer cells

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Cerquetti, Lidia; Sampaoli, Camilla [Endocrinology, Department of Clinical and Molecular Medicine, Sant' Andrea Hospital, Faculty of Medicine and Psychology ' Sapienza' University of Rome, Via di Grottarossa, 1035-00189 Rome (Italy); Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy); Amendola, Donatella; Bucci, Barbara [Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy); Masuelli, Laura [Department of Experimental Medicine, ' Sapienza' University of Rome, Rome (Italy); Marchese, Rodolfo [Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy); Misiti, Silvia [Endocrinology, Department of Clinical and Molecular Medicine, Sant' Andrea Hospital, Faculty of Medicine and Psychology ' Sapienza' University of Rome, Via di Grottarossa, 1035-00189 Rome (Italy); Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy); De Venanzi, Agostino; Poggi, Maurizio; Toscano, Vincenzo [Endocrinology, Department of Clinical and Molecular Medicine, Sant' Andrea Hospital, Faculty of Medicine and Psychology ' Sapienza' University of Rome, Via di Grottarossa, 1035-00189 Rome (Italy); Stigliano, Antonio, E-mail: antonio.stigliano@uniroma1.it [Endocrinology, Department of Clinical and Molecular Medicine, Sant' Andrea Hospital, Faculty of Medicine and Psychology ' Sapienza' University of Rome, Via di Grottarossa, 1035-00189 Rome (Italy); Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy)

2011-06-10

Thiazolidinediones, specific peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) ligands, used in type-2 diabetes therapy, show favourable effects in several cancer cells. In this study we demonstrate that the growth of H295R and SW13 adrenocortical cancer cells is inhibited by rosiglitazone, a thiazolidinediones member, even though the mechanisms underlying this effect appeared to be cell-specific. Treatment with GW9662, a selective PPAR-{gamma}-inhibitor, showed that rosiglitazone acts through both PPAR-{gamma}-dependent and -independent mechanisms in H295R, while in SW13 cells the effect seems to be independent of PPAR-{gamma}. H295R cells treated with rosiglitazone undergo an autophagic process, leading to morphological changes detectable by electron microscopy and an increased expression of specific proteins such as AMPK{alpha} and beclin-1. The autophagy seems to be independent of PPAR-{gamma} activation and could be related to an increase in oxidative stress mediated by reactive oxygen species production with the disruption of the mitochondrial membrane potential, triggered by rosiglitazone. In SW13 cells, flow cytometry analysis showed an arrest in the G0/G1 phase of the cell cycle with a decrease of cyclin E and cdk2 activity, following the administration of rosiglitazone. Our data show the potential role of rosiglitazone in the therapeutic approach to adrenocortical carcinoma and indicate the molecular mechanisms at the base of its antiproliferative effects, which appear to be manifold and cell-specific in adrenocortical cancer lines.

US-guided percutaneous radiofrequency thermal ablation for the treatment of solid benign hyperfunctioning or compressive thyroid nodules.

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Deandrea, Maurilio; Limone, Paolo; Basso, Edoardo; Mormile, Alberto; Ragazzoni, Federico; Gamarra, Elena; Spiezia, Stefano; Faggiano, Antongiulio; Colao, Annamaria; Molinari, Filippo; Garberoglio, Roberto

2008-05-01

The aim of the study was to define the effectiveness and safety of ultrasound-guided percutaneous radiofrequency (RF) thermal ablation in the treatment of compressive solid benign thyroid nodules. Thirty-one patients not eligible for surgery or radioiodine (131I) treatment underwent RF ablation for benign nodules; a total of 33 nodules were treated (2 patients had 2 nodules treated in the same session): 10 cold nodules and 23 hyperfunctioning. Fourteen patients complained of compressive symptoms. Nodule volume, thyroid function and compressive symptoms were evaluated before treatment and at 1, 3 and 6 mo. Ultrasound-guided RF ablation was performed using a Starbust RITA needle, with nine expandable prongs; total exposure time was 6 to 10 min at 95 degrees C in one area or more of the nodule. Baseline volume (measured at the time of RF ablation) was 27.7 +/- 21.5 mL (mean +/- SD), but significantly decreased during follow-up: 19.2 +/- 16.2 at 1 mo (-32.7%; p nodules remained euthyroid: five patients with hot nodules normalized thyroid function, and the remaining sixteen showed a partial remission of hyperthyroidism. Besides a sensation of heat and mild swelling of the neck, no major complications were observed. Improvement in compressive symptoms was reported by 13 patients, with a reduction on severity scale from 6.1 +/- 1.4 to 2.2 +/- 1.9 (p nodules. Hyperfunction was fully controlled in 24% of patients and partially reduced in the others.

Early and delayed pinhole MIBI SPECT in detecting hyperfunctioning parathyroid glands: a comparison with peroperative γ probe.

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Gültekin, Salih Sinan; Kir, Metin; Tuğ, Tuğbay; Demirer, Seher; Genç, Yasemin

2011-10-01

This study was conducted to evaluate the early and delayed pinhole MIBI single photon emission computed tomography (pSPECT) images in detecting hyperfunctioning parathyroid glands, to make a comparison with peroperative γ probe (GP) findings. Planar, early, and delayed pSPECT scans and skin in-vivo and ex-vivo GP counts were obtained in 22 patients with hyperparathyroidism. All data were analyzed statistically on the basis of localization of the lesions, using the histopathological findings as the gold standard. Histopathological examinations revealed 18 of 44 adenomas, 18 of 44 hyperplasic glands, two of 44 lymph nodules, five of 44 thyroid nodules, and one of 44 normal parathyroid glands. Sensitivity and specificity were found to be 36 and 100% for planar, 69 and 75% for early pSPECT, 86 and 88% for delayed pSPECT scans, and similarly, 78 and 75% on skin, 92 and 75% in-vivo and 83 and 100% ex-vivo GP counts, respectively. For distinction ability of GP counts between three groups of lesions, there was a statistically significant difference among the three groups for ex-vivo GP counts but not between groups of adenomas and hyperplasic lesions for in-vivo GP counts. Early and delayed pSPECT scans play a complementary role on the planar scans. Delayed pSPECT scans and in-vivo GP counts are equally valuable to localize both single and multiple hyperfunctioning parathyroid glands. Ex-vivo GP counts seem to be better for making a distinction among types of lesions.

A case of low renin hyperaldosteronism considered to be aldosterone-producing adrenocortical adenoma by CT image of adrenal gland

International Nuclear Information System (INIS)

Hayashi, Kozo; Tsuchihashi, Yoshihiro; Ito, Kazuro; Ozono, Noboru

1983-01-01

A case was reported in which hypertension, hypopotassemia, low plasma renin activity and hyperaldosteronemia were observed. Imaging suggested adrenocortical adenoma, leading to the diagnosis of low renin hyperaldosteronism. (Chiba, N.)

The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

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Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

2015-01-01

The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

Cell cycle dependent RRM2 may serve as proliferation marker and pharmaceutical target in adrenocortical cancer.

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Grolmusz, Vince Kornél; Karászi, Katalin; Micsik, Tamás; Tóth, Eszter Angéla; Mészáros, Katalin; Karvaly, Gellért; Barna, Gábor; Szabó, Péter Márton; Baghy, Kornélia; Matkó, János; Kovalszky, Ilona; Tóth, Miklós; Rácz, Károly; Igaz, Péter; Patócs, Attila

2016-01-01

Adrenocortical cancer (ACC) is a rare, but agressive malignancy with poor prognosis. Histopathological diagnosis is challenging and pharmacological options for treatment are limited. By the comparative reanalysis of the transcriptional malignancy signature with the cell cycle dependent transcriptional program of ACC, we aimed to identify novel biomarkers which may be used in the histopathological diagnosis and for the prediction of therapeutical response of ACC. Comparative reanalysis of publicly available microarray datasets included three earlier studies comparing transcriptional differences between ACC and benign adrenocortical adenoma (ACA) and one study presenting the cell cycle dependent gene expressional program of human ACC cell line NCI-H295R. Immunohistochemical analysis was performed on ACC samples. In vitro effects of antineoplastic drugs including gemcitabine, mitotane and 9-cis-retinoic acid alone and in combination were tested in the NCI-H295R adrenocortical cell line. Upon the comparative reanalysis, ribonucleotide reductase subunit 2 (RRM2), responsible for the ribonucleotide dezoxyribonucleotide conversion during the S phase of the cell cycle has been validated as cell cycle dependently expressed. Moreover, its expression was associated with the malignancy signature, as well. Immunohistochemical analysis of RRM2 revealed a strong correlation with Ki67 index in ACC. Among the antiproliferative effects of the investigated compounds, gemcitabine showed a strong inhibition of proliferation and an increase of apoptotic events. Additionally, RRM2 has been upregulated upon gemcitabine treatment. Upon our results, RRM2 might be used as a proliferation marker in ACC. RRM2 upregulation upon gemcitabine treatment might contribute to an emerging chemoresistance against gemcitabine, which is in line with its limited therapeutical efficacy in ACC, and which should be overcome for successful clinical applications.

Virilization in a Girl with Adrenocortical Adenoma: A Case Report

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Tahniyah Haq

2012-07-01

Full Text Available We present a case of Cushing’s syndrome and virilization in a 15 year old girl which was suspected to be due to an adrenal carcinoma. She presented with features of virilization in addition to those of hypercortisilism. Her high androgen levels especially dehydroepiandrosterone sulfate (DHEAS were also in favor of an adrenal carcinoma. An unenhanced computerized tomography (CT scan showed a mass (size: 5.3 cm in the right adrenal gland with a soft tissue intensity of more than 10 HU which was suggestive of adrenal carcinoma. But, histopathology of the resected mass revealed a benign adrenocortical adenoma. Ibrahim Med. Coll. J. 2012; 6(2: 70-72

Treatment of hyperfunctioning thyroid nodules by percutaneous ethanol injection.

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Larijani, Bagher; Pajouhi, Mohammad; Ghanaati, Hossein; Bastanhagh, Mohammad-Hassan; Abbasvandi, Fereshteh; Firooznia, Kazem; Shirzad, Mahmood; Amini, Mohammad-Reza; Sarai, Maryam; Abbasvandi, Nasreen; Baradar-Jalili, Reza

2002-12-06

BACKGROUND: Autonomous thyroid nodules can be treated by a variety of methods. We assessed the efficacy of percutaneous ethanol injection in treating autonomous thyroid nodules. METHODS: 35 patients diagnosed by technetium-99 scanning with hyperfunctioning nodules and suppressed sensitive TSH (sTSH) were given sterile ethanol injections under ultrasound guidance. 29 patients had clinical and biochemical hyperthyroidism. The other 6 had sub-clinical hyperthyroidism with suppressed sTSH levels (thyroid hormone levels. Ethanol injections were performed once every 1-4 weeks. Ethanol injections were stopped when serum T3, T4 and sTSH levels had returned to normal, or else injections could no longer be performed because significant side effects. Patients were followed up at 3, 6 and, in 15 patients, 24 months after the last injection. RESULTS: Average pre-treatment nodule volume [18.2 PlusMinus; 12.7 ml] decreased to 5.7 PlusMinus; 4.6 ml at 6 months follow-up [P thyroid hormone levels at 3 and 6 months follow-up [P 0.05]. Ethanol injections were well tolerated by the patients, with only 2 cases of transient dysphonia. CONCLUSION: Our findings indicate that ethanol injection is an alternative to surgery or radioactive iodine in the treatment of autonomous thyroid nodules.

Noninvasive monitoring of adrenocortical function in captive jaguars (Panthera onca).

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Conforti, Valéria A; Morato, Ronaldo G; Augusto, Anderson M; de Oliveira e Sousa, Lúcio; de Avila, David M; Brown, Janine L; Reeves, Jerry J

2012-01-01

Jaguars are threatened with extinction throughout their range. A sustainable captive population can serve as a hedge against extinction, but only if they are healthy and reproduce. Understanding how jaguars respond to stressors may help improve the captive environment and enhance their wellbeing. Thus, our objectives were to: (1) conduct an adrenocorticotrophic hormone (ACTH) challenge to validate a cortisol radioimmunoassay (RIA) for noninvasive monitoring of adrenocortical function in jaguars; (2) investigate the relationship between fecal corticoid (FCM) and androgen metabolite (FAM) concentrations in males during the ACTH challenge; and (3) establish a range of physiological concentrations of FCMs for the proposed protocol. Seven jaguars (3 M, 4 F) received 500 IU/animal of ACTH. Pre- and post-ACTH fecal samples were assayed for corticoid (M and F) and androgen metabolites (M) by RIA. Concentrations of FCMs increased (P80.01) after ACTH injection (pre-ACTH: 0.90 ± 0.12 µg/g dry feces; post-ACTH: 2.55 ± 0.25 µg/g). Considering pre- and post-ACTH samples, FCM concentrations were higher (P80.01) in males (2.15 ± 0.20 µg/g) than in females (1.30 ± 0.20 µg/g), but the magnitude of the response to ACTH was comparable (P>0.05) between genders. After ACTH injection, FAMs increased in two (of 3) males; in one male, FCMs and FAMs were positively correlated (0.60; P80.01). Excretion of FCMs was assessed in 16 jaguars (7 M, 9 F) and found to be highly variable (range, 80.11-1.56 µg/g). In conclusion, this study presents a cortisol RIA for monitoring adrenocortical function in jaguars noninvasively. © 2011 Wiley Periodicals, Inc.

Effects of centrifugation on gonadal and adrenocortical steroids in rats

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Kakihana, R.; Butte, J. C.

1980-01-01

Many endocrine systems are sensitive to external changes in the environment. Both the pituitary adrenal and pituitary gonadal systems are affected by stress including centrifugation stress. The effect of centrifugation on the pituitary gonadal and pituitary adrenocortical systems was examined by measuring the gonadal and adrenal steroids in the plasma and brain following different duration and intensity of centrifugation stress in rats. Two studies were completed and the results are presented. The second study was carried out to describe the developmental changes of brain, plasma and testicular testosterone and dihydrotestosterone in Sprague Dawley rats so that the effect of centrifugation stress on the pituitary gonadal syatem could be better evaluated in future studies.

Single phase computed tomography is equivalent to dual phase method for localizing hyperfunctioning parathyroid glands in patients with primary hyperparathyroidism: a retrospective review

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Fanny Morón

2017-08-01

Full Text Available Objective This study aims to compare the sensitivity of dual phase (non-contrast and arterial versus single phase (arterial CT for detection of hyper-functioning parathyroid glands in patients with primary hyperparathyroidism. Methods The CT scans of thirty-two patients who have biochemical evidence of primary hyperparathyroidism, pathologically proven parathyroid adenomas, and pre-operative multiphase parathyroid imaging were evaluated retrospectively in order to compare the adequacy of single phase vs. dual phase CT scans for the detection of parathyroid adenomas. Results The parathyroid adenomas were localized in 83% of cases on single arterial phase CT and 80% of cases on dual phase CT. The specificity for localization of parathyroid tumor was 96% for single phase CT and 97% for dual phase CT. The results were not significantly different (p = 0.695. These results are similar to those found in the literature for multiphase CT of 55–94%. Conclusions Our study supports the use of a single arterial phase CT for the detection of hyperfunctioning parathyroid adenomas. Advances in knowledge: a single arterial phase CT has similar sensitivity for localizing parathyroid adenomas as dual phase CT and significantly reduces radiation dose to the patient.

If It Goes up, Must It Come Down? Chronic Stress and the Hypothalamic-Pituitary Adrenocortical Axis in Humans

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Miller, Gregory E.; Chen, Edith; Zhou, Eric S.

2007-01-01

The notion that chronic stress fosters disease by activating the hypothalamic-pituitary adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed…

An unusual accumulation of technetium-99m-sestamibi (99mTc-MIBI) mimicking an ectopic hyperfunctioning parathyroid tissue: usefulness of CT/SPECT technology in a single device

International Nuclear Information System (INIS)

Kienast, O.; Traub, T.; Dobrozemsky, G.; Dudczak, R.; Kurtaran, A.; Kletzmayr, J.; Kainberger, F.

2002-01-01

Full text: 99mTc-MIBI dual phase scintigraphy is a well established imaging modality in detecting hyperfunctioning parathyroid tissue. The authors report a case of 99mTc-MIBI scintigraphy showing MIBI-accumulation in projection of the upper mediastinum suspicious for hyperfunctioning parathyroid tissue. Further anatomical localization achieved by combined CT/SPECT technology revealed no mediastinal mass. A 71-year-old man with renal transplantation following chronic renal failure experienced hypercalcemia, hyperphosphatemia and elevation of serum parathyroid hormone levels. Ultrasonography of the neck revealed no enlarged parathyroid glands and further diagnostic work-up has been performed. A 99mTc-MIBI dual phase scintigraphy showed no abnormal accumulation in the typical parathyroid region but a focal activity in projection of the upper mediastinum was detected. The SPECT imaging of the neck and upper chest showed the accumulation in anterior location. This finding was interpreted as an ectopic (mediastinal) hyperfunctioning parathyroid tissue. In order to localize the focus, a CT/SPECT study with a single device system (GE Medical Systems Millennium VG gamma camera with Hawkeye) was done. This is an imaging system composed of a low current x-ray tube and a set of detectors mounted onto the camera's slip ring gantry. On registered and fused anatomical/functional images (CT/99mTc-MIBI SPECT), the increased accumulation of 99mTc-MIBI was shown to be an accumulation in the upper sternum. Further radiological examination revealed no abnormality in the sternum. This case illustrates the usefulness of the combined CT/SPECT imaging strategy with a single device in preventing unnecessary diagnostic/therapeutic interventions in patients with hyperthyroidism and abnormal 99mTc-MIBI scintigraphy. (author)

Role of changes in functional status of hypothalamic-pituitary-adrenocortical axis in immunoenhancement after low dose radiation

International Nuclear Information System (INIS)

Liu Shuzheng; Zhao Yong; Han Zhenbo

1994-01-01

Whole-body irradiation (WBI) of mice with 75 mGy X-rays caused increase in 5-hydroxytryptamine (5HT) content of hypothalamus and decrease in serum adrenocorticotropic hormone (ACTH) and corticosterone (CS) level, accompanied with potentiation of immune functions, expressed as increased spontaneous incorporation of 3 H-TdR into thymocytes, augmented proliferative reaction of the splenocytes to Con A and increased production of interleukin-2 by the splenocytes. After intra hypothalamic injection of 5HT there occurred a lowering of serum ACTH level and enhancement of immune reactivity of the splenic and thymic lymphocytes. It is assumed that low dose radiation could influence the central 5-hydroxytryptaminergic neurons causing increase in hypothalamic 5HT content and this, in turn, decreases pituitary secretion of ACTH with a down-regulation of the adrenocortical function. This would partially release the tonic suppression normally exerted on the immune organs by the hypothalamic-pituitary-adrenocortical axis, thus leading to potentiation of immune functions. These neuroendocrine changes should be considered as an important factor in the analysis of the mechanism of immunoenhancement after WBI with low doses

Association of the M1V PRKAR1A mutation with primary pigmented nodular adrenocortical disease in two large families

NARCIS (Netherlands)

Pereira, Alberto M.; Hes, Frederik J.; Horvath, Anelia; Woortman, Sanne; Greene, Elizabeth; Bimpaki, Eirini; Alatsatianos, Anton; Boikos, Sosipatros; Smit, Johannes W.; Romijn, Johannes A.; Nesterova, Maria; Stratakis, Constantine A.

2010-01-01

Carney complex (CNC) is a familial multiple neoplasia syndrome frequently associated with primary pigmented nodular adrenocortical disease (PPNAD), a bilateral form of micronodular adrenal hyperplasia that leads to Cushing's syndrome (CS). Germline PRKAR1A mutations cause CNC and only rarely

Adrenocortical Regulation, Eating in the Absence of Hunger and BMI in Young Children

OpenAIRE

Francis, L. A.; Granger, D. A.; Susman, E. J.

2012-01-01

The purpose of this study was to examine relations among adrenocortical regulation, eating in the absence of hunger, and body mass index (BMI) in children ages 5 to 9 years (N = 43). Saliva was collected before and after the Trier Social Stress Test for children (TSST-C), and was later assayed for cortisol. Area under the curve with respect to increase (AUCi) was used as a measure of changes in cortisol release from baseline to 60 minutes post-TSST-C. Age- and sex-specific BMI scores were cal...

Extension of adrenocortical carcinoma into the right atrium – echocardiographic diagnosis: A case report

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Rozenman Yoseph

2003-05-01

Full Text Available Abstract Background Adrenocortical carcinoma is a rare, highly malignant tumor. Cardiac involvement of the tumor is very rare. Echocardiography facilitates the evaluation of the cardiac involvement of the tumor. Case Presentation We describe a patient with an adrenal tumor. Transthoracic echo showed its extension into the right atrium. Accordingly, a combined abdominal and cardiac operation was performed, monitored by transesophageal echocardiography. Conclusion This case highlights the importance of echocardiography in revealing the cardiac involvement by this tumor and in planning the operative procedure.

The effect of a maternal history of childhood abuse on adrenocortical attunement in mothers and their toddlers.

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Fuchs, Anna; Moehler, Eva; Resch, Franz; Kaess, Michael

2017-07-01

We investigated circadian mother-child adrenocortical attunement in the context of a maternal history of childhood abuse (HoA). Mothers were screened after birth using the Childhood Trauma Questionnaire. Women reporting moderate or severe abuse formed the HoA group (n = 37; HoAG) and were compared with a non-maltreated comparison group (n = 45; CG). Three years later, cortisol awakening response (CAR) and diurnal slope (DSL) were assessed. Mother-child interaction was coded using the Emotional Availability Scales at 12 months of age. For the CAR, we found adrenocortical attunement only in the HoAG (2-way interaction: p = .004), particularly if mothers scored low on structuring (3-way interaction: p = .042) and children scored low on responsiveness (3-way interaction: p = .044). DSL-attunement was dependent on maternal sensitivity (3-way interaction: p = .012) and child involvement (3-way interaction: p = .012). In the context of a maternal HoA, it seems possible for mother-child-dyads to show less optimal interactional quality but be stronger attuned to each other biologically. © 2017 Wiley Periodicals, Inc.

Adrenocortical tumors in children

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R.C. Ribeiro

2000-10-01

Full Text Available Childhood adrenocortical tumors (ACT are rare. In the USA, only about 25 new cases occur each year. In Southern Brazil, however, approximately 10 times that many cases are diagnosed each year. Most cases occur in the contiguous states of São Paulo and Paraná. The cause of this higher rate has not been identified. Familial genetic predisposition to cancer (p53 mutations and selected genetic syndromes (Beckwith-Wiedemann syndrome have been associated with childhood ACT in general but not with the Brazilian counterpart. Most of the affected children are young girls with classic endocrine syndromes (virilizing and/or Cushing. Levels of urinary 17-ketosteroids and plasma dehydroepiandrosterone sulfate (DHEA-S, which are abnormal in approximately 90% of the cases, provide the pivotal clue to a diagnosis of ACT. Typical imaging findings of pediatric ACT consist of a large, well-defined suprarenal tumor containing calcifications with a thin capsule and central necrosis or hemorrhage. The pathologic classification of pediatric ACT is troublesome. Even an experienced pathologist can find it difficult to differentiate carcinoma from adenoma. Surgery is the single most important procedure in the successful treatment of ACT. The role of chemotherapy in the management of childhood ACT has not been established although occasional tumors are responsive to mitotane or cisplatin-containing regimens. Because of the heterogeneity and rarity of the disease, prognostic factors have been difficult to establish in pediatric ACT. Patients with incomplete tumor resection or with metastatic disease at diagnosis have a dismal prognosis. In patients with localized and completely resected tumors, the size of the tumor has predictive value. Patients with large tumors have a much higher relapse rate than those with small tumors.

Species-specific sensitivity to selenium-induced impairment of cortisol secretion in adrenocortical cells of rainbow trout (Oncorhynchus mykiss) and brook trout (Salvelinus fontinalis)

International Nuclear Information System (INIS)

Miller, L.L.; Hontela, A.

2011-01-01

Species differences in physiological and biochemical attributes exist even among closely related species and may underlie species-specific sensitivity to toxicants. Rainbow trout (RT) are more sensitive than brook trout (BT) to the teratogenic effects of selenium (Se), but it is not known whether all tissues exhibit this pattern of vulnerability. In this study, primary cultures of RT and BT adrenocortical cells were exposed to selenite (Na 2 SO 3 ) and selenomethionine (Se-Met) to compare cell viability and ACTH-stimulated cortisol secretion in the two fish species. Cortisol, the primary stress hormone in fish, facilitates maintenance of homeostasis when fish are exposed to stressors, including toxicants. Cell viability was not affected by Se, but selenite impaired cortisol secretion, while Se-Met did not (RT and BT EC 50 > 2000 mg/L). RT cells were more sensitive (EC 50 = 8.7 mg/L) to selenite than BT cells (EC 50 = 90.4 mg/L). To identify the targets where Se disrupts cortisol synthesis, selenite-impaired RT and BT cells were stimulated with ACTH, dbcAMP, OH-cholesterol, and pregnenolone. Selenite acted at different steps in the cortisol biosynthesis pathway in RT and BT cells, confirming a species-specific toxicity mechanism. To test the hypothesis that oxidative stress mediates Se-induced toxicity, selenite-impaired RT cells were exposed to NAC, BSO and antioxidants (DETCA, ATA, Vit A, and Vit E). Inhibition of SOD by DETCA enhanced selenite-induced cortisol impairment, indicating that oxidative stress plays a role in Se toxicity; however, modifying GSH content of the cells did not have an effect. The results of this study, with two closely related salmonids, provided additional evidence for species-specific differences in sensitivity to Se which should be considered when setting thresholds and water quality guidelines. - Research Highlights: → We investigated species-specific sensitivity to Se in trout adrenocortical cells. → Selenite, not Se-Met, disrupts

Comparisons among serum, egg albumin and yolk concentrations of corticosterone as biomarkers of basal and stimulated adrenocortical activity of laying hens.

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Cook, N J; Renema, R; Wilkinson, C; Schaefer, A L

2009-09-01

1. Serial blood samples from individual birds were analysed for corticosterone concentrations under basal and stimulated conditions, and matched to eggs from the same birds for comparison to albumin and yolk concentrations of corticosterone. 2. Serum corticosterone exhibited increases in response to stimulation by ACTH and Handling stress. There were no significant increases in egg albumin or yolk concentrations of corticosterone following stimulation. 3. Several significant correlations were observed between the mean and area under the curve (AUC) measurements of serum corticosterone concentrations with albumin and yolk corticosterone concentrations in eggs laid from 1 to 2 d later. 4. The results demonstrated a relationship between endogenous concentrations of serum corticosterone that reflected daily adrenocortical output with albumin and yolk corticosterone concentrations in eggs laid the following day. 5. The results do not support the concept of albumin and yolk concentrations of corticosterone as biomarkers of acute adrenocortical responses to stimulation.

Non-hyperfunctioning nodules from multinodular goiters: a minor role in pathogenesis for somatic activating mutations in the TSH-receptor and Gsalpha subunit genes.

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Derrien, C; Sonnet, E; Gicquel, I; Le Gall, J Y; Poirier, J Y; David, V; Maugendre, D

2001-05-01

Constitutive activation of the cAMP pathway stimulates thyrocyte proliferation. Gain-of-function mutations in Gsalpha protein have already been identified in thyroid nodules which have lost the ability to trap iodine. In contrast, most of the studies failed to detect somatic activating mutations in the thyrotropin receptor (TSH-R) in non-hyperfunctioning thyroid tumors. The aim of this study was to screen for mutations TSH-R exon 10, encoding the whole intracytoplasmic area involved in signal transduction, and Gsalpha exons 8 and 9, containing the two hot-spot codons 201 and 227, in a subset of non-hyperfunctioning nodules from multinodular goiter. Identified by matching ultrasonography and scintiscan, 22 eufunctioning (normal 99Tc uptake) and 15 nonfunctioning (decreased 99Tc uptake) nodules from 27 non-toxic multinodular goiters were isolated. After DNA extraction, TSH-R exon 10 was analyzed by direct sequencing of the PCR products and Gsalpha exons 8 and 9 by Denaturing Gradient Gel Electrophoresis. No mutation of TSH-R or Gsalpha was detected in the 37 nodules analyzed. This absence of mutation, despite the use of two sensitive screening methods associated with the analysis of the TSH-R whole intracytoplasmic area and Gsalpha two hot-spot codons, suggests that TSH-R and Gsalpha play a minor role in the pathogenesis of non-toxic nodules from multinodular goiters.

Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery.

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Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

2015-05-01

Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery.

Autonomously hyperfunctioning cystic nodule harbouring thyroid carcinoma - Case report and literature review.

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Lima, Maria João; Soares, Virgínia; Koch, Pedro; Silva, Artur; Taveira-Gomes, António

2018-01-01

Hyperthyroidism is rarely associated with malignancy, but it cannot rule out thyroid cancer. Although there is published data describing this coexistence, thyroid carcinomas inside autonomously functioning nodules are uncommon. A 49-year-old woman presented with a cervical mass, unexplained weight loss and anxiousness, sweating and insomnia. On physical examination, she had a palpable left thyroid nodule. Thyroid function tests showed suppressed TSH (nodule. 99mTC thyroid scintigraphy showed a hyperfunctioning nodule with suppression of the remainder parenchyma. Fine-needle aspiration cytology was nondiagnostic (cystic fluid). The patient was started on thiamazole 5 mg daily with subsequent normalization of thyroid function, but she developed cervical foreign body sensation and a left hemithyroidectomy was performed. Histology showed a 4 cm cystic nodule with a follicular variant papillary carcinoma and the patient underwent completion thyroidectomy, followed by radio-iodine ablation. Published literature showed an increased prevalence of autonomously functioning nodules, harbouring thyroid carcinomas in adults. Papillary carcinoma is the most frequently described but the follicular variant is rare. Although rare, thyroid cancer is not definitively excluded in hyperthyroid patients and it should always be considered as differential diagnosis. Copyright © 2018. Published by Elsevier Ltd.

Surgical management and clinical prognosis of adrenocortical carcinoma.

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Dong, Dexin; Li, Hanzhong; Yan, Weigang; Ji, Zhigang; Mao, Quanzong

2012-01-01

To study the relationship between surgical management and prognosis of adrenocortical carcinoma (ACC) in order to guide the surgical management of ACC. Clinical data of 45 cases of ACC treated in our hospital were retrospectively analyzed. The 45 cases included 3 cases in stage I, 12 cases in stage II, 7 cases in stage III, and 23 cases in stage IV. 17 cases underwent complete excision, 14 cases underwent palliative excision, 8 cases had non-operative treatment and 6 cases gave up treatment. All patients were followed up from 2 to 141 months. The average survival time of 31 patients with surgery was 32.46 months, and the average survival time of 14 patients without surgery was 4.75 months. There were statistically significant differences between the two groups (p 0.05). Surgery is considered to be the only method to cure ACC. For ACC in stage I and II, tumor resection is the most effective treatment, and second surgical operation is recommended for local recurrence. For ACC in stage III, extensive surgical operation is recommended, and for ACC in stage IV, surgical operation has no effect on the prognosis. Copyright © 2012 S. Karger AG, Basel.

Adrenocortical Secreting Mass in a Patient with Gardner's Syndrome: A Case Report

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Nabila Mejdoub Rekik

2010-01-01

Full Text Available Gardner's syndrome (GS is a dysplasia characterized by neoformations of the intestine, soft tissue, and osseous tissue. Endocrine neoplasms have occasionally been reported in association with GS. Adrenal masses in GS are rare, and few have displayed clinical manifestations. In the current paper, The authors report a 37-year-old male patient with GS including familial adenomatous polyposis (FAP and mandible osteoma who presented with an incidental adrenal mass. Computerized tomography adrenal scan identified bilateral masses. Functional analyses showed a hormonal secretion pattern consistent with pre-Cushing's syndrome. Other extraintestinal manifestations were hypertrophy of the pigmented layer of the retina and histiocytofibroma in the right leg. This paper describes a rare association of adrenocortical secreting mass in an old male patient with Gardner syndrome.

Primary aldosteronism and hypercortisolism due to bilateral functioning adrenocortical adenomas.

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Oki, Kenji; Yamane, Kiminori; Sakashita, Yu; Kamei, Nozomu; Watanabe, Hiroshi; Toyota, Naoyuki; Shigeta, Masanobu; Sasano, Hironobu; Kohno, Nobuoki

2008-10-01

A 50-year-old male patient with a 15-year history of hypertension was referred to our hospital for evaluation of bilateral adrenal tumors. No Cushingoid features were observed. Computed tomographic scan showed 10-mm masses in each adrenal gland. Preoperative endocrinological examinations revealed autonomous cortisol and aldosterone secretion in this patient. The results of a subsequent adrenal venous catheterization study were consistent with the presence of a left cortisol-producing tumor and a right aldosterone-producing tumor. A left partial adrenalectomy was performed initially, but cortisol and aldosterone over-secretion persisted. Accordingly, the patient underwent a right adrenalectomy. Pathological examination of the resected specimens, including immunohistochemical analysis, demonstrated that both adenomas possibly produced cortisol and aldosterone. This is an extremely rare case of bilateral adrenal tumors, in which the left adrenocortical tumor produced and secreted cortisol or both cortisol and aldosterone and the right one produced and secreted both aldosterone and cortisol, as confirmed by clinical findings and pathological studies using immunohistochemical analysis.

Efficacy of dexamethasone suppression test during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome.

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Chen, Shi; Li, Ran; Lu, Lin; Duan, Lian; Zhang, Xuebin; Tong, Anli; Pan, Hui; Zhu, Huijuan; Lu, Zhaolin

2018-01-01

To evaluate the cut-off value of the ratio of 24 h urinary free cortisol (24 h UFC) levels post-dexamethasone to prior-dexamethasone in dexamethasone suppression test (DST) during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome. Retrospective study. The patients diagnosed with primary pigmented nodular adrenocortical disease (PPNAD, n = 25), bilateral macronodular adrenal hyperplasia (BMAH, n = 27), and adrenocortical adenoma (ADA, n = 84) were admitted to the Peking Union Medical College Hospital from 2001 to 2016. Serum cortisol, adrenocorticotropic hormone (ACTH), and 24 h UFC were measured before and after low-dose dexamethasone suppression test (LDDST) and high-dose dexamethasone suppression test (HDDST). After LDDST and HDDST, 24 h UFC elevated in patients with PPNAD (paired t-test, P = 0.007 and P = 0.001), while it remained unchanged in the BMAH group (paired t-test, P = 0.471 and P = 0.414) and decreased in the ADA group (paired t-test, P = 0.002 and P = 0.004). The 24 h UFC level after LDDST was higher in PPNAD and BMAH as compared to ADA (P < 0.017), while no significant difference was observed between PPNAD and BMAH. After HDDST, 24 h UFC was higher in patients with PPNAD as compared to that of ADA and BMAH (P < 0.017). The cut-off value of 24 h UFC (Post-L-Dex)/(Pre-L-Dex) was 1.16 with 64.0% sensitivity and 77.9% specificity, and the cut-off value of 24 h UFC (Post-H-Dex)/(Pre-H-Dex) was 1.08 with 84.0% sensitivity and 75.6% specificity. The ratio of post-dexamethasone to prior-dexamethasone had a unique advantage in distinguishing PPNAD from BMAH and ADA.

Childhood Adrenocortical Tumours: a Review

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Marques-Pereira Rosana

2006-05-01

Full Text Available Abstract Childhood adrenocortical tumour (ACT is not a common disease, but in southern Brazil the prevalence is 15 times higher than in other parts of the world. One hundred and thirty-seven patients have been identified and followed by our group over the past four decades. Affected children are predominantly girls, with a female-to-male ratio of 3.5:1 in patients below 4 years of age. Virilization alone (51.6% or mixed with Cushing's syndrome (42.0% was the predominant clinical picture observed in these patients. Tumours are unilateral, affecting both glands equally. TP53 R337H germline mutations underlie most childhood ACTs in southern Brazil. Epidemiological data from our casuistic studies revealed that this mutation has ~10% penetrance for ACT. Surgery is the definitive treatment, and a complete resection should always be attempted. Although adjuvant chemotherapy has shown some encouraging results, its influence on overall outcome is small. The survival rate is directly correlated to tumour size; patients with small, completely excised tumours have survival rates close to 90%, whereas in those patients with inoperable tumours and/or metastatic disease it is less than 10%. In the group of patients with large, excisable tumours, half of them have an intermediate outcome. Recent molecular biology techniques and genomic approaches may help us to better understand the pathogenesis of ACT, the risk of developing a tumour when TP53 R337H is present, and to predict its outcome. An ongoing pilot study consisting of close monitoring of healthy carriers of the TP53 R337H mutation - siblings and first-degree relatives of known affected cases - aims at the early detection of ACTs and an improvement of the cure rate.

Adrenal incidentalomas showing unilateral concordant visualization by adrenocortical scintigraphy. Comparison with adenomas in Cushing's syndrome

International Nuclear Information System (INIS)

Tani, Atsushi; Nakajo, Masayuki; Tsuchimochi, Shinsaku; Nakabeppu, Yoshiaki; Umanodan, Tomokazu

2000-01-01

An adrenocortical adenoma causing Cushing's syndrome (Cushing's adenoma) produces a unilateral concordant visualization (UCV) imaging pattern in which the adenoma is only visualized on radioiodocholesterol adrenocortical scintigraphy. But because this imaging pattern is also noted in some patients with adrenal incidentalomas, we examined whether the UCV-incidentaloma was essentially identical with Cushing's adenoma and would develop Cushing's syndrome. The subjects were 9 patients with UCV-incidentalomas (mean size, 30 mm; range, 20-45 mm) and 6 patients with Cushing's adenomas (mean size, 28 mm; range, 25-35 mm). Endocrinological evaluations showed several abnormalities including blunted diurnal rhythm of plasma cortisol within the normal range, low plasma ACTH and/or high 24-hr urinary 17-OHCS levels in 8 of 9 patients with UCV-incidentalomas, but these abnormalities did not meet the diagnostic criteria of Cushing's syndrome. Adrenal uptake of the tracer in the patients with UCV-incidentalomas was not statistically different from that in the patients with Cushing's adenomas and had no relationship with hormonal values in either patient group. Tumor size on CT correlated with the levels of 24-hr urinary 17-OHCS (r=0.75, p=0.02) and plasma cortisol at 7:00 (r=0.82, p=0.007) in the patients with UCV-incidentalomas, but not in the patients with Cushing's adenomas. Although 3 UCV-incidentalomas increased slightly in size, none of 9 patients with UCV-incidentalomas has developed Cushing's syndrome for 4 to 52 months. These results suggest that the UCV-incidentaloma may be essentially different from the Cushing's adenoma and unlikely to develop Cushing's syndrome. (author)

Oncocytic adrenocortical neoplasms--a clinicopathologic study of 13 new cases emphasizing the importance of their recognition.

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Wong, Daniel D; Spagnolo, Dominic V; Bisceglia, Michele; Havlat, Marek; McCallum, Dugald; Platten, Michael A

2011-04-01

Oncocytic adrenocortical neoplasms (OANs) are a rare but important subtype of adrenal tumors with unique clinical and morphological features. We present 13 previously unpublished cases, of which 3 were classified as benign, 2 as having borderline malignant potential, and 8 as malignant according to the Lin-Weiss-Bisceglia criteria. Seven tumors (54%) showed evidence of endocrine activity. All were composed of more than 90% oncocytes confirmed immunohistochemically using the antimitochondrial antibody mES-13 and ultrastructurally in 4 cases. Small oncocytes were a frequent finding that challenges the conventional notion of oncocytes as necessarily having abundant cytoplasm. Most cases were immunoreactive for vimentin, synaptophysin, inhibin-α, melan A, and calretinin, the latter being a novel finding in this group of neoplasms. Cytokeratin positivity with AE1/AE3 and CAM5.2 was variable. The literature was comprehensively reviewed to identify all cases of OANs reported to date. Hormone production is not as uncommon as previously believed, occurring in 30%. The Lin-Weiss-Bisceglia criteria were retrospectively applied to all published cases with sufficient information and were shown to effectively separate tumors according to their future risk of recurrence and survival using Kaplan-Meier survival curves (log-rank test, P interval = 27.5-88.5 months), providing the first preliminary evidence that the prognosis of malignant OANs is likely to be more favorable than conventional adrenocortical carcinomas, in which the reported median survival is between 14 and 32 months. Copyright © 2011 Elsevier Inc. All rights reserved.

Association of hyperfunctioning thyroid adenoma with thyroid cancer presenting as "trapping only" nodule at 99mTcO4- scintigraphy.

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dell'Erba, L; Gerundini, P; Caputo, M; Bagnasco, M

2003-11-01

Rarely may a non-hyperfunctioning thyroid nodule present as "hot" at Technetium-99m pertechnetate (99mTcO4-) and "cold" at radioiodine scintigraphy at late acquisitions. We report the case of a hyperthyroid female patient whose 99mTcO4- scintigraphy showed two "hot" nodules, whereas Iodide-131 (131I-) revealed a lack of indicator uptake by the larger, and intense uptake by the smaller nodule. The patient underwent surgery: histology demonstrated that the larger nodule, mismatched at pertechnetate vs iodine scintigraphy, was a papillary carcinoma. Our suggestion is to perform thyroid scintigraphy with radioiodine in hyperthyroid patients with more than one nodule concentrating pertechnetate, especially when an ultrasonographic pattern possibly suspect for malignancy is present.

Differentiating pheochromocytoma from lipid-poor adrenocortical adenoma by CT texture analysis: feasibility study.

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Zhang, Gu-Mu-Yang; Shi, Bing; Sun, Hao; Jin, Zheng-Yu; Xue, Hua-Dan

2017-09-01

To investigate the feasibility of using CT texture analysis (CTTA) to differentiate pheochromocytoma from lipid-poor adrenocortical adenoma (lp-ACA). Ninety-eight pheochromocytomas and 66 lp-ACAs were included in this retrospective study. CTTA was performed on unenhanced and enhanced images. Receiver operating characteristic (ROC) analysis was performed, and the area under the ROC curve (AUC) was calculated for texture parameters that were significantly different for the objective. Diagnostic accuracies were evaluated using the cutoff values of texture parameters with the highest AUCs. Compared to lp-ACAs, pheochromocytomas had significantly higher mean gray-level intensity (Mean), entropy, and mean of positive pixels (MPP), but lower skewness and kurtosis on unenhanced images (P feasible to use CTTA to differentiate pheochromocytoma from lp-ACA.

Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo

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Kertes, Darlene A.; Kamin, Hayley S.; Hughes, David A.; Rodney, Nicole C.; Bhatt, Samarth; Mulligan, Connie J.

2016-01-01

Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which…

Role of glutathione redox cycle and catalase in defense against oxidative stress induced by endosulfan in adrenocortical cells of rainbow trout (Oncorhynchus mykiss)

International Nuclear Information System (INIS)

Dorval, J.; Hontela, A.

2003-01-01

The role of antioxidants in maintaining the functional integrity of adrenocortical cells during in vitro exposure to endosulfan, an organochlorine pesticide, was investigated in rainbow trout (Oncorhynchus mykiss). Aminotriazole (ATA), an inhibitor of catalase (CAT), L-buthionine sulfoximine (L-BSO), an inhibitor of glutathione (GSH) synthesis, and N-acetyl cysteine (NAC), a glutathione precursor, were used to investigate the role of CAT and GSH redox cycle in protection against the adrenal toxicity of endosulfan, a pesticide that impairs cell viability (LC 50 366 μM) and cortisol secretion (EC 50 19 μM) in a concentration-related manner. Pretreatment with ATA and L-BSO enhanced the toxicity of endosulfan (LC 50 and EC 50 , respectively, 302 and 2.6 μM with ATA, 346 and 3.1 μM with L-BSO), while pretreatment with NAC had no significant effect on cell viability and increased the EC 50 of endosulfan to 51 μM. CAT activity was significantly reduced following exposure to endosulfan when cells were pretreated with ATA. Pretreatment with L-BSO significantly decreased glutathione peroxidase (GPx) activity and reduced glutathione (GSH) levels in a concentration-related manner following exposure to endosulfan, while GSH levels were significantly higher in NAC pretreated cells compared to untreated cells. Finally, pretreatment with ATA and L-BSO increased, while pretreatment with NAC decreased, lipid hydroperoxides (LOOH) levels. CAT, GPx, and GSH were identified as important antioxidants in maintaining the function and integrity of rainbow trout adrenocortical cells and ATA, L-BSO, and NAC were identified as effective modulators of CAT and GSH redox cycle. Moreover, this study suggests that the glutathione redox cycle may be more efficient than catalase in protecting adrenocortical cells against endosulfan-induced oxidative stress

The Role of the Pituitary-Adrenocortical Axis System in the Regulation of Secretion of Digestive Glands of Wrestlers during Sports and Postsports Ontogenesis

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Panov, Sergei F.; Panova, Irina P.; Volunskaya, Elena V.; Chebotarev, Andrei V.

2016-01-01

According to many researchers its necessary to research a hormonal profile in order to determine mechanisms of regulation of functions of the digestive conveyor during sports activities. In the paper the results of the carried out research on studying of a role of pituitary-adrenocortical axis system of adaptive reactions in activities of the…

The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.

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Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E

2014-06-01

Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ- and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD. © 2014 British Society for Immunology.

Estudio de 34 pacientes con incidentaloma suprarrenal A study of 34 cases of adrenal incidentaloma

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Raúl A. Chervin

2007-08-01

clinical concern. Although in most cases they are benign and hormonally nonfunctioning, it is important to appropriately identify those few cases of malignant or hyperfunctioning lesions of surgical resolution. Although several proposals for an optimal diagnostic strategy have been designed, controversy over a series of questions still persists. In the present retrospective study we analyzed 34 patients with adrenal incidentaloma. Of these, 32% of the patients displayed hyperfunctioning pathologies that included subclinical Cushing's syndrome in four patients, probable primary hyperaldosteronism in two, late onset congenital adrenal hyperplasia in one, adrenocortical carcinoma in one and pheochromocytoma in three. CT and/or MRI permitted the identification of adenomas and were crucial to decide on surgery in two patients with nonfunctioning pheochromocytomas and in a patient carrying a primitive adrenocortical carcinoma, a diagnosis also suggested by a mixed pattern of hypersecretion of androgens and cortisol. In a diabetic and hypertensive patient with subclinical Cushing's syndrome both comorbidities were solved by surgery. Nonfunctioning tumors were mainly adenomas (87% with individual cases of histoplasmosis, pseudocyst, idiopathic adrenal hyperplasia and mielolipoma. Six of the eight operated patients presented malignant and/or hyperfunctioning tumors. The pathology associated with incidentalomas represents a broad spectrum of risk for patients and reaffirms the necessity for a meticulous clinical, biochemical, and imaging evaluation in order to make appropriate decisions.

Appearance of Graves' disease after percutaneous ethanol injection for the treatment of hyperfunctioning thyroid adenoma.

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Monzani, F; Del Guerra, P; Caraccio, N; Casolaro, A; Lippolis, P V; Goletti, O

1997-05-01

In this report we describe an unusual patient with hyperfunctioning thyroid adenoma in whom percutaneous ethanol injection (p.e.i.) therapy was followed by typical Graves' disease. His history revealed the presence of a sister with Hashimoto's thyroiditis. 99-mTc thyroid scintiscan showed focal uptake in the nodule, with suppression of extranodular parenchyma. P.e.i. therapy was followed by the development of severe hyperthyroidism. One month after a second p.e.i. cycle, recurrence of hyperthyroidism associated with diffuse 99-mTc uptake by the gland was observed. TSH-receptor and thyroglobulin autoantibodies were undetectable before p.e.i. therapy, appeared during the first cycle, and showed a further increase after the second p.e.i. therapy cycle. Though spontaneous switch to Graves' disease cannot be excluded in patients with toxic nodules, the massive release of thyroid materials from follicular cells, among these TSH-receptor antigenic components partially denatured by ethanol, may indeed trigger an autoimmune response to the TSH-receptor, thus accounting for this observation. Patients with possible autoimmune disposition, as selected by familiar history and/or laboratory markers should be carefully monitored during p.e.i. treatment.

Thyrotropin receptor mutations and thyroid hyperfunctioning adenomas ten years after their first discovery: unresolved questions.

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Arturi, F; Scarpelli, D; Coco, A; Sacco, R; Bruno, R; Filetti, S; Russo, D

2003-04-01

Ten years after the first description of activating mutations in the thyroid stimulating hormone receptor (TSHR) gene in sporadic autonomous hyperfunctioning thyroid adenomas, there is general agreement in assigning a major pathogenic role of this genetic abnormality, acting via the constitutive activation of the cAMP pathway, in both the growth and functional characteristic of these tumours. From the beginning, however, the pathophysiological and clinical relevance of somatic TSHR mutations has been debated and some arguments still exist against a fully causative role of these mutations and the practical value of detecting these mutations for the diagnosis, treatment and prognosis of thyroid hot nodules. Some major issues will be examined herein, including (a) the frequency of TSHR alterations in various reports showing that the genetic abnormality underlying the pathogenesis of a substantial subset of thyroid tumours has yet to be identified; (b) the limitations of the present experimental models, which suggest greater caution in the interpretation of in vitro results; (c) the still unresolved question of absence of genotype-phenotype correlation. Clarification of these issues may hopefully provide new and useful tools for improving the clinical management of this disease.

Ultrasound-guided laser thermal ablation in the treatment of autonomous hyperfunctioning thyroid nodules and compressive nontoxic nodular goiter.

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Spiezia, Stefano; Vitale, Giovanni; Di Somma, Carolina; Pio Assanti, Angelo; Ciccarelli, Antonio; Lombardi, Gaetano; Colao, Annamaria

2003-10-01

Percutaneous laser thermal ablation (LTA) has been applied in several tumors. In this study we evaluated the safety and long-term efficacy of LTA in the treatment of benign thyroid nodules. Seven patients with autonomous hyperfunctioning thyroid nodule (group A) and five patients with compressive nodular goiter (group B) were treated with LTA. Up to three needles were positioned centrally in the thyroid nodule and laser fiber was placed in the lumen of the needle. Laser illumination was performed reaching a maximal energy deposition of 1800 J per fiber. Thyroid nodule volume, endocrinologic, and clinical evaluation were performed at baseline, 3, and 12 months after the treatment. Scintigraphy was performed at diagnosis and 12 months after the first session in group A. In group A, mean thyroid volume decreased from 3.15 +/- 1.26 mL to 0.83 +/- 0.49 mL (p thyroid volume decreased from 11.14 +/- 4.99 mL to 3.73 +/- 1.47 mL (p thyroid nodules.

Resveratrol inhibits steroidogenesis in human fetal adrenocortical cells at the end of first trimester

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Savchuk, Iuliia; Morvan, Marie-Line; Søeborg, Tue

2017-01-01

SCOPE: Resveratrol has a diverse array of healthful effects on metabolic parameters in different experimental paradigms but has also potential to inhibit steroidogenesis in rodent adrenals. The aim of the present study was to characterize the effects of resveratrol on human fetal adrenal...... steroidogenesis at gestational weeks (GW) 9-12. METHODS AND RESULTS: Adrenals from aborted fetuses (GW10-12) were used to prepare primary cultures of human fetal adrenocortical cells (HFAC). HFAC were treated in the presence or absence of ACTH (10 ng/ml) with or without resveratrol (10 μM) for 24 hours....... The production of steroids by HFAC was analyzed by gas and liquid chromatography coupled to tandem/mass spectrometry. The expression of steroidogenic enzymes at GW 9-12 was quantified by automated Western blotting. We observed that resveratrol significantly suppressed synthesis of dehydroepiandrosterone (DHEA...

Tumor-specific loss of 11p15.5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma

International Nuclear Information System (INIS)

Henry, I.; Grandjouan, S.; Couillin, P.

1989-01-01

The authors have compared constitutional and tumor genotypes in nine cases of hereditary Wilms tumor (WT) and in three unrelated cases of familial adrenocortical carcinoma (ADCC). Since susceptibility to these tumors can be observed in malformation syndromes associated with a constitutional deletion of band 11p13 (WT) and with a constitutional duplication of band 11p15.5 (WT, ADCC), they investigated these two candidate regions by using 11p polymorphic markers. As expected, somatic chromosomal events, resulting in a loss of heterozygosity limited to region 11p15.5, were observed in the tumor of two familial cases of adrenocortical carcinoma. Surprisingly, however, analysis of the WT of two patients with a constitutional deletion of band 11p13, associated with aniridia, genitourinary abnormalities, and mental retardation (WAGR syndrome), revealed a loss of heterozygosity limited to region 11p15.5. These data therefore suggest that observation of a specific loss of heterozygosity may not necessarily point to the site of the initial germinal mutation. Together with previous similar observations of a loss of heterozygosity limited to 11p15.5 in breast cancer and in rhabdomyosarcoma, the data suggest that region 11p15.5 may carry a non-tissue-specific gene that could be involved in genetic predisposition, in tumor progression, or in both

Hyperfunctional Voice Disorder in Children With Attention Deficit Hyperactivity Disorder (ADHD). A Phenotypic Characteristic?

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Barona-Lleo, Luz; Fernandez, Secundino

2016-01-01

The purpose of this study was to detect specific vocal aerodynamic patterns in attention deficit hyperactivity disorder (ADHD) patients and to define a possible new phenotypic feature of this disorder that must be diagnosed and treated. This is a prospective study. Seventy-nine children aged 5-13 years were recruited: 44 children with ADHD diagnosis and 35 children, as a control group, matched according to age and gender. All children were evaluated in the voice laboratory. Each subject repeated sustained vowels, syllables, words, and sentences several times. Intraoral pressure, transglottal airflow, microphone, and electroglottograph results were recorded and analyzed. Children affected by ADHD, with adequate tolerance, were evaluated endoscopically and by the speech therapist. The aerodynamic analysis shows that the subglottal pressure is higher and transglottal airflow is lower in ADHD children compared with the children of the control group. Those differences are statistically significant. The endoscopic physical examination showed vocal nodules in 25 children (78.125%) and hyperfunctional vocal behavior in all ADHD children studied. We proposed that every child with ADHD disorder must be evaluated from a laryngeal point of view (otolaryngologist and speech therapist) as an important part of the diagnosis and global treatment. It could be considered as a new phenotypic characteristic of this disorder. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

A case report of hyperfunctioning metastatic thyroid cancer and rare I-131 avid liver metastasis

International Nuclear Information System (INIS)

Kunawudhi, Anchisa; Promteangtrong, Chetsadaporn; Chotipanich, Chanisa

2016-01-01

Thyroid cancer is usually, relatively hypofunctional; most patients with thyroid cancer are clinically euthyroid. The combination of thyroid cancer and thyrotoxicosis is not common. We herein, report a case of follicular thyroid cancer with hyperfunctioning metastasis in a 43-year-old woman who presented with thyrotoxicosis, a cold right thyroid nodule, and low I-131 uptake at the thyroid bed. An additional total body scan with I-131 revealed a large radioiodine avid osteolytic bone metastasis with soft tissue masses and liver metastasis. The patient received treatment with total thyroidectomy, methimazole, and I-131 at a cumulative dose of 600 mCi along with recombinant human thyroid-stimulating hormone before the first I-131 treatment and palliative radiation. The patient had normal liver function test and experienced a mild degree of bone marrow suppression after I-131. At the 2-year follow-up, the patient was still alive with the progression of bone metastases but was doing well with less severe thyrotoxicosis, good ambulation, and an Eastern Cooperative Oncology Group performance status of 2. Clinicians should be aware of the unusual concurrent presentation of thyrotoxicosis and thyroid cancer, a differential diagnosis in patients with thyrotoxicosis and low or normal radioiodine uptake over the neck and also potential pitfalls during radionuclide treatment

In vivo and in vitro evaluation of [18F]FETO with respect to the adrenocortical and GABAergic system in rats

International Nuclear Information System (INIS)

Mitterhauser, Markus; Wadsak, Wolfgang; Wabnegger, Leila; Sieghart, Werner; Viernstein, Helmut; Kletter, Kurt; Dudczak, Robert

2003-01-01

11β-Hydroxylase (CYP11B1, P450 11β ) plays an important role in the biosynthesis of cortisol and aldosterone and has been shown to be a good target for the in vivo imaging of adrenocortical incidentalomas in nuclear medicine. [ 11 C]Metomidate (MTO), a potent inhibitor of this enzyme, is used for positron emission tomography (PET) imaging of adrenocortical pathology. The synthesis of (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid 2-[ 18 F]fluoroethylester (FETO), a close analogue to MTO and etomidate (ETO), has been presented recently, and the present investigation aimed to characterise the in vivo distribution of FETO. Since ETO is a well-known anaesthetic drug acting via the GABAergic system, the interaction of FETO with GABA A receptors was also evaluated. Eighteen male Sprague-Dawley rats were injected with 1.73-3.06 MBq of FETO into a tail vein after venodilatation in a 40 C water bath. Rats were sacrificed by exsanguination from the abdominal aorta under deep ether anaesthesia after 10 (n=6), 30 (n=6) or 60 min (n=6); organs were removed, weighed and counted. For binding experiments, rat cerebellar membranes were incubated for 90 min at 4 C in TC-50 buffer, 150 mM NaCl and 2 nM of [ 3 H]flunitrazepam in the absence or presence of 10 μM diazepam or various concentrations of ETO, MTO and FETO. In vivo evaluation evinced very high uptake in the adrenal glands (7.52%±1.19% ID/g at 30 min), followed by lung (1.18%±0.19% ID/g, 10 min), liver (0.59%±0.13% ID/g, 10 min) and duodenum (0.7%±0.29% ID/g, 60 min). No defluorination nor fluoroethyl-ester cleavage was observed. When brain regions were compared with the thalamus (the reference region), highest relative uptake was seen in the cortex (2.34), followed by ''rest brain'' (2.13) and cerebellum (1.96). FETO and ETO were able to increase the binding of [ 3 H]flunitrazepam with similar potencies and to a comparable extent. It is concluded that FETO shows characteristics suitable for the imaging of

A mathematical model of the hypothalamo-pituitary-adrenocortical system and its stability analysis

Energy Technology Data Exchange (ETDEWEB)

Savic, Danka [Vinca Institute of Nuclear Sciences, Laboratory for Theoretical and Condensed Matter Physics, P.O. Box 522, Belgrade 11001 (Serbia and Montenegro)] e-mail: dankasav@eunet.yu; Jelic, Smiljana [Vinca Institute of Nuclear Sciences, Laboratory for Theoretical and Condensed Matter Physics, P.O. Box 522, Belgrade 11001 (Serbia and Montenegro)

2005-10-01

It is commonly assumed that the hypothalamo-pituitary-adrenocortical (HPA) axis generates oscillations, because a regular daily rhythm of its component hormones is observed. We offer another plausible explanation of the origin of its circadian oscillations: HPA just responds to an independent external pacemaker (from the suprachiazmatic nucleus, SCN). Five versions (with and without time delay) of a qualitative non-phenomenological mathematical model of the HPA axis as a feedback mechanism are constructed wherein all the terms in the equations are introduced according to the rules of chemical kinetics, i.e. are physicochemically interpretable. The dynamics of the HPA axis model was examined using linear stability analysis. The results show stability of this system, meaning that it does not generate diurnal oscillations. Computer simulation based on this model shows oscillations that are system's response to an external pulsing activator (SCN) implying that the observed time-periodic pattern does not have to be an intrinsic property of the HPA axis.

A mathematical model of the hypothalamo-pituitary-adrenocortical system and its stability analysis

International Nuclear Information System (INIS)

Savic, Danka; Jelic, Smiljana

2005-01-01

It is commonly assumed that the hypothalamo-pituitary-adrenocortical (HPA) axis generates oscillations, because a regular daily rhythm of its component hormones is observed. We offer another plausible explanation of the origin of its circadian oscillations: HPA just responds to an independent external pacemaker (from the suprachiazmatic nucleus, SCN). Five versions (with and without time delay) of a qualitative non-phenomenological mathematical model of the HPA axis as a feedback mechanism are constructed wherein all the terms in the equations are introduced according to the rules of chemical kinetics, i.e. are physicochemically interpretable. The dynamics of the HPA axis model was examined using linear stability analysis. The results show stability of this system, meaning that it does not generate diurnal oscillations. Computer simulation based on this model shows oscillations that are system's response to an external pulsing activator (SCN) implying that the observed time-periodic pattern does not have to be an intrinsic property of the HPA axis

Familial isolated primary pigmented nodular adrenocortical disease associated with a novel low penetrance PRKAR1A gene splice site mutation

DEFF Research Database (Denmark)

Storr, Helen L; Metherell, Louise A; Dias, Renuka

2010-01-01

Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating germline protein kinase A regulatory subunit type 1-alpha (PRKAR1A) mutations and loss of heterozygosity at the 17q22-24 locus in approximately 50% patients. PRKAR1A mutations are observed in both isolated PP...... PPNAD (iPPNAD) and Carney complex (CNC). Most mutations result in a functionally null-allele and exhibit high penetrance. We genotyped members of an extended family for a novel PRKAR1A mutation and undertook detailed phenotyping for CNC in the affected individuals....

Adrenal incidentalomas showing unilateral concordant visualization by adrenocortical scintigraphy. Comparison with adenomas in Cushing's syndrome

Energy Technology Data Exchange (ETDEWEB)

Tani, Atsushi; Nakajo, Masayuki; Tsuchimochi, Shinsaku; Nakabeppu, Yoshiaki; Umanodan, Tomokazu [Kagoshima Univ. (Japan). Faculty of Medicine

2000-06-01

An adrenocortical adenoma causing Cushing's syndrome (Cushing's adenoma) produces a unilateral concordant visualization (UCV) imaging pattern in which the adenoma is only visualized on radioiodocholesterol adrenocortical scintigraphy. But because this imaging pattern is also noted in some patients with adrenal incidentalomas, we examined whether the UCV-incidentaloma was essentially identical with Cushing's adenoma and would develop Cushing's syndrome. The subjects were 9 patients with UCV-incidentalomas (mean size, 30 mm; range, 20-45 mm) and 6 patients with Cushing's adenomas (mean size, 28 mm; range, 25-35 mm). Endocrinological evaluations showed several abnormalities including blunted diurnal rhythm of plasma cortisol within the normal range, low plasma ACTH and/or high 24-hr urinary 17-OHCS levels in 8 of 9 patients with UCV-incidentalomas, but these abnormalities did not meet the diagnostic criteria of Cushing's syndrome. Adrenal uptake of the tracer in the patients with UCV-incidentalomas was not statistically different from that in the patients with Cushing's adenomas and had no relationship with hormonal values in either patient group. Tumor size on CT correlated with the levels of 24-hr urinary 17-OHCS (r=0.75, p=0.02) and plasma cortisol at 7:00 (r=0.82, p=0.007) in the patients with UCV-incidentalomas, but not in the patients with Cushing's adenomas. Although 3 UCV-incidentalomas increased slightly in size, none of 9 patients with UCV-incidentalomas has developed Cushing's syndrome for 4 to 52 months. These results suggest that the UCV-incidentaloma may be essentially different from the Cushing's adenoma and unlikely to develop Cushing's syndrome. (author)

State of the art knowledge in adrenocortical and behavioral responses to environmental challenges in a threatened South American ratite: Implications to in situ and ex-situ conservation.

Science.gov (United States)

Luis, Navarro Joaquín; Lèche, Alvina; Costa, Natalia S Della; Cortez, Marilina Vera; Marin, Raúl H; Martella, Mónica B

2018-04-12

The Greater Rhea (Rhea americana) is an endemic ratite to South America, whose wild populations have undergone a remarkable decrease due to habitat degradation and fragmentation by the expansion of the agricultural frontier, poaching and predation by dogs. Anthropogenic perturbations in wild environments, as well as the management in captivity, can generate different stress responses in this species, thus, the monitoring of adrenocortical and behavioral activities are considered primary assessment tools with both conservation and welfare implications. In this review we analyze and integrate the different measurements of glucocorticoids (in plasma, feces, and yolk) carried out in different captive and wild populations, taking into account the diverse predictable and unpredictable conditions to which the Greater Rhea responds in each of those environments. In addition, the translocation of this bird is presented as an application of stress physiology in field ecology for conservation purposes, in which we evaluated how this species responds when it is released into a novel environment. Our results indicate that this ratite has a striking high sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis compared to that of other bird species and shows a wide variety of adrenocortical responses depending on the environment in which it lives. This suggests that its HPA axis has a phenotypic plasticity that enables the rhea to cope with the environmental challenges. In this sense, we propose that one of the routes of this plasticity could be mediated by the maternal transfer of steroid hormones to the egg. Finally, we discuss the importance of integrating the monitoring of the adrenocortical response along with the environmental variables that define the life history of the species, in management and conservation programs ex-situ and in situ. Copyright © 2018. Published by Elsevier Inc.

In vivo and in vitro evaluation of [{sup 18}F]FETO with respect to the adrenocortical and GABAergic system in rats

Energy Technology Data Exchange (ETDEWEB)

Mitterhauser, Markus [Department of Nuclear Medicine, AKH Wien, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Department of Pharmaceutic Technology and Biopharmaceutics, University of Vienna (Austria); Hospital Pharmacy of the General Hospital of Vienna (Austria); Wadsak, Wolfgang [Department of Nuclear Medicine, AKH Wien, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Department of Inorganic Chemistry, University of Vienna (Austria); Ludwig-Boltzmann-Institute for Nuclear Medicine, Vienna (Austria); Wabnegger, Leila; Sieghart, Werner [Institute for Brain Research, University of Vienna (Austria); Viernstein, Helmut [Department of Pharmaceutic Technology and Biopharmaceutics, University of Vienna (Austria); Kletter, Kurt [Department of Nuclear Medicine, AKH Wien, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Dudczak, Robert [Department of Nuclear Medicine, AKH Wien, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria)

2003-10-01

11{beta}-Hydroxylase (CYP11B1, P450{sub 11{beta}}) plays an important role in the biosynthesis of cortisol and aldosterone and has been shown to be a good target for the in vivo imaging of adrenocortical incidentalomas in nuclear medicine. [{sup 11}C]Metomidate (MTO), a potent inhibitor of this enzyme, is used for positron emission tomography (PET) imaging of adrenocortical pathology. The synthesis of (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid 2-[{sup 18}F]fluoroethylester (FETO), a close analogue to MTO and etomidate (ETO), has been presented recently, and the present investigation aimed to characterise the in vivo distribution of FETO. Since ETO is a well-known anaesthetic drug acting via the GABAergic system, the interaction of FETO with GABA{sub A} receptors was also evaluated. Eighteen male Sprague-Dawley rats were injected with 1.73-3.06 MBq of FETO into a tail vein after venodilatation in a 40 C water bath. Rats were sacrificed by exsanguination from the abdominal aorta under deep ether anaesthesia after 10 (n=6), 30 (n=6) or 60 min (n=6); organs were removed, weighed and counted. For binding experiments, rat cerebellar membranes were incubated for 90 min at 4 C in TC-50 buffer, 150 mM NaCl and 2 nM of [{sup 3}H]flunitrazepam in the absence or presence of 10 {mu}M diazepam or various concentrations of ETO, MTO and FETO. In vivo evaluation evinced very high uptake in the adrenal glands (7.52%{+-}1.19% ID/g at 30 min), followed by lung (1.18%{+-}0.19% ID/g, 10 min), liver (0.59%{+-}0.13% ID/g, 10 min) and duodenum (0.7%{+-}0.29% ID/g, 60 min). No defluorination nor fluoroethyl-ester cleavage was observed. When brain regions were compared with the thalamus (the reference region), highest relative uptake was seen in the cortex (2.34), followed by ''rest brain'' (2.13) and cerebellum (1.96). FETO and ETO were able to increase the binding of [{sup 3}H]flunitrazepam with similar potencies and to a comparable extent. It is concluded

Synthetic high-density lipoprotein nanodisks for targeted withalongolide delivery to adrenocortical carcinoma

Directory of Open Access Journals (Sweden)

Kuai R

2017-09-01

Full Text Available Rui Kuai,1,2,* Chitra Subramanian,3,* Peter T White,3,* Barbara N Timmermann,4 James J Moon,1,2,5 Mark S Cohen,3,6 Anna Schwendeman1,2 1Department of Pharmaceutical Sciences, College of Pharmacy, 2Biointerfaces Institute, University of Michigan, 3Department of Surgery, University of Michigan, Ann Arbor, MI, 4Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, 5Department of Biomedical Engineering, 6Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA *These authors contributed equally to this work Abstract: Adrenocortical carcinoma (ACC is a rare endocrine malignancy and has a 5-year survival rate of <35%. ACC cells require cholesterol for steroid hormone production, and this requirement is met via expression on the cell surface of a high level of SRB1, responsible for the uptake of high-density lipoproteins (HDLs, which carry and transport cholesterol in vivo. Here, we describe how this natural lipid carrier function of SRB1 can be utilized to improve the tumor-targeted delivery of a novel natural product derivative – withalongolide A 4,19,27-triacetate (WGA-TA – which has shown potent antitumor efficacy, but poor aqueous solubility. Our strategy was to use synthetic HDL (sHDL nanodisks, which are effective in tumor-targeted delivery due to their smallness, long circulation half-life, documented safety, and ability to bind to SRB1. In this study, we prepared sHDL nanodisks using an optimized phospholipid composition combined with ApoA1 mimetic peptide (22A, which has previously been tested in clinical trials, to load WGA-TA. Following optimization, WGA-TA nanodisks showed drug encapsulation efficiency of 78%, a narrow particle size distribution (9.81±0.41 nm, discoid shape, and sustained drug release in phosphate buffered saline. WGA-TA-sHDL nanodisks exhibited higher cytotoxicity in the ACC cell line H295R half maximal inhibitory concentration ([IC50] 0.26±0.045 µM than free WGA-TA (IC50 0.492±0

Human Adrenocortical Remodeling Leading to Aldosterone-Producing Cell Cluster Generation

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Koshiro Nishimoto

2016-01-01

Full Text Available Background. The immunohistochemical detection of aldosterone synthase (CYP11B2 and steroid 11β-hydroxylase (CYP11B1 has enabled the identification of aldosterone-producing cell clusters (APCCs in the subcapsular portion of the human adult adrenal cortex. We hypothesized that adrenals have layered zonation in early postnatal stages and are remodeled to possess APCCs over time. Purposes. To investigate changes in human adrenocortical zonation with age. Methods. We retrospectively analyzed adrenal tissues prepared from 33 autopsied patients aged between 0 and 50 years. They were immunostained for CYP11B2 and CYP11B1. The percentage of APCC areas over the whole adrenal area (AA/WAA, % and the number of APCCs (NOA, APCCs/mm2 were calculated by four examiners. Average values were used in statistical analyses. Results. Adrenals under 11 years old had layered zona glomerulosa (ZG and zona fasciculata (ZF without apparent APCCs. Some adrenals had an unstained (CYP11B2/CYP11B1-negative layer between ZG and ZF, resembling the rat undifferentiated cell zone. Average AA/WAA and NOA correlated with age, suggesting that APCC development is associated with aging. Possible APCC-to-APA transitional lesions were incidentally identified in two adult adrenals. Conclusions. The adrenal cortex with layered zonation remodels to possess APCCs over time. APCC generation may be associated with hypertension in adults.

Percutaneous laser ablation of unresectable primary and metastatic adrenocortical carcinoma

Energy Technology Data Exchange (ETDEWEB)

Pacella, Claudio M. [Regina Apostolorum Hospital, Department of Diagnostic Imaging and Interventional Radiology, Via San Francesco 50, Albano Laziale, Rome 00041 (Italy)], E-mail: claudiomaurizio.pacella@fastwebnet.it; Stasi, Roberto; Bizzarri, Giancarlo; Pacella, Sara; Graziano, Filomena Maria; Guglielmi, Rinaldo; Papini, Enrico [Regina Apostolorum Hospital, Department of Diagnostic Imaging and Interventional Radiology, Via San Francesco 50, Albano Laziale, Rome 00041 (Italy)

2008-04-15

Purpose: To evaluate the feasibility, safety, and clinical benefits of percutaneous laser ablation (PLA) in patients with unresectable primary and metastatic adrenocortical carcinoma (ACC). Patients and methods: Four patients with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound-guided PLA. In one case the procedure was performed also on the primary tumor. Results: After three sessions of PLA, the primary tumor of 15 cm was ablated by 75%. After 1-4 (median 1) sessions of PLA, five liver metastases ranging from 2 to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by 75%. There were no major complications. Treatment resulted in an improvement of performance status and a reduction of the daily dosage of mitotane in all patients. The three patients with liver metastases presented a marked decrease of 24-h urine cortisol levels, an improved control of hypertension and a mean weight loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9-48 months), two patients have died of tumor progression, while two other patients remain alive and free of disease. Conclusions: Percutaneous laser ablation is a feasible, safe and well tolerated procedure for the palliative treatment of unresectable primary and metastatic ACC. Further study is required to evaluate the impact of PLA on survival.

Percutaneous laser ablation of unresectable primary and metastatic adrenocortical carcinoma

International Nuclear Information System (INIS)

Pacella, Claudio M.; Stasi, Roberto; Bizzarri, Giancarlo; Pacella, Sara; Graziano, Filomena Maria; Guglielmi, Rinaldo; Papini, Enrico

2008-01-01

Purpose: To evaluate the feasibility, safety, and clinical benefits of percutaneous laser ablation (PLA) in patients with unresectable primary and metastatic adrenocortical carcinoma (ACC). Patients and methods: Four patients with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound-guided PLA. In one case the procedure was performed also on the primary tumor. Results: After three sessions of PLA, the primary tumor of 15 cm was ablated by 75%. After 1-4 (median 1) sessions of PLA, five liver metastases ranging from 2 to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by 75%. There were no major complications. Treatment resulted in an improvement of performance status and a reduction of the daily dosage of mitotane in all patients. The three patients with liver metastases presented a marked decrease of 24-h urine cortisol levels, an improved control of hypertension and a mean weight loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9-48 months), two patients have died of tumor progression, while two other patients remain alive and free of disease. Conclusions: Percutaneous laser ablation is a feasible, safe and well tolerated procedure for the palliative treatment of unresectable primary and metastatic ACC. Further study is required to evaluate the impact of PLA on survival

Patient-specific workup of adrenal incidentalomas

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Romy R. de Haan

Full Text Available Purpose: : To develop a clinical prediction model to predict a clinically relevant adrenal disorder for patients with adrenal incidentaloma. Materials and methods: : This retrospective study is approved by the institutional review board, with waiver of informed consent. Natural language processing is used for filtering of adrenal incidentaloma cases in all thoracic and abdominal CT reports from 2010 till 2012. A total of 635 patients are identified. Stepwise logistic regression is used to construct the prediction model. The model predicts if a patient is at risk for malignancy or hormonal hyperfunction of the adrenal gland at the moment of initial presentation, thus generates a predicted probability for every individual patient. The prediction model is evaluated on its usefulness in clinical practice using decision curve analysis (DCA based on different threshold probabilities. For patients whose predicted probability is lower than the predetermined threshold probability, further workup could be omitted. Results: : A prediction model is successfully developed, with an area under the curve (AUC of 0.78. Results of the DCA indicate that up to 11% of patients with an adrenal incidentaloma can be avoided from unnecessary workup, with a sensitivity of 100% and specificity of 11%. Conclusion: : A prediction model can accurately predict if an adrenal incidentaloma patient is at risk for malignancy or hormonal hyperfunction of the adrenal gland based on initial imaging features and patient demographics. However, with most adrenal incidentalomas labeled as nonfunctional adrenocortical adenomas requiring no further treatment, it is likely that more patients could be omitting from unnecessary diagnostics. Keywords: Adrenal incidentaloma, Patient-specific workup, Prediction model

Kindergarten stressors and cumulative adrenocortical activation: the "first straws" of allostatic load?

Science.gov (United States)

Bush, Nicole R; Obradović, Jelena; Adler, Nancy; Boyce, W Thomas

2011-11-01

Using an ethnically diverse longitudinal sample of 338 kindergarten children, this study examined the effects of cumulative contextual stressors on children's developing hypothalamic-pituitary-adrenocortical (HPA) axis regulation as an early life indicator of allostatic load. Chronic HPA axis regulation was assessed using cumulative, multiday measures of cortisol in both the fall and spring seasons of the kindergarten year. Hierarchical linear regression analyses revealed that contextual stressors related to ethnic minority status, socioeconomic status, and family adversity each uniquely predicted children's daily HPA activity and that some of those associations were curvilinear in conformation. Results showed that the quadratic, U-shaped influences of family socioeconomic status and family adversity operate in different directions to predict children's HPA axis regulation. Results further suggested that these associations differ for White and ethnic minority children. In total, this study revealed that early childhood experiences contribute to shifts in one of the principal neurobiological systems thought to generate allostatic load, confirming the importance of early prevention and intervention efforts. Moreover, findings suggested that analyses of allostatic load and developmental theories accounting for its accrual would benefit from an inclusion of curvilinear associations in tested predictive models.

Expression of StAR and Key Genes Regulating Cortisol Biosynthesis in Near Term Ovine Fetal Adrenocortical Cells: Effects of Long-Term Hypoxia.

Science.gov (United States)

Vargas, Vladimir E; Myers, Dean A; Kaushal, Kanchan M; Ducsay, Charles A

2018-02-01

We previously demonstrated decreased expression of key genes regulating cortisol biosynthesis in long-term hypoxic (LTH) sheep fetal adrenals compared to controls. We also showed that inhibition of the extracellular signal-regulated kinases (ERKs) with the mitogen-activated protein kinase (MEK)/ERK inhibitor UO126 limited adrenocorticotropic (ACTH)-induced cortisol production in ovine fetal adrenocortical cells (FACs), suggesting a role for ERKs in cortisol synthesis. This study was designed to determine whether the previously observed decrease in LTH cytochrome P45011A1/cytochrome P450c17 (CYP11A1/CYP17) in adrenal glands was maintained in vitro, and whether ACTH alone with or without UO126 treatment had altered the expression of CYP11A1, CYP17, and steroidogenic acute regulatory protein (StAR) in control versus LTH FACs. Ewes were maintained at high altitude (3820 m) from ∼40 days of gestation (dG). At 138 to 141 dG, fetal adrenal glands were collected from LTH (n = 5) and age-matched normoxic controls (n = 6). Fetal adrenocortical cells were challenged with ACTH (10 -8 M) with or without UO126 (10 µM) for 18 hours. Media samples were collected for cortisol analysis and messenger RNA (mRNA) for CYP11A1, CYP17, and StAR was quantified by quantitative real-time polymerase chain reaction. Cortisol was higher in the LTH versus control ( P StAR mRNA was decreased in LTH versus control ( P StAR expression.

Surgical resection of synchronously metastatic adrenocortical cancer.

Science.gov (United States)

Dy, Benzon M; Strajina, Veljko; Cayo, Ashley K; Richards, Melanie L; Farley, David R; Grant, Clive S; Harmsen, William S; Evans, Doug B; Grubbs, Elizabeth G; Bible, Keith C; Young, William F; Perrier, Nancy D; Que, Florencia G; Nagorney, David M; Lee, Jeffrey E; Thompson, Geoffrey B

2015-01-01

Metastatic adrenocortical carcinoma (ACC) is rapidly fatal, with few options for treatment. Patients with metachronous recurrence may benefit from surgical resection. The survival benefit in patients with hematogenous metastasis at initial presentation is unknown. A review of all patients undergoing surgery (European Network for the Study of Adrenal Tumors) stage IV ACC between January 2000 and December 2012 from two referral centers was performed. Kaplan-Meier estimates were analyzed for disease-free and overall survival (OS). We identified 27 patients undergoing surgery for stage IV ACC. Metastases were present in the lung (19), liver (11), and brain (1). A complete resection (R0) was achieved in 11 patients. The median OS was improved in patients undergoing R0 versus R2 resection (860 vs. 390 days; p = 0.02). The 1- and 2-year OS was also improved in patients undergoing R0 versus R2 resection (69.9 %, 46.9 % vs. 53.0 %, 22.1 %; p = 0.02). Patients undergoing neoadjuvant therapy (eight patients) had a trend towards improved survival at 1, 2, and 5 years versus no neoadjuvant therapy (18 patients) [83.3 %, 62.5 %, 41.7 % vs. 56.8 %, 26.6 %, 8.9 %; p = 0.1]. Adjuvant therapy was associated with improved recurrence-free survival at 6 months and 1 year (67 %, 33 % vs. 40 %, 20 %; p = 0.04) but not improved OS (p = 0.63). Sex (p = 0.13), age (p = 0.95), and location of metastasis (lung, p = 0.51; liver, p = 0.67) did not correlate with OS after operative intervention. Symptoms of hormonal excess improved in 86 % of patients. Operative intervention, especially when an R0 resection can be achieved, following systemic therapy may improve outcomes, including OS, in select patients with stage IV ACC. Response to neoadjuvant chemotherapy may be of use in defining which patients may benefit from surgical intervention. Adjuvant therapy was associated with decreased recurrence but did not improve OS.

Biology is Destiny: A Case of Adrenocortical Carcinoma Diagnosed and Resected at Inception in a Patient Under Close Surveillance for Lung Cancer.

Science.gov (United States)

Miron, Benjamin; Ristau, Benjamin T; Tomaszewski, Jeffrey J; Jones, Josh; Milestone, Bart; Wong, Yu-Ning; Uzzo, Robert G; Edmondson, Donna; Scott, Walter; Kutikov, Alexander

2016-11-01

Adrenocortical carcinoma (ACC) is a rare malignancy that is generally associated with a poor prognosis whose existence dictates the management of incidental renal masses. We report a case of ACC diagnosed and treated at its apparent inception in a patient undergoing close surveillance imaging of a prior malignancy. Despite timely detection and resection of a localized ACC this patient rapidly progressed to systemic disease. This case highlights the rapid growth kinetics of ACC and puts into perspective the challenges associated with the established treatment paradigm for patients diagnosed with an adrenal mass.

Biology is Destiny: A Case of Adrenocortical Carcinoma Diagnosed and Resected at Inception in a Patient Under Close Surveillance for Lung Cancer

Directory of Open Access Journals (Sweden)

Benjamin Miron

2016-11-01

Full Text Available Adrenocortical carcinoma (ACC is a rare malignancy that is generally associated with a poor prognosis whose existence dictates the management of incidental renal masses. We report a case of ACC diagnosed and treated at its apparent inception in a patient undergoing close surveillance imaging of a prior malignancy. Despite timely detection and resection of a localized ACC this patient rapidly progressed to systemic disease. This case highlights the rapid growth kinetics of ACC and puts into perspective the challenges associated with the established treatment paradigm for patients diagnosed with an adrenal mass.

Chloroquine enhances the efficacy of cisplatin by suppressing autophagy in human adrenocortical carcinoma treatment

Directory of Open Access Journals (Sweden)

Qin L

2016-03-01

Full Text Available Liang Qin,1,* Tianyuan Xu,1,* Leilei Xia,1 Xianjin Wang,1 Xiang Zhang,1 Xiaohua Zhang,1 Zhaowei Zhu,1 Shan Zhong,1 Chuandong Wang,2 Zhoujun Shen1 1Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 2Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: It has been demonstrated that chloroquine (CQ enhances the efficacy of chemotherapy. However, little is known about whether CQ could enhance the efficacy of cisplatin (DDP in the treatment of adrenocortical carcinoma (ACC. In this study, we explore the efficacy and mechanism by which CQ affects DDP sensitivity in human ACC in vitro and in vivo.Methods: The autophagic gene Beclin-1 expression was detected by immunohistochemistry, and the protein levels were analyzed using immunoblotting assays of ACC tissues and normal adrenal cortex tissues. The ACC SW13 cells were treated with DDP and/or CQ. The cell viability assay was performed using the MTT method. Qualitative autophagy detection was performed by monodansylcadaverine staining of autophagic vacuoles. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to count cell apoptosis by flow cytometry. The autophagy-related protein (Beclin-1, LC3, and p62 and apoptosis relative protein (Bax and Bcl-2 levels were evaluated with Western blot analysis. Furthermore, a murine model of nude BALB/c mice bearing SW13 cell xenografts was established to evaluate the efficacy of concomitant therapy.Results: The expression of the autophagic gene Beclin-1 was significantly downregulated in ACC tissues compared to normal adrenal cortex tissues. The Beclin-1 protein level in ACC tissues was lower than that in normal adrenal cortex tissues (P<0.05. In vitro concomitant therapy (DDP and CQ was more

Role of Endocrine Gland-Derived Vascular Endothelial Growth Factor (EG-VEGF) and Its Receptors in Adrenocortical Tumors.

Science.gov (United States)

Heck, Dorothee; Wortmann, Sebastian; Kraus, Luitgard; Ronchi, Cristina L; Sinnott, Richard O; Fassnacht, Martin; Sbiera, Silviu

2015-12-01

Angiogenesis is essential for tumor growth and metastasis. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor predominantly expressed in steroidogenic organs like the adrenal gland, ovary, testes, and placenta. EG-VEGF has antiapoptotic, mitogenic, and chemoattractive properties mediated via the two G protein-coupled receptors prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2). We investigated the expression of EG-VEGF and its receptors in a large number of normal adrenal glands (NAG), adrenocortical adenomas (ACA), and carcinomas (ACC) using real-time PCR (NAG, n = 12; ACA, n = 24; and ACC, n = 30) and immunohistochemistry (NAG, n = 9; ACA, n = 23; and ACC, n = 163) and evaluated its impact on patients' survival. EG-VEGF, PKR1, and PKR2 mRNA and protein are expressed in NAG and the vast majority of ACA and ACC samples. The mean EG-VEGF mRNA expression was significantly lower in ACC (606.5 ± 77.1 copies) compared to NAG (4,043 ± 1,111) and cortisol-producing adenomas (CPA) (4,433 ± 2,378) (p < 0.01 and p < 0.05, respectively). However, cytoplasmic and nuclear EG-VEGF protein expression was either significantly higher or similar in ACC (H score 2.4 ± 0.05, p < 0.05 and 1.7 ± 0.08, n.s., respectively) compared to NAG (1.8 ± 0.14 and 1.7 ± 0.2). Nuclear protein expression of either EG-VEGF or PKR1 or both is predictive for a higher mortality compared to patients without nuclear expression (hazard ratio (HR) = 5.15; 95% confidence interval (CI) = 1.24-21.36, n = 100, p = 0.02 independent of age, sex, and tumor stage). These findings suggest that EG-VEGF and its receptor PKR1 might play a role in the pathogenesis of adrenocortical tumors and could serve as prognostic markers for this rare malignant disease.

Adrenocortical carcinoma, an unusual extracolonic tumor associated with Lynch II syndrome.

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Medina-Arana, V; Delgado, L; González, L; Bravo, A; Díaz, H; Salido, E; Riverol, D; González-Aguilera, J J; Fernández-Peralta, A M

2011-06-01

Lynch syndrome (LS) is an autosomal dominant condition that predisposes to colorectal cancer and specific other tumors. Extracolonic tumors occur mainly in the endometrium, stomach, ovary, small intestine and urinary tract. The presence of rare tumors in patients belonging to families who have Lynch syndrome is always interesting, because the question arises whether these tumors should be considered as a coincidence or are related with the syndrome. In this last case, they are also the result of the defect in the mismatch repair system, opening the possibility of extending the tumor spectrum associated with the syndrome. Here we describe a patient from a Lynch syndrome family with a germline mutation c.2063T>G (p.M688R) in the MSH2 gene, who developed an adrenal cortical carcinoma, a tumor not usually associated with LS. We analyzed the adrenocortical tumour for microsatellite instability (MSI), LOH and the presence of the germline c.2063T>G (M688R) mutation. The adrenal cortical carcinoma showed the MSH2 mutation, loss of heterozygosity of the normal allele in the MSH2 gene and loss of immunohistochemical expression for MSH2 protein, but no microsatellite instability. Additionally, the adrenal cortical carcinoma did not harbour a TP53 mutation. The molecular study indicates that this adrenal cortical cancer is probably due to the mismatch repair defect.

Hair cortisol measurement in mitotane-treated adrenocortical cancer patients.

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Manenschijn, L; Quinkler, M; van Rossum, E F C

2014-04-01

The only approved drug for the treatment of adrenocortical cancer (ACC) is mitotane. Mitotane is adrenolytic and therefore, hydrocortisone replacement therapy is necessary. Since mitotane increases cortisol binding globulin (CBG) and induces CYP3A4 activity, high doses of hydrocortisone are thought to be required. Evaluation of hydrocortisone therapy in mitotane-treated patients has been difficult since there is no good marker to evaluate hydrocortisone therapy. Measurement of cortisol in scalp hair is a novel method that offers the opportunity to measure long-term cortisol levels. Our aim was to evaluate whether hair cortisol measurements could be useful in evaluating recent hydrocortisone treatment in mitotane-treated ACC patients. Hair cortisol levels were measured in 15 mitotane-treated ACC patients on hydrocortisone substitution and 96 healthy individuals. Cortisol levels were measured in 3 cm hair segments, corresponding to a period of 3 months. Hair cortisol levels were higher in ACC patients compared to healthy individuals (pcortisol levels above the reference range. None of the patients had hair cortisol levels below normal. In contrast to hydrocortisone doses (β=0.03, p=0.93), hair cortisol levels were associated with BMI (β=0.53, p=0.042). There was no correlation between hair cortisol levels and hydrocortisone doses (β=0.41, p=0.13). Almost half of the ACC patients had high hair cortisol levels, suggesting long-term over-substitution of hydrocortisone in some of the patients, whereas none of the patients was under-substituted. Hair cortisol measurements might be useful in long-term monitoring hydrocortisone treatment in mitotane-treated ACC patients. © Georg Thieme Verlag KG Stuttgart · New York.

Masked volume wise principal component analysis of small adrenocortical tumours in dynamic [11C]-metomidate positron emission tomography

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Razifar, Pasha; Hennings, Joakim; Monazzam, Azita; Hellman, Per; Långström, Bengt; Sundin, Anders

2009-01-01

In previous clinical Positron Emission Tomography (PET) studies novel approaches for application of Principal Component Analysis (PCA) on dynamic PET images such as Masked Volume Wise PCA (MVW-PCA) have been introduced. MVW-PCA was shown to be a feasible multivariate analysis technique, which, without modeling assumptions, could extract and separate organs and tissues with different kinetic behaviors into different principal components (MVW-PCs) and improve the image quality. In this study, MVW-PCA was applied to 14 dynamic 11C-metomidate-PET (MTO-PET) examinations of 7 patients with small adrenocortical tumours. MTO-PET was performed before and 3 days after starting per oral cortisone treatment. The whole dataset, reconstructed by filtered back projection (FBP) 0–45 minutes after the tracer injection, was used to study the tracer pharmacokinetics. Early, intermediate and late pharmacokinetic phases could be isolated in this manner. The MVW-PC1 images correlated well to the conventionally summed image data (15–45 minutes) but the image noise in the former was considerably lower. PET measurements performed by defining 'hot spot' regions of interest (ROIs) comprising 4 contiguous pixels with the highest radioactivity concentration showed a trend towards higher SUVs when the ROIs were outlined in the MVW-PC1 component than in the summed images. Time activity curves derived from '50% cut-off' ROIs based on an isocontour function whereby the pixels with SUVs between 50 to 100% of the highest radioactivity concentration were delineated, showed a significant decrease of the SUVs in normal adrenal glands and in adrenocortical adenomas after cortisone treatment. In addition to the clear decrease in image noise and the improved contrast between different structures with MVW-PCA, the results indicate that the definition of ROIs may be more accurate and precise in MVW-PC1 images than in conventional summed images. This might improve the precision of PET

Increased expression of G-protein-coupled receptor kinases 3 and 4 in hyperfunctioning thyroid nodules.

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Voigt, Carsten; Holzapfel, Hans-Peter; Meyer, Silke; Paschke, Ralf

2004-07-01

G-protein-coupled receptor kinases (GRKs) are implicated in the pathophysiology of human diseases such as arterial hypertension, heart failure and rheumatoid arthritis. While G-protein-coupled receptor kinases 2 and 5 have been shown to be involved in the desensitization of the rat thyrotropin receptor (TSHR), their role in the pathophysiology of hyperfunctioning thyroid nodules (HTNs) is unknown. Therefore, we analyzed the expression pattern of the known GRKs in human thyroid tissue and investigated their function in the pathology of HTNs. The expression of different GRKs in human thyroid and HTNs was measured by Western blotting. The influence of GRK expression on TSHR function was analyzed by coexpression experiments in HEK 293 cells. We demonstrate that in addition to GRKs 2, 5 and 6, GRKs 3 and 4 are also expressed in the human thyroid. GRKs 2, 3, 5 and 6 are able to desensitize the TSHR in vitro. This GRK-induced desensitization is amplified by the additional over-expression of beta-arrestin 1 or 2. We did not find any mutations in the GRKs 2, 3 and 5 from 14 HTNs without TSHR mutations and Gsalpha mutations. The expression of GRKs 3 and 4 was increased in HTNs independently from the existence of TSHR mutations or Gsalpha mutations. In conclusion, the increased expression of GRK 3 in HTNs and the ability of GRK 3 to desensitize the TSHR in vitro, suggest a potential role for GRK 3 as a negative feedback regulator for the constitutively activated cAMP pathway in HTNs.

18F-Labelled metomidate analogues as adrenocortical imaging agents

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Erlandsson, Maria; Karimi, Farhad; Lindhe, Orjan; Langstroem, Bengt

2009-01-01

Introduction: Two- and one-step syntheses of 18 F-labelled analogues of metomidate, such as 2-[ 18 F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[ 18 F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[ 18 F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[ 18 F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[ 18 F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Methods: Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[ 18 F]fluoroethyl 4-methylbenzenesulfonate or 3-[ 18 F]fluoropropyl 4-methylbenzenesulfonate. These were used as 18 F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. Results: The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46±3% and 79±30%, respectively. Conclusion: Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

Adrenocortical responses to offspring-directed threats in two open-nesting birds.

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Butler, Luke K; Bisson, Isabelle-Anne; Hayden, Timothy J; Wikelski, Martin; Romero, L Michael

2009-07-01

Dependent young are often easy targets for predators, so for many parent vertebrates, responding to offspring-directed threats is a fundamental part of reproduction. We tested the parental adrenocortical response of the endangered black-capped vireo (Vireo atricapilla) and the common white-eyed vireo (V. griseus) to acute and chronic threats to their offspring. Like many open-nesting birds, our study species experience high offspring mortality. Parents responded behaviorally to a predator decoy or human 1-2m from their nests, but, in contrast to similar studies of cavity-nesting birds, neither these acute threats nor chronic offspring-directed threats altered plasma corticosterone concentrations of parents. Although parents in this study showed no corticosterone response to offspring-directed threats, they always increased corticosterone concentrations in response to capture. To explain these results, we propose that parents perceive their risk of nest-associated death differently depending on nest type, with cavity-nesting adults perceiving greater risk to themselves than open-nesters that can readily detect and escape from offspring-directed threats. Our results agree with previous studies suggesting that the hypothalamic-pituitary-adrenal axis, a major physiological mechanism for coping with threats to survival, probably plays no role in coping with threats to offspring when risks to parents and offspring are not correlated. We extend that paradigm by demonstrating that nest style may influence how adults perceive the correlation between offspring-directed and self-directed threats.

Cyclic estrous-like behavior in a spayed cat associated with excessive sex-hormone production by an adrenocortical carcinoma.

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Meler, Erika N; Scott-Moncrieff, J Catharine; Peter, Augustine T; Bennett, Sara; Ramos-Vara, Jose; Salisbury, S Kathleen; Naughton, James F

2011-06-01

A 15-year-old, spayed female domestic shorthair cat was evaluated for 1-year duration of cyclic intermittent estrous behavior. Diagnostic testing performed before referral, including baseline progesterone concentration, human chorionic gonadotropin (hCG) hormone stimulation test and surgical exploratory laparotomy, had remained inconclusive for a remnant ovary. Evaluation of sex hormones before and after adrenocorticotropic hormone (ACTH) administration revealed increased basal concentrations of androstenedione, estradiol, progesterone, and 17α-hydroxyprogesterone and normal ACTH-stimulated hormone concentrations. Enlargement of the right adrenal gland was identified by abdominal ultrasound. The cat underwent an adrenalectomy and histopathology of the excised adrenal gland was consistent with an adrenocortical carcinoma. Clinical signs resolved immediately following surgery, and most hormone concentrations declined to within or below the reference interval (RI) by 2 months after surgery. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Agonist-induced desensitization of adenylyl cyclase in Y1 adrenocortical tumor cells

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Olson, M.F.; Tsao, J.; Pon, D.J.; Schimmer, B.P.

1991-01-01

Y1 adrenocortical tumor cells (Y1DS) and Y1 mutants resistant to ACTH-induced desensitization of adenylyl cyclase (Y1DR) were transfected with a gene encoding the mouse beta 2-adrenergic receptor (beta 2-AR). Transfectants expressed beta 2-ARs that were able to stimulate adenylyl cyclase activity and steroid biosynthesis. These transfectants were used to explore the basis for the DR mutation in Y1 cells. The authors demonstrate that beta-adrenergic agonists desensitize the adenylyl cyclase system in transfected Y1DS cells whereas transfected Y1DR cells are resistant to desensitization by beta-adrenergic agonists. The fate of the beta 2-ARs during desensitization was evaluated by photoaffinity labelling with [125I]iodocyanopindolol diazerine. Desensitization of Y1DS transfectants was accompanied by a modest loss in receptor density that was insufficient to account for the complete loss of responsiveness to beta-adrenergic agonists. The extent of receptor loss induced by beta-adrenergic agonists in Y1DR transfectants exceeded that in the Y1DS transfectants indicating that the mutation which protects Y1DR cells from agonist-induced desensitization is prior to receptor down-regulation in the desensitization pathway. From these results we infer that ACTH and isoproterenol desensitize adenylyl cyclase by a common pathway and that receptor loss is not a major component of the desensitization process in these cells

Adrenocortical carcinoma: the dawn of a new era of genomic and molecular biology analysis.

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Armignacco, R; Cantini, G; Canu, L; Poli, G; Ercolino, T; Mannelli, M; Luconi, M

2018-05-01

Over the last decade, the development of novel and high penetrance genomic approaches to analyze biological samples has provided very new insights in the comprehension of the molecular biology and genetics of tumors. The use of these techniques, consisting of exome sequencing, transcriptome, miRNome, chromosome alteration, genome, and epigenome analysis, has also been successfully applied to adrenocortical carcinoma (ACC). In fact, the analysis of large cohorts of patients allowed the stratification of ACC with different patterns of molecular alterations, associated with different outcomes, thus providing a novel molecular classification of the malignancy to be associated with the classical pathological analysis. Improving our knowledge about ACC molecular features will result not only in a better diagnostic and prognostic accuracy, but also in the identification of more specific therapeutic targets for the development of more effective pharmacological anti-cancer approaches. In particular, the specific molecular alteration profiles identified in ACC may represent targetable events by the use of already developed or newly designed drugs enabling a better and more efficacious management of the ACC patient in the context of new frontiers of personalized precision medicine.

Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling

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Luconi Michaela

2008-07-01

Full Text Available Rosiglitazone (RGZ, a thiazolidinedione ligand of the peroxisome proliferator-activated receptor (PPAR-γ, has been recently described as possessing antitumoral properties. We investigated RGZ effect on cell proliferation in two cell line models (SW13 and H295R of human adrenocortical carcinoma (ACC and its interaction with the signaling pathways of the activated IGF-I receptor (IGF-IR. We demonstrate a high expression of IGF-IR in the two cell lines and in ACC. Cell proliferation is stimulated by IGF-I in a dose- and time-dependent manner and is inhibited by RGZ. The analysis of the main intracellular signaling pathways downstream of the activated IGF-IR, phosphatidyl inositol 3-kinase (PI3K-Akt, and extracellular signal-regulated kinase (ERK1/2 cascades reveals that RGZ rapidly interferes with the Akt and ERK1/2 phosphorylation/activation which mediates IGF-I stimulated proliferation. In conclusion, our results suggest that RGZ exerts an inhibitory effect on human ACC cell proliferation by interfering with the PI3K/Akt and ERK1/2 signaling pathways downstream of the activated IGF-IR.

Germline PRKACA amplification leads to Cushing syndrome caused by 3 adrenocortical pathologic phenotypes.

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Carney, J Aidan; Lyssikatos, Charalampos; Lodish, Maya B; Stratakis, Constantine A

2015-01-01

We describe the pathology of 5 patients with germline PRKACA copy number gain and Cushing syndrome: 4 males and 1 female, aged 2 to 43 years, including a mother and son. Imaging showed normal or slightly enlarged adrenal glands in 4 patients and a unilateral mass in the fifth. Biochemically, the patients had corticotropin-independent hypercortisolism. Four underwent bilateral adrenalectomy; unilateral adrenalectomy was performed in the patient with the adrenal mass. Pathologically, 3 patients, including the 1 with the tumor (adenoma), had primary pigmented nodular adrenocortical disease with extranodular cortical atrophy and mild intracapsular and extracapsular extension of cortical cells. The other 2 patients had cortical hyperplasia and prominent capsular and extracapsular micronodular cortical hyperplasia. Immunoperoxidase staining revealed differences for synaptophysin, inhibin-A, and Ki-67 (nuclei) in the atrophic cortices (patients 1, 2, and 3) and hyperplastic cortices (patients 4 and 5) and for Ki-67 (nuclei) and vimentin in the extracortical nodules in the 2 groups of patients. β-Catenin stained the cell membrane, cytoplasm, and nuclei of the adenoma. The patients were well at follow-up (1-23 years); 24-hour urinary cortisol excretion was elevated in the patient who had unilateral adrenalectomy. Copyright © 2014 Elsevier Inc. All rights reserved.

Molecular Profiling of Refractory Adrenocortical Cancers and Predictive Biomarkers to Therapy

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Sherri Z. Millis

2015-01-01

Full Text Available Purpose Current first-line chemotherapy for patients with metastatic adrenocortical cancer (ACC includes doxorubicin, etoposide, cisplatin, and mitotane with a reported response rate of only 23.2%. New therapeutic leads for patients with refractory tumors are needed; there is no standard second-line treatment. Methods Samples from 135 ACC tumors were analyzed by immunohistochemistry, in situ hybridization (FISH or CISH, and/or gene sequencing at a single commercial reference laboratory (Caris Life Sciences to identify markers associated with drug sensitivity and resistance. Results Overexpression of proteins related to demonstrated chemotherapy sensitivity or resistance included topoisomerase 1, progesterone receptor, and topoisomerase 2-alpha in 46%, 63%, and 42% of cases, respectively. Loss of excision repair cross-complementary group 1 (ERCC1, phosophatase and tensin homolog, O(6-methylguanine-methyltransferase, and ribonucleotide reductase M1 (RRM1 was identified in 56%, 59%, 71%, and 58% of cases, respectively. Other aberrations included overexpression of programmed death-ligand 1 or programmed cell death protein 1 tumor-infiltrating lymphocytes in >40% of cases. In all, 35% of cases had a mutation in the canonical Wnt signaling pathway (either CTNNB1 or APC and 48% had a mutation in TP53. No other genomic alterations were identified. Conclusion Biomarker alterations in ACC may be used to direct therapies, including recommendations for and potential resistance of some patients to traditional chemotherapies, which may explain the low response rate in the unselected population. Limited outcomes data support the use of mitotane and platinum therapies for patients with low levels of the proteins RRM1 and ERCC1.

Cytodiagnosis of myxoid adrenocortical carcinoma and role of immunocytochemistry to differentiate it from renal cell carcinoma

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Santosh Kumar Mondal

2014-01-01

Full Text Available Adrenocortical carcinoma (ACC is a rare malignancy and cytodiagnosis of this tumor is not routinely encountered by a cytopathologist. Here, we report a case of ACC initially diagnosed by computed tomography (CT-guided fine needle aspiration cytology (FNAC with the help of immunocytochemistry. A 48-year-old lady presented with flank pain and abdominal mass for the last 6 months. A CT scan of her abdomen revealed a large mass arising from the upper part of the left kidney. CT-guided FNAC was performed. Cytologic smears showed pleomorphic large cells arranged discretely and in small aggregates against a myxoid background. The cells had a high nucleocytoplasmic ratio, anisonucleosis and conspicuous nucleoli. Based on cytomorphology, differential diagnoses of ACC and renal cell carcinoma (RCC were made. On immunocytochemistry, the tumor cells were synaptophysin, inhibin, vimentin and Melan-A positive but cytokeratin and epithelial membrane antigen negative. Thus, a cytodiagnosis of myxoid ACC was made and histopathologic examination was suggested. Subsequent histologic examination and immunohistochemistry proved the case to be myxoid ACC.

{sup 18}F-Labelled metomidate analogues as adrenocortical imaging agents

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Erlandsson, Maria; Karimi, Farhad [Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, S-751 23 Uppsala (Sweden); Lindhe, Orjan [Uppsala Imanet, GE Healthcare, Box 967, S-751 09 Uppsala (Sweden); Langstroem, Bengt [Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, S-751 23 Uppsala (Sweden)], E-mail: bengt.langstrom@biorg.uu.se

2009-05-15

Introduction: Two- and one-step syntheses of {sup 18}F-labelled analogues of metomidate, such as 2-[{sup 18}F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[{sup 18}F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[{sup 18}F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[{sup 18}F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[{sup 18}F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Methods: Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[{sup 18}F]fluoroethyl 4-methylbenzenesulfonate or 3-[{sup 18}F]fluoropropyl 4-methylbenzenesulfonate. These were used as {sup 18}F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. Results: The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46{+-}3% and 79{+-}30%, respectively. Conclusion: Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

Adrenocortical regulation, eating in the absence of hunger and BMI in young children.

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Francis, L A; Granger, D A; Susman, E J

2013-05-01

The purpose of this study was to examine relations among adrenocortical regulation, eating in the absence of hunger, and body mass index (BMI) in children ages 5-9years (N=43). Saliva was collected before and after the Trier Social Stress Test for Children (TSST-C), and was later assayed for cortisol. Area under the curve with respect to increase (AUCi) was used as a measure of changes in cortisol release from baseline to 60min post-TSST-C. Age- and sex-specific BMI scores were calculated from measured height and weight, and eating in the absence of hunger was assessed using weighed food intake during a behavioral procedure. We also included a measure of parents' report of child impulsivity, as well as family demographic information. Participants were stratified by age into younger (5-7years) and older (8-9years) groups. In younger children, parents' reports of child impulsivity were significantly and positively associated with BMI; cortisol AUCi was not associated with BMI or eating in the absence of hunger. In older children, however, greater stress-related cortisol AUCi was related to higher BMI scores and greater energy intake in the absence of hunger. The results suggest that cortisol AUCi in response to psychosocial stress may be linked to problems with energy balance in children, with some variation by age. Published by Elsevier Ltd.

Assessment of the role of transcript for GATA-4 as a marker of unfavorable outcome in human adrenocortical neoplasms

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Martin Regina M

2004-07-01

Full Text Available Abstract Background Malignant neoplasia of the adrenal cortex is usually associated with very poor prognosis. When adrenocortical neoplasms are diagnosed in the early stages, distinction between carcinoma and adenoma can be very difficult to accomplish, since there is yet no reliable marker to predict tumor recurrence or dissemination. GATA transcription factors play an essential role in the developmental control of cell fate, cell proliferation and differentiation, organ morphogenesis, and tissue-specific gene expression. Normal mouse adrenal cortex expresses GATA-6 while its malignant counterpart only expresses GATA-4. The goal of the present study was to assess whether this reciprocal change in the expression of GATA factors might be relevant for predicting the prognosis of human adrenocortical neoplasms. Since human adrenal cortices express luteinizing hormone (LH/hCG receptor and the gonadotropins are known to up-regulate GATA-4 in gonadal tumor cell lines, we also studied the expression of LH/hCG receptor. Methods We conducted a study on 13 non-metastasizing (NM and 10 metastasizing/recurrent (MR tumors obtained from a group of twenty-two adult and pediatric patients. The expression of GATA-4, GATA-6, and LH/hCG receptor (LHR in normal and tumoral human adrenal cortices was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR complemented by dot blot hybridization. Results Messenger RNA for GATA-6 was detected in normal adrenal tissue, as well as in the totality of NM and MR tumors. GATA-4, by its turn, was detected in normal adrenal tissue, in 11 out of 13 NM tumors, and in 9 of the 10 MR tumors, with larger amounts of mRNA found among those presenting aggressive clinical behavior. Transcripts for LH receptor were observed both in normal tissue and neoplasms. A more intense LHR transcript accumulation was observed on those tumors with better clinical outcome. Conclusion Our data suggest that the expression of GATA-6 in

Polychlorinated biphenyl 126 stimulates basal and inducible aldosterone biosynthesis of human adrenocortical H295R cells

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Li, L.-A.; Wang, P.-W.; Chang, Louis W.

2004-01-01

To understand the effects of polychlorinated biphenyls (PCBs) on adrenal aldosterone biosynthesis, we have performed a systematical study to characterize the corresponding steroidogenic response of human adrenocortical cell line H295R to PCB126 exposure. We found that PCB126 at high concentrations stimulated basal and inducible aldosterone production. The aldosterone induction occurred concomitantly with activation of the CYP11B2 gene. Despite the fact that PCB126 acted in synergy with both potassium and angiotensin II (Ang II) in activation of aldosterone synthesis, PCB126 only modestly increased CYP11B2 mRNA expression in the presence of Ang II contrary to the synergistic transcriptional induction elicited by PCB126 and potassium. This implicated that PCB126 had differential interactions with the potassium and Ang II signaling systems in the regulation of aldosterone biosynthesis. In addition, high concentrations of PCB126 elevated transcriptional expression of the type I Ang II receptor (AT 1 ) and might thus sensitize the cellular Ang II responsiveness in both basal and inducible aldosterone biosynthesis. SF-1 was not involved in the PCB126-induced transcriptional regulation despite its importance in steroidogenic gene activation

StAR Protein Stability in Y1 and Kin-8 Mouse Adrenocortical Cells.

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Clark, Barbara J; Hudson, Elizabeth A

2015-03-04

The steroidogenic acute regulatory protein (STAR) protein expression is required for cholesterol transport into mitochondria to initiate steroidogenesis in the adrenal and gonads. STAR is synthesized as a 37 kDa precursor protein which is targeted to the mitochondria and imported and processed to an intra-mitochondrial 30 kDa protein. Tropic hormone stimulation of the cAMP-dependent protein kinase A (PKA) signaling pathway is the major contributor to the transcriptional and post-transcriptional regulation of STAR synthesis. Many studies have focused on the mechanisms of cAMP-PKA mediated control of STAR synthesis while there are few reports on STAR degradation pathways. The objective of this study was to determine the effect of cAMP-PKA-dependent signaling on STAR protein stability. We have used the cAMP-PKA responsive Y1 mouse adrenocortical cells and the PKA-deficient Kin-8 cells to measure STAR phosphorylation and protein half-life. Western blot analysis and standard radiolabeled pulse-chase experiments were used to determine STAR phosphorylation status and protein half-life, respectively. Our data demonstrate that PKA-dependent STAR phosphorylation does not contribute to 30 kDa STAR protein stability in the mitochondria. We further show that inhibition of the 26S proteasome does not block precursor STAR phosphorylation or steroid production in Y1 cells. These data suggest STAR can maintain function and promote steroidogenesis under conditions of proteasome inhibition.

Adrenocortical and Adipose Responses to High-Altitude-Induced, Long-Term Hypoxia in the Ovine Fetus

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Dean A. Myers

2012-01-01

Full Text Available By late gestation, the maturing hypothalamo-pituitary-adrenal (HPA axis aids the fetus in responding to stress. Hypoxia represents a significant threat to the fetus accompanying situations such as preeclampsia, smoking, high altitude, and preterm labor. We developed a model of high-altitude (3,820 m, long-term hypoxia (LTH in pregnant sheep. We describe the impact of LTH on the fetal HPA axis at the level of the hypothalamic paraventricular nucleus (PVN, anterior pituitary corticotrope, and adrenal cortex. At the PVN and anterior pituitary, the responses to LTH are consistent with hypoxia being a potent activator of the HPA axis and potentially maladaptive, while the adrenocortical response to LTH appears to be primarily adaptive. We discuss mechanisms involved in the delicate balance between these seemingly opposing responses that preserve the normal ontogenic rise in fetal plasma cortisol essential for organ maturation and in this species, birth. Further, we examine the response to, and ramifications of, an acute secondary stressor in the LTH fetus. We provide an integrative model on the potential role of adipose in modulating these responses to LTH. Integration of these adaptive responses to LTH plays a key role in promoting normal fetal growth and development under conditions of a chronic stress.

Rapid and Complete Remission of Metastatic Adrenocortical Carcinoma Persisting 10 Years After Treatment With Mitotane Monotherapy

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Ghorayeb, Nada El; Rondeau, Geneviève; Latour, Mathieu; Cohade, Christian; Olney, Harold; Lacroix, André; Perrotte, Paul; Sabourin, Alexis; Mazzuco, Tania L; Bourdeau, Isabelle

2016-01-01

Abstract Mitotane has been used for more than 5 decades as therapy for adrenocortical carcinoma (ACC). However its mechanism of action and the extent of tumor response remain incompletely understood. To date no cases of rapid and complete remission of metastatic ACC with mitotane monotherapy has been reported. A 52-year-old French Canadian man presented with metastatic disease 2 years following a right adrenalectomy for stage III nonsecreting ACC. He was started on mitotane which was well tolerated despite rapid escalation of the dose. The patient course was exceptional as he responded to mitotane monotherapy after only few months of treatment. Initiation of chemotherapy was not needed and he remained disease-free with good quality of life on low maintenance dose of mitotane during the following 10 years. A germline heterozygous TP53 exon 4 polymorphism c.215C>G (p. Pro72Arg) was found. Immunohistochemical stainings for IGF-2 and cytoplasmic β-catenin were positive. Advanced ACC is an aggressive disease with poor prognosis and the current therapeutic options remain limited. These findings suggest that mitotane is a good option for the treatment of metastatic ACC and might result in rapid complete remission in selected patients. PMID:27043680

Salivary cortisol as an indicator of adrenocortical function in healthy infants, using massage therapy

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Monalisa de Cássia Fogaça

Full Text Available CONTEXT AND OBJECTIVE: The evaluation of adrenocortical function with the use of therapeutic massage has been little studied in Brazil. The purpose of this study was to evaluate the salivary cortisol levels before and after Shantala massage therapy on healthy infants. DESIGN AND SETTING: Prospective case series, in a public nursery, in São Paulo. METHODS: Saliva was obtained from 11 infants at the times of 8:00-9:00 a.m. and 4:00-5:00 p.m. in a nursery and 9:00-10:00 p.m. at home. They received a 15-minute therapeutic massage on two consecutive days, and saliva was collected before and after the massage. The procedure was repeated after a one-week interval. Cortisol values (intra-assay < 5%; inter-assay < 10% at different times of the day were compared by ANOVA. RESULTS: The mean cortisol values (nmol/l ± SD on the first day were: morning (M = 14.1 ± 5.7, afternoon (A = 8.3 ± 2.7, night (N = 3.3 ± 1.1; after two consecutive days of therapeutic massage: M = 22.3 ± 13.5, A = 13.4 ± 6.0, N = 5.8 ± 3.5; after a one-week interval: M = 15.8 ± 7.7, A = 14.3 ± 7.7, N = 3.4 ± 2.0. CONCLUSION: There was a modification in the salivary cortisol values following massage, thus reflecting possible adaptation of the hypothalamic-pituitary-adrenal axis.

Localization diagnosis of hyperfunctional parathyroid gland using 99Tcm-MIBI and 99TcmO4- imaging

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Zhang Fenru; Deng Huixing; Duan Xiaoyi; Xue Jianjun; Gao Rui

2010-01-01

Objective: To study the localization diagnosis value of nuclide imaging by 99 Tc m -MIBI double phase parathyroid combined with 99 Tc m O 4 - thyroid imaging in patients with hyperparathyroidism (HPT). Methods: Patients with primary HPT were 36 cases. Control groups were 10 cases with thyroid disease. Early phase imaging was performed in 15 minute after injecting imaging agent 99 Tc m -MIBI. Delay phase imaging was performed in 2 hours. 36 HPT patients and 10 cases control groups were also performed 99 Tc m O 4 - thyroid imaging 24 hours later. The two kinds of imaging were compared with each other, were analyzed, and were underwent imaging subtracted by eyes and imaging results judgment. Results: In 36 cases of HPT patients, 34 cases showed positive result imaging with 99 Tc m -MIBI/ 99 Tc m O 4 - imaging. 2 cases showed false negative result. Positive rate was 94.44 % with 99 Tc m -MIBI/ 99 Tc m O 4 - imaging. The positive result imaging showed abnormal increased uptake of 99 Tc m -MIBI. In 36 cases of HPT patients, 12 cases showed positive result with single 99 Tc m -MIBI imaging. 4 cases showed false negative imaging. 20 cases showed ambiguous positive results. Positive rate was 88.89% (55.56% was ambiguous positive results) with single 99 Tc m -MIBI imaging. In 10 cases control groups, 3 cases showed false positive results with single 99 Tc m -MIBI imaging. 1 case showed ambiguous false positive results. No case showed false positive result with 99 Tc m -MIBI/ 99 Tc m O 4 - imaging. Conclusion: 99 Tc m -MIBI parathyroid double phase imaging combined with 99 Tc m O 4 - thyroid imaging have important value for diagnoses and localization of hyperparathyroidism. 99 Tc m -MIBI/ 99 Tc m O 4 - imaging have higher positive rate and higher specificity than single 99 Tc m -MIBI imaging for diagnoses and localization of hyperfunction parathyroid gland. (authors)

Adrenocortical Production Is Associated with Higher Levels of Luteinizing Hormone in Nonobese Women with Polycystic Ovary Syndrome

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Luciana Tock

2014-01-01

Full Text Available Objective. Insulin resistance (IR and ovarian and adrenal hyperandrogenism are a common finding in women with polycystic ovary syndrome (PCOS. The aim of the present study was to access possible differences in insulin resistance, gonadotropins, and androgens production in obese and nonobese PCOS women. Study Design. We studied 37 PCOS women (16 nonobese and 21 obese and 18 nonobese controls. Fasting glucose, insulin, androgens, and gonadotropins levels were determined. Salivary cortisol was measured basal and in the morning after dexamethasone (DEX 0.25 mg. Results. Nonobese PCOS women showed higher basal salivary cortisol and serum dehydroepiandrosterone sulfate and luteinizing hormone (LH levels than controls and obese PCOS. These hormones levels did not differ between the obese and control groups. After DEX administration no differences were found between the three groups. In PCOS women, salivary cortisol levels showed negative correlation with BMI (r=-0.52; P=0.001 and insulin (r=-0.47; P=0.003 and positive correlation with LH (r=0.40; P=0.016. Conclusion. Our results show an increased adrenocortical production in nonobese PCOS women, not related to IR and associated with a normal hypothalamic-pituitary-adrenal suppression. Higher LH levels might be involved in this event.

Adrenal metabolism of mitotane and related compounds

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Djanegara, T.K.S.

1989-01-01

Mitotane (o,p'-DDD; 1-[2-chlorophenyl]-1-[4-chlorophenyl]-2,2-dichloroethane) has been used in the treatment of Cushing's syndrome due to adrenal hyperfunction and it the drug of choice for adrenocortical carcinoma. The object of this investigation is to study the biotransformation of o,p'-DDD and p,p'-DDD in dogs and bovine adrenal cortex to explain its selective toxicity and mechanism of action. The in vitro biotransformation of 14 C-labeled o,p'-DDD and p,p'-DDD by dog and bovine adrenal cortex as studied. Of the cortex subcellular fractions, the cytosol fraction was found to be the most active in metabolizing the substrates, followed by the mitochondrial fraction. This metabolism including that in cytosolic fractions, did not take place with boiled enzyme preparations and required an NADPH generating system. This study has been directed towards establishing the metabolic activation mechanism which may account for the adrenocorticolytic effect of mitotane in contrast to detoxication by the liver. HPLC and TLC metabolic profiles have been generated from incubations of bovine and dog adrenal cortex homogenates and their subfractions for 14 C-labeled p,p'-DDD, o,p'-DDD and its monochloroethylene derivative, o,p'-DDMU

Novelty-induced emotional arousal modulates cannabinoid effects on recognition memory and adrenocortical activity.

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Campolongo, Patrizia; Morena, Maria; Scaccianoce, Sergio; Trezza, Viviana; Chiarotti, Flavia; Schelling, Gustav; Cuomo, Vincenzo; Roozendaal, Benno

2013-06-01

Although it is well established that cannabinoid drugs can influence cognitive performance, the findings-describing both enhancing and impairing effects-have been ambiguous. Here, we investigated the effects of posttraining systemic administration of the synthetic cannabinoid agonist WIN55,212-2 (0.1, 0.3, or 1.0 mg/kg) on short- and long-term retention of object recognition memory under two conditions that differed in their training-associated arousal level. In male Sprague-Dawley rats that were not previously habituated to the experimental context, WIN55,212-2 administered immediately after a 3-min training trial, biphasically impaired retention performance at a 1-h interval. In contrast, WIN55,212-2 enhanced 1-h retention of rats that had received extensive prior habituation to the experimental context. Interestingly, immediate posttraining administration of WIN55,212-2 to non-habituated rats, in doses that impaired 1-h retention, enhanced object recognition performance at a 24-h interval. Posttraining WIN55,212-2 administration to habituated rats did not significantly affect 24-h retention. In light of intimate interactions between cannabinoids and the hypothalamic-pituitary-adrenal axis, we further investigated whether cannabinoid administration might differently influence training-induced glucocorticoid activity in rats in these two habituation conditions. WIN55,212-2 administered after object recognition training elevated plasma corticosterone levels in non-habituated rats whereas it decreased corticosterone levels in habituated rats. Most importantly, following pretreatment with the corticosterone-synthesis inhibitor metyrapone, WIN55,212-2 effects on 1- and 24-h retention of non-habituated rats became similar to those seen in the low-aroused habituated animals, indicating that cannabinoid-induced regulation of adrenocortical activity contributes to the environmentally sensitive effects of systemically administered cannabinoids on short- and long

Effect of KCNJ5 Mutations on Gene Expression in Aldosterone-Producing Adenomas and Adrenocortical Cells

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Monticone, Silvia; Hattangady, Namita G.; Nishimoto, Koshiro; Mantero, Franco; Rubin, Beatrice; Cicala, Maria Verena; Pezzani, Raffaele; Auchus, Richard J.; Ghayee, Hans K.; Shibata, Hirotaka; Kurihara, Isao; Williams, Tracy A.; Giri, Judith G.; Bollag, Roni J.; Edwards, Michael A.; Isales, Carlos M.

2012-01-01

Context: Primary aldosteronism is a heterogeneous disease that includes both sporadic and familial forms. A point mutation in the KCNJ5 gene is responsible for familial hyperaldosteronism type III. Somatic mutations in KCNJ5 also occur in sporadic aldosterone producing adenomas (APA). Objective: The objective of the study was to define the effect of the KCNJ5 mutations on gene expression and aldosterone production using APA tissue and human adrenocortical cells. Methods: A microarray analysis was used to compare the transcriptome profiles of female-derived APA samples with and without KCNJ5 mutations and HAC15 adrenal cells overexpressing either mutated or wild-type KCNJ5. Real-time PCR validated a set of differentially expressed genes. Immunohistochemical staining localized the KCNJ5 expression in normal adrenals and APA. Results: We report a 38% (18 of 47) prevalence of KCNJ5 mutations in APA. KCNJ5 immunostaining was highest in the zona glomerulosa of NA and heterogeneous in APA tissue, and KCNJ5 mRNA was 4-fold higher in APA compared with normal adrenals (P APA with and without KCNJ5 mutations displayed slightly different gene expression patterns, notably the aldosterone synthase gene (CYP11B2) was more highly expressed in APA with KCNJ5 mutations. Overexpression of KCNJ5 mutations in HAC15 increased aldosterone production and altered expression of 36 genes by greater than 2.5-fold (P APA, and our data suggest that these mutations increase expression of CYP11B2 and NR4A2, thus increasing aldosterone production. PMID:22628608

The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity.

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Mete, Ozgur; Duan, Kai

2018-01-01

Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype-phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations ( KCNJ5, ATP1A1, ATP2B3 , and CACNA1D ) involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5 -mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3 , and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations ( PRKACA, PRKAR1A, GNAS, PDE11A , and PDE8B ) involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH) have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

A Novel PRKAR1A Mutation Identified in a Patient with Isolated Primary Pigmented Nodular Adrenocortical Disease

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Sira Korpaisarn

2017-08-01

Full Text Available Primary pigmented nodular adrenocortical disease (PPNAD is a rare cause of Cushing syndrome, especially the isolated form without Carney complex, associated with germline mutations in PRKAR1A, the protein kinase A regulatory subunit type 1 alpha gene. We report a 31-year-old female who presented with secondary amenorrhea, cushingoid appearance, and hypertension without Carney complex. Biochemical laboratory examinations confirmed the ACTH-independent adrenal Cushing syndrome with negative Liddle test. A small right adrenal adenoma of 0.8 cm was shown on computed tomography while magnetic resonance imaging revealed nodularity of both adrenal glands. The histological report confirmed PPNAD using laparoscopic right adrenalectomy, and subsequent left adrenalectomy was performed 6 months later. She had inherited heterozygosity of a novel germline mutation of the PRKAR1A gene (g.114213T>G or c.709-5T>G. This splice site mutation results in exon 8 skipping. Her father carrying the same mutation had no clinical features of either PPNAD or Carney complex. This novel PRKAR1A gene mutation, c.709-5T>G, is reported here for the first time manifesting as an incomplete clinical expression of the isolated form of PPNAD and being inherited with low penetrance unlike other inherited mutations of the Carney complex which have a penetrance of almost 100%.

Detection of adrenocortical autoantibodies in Addison's disease with a peroxidase-labelled protein A technique

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R.C. Silva

1998-09-01

Full Text Available Adrenocortical autoantibodies (ACA, present in 60-80% of patients with idiopathic Addison's disease, are conventionally detected by indirect immunofluorescence (IIF on frozen sections of adrenal glands. The large-scale use of IIF is limited in part by the need for a fluorescence microscope and the fact that histological sections cannot be stored for long periods of time. To circumvent these restrictions we developed a novel peroxidase-labelled protein A (PLPA technique for the detection of ACA in patients with Addison's disease and compared the results with those obtained with the classical IIF assay. We studied serum samples from 90 healthy control subjects and 22 patients with Addison's disease, who had been clinically classified into two groups: idiopathic (N = 13 and granulomatous (N = 9. ACA-PLPA were detected in 10/22 (45% patients: 9/13 (69% with the idiopathic form and 1/9 (11% with the granulomatous form, whereas ACA-IIF were detected in 11/22 patients (50%: 10/13 (77% with the idiopathic form and 1/9 (11% with the granulomatous form. Twelve of the 13 idiopathic addisonians (92% were positive for either ACA-PLPA or ACA-IIF, but only 7 were positive by both methods. In contrast, none of 90 healthy subjects was found to be positive for ACA. Thus, our study shows that the PLPA-based technique is useful, has technical advantages over the IIF method (by not requiring the use of a fluorescence microscope and by permitting section storage for long periods of time. However, since it is only 60% concordant with the ACA-IIF method, it should be considered complementary instead of an alternative method to IIF for the detection of ACA in human sera.

Effects of Insufficient Sleep on Pituitary-Adrenocortical Response to CRH Stimulation in Healthy Men.

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Guyon, Aurore; Morselli, Lisa L; Balbo, Marcella L; Tasali, Esra; Leproult, Rachel; L'Hermite-Balériaux, Mireille; Van Cauter, Eve; Spiegel, Karine

2017-06-01

Severe sleep restriction results in elevated evening cortisol levels. We examined whether this relative hypercortisolism is associated with alterations in the pituitary-adrenocortical response to evening corticotropin-releasing hormone (CRH) stimulation. Eleven subjects participated in 2 sessions (2 nights of 10 hours vs. 4 hours in bed) in randomized order. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 09:00 to 24:00 for adrenocorticotropic hormone (ACTH) and cortisol measurements, and perceived stress was assessed hourly. Ovine CRH was injected at 18:00 (1 µg/kg body weight). Prior to CRH injection, baseline ACTH, but not cortisol, levels were elevated after sleep restriction. Relative to the well-rested condition, sleep restriction resulted in a 27% decrease in overall ACTH response to CRH (estimated by the incremental area under the curve from 18:00 to 24:00; p = .002) while the cortisol response was decreased by 21% (p = .083). Further, the magnitude of these decreases was correlated with the individual amount of sleep loss (ACTH: rSp = -0.65, p = .032; cortisol: rSp = -0.71, p = .015). The acute post-CRH increment of cortisol was reduced (p = .002) without changes in ACTH reactivity, suggesting decreased adrenal sensitivity. The rate of decline from peak post-injection levels was reduced for cortisol (p = .032), but not for ACTH. Scores of perceived stress were unaffected by CRH injection and were low and similar under both sleep conditions. Sleep restriction is associated with a reduction of the overall ACTH and cortisol responses to evening CRH stimulation, and a reduced reactivity and slower recovery of the cortisol response. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Gemcitabine-Based Chemotherapy in Adrenocortical Carcinoma: A Multicenter Study of Efficacy and Predictive Factors.

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Henning, Judith E K; Deutschbein, Timo; Altieri, Barbara; Steinhauer, Sonja; Kircher, Stefan; Sbiera, Silviu; Wild, Vanessa; Schlötelburg, Wiebke; Kroiss, Matthias; Perotti, Paola; Rosenwald, Andreas; Berruti, Alfredo; Fassnacht, Martin; Ronchi, Cristina L

2017-11-01

Adrenocortical carcinoma (ACC) is rare and confers an unfavorable prognosis in advanced stages. Other than combination chemotherapy with cisplatin, etoposide, doxorubicin, and mitotane, the second- and third-line regimens are not well-established. Gemcitabine (GEM)-based chemotherapy was suggested in a phase 2 clinical trial with 28 patients. In other solid tumors, human equilibrative nucleoside transporter type 1 (hENT1) and/or ribonucleotide reductase catalytic subunit M1 (RRM1) expression have been associated with resistance to GEM. To assess the efficacy of GEM-based chemotherapy in ACC in a real-world setting and the predictive role of molecular parameters. Retrospective multicenter study. Referral centers of university hospitals. A total of 145 patients with advanced ACC were treated with GEM-based chemotherapy (132 with concomitant capecitabine). Formalin-fixed paraffin-embedded tumor material was available for 70 patients for immunohistochemistry. The main outcome measures were progression-free survival (PFS) and an objective response to GEM-based chemotherapy. The secondary objective was the predictive role of hENT1 and RRM1. The median PFS for the patient population was 12 weeks (range, 1 to 94). A partial response or stable disease was achieved in 4.9% and 25.0% of cases, with a median duration of 26.8 weeks. Treatment was generally well tolerated, with adverse events of grade 3 or 4 occurring in 11.0% of cases. No substantial effect of hENT1 and/or RRM1 expression was observed in response to GEM-based chemotherapy. GEM-based chemotherapy is a well-tolerated, but modestly active, regimen against advanced ACC. No reliable molecular predictive factors could be identified. Owing to the scarce alternative therapeutic options, GEM-based chemotherapy remains an important option for salvage treatment for advanced ACC. Copyright © 2017 Endocrine Society

Vincristine, cisplatin, teniposide, and cyclophosphamide combination in the treatment of recurrent or metastatic adrenocortical cancer.

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Khan, Tanweera S; Sundin, Anders; Juhlin, Claes; Wilander, Erik; Oberg, Kjell; Eriksson, Barbro

2004-01-01

The efficacy and tolerability of a combination of vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) in 11 patients (median age, 45 yr) with recurrent and/or metastatic adrenocortical cancer (ACC) (seven functional and four nonfunctional) were evaluated. All patients received this regimen after the failure of streptozocin and o,p'-DDD (SO) combination therapy. The regimen comprised cyclophosphamide, 600 mg/m2, and vincristine, 1.5 mg/m2, maximum dose 2.0 mg (d 1); cisplatin, 100 mg/m2 (d 2) and teniposide, 150 mg/m2 (d 4). Cycles were repeated every 4 wk. One to eight cycles (median, six cycles) of OPEC were administered to each patient. The median duration of treatment was 6 mo. The overall 2-yr survival rate was 82% and the median survival since diagnosis was 44 mo while it was 21 mo since start of OPEC therapy. Responses were obtained in nine patients: partial response in two patients, and stable disease in seven patients. The median duration of response was 6.75 mo. A total of 60 cycles of chemotherapy were given to all patients; grade 1-2 toxicity occurred in 57 cycles, while grade 3 toxicity was observed only in two cycles, according to NCI's Common Toxicity Criteria. We conclude that the OPEC regimen may be considered in recurrent or metastatic ACC as a second-line medical treatment. However, the combination is accompanied by considerable side effects and dose modifications are necessary in order to be able to recommend the treatment. This regimen needs further evaluation compared with SO therapy preferably in a randomized multicenter trial.

The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity

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Ozgur Mete

2018-03-01

Full Text Available Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype–phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations (KCNJ5, ATP1A1, ATP2B3, and CACNA1D involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5-mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3, and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations (PRKACA, PRKAR1A, GNAS, PDE11A, and PDE8B involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism.

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Russo, Marco; Scollo, Claudia; Pellegriti, Gabriella; Cotta, Oana Ruxandra; Squatrito, Sebastiano; Frasca, Francesco; Cannavò, Salvatore; Gullo, Damiano

2016-04-01

Mitotane, a steroidogenesis inhibitor with adrenolytic properties used to treat adrenocortical cancer (ACC), can affect thyroid function. A reduction of FT4 levels with normal FT3 and TSH has been described in these patients. Using an in vitro murine model, the secretory capacity of thyrotrophic cells has been shown to be inhibited by mitotane. To investigate the pathogenesis of thyroid abnormalities in mitotane-treated patients with ACC. In five female patients with ACC (median age 47; range 31-65) treated with mitotane (dosage 1·5 g/day; 1·0-3·0), we analysed the pattern of TSH and thyroid function index (FT4, FT3 and FT3/FT4 ratio) compared to an age- and gender-matched control group. The in vivo secretory activity of the thyrotrophic cells was evaluated using a standard TRH test (200 μg), and the response was compared to both a group of age-matched female controls (n = 10) and central hypothyroid patients (n = 10). Basal TSH (median 1·54 mU/l; range 1·20-2·17) was normal and scattered around our median reference value, FT3 levels (median 3·80 pmol/l; 3·30-4·29) were normal but below the median reference value of 4·37 pmol/l and FT4 levels were below the normal range in all patients (median 8·40 pmol/l; 7·6-9·9). FT3/FT4 ratio was in the upper range in 4 patients and higher than normal in one patient. A blunted TSH response to TRH was observed in mitotane-treated patients. ΔTSH (absolute TSH response, peak TSH minus basal TSH) was 3·65 (range 3·53-5·26), 12·37 (range 7·55-19·97) and 1·32 mU/l (range 0·52-4·66) in mitotane-treated patients, controls and central hypothyroid patients, respectively. PRL secretion was normal. Mitotane-treated patients with ACC showed low FT4, normal FT3 and TSH and impaired TSH response to TRH, characteristic of central hypothyroidism. Furthermore, the elevated FT3/FT4 ratio of these subjects reflects an enhanced T4 to T3 conversion rate, a compensatory mechanism characteristic of thyroid function changes

The involvement of the hypothalamopituitary-adrenocortical axis in stress physiology and its significance in the assessment of animal welfare in cattle

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Emma J. Brown

2017-04-01

Full Text Available The intensification of cattle production has raised concern for animal welfare due to the stress that is associated with farming practices. The welfare of an animal is determined by the animal’s ability to cope with or adapt to its continuously changing environment and the biological cost that is associated with this adaptation and maintenance. Stressors arise from various psychological, physiological and physical aspects of farming practices due to management and human–cattle interactions. Measuring the activity of the hypothalamopituitary-adrenocortical (HPA axis with plasma cortisol levels is a useful method for determining the effects of stress on animals as it is stimulated at the onset of a perceived stress. The activation of the HPA axis affects various target tissues or systems and can result in suppression of the immune system, increased susceptibility to disease and adverse effects on reproductive success in prenatal and neonatal calves. Although some levels of stress associated with farming practices are unavoidable, improvements in farming methods need to be implemented in order to maintain or increase the efficiency of cattle production in a way that does not compromise the welfare of the animal.

Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

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Tonacchera, M; Vitti, P; Agretti, P; Ceccarini, G; Perri, A; Cavaliere, R; Mazzi, B; Naccarato, A G; Viacava, P; Miccoli, P; Pinchera, A; Chiovato, L

1999-11-01

The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

Naturally Occurring Adrenocortical Insufficiency--An Epidemiological Study Based on a Swedish-Insured Dog Population of 525,028 Dogs.

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Hanson, J M; Tengvall, K; Bonnett, B N; Hedhammar, Å

2016-01-01

Naturally occurring adrenocortical insufficiency (NOAI) in dogs is considered an uncommon disease with good prognosis with hormonal replacement treatment. However, there are no epidemiological studies with estimates for the general dog population. To investigate the epidemiological characteristics of NOAI in a large population of insured dogs. Data were derived from 525,028 client-owned dogs insured by a Swedish insurance company representing 2,364,652 dog-years at risk (DYAR) during the period between 1995-2006. Retrospective cohort study. Incidence rates, prevalences, and relative risks for dogs with NOAI (AI with no previous claim for hypercortisolism), were calculated for the whole dog population, and for subgroups divided by breed and sex. Mortality rates were calculated and compared in dogs with NOAI and the remaining dogs overall. In total 534 dogs were identified with NOAI. The overall incidence was 2.3 cases per 10,000 DYAR. The relative risk of disease was significantly higher in the Portuguese Water Dog, Standard Poodle, Bearded Collie, Cairn Terrier, and Cocker Spaniel compared with other breeds combined. Female dogs overall were at higher risk of developing AI than male dogs (RR 1.85; 95% CI, 1.55-2.22; P dogs with NOAI than in dogs overall. The data supports the existence of breed-specific differences in incidence rates of NOAI in dogs. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Effectiveness of 131I nor-cholesterol uptake per unit volume of adrenal adenoma in the diagnosis of aldosteronoma

International Nuclear Information System (INIS)

Kita, Tamotsu; Tomita, Hiroko; Sakaguchi, Chiharu

2010-01-01

Diagnosis of adrenal adenomas for patients with primary aldosteronism is sometimes difficult only by referring to the visualization pattern in adrenocortical scintigraphy without regards to standard scintigraphy or suppression scintigraphy with dexamethasone. We studied if quantitative evaluation of the standard scintigraphy without dexamethasone suppression can be useful to diagnose aldosteronomas. Twenty-nine patients who had undergone adrenalectomy with different clinical manifestations (16 patients with primary aldosteronism, 6 patients with Cushing's syndrome and 7 patients without hormonal abnormality) were included in the study. Volume of the adrenocortical adenomas, 131 I nor-cholesterol uptake of the adrenocortical adenomas, and 131 I nor-cholesterol uptake per unit volume of the adrenocortical adenomas were compared between the 3 groups. The volume of adrenocortical adenomas in the patients with primary aldosteronism was significantly lower than those in the other two groups (Cushing's syndrome p 131 I nor-cholesterol uptake of adrenocortical adenoma. The 131 I nor-cholesterol uptake per unit volume of adrenocortical adenomas was significantly higher in the patients with primary aldosteronism than those in the other two groups (Cushing's syndrome p 131 I nor-cholesterol uptake per unit volume of adenoma obtained from adrenocortical scintigraphy without dexamethasone suppression can be useful in the diagnosis of aldosteronoma. (author)

Adjuvant Radiation Therapy Improves Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma

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Sabolch, Aaron; Else, Tobias; Griffith, Kent A.; Ben-Josef, Edgar; Williams, Andrew; Miller, Barbra S.; Worden, Francis; Hammer, Gary D.; Jolly, Shruti

2015-01-01

Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. Methods and Materials: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. Results: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Conclusions: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed

High-Throughput Screening of Chemical Effects on Steroidogenesis Using H295R Human Adrenocortical Carcinoma Cells.

Science.gov (United States)

Karmaus, Agnes L; Toole, Colleen M; Filer, Dayne L; Lewis, Kenneth C; Martin, Matthew T

2016-04-01

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ≥ 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A distinct pattern was observed between imidazole and triazole fungicides suggesting potentially distinct mechanisms of action. From a chemical testing and prioritization perspective, this assay platform provides a robust model for high-throughput screening of chemicals for effects on steroidogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

Adjuvant Radiation Therapy Improves Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Sabolch, Aaron [Department of Radiation Oncology, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Else, Tobias [Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Griffith, Kent A. [Center for Cancer Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Mchigan (United States); Ben-Josef, Edgar [Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Williams, Andrew [University of Michigan Medical School, Ann Arbor, Mchigan (United States); Miller, Barbra S. [Division of Endocrine Surgery, Department of General Surgery, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Worden, Francis [Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Hammer, Gary D. [Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Jolly, Shruti, E-mail: shrutij@med.umich.edu [Department of Radiation Oncology, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States)

2015-06-01

Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. Methods and Materials: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. Results: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Conclusions: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.

Amplification of 9q34 in childhood adrenocortical tumors: a specific feature unrelated to ethnic origin or living conditions

Directory of Open Access Journals (Sweden)

Figueiredo B.C.

2000-01-01

Full Text Available Adrenocortical tumors (ACT in children under 15 years of age exhibit some clinical and biological features distinct from ACT in adults. Cell proliferation, hypertrophy and cell death in adrenal cortex during the last months of gestation and the immediate postnatal period seem to be critical for the origin of ACT in children. Studies with large numbers of patients with childhood ACT have indicated a median age at diagnosis of about 4 years. In our institution, the median age was 3 years and 5 months, while the median age for first signs and symptoms was 2 years and 5 months (N = 72. Using the comparative genomic hybridization technique, we have reported a high frequency of 9q34 amplification in adenomas and carcinomas. This finding has been confirmed more recently by investigators in England. The lower socioeconomic status, the distinctive ethnic groups and all the regional differences in Southern Brazil in relation to patients in England indicate that these differences are not important to determine 9q34 amplification. Candidate amplified genes mapped to this locus are currently being investigated and Southern blot results obtained so far have discarded amplification of the abl oncogene. Amplification of 9q34 has not been found to be related to tumor size, staging, or malignant histopathological features, nor does it seem to be responsible for the higher incidence of ACT observed in Southern Brazil, but could be related to an ACT from embryonic origin.

Activation in the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system in women with carpal tunnel syndrome.

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Fernández-de-Las-Peñas, César; Díaz-Rodríguez, Lourdes; Salom-Moreno, Jaime; Galiano-Castillo, Noelia; Valverde-Herreros, Lis; Martínez-Martín, Javier; Pareja, Juan A

2014-08-01

The aim of this study is to investigate the differences in salivary cortisol (hypothalamic-pituitary-adrenocortical [HPA] axis), α-amylase activity (sympathetic nervous system [SNS]), and immunoglobulin A (IgA; immune system) concentrations between women with carpal tunnel syndrome (CTS) and healthy women. A cross-sectional study. Activation of HPA, SNS, and immune system in CTS has not been clearly determined. One hundred two women (age: 45 ± 7 years) with electrodiagnostic and clinical diagnosis of CTS and 102 matched healthy women. The intensity of the pain was assessed with a Numerical Pain Rating Scale (0-10), and disability was determined with Boston Carpal Tunnel Questionnaire. Salivary cortisol concentration, α-amylase activity, salivary flow rate, and IgA concentration were collected from nonstimulated saliva. Women with CTS exhibited lower salivary flow rate (P  0.2) were found between groups as a total. Women with severe CTS exhibited lower salivary flow rate (P < 0.001), higher α-amylase activity (P = 0.002), and higher cortisol concentration (P = 0.03) than healthy women and than those with minimal/moderate CTS (P < 0.05). Within women with CTS, significant positive associations between α-amylase activity and the intensity of pain were found: the highest the level of pain, the higher the α-amylase activity, i.e., higher SNS activation. These results suggest that women with severe CTS exhibit changes in activation in the HPA axis and SNS but not in the humoral immune system. Activation of the SNS was associated with the intensity of pain. Future studies are needed to elucidate the direction of this relationship. Wiley Periodicals, Inc.

Association of mitotane with chylomicrons and serum lipoproteins: practical implications for treatment of adrenocortical carcinoma.

Science.gov (United States)

Kroiss, Matthias; Plonné, Dietmar; Kendl, Sabine; Schirmer, Diana; Ronchi, Cristina L; Schirbel, Andreas; Zink, Martina; Lapa, Constantin; Klinker, Hartwig; Fassnacht, Martin; Heinz, Werner; Sbiera, Silviu

2016-03-01

Oral mitotane (o,p'-DDD) is a cornerstone of medical treatment for adrenocortical carcinoma (ACC). Serum mitotane concentrations >14  mg/l are targeted for improved efficacy but not achieved in about half of patients. Here we aimed at a better understanding of intestinal absorption and lipoprotein association of mitotane and metabolites o,p'-dichlorodiphenylacetic acid (o,p'-DDA) and o,p'-dichlorodiphenyldichloroethane (o,p'-DDE). Lipoproteins were isolated by ultracentrifugation from the chyle of a 29-year-old patient and serum from additional 14 ACC patients treated with mitotane. HPLC was applied for quantification of mitotane and metabolites. We assessed NCI-H295 cell viability, cortisol production, and expression of endoplasmic reticulum (ER) stress marker genes to study the functional consequences of mitotane binding to lipoproteins. Chyle of the index patient contained 197  mg/ml mitotane, 53  mg/ml o,p'-DDA, and 51  mg/l o,p'-DDE. Of the total mitotane in serum, lipoprotein fractions contained 21.7±21.4% (VLDL), 1.9±0.8% (IDL), 8.9±5.5% (LDL1), 18.9±9.6% (LDL2), 10.1±4.0% (LDL3), and 26.3±13.0% (HDL2). Only 12.3±5.5% were in the lipoprotein-depleted fraction. Mitotane content of lipoproteins directly correlated with their triglyceride and cholesterol content. O,p'-DDE was similarly distributed, but 87.9±4.2% of o,p'-DDA found in the HDL2 and lipoprotein-depleted fractions. Binding of mitotane to human lipoproteins blunted its anti-proliferative and anti-hormonal effects on NCI-H295 cells and reduced ER stress marker gene expression. Mitotane absorption involves chylomicron binding. High concentrations of o,p'-DDA and o,p'-DDE in chyle suggest intestinal mitotane metabolism. In serum, the majority of mitotane is bound to lipoproteins. In vitro, lipoprotein binding inhibits activity of mitotane suggesting that lipoprotein-free mitotane is the therapeutically active fraction. © 2016 European Society of Endocrinology.

The effect of oxygen on aldosterone release from bovine adrenocortical cells in vitro: PO2 versus steroidogenesis.

Science.gov (United States)

Raff, H; Kohandarvish, S

1990-08-01

Hypoxia decreases plasma aldosterone in vivo without a decrease in PRA, angiotensin II (ANG II), ACTH, or cortisol. The present study evaluated whether this could be due to a direct, specific inhibitory effect on the zona glomerulosa related to the magnitude of the decrease in oxygen (O2). Bovine adrenocortical cells were dispersed with collagenase and studied in vitro within 48 h. Cells were stimulated for 2 h with ANG II (0.1-1000 nM) or (Bu)2cAMP (0.3-3 mM) under oxygen levels ranging from 0 to 100% O2 (PO2 from 66 +/- 4 to 561 +/- 46 torr) vs. a reference gas mixture (21% O2 PO2 approximately 140 torr). Exposure to 123 +/- 8, 110 +/- 12, 100 +/- 16, and 66 +/- 4 torr led to 27%, 30%, 40% and 70% inhibition, respectively, of 3 nM ANG II-stimulated aldosterone secretion as compared to 140 +/- 16 torr (reference). Exposure to hyperoxia (288 +/- 36 to 561 +/- 46 torr) led to a small (10%) increase in ANG II-stimulated aldosterone secretion which was not statistically significant. The P50 (half-maximal PO2) for aldosteronogenesis was approximately 95 torr. The results for other doses of ANG II and for cAMP were similar. The inhibitory effect of low O2 was reversed by returning the cells to reference conditions (140 +/- 16 torr). Cortisol secretion was not significantly affected by changes in oxygen tension. We conclude that small changes in O2 within the physiological range directly and specifically inhibit aldosteronogenesis in a dose-dependent manner with a P50 of approximately 95 torr. Inhibition of cAMP-stimulated aldosterone secretion suggests a postreceptor site of action. This direct, reversible, and specific effect on the zona glomerulosa of the adrenal cortex may account for the dissociation of renin and aldosterone during hypoxia in vivo.

Ambulatory Care Data Base (ACDB) Data Dictionary Sequential Files of Phase 1

Science.gov (United States)

1989-11-01

BRONCHODILATOR DEP 49397 ASTHMA, STERIOD DEP 49398 ASTHMA, EXERCISE INDUCED 49399 ASTHMA, OCCUPATIONAL 4914 BRONCHIECTASIS 495 ALVEOLITIS, ALLERGIC...ACROMEGALY 25300 ACROMEGALY & GIGANTISM 2531 PITUITARY HYPERFUNCTION, ANTERIOR, OTH & UNSP 25311 RYPERPROLACTINEMIA ANT PIT HYPERFUNCT 25312 AMENORRHEA ...UNSPEC 32792 DELERIUM, SUBS UNSPEC 32793 DEMENTIA, DRUG INDUCED , SUBS UNSPEC 32794 AMNESTIC DISORDER, DRUG INDUCED , SUBS, UNSPEC 32795 DELUSIONAL

Ambulatory Care Data Base (ACDB) Data Dictionary Sequential Files of Phase 2.

Science.gov (United States)

1992-04-01

ASTHMA, BRONCHODILATOR DEP 49397 ASTHMA, STERIOD DEP 49398 ASTHMA, EXERCISE INDUCED 49399 ASTHMA, OCCUPATIONAL 494 BRONCHI ECTAS IS 495 ALVEOLITIS...ACROMEGALY 25300 ACROMEGALY & GIGANTISM 2531 PITUITARY HYPERFUNCTION, ANTERIOR, OTH & UNSP 25311 HYPERPROLACTINEMIA ANT PIT HYPERFUNCT 25312 AMENORRHEA ...DISORDER 32790 INTOXICATION, SUBS, UNSPEC 32791 WITHDRAWAL, SUBS, UNSPEC 32792 DELERIUM, SUBS UNSPEC 32793 DEMENTIA, DRUG INDUCED , SUBS UNSPEC 32794

Adrenocortical and adrenomedullary homologs in eight species of adult and developing teleosts: morphology, histology, and immunohistochemistry.

Science.gov (United States)

Grassi Milano, E; Basari, F; Chimenti, C

1997-12-01

Morphology, histology, and immunohistochemistry of the adrenocortical and adrenomedullary homologs (adrenal glands) of the following developing and adult teleosts were examined: Salmoniformes-Oncorhynchus mykiss (rainbow trout), Salmo trutta fario (brown trout), Coregonus lavaretus (white fish); Cyprinodontiformes-Gambusia affinis (mosquito fish). Perciformes-Dicentrarchus labrax (sea bass), Sparus aurata (sea bream), Diplodus sargus (white bream), Oblada melanura (saddled bream). The anatomical relationships of the gland with the renal system and venous vessels were also noted. In adults of all species steroidogenic and catecholaminergic chromaffin cells were found in the head kidney, which is pronephric in origin and subsequently transformed into a hematopoietic lymphatic organ. In Perciformes, chromaffin cells are distributed around the anterior and posterior cardinal veins and ducts of Cuvier; in Salmoniformes, around the posterior cardinal veins and in the hematopoietic tissue; and in G. affinis, around the ducts of Cuvier and posterior cardinal veins, while a few are visible also around the sinus venosus. In Perciformes and Salmoniformes, numerous chromaffin cells are also present in the posterior kidney, derived from the opisthonephros, in contact with the caudal vein. Steroidogenic cells are always confined to the head kidney. During development chromaffin and steroidogenic cells appear early after hatching in the pronephric kidney, at the level of the ducts of Cuvier and of the cephalic part of the posterior cardinal veins. Later, chromaffin cells in Perciformes reach the anterior cardinal veins, and subsequently, in both Perciformes and Salmoniformes, they reach the developing posterior kidney. Their localization along the posterior kidney is still in progress about 4 months after hatching and is completed about a year after hatching. These findings support the concept that the structure of the adrenal gland in teleosts is intermediate between that of the

Hiperfonksiyon gösteren intratiroidal paratiroid adenomu : olgu sunumu

OpenAIRE

MD, Süleyman Büyükberber; MD, Ertuğrul Ertaş; MD, Ertan Bülbüloğlu; MD, Orhan Şencan; MD, Kamran Mahmutyazıcıoğlu; MD, Süleyman Özen; MD, N. Engin Aydın

2015-01-01

As the incidence of thyroid nodules are high in patients with hyperparathyroidism, diagnosis and treatment of intrathyroidal parathyroidal adenomas are difficult. A case of intrathyroidal hyperfunctioning parathyroid adenoma is reported and the diagnosis and treatment of intrathyroidal hyperfunctioning parathyroid adenomas are discussed. [Journal of Turgut Özal Medical Center 1996;3(2):110-112] Key words: Intrathyroidal parathyroidal adenoma, primer hyperparathyroidism

Expression of G(alpha)(s) proteins and TSH receptor signalling in hyperfunctioning thyroid nodules with TSH receptor mutations.

Science.gov (United States)

Holzapfel, Hans-Peter; Bergner, Beate; Wonerow, Peter; Paschke, Ralf

2002-07-01

Constitutively activating mutations of the thyrotrophin receptor (TSHR) are the main molecular cause of hyperfunctioning thyroid nodules (HTNs). The G protein coupling is an important and critical step in the TSHR signalling which mainly includes G(alpha)(s), G(alpha)(i) and G(alpha)(q)/11 proteins. We investigated the in vitro consequences of overexpressing G(alpha) proteins on signalling of the wild-type (WT) or mutated TSHR. Moreover, we investigated whether changes in G(alpha) protein expression are pathophysiologically relevant in HTNs or cold thyroid nodules (CTNs). Wild-type TSH receptor and mutated TSH receptors were coexpressed with G(alpha)(s), G(alpha)(i) or G(alpha)(q)/11, and cAMP and inositol phosphate (IP) production was measured after stimulation with TSH. The expression of G(alpha)(s), G(alpha)(i) and G(alpha)(q)/11 proteins was examined by Western blotting in 28 HTNs and 14 CTNs. Coexpression of G(alpha)(s) with the WT TSH receptor in COS 7 cells significantly increased the basal and TSH-stimulated cAMP accumulation while coexpression of the G(alpha)(q) or G(alpha)11 protein significantly increased the production of cAMP and inositol triphosphate (IP(3)). The coexpression of the TSH receptor mutants (I486F, DEL613-621), known to couple constitutively to G(alpha)(s) and G(alpha)(q) with G(alpha)(s) and G(alpha)(q)/11, significantly increased the basal and stimulated cAMP and IP(3) accumulation. Coexpression of the TSH receptor mutant V556F with G(alpha)(s) only increased the basal and stimulated cAMP production while its coexpression with G(alpha)(q)/11 increased the basal and stimulated IP(3) signalling. The expression of G(alpha)(s) protein subunits determined by Western blotting was significantly decreased in 14 HTNs with a constitutively activating TSH receptor mutation in comparison with the corresponding surrounding tissue, while in 14 HTNs without TSH receptor or G(alpha)(s) protein mutation and in 14 CTNs the expression of G

No effect of pinealectomy on the parallel shift in circadain rhythms of adrenocortical activity and food intake in blinded rats.

Science.gov (United States)

Takahashi, K; Inoue, K; Takahashi, Y

1976-10-01

Twenty-four-hr patterns of plasma corticosterone levels were determined at 4-hr intervals every 3-4 weeks in sighted and blinded pinealectomized rats of adult age. Through the whole period of the experiment, 24-hr patterns of food intake were also measured weekly. The sighted rats manifested the same 24-hr patterns of plasma corticosterone levels and food intake for 15 weeks after pinealectomy as those observed in the intact control rats. The magnitude of peak levels of plasma corticosterone and the amount of food intake did not differ between the two groups. A phase shift in circadian rhythms of plasma corticosterone levels and food intake was observed in both groups of blinded rats, with and without pinealectomy. Between the two groups, the patterns of phase shift were essentially similar for 10 weeks examined after optic enucleation. The peak elevation of plasma levels took place at 11 p.m. at the end of the 4th week after optic enucleation. Thereafter, 4- to 8-hr delay of peak appearance was observed every 3 weeks. No significant differences were found in peak values between the two groups of blinded rats. Furthermore, the circadian rhythm of food intake shifted in parallel with that of plasma corticosterone levels. A phase reversal of these two activities was observed between the 8th and 10th week after the operation. These results indicate that the pineal gland does not play any important role either in the maintenance of normal circadian periodicities of adrenocortical activity and food intake or in the shift in circadian rhythms of the two activities in the blinded rats.

Use of Radiofrequency Ablation in Benign Thyroid Nodules: A Literature Review and Updates

OpenAIRE

Wong, KP; Lang, HHB

2013-01-01

Successful thermal ablation using radiofrequency has been reported in various tumors including liver or kidney tumors. Nonsurgical minimally invasive ablative therapy such as radiofrequency ablation (RFA) has been reported to be a safe and efficient treatment option in managing symptomatic cold thyroid nodules or hyperfunctioning thyroid nodules. Pressure and cosmetic symptoms have been shown to be significantly improved both in the short and long terms after RFA. For hyperfunctioning thyroid...

The natural history of thyroid autonomy and hot nodules.

Science.gov (United States)

Corvilain, B

2003-02-01

Solitary hyperfunctioning thyroid adenomas are benign monoclonal tumors characterized by their capacity to grow and produce thyroxine (T4) and triiodothyronine (T3) autonomously, i.e. in the absence of thyrotropin (TSH). Mutations of the TSH receptor (TSH-R) have been found in the majority of solitary hyperfunctioning thyroid adenomas. On radioisotope scanning they generally appear as hot nodules because they concentrate radioiodide or 99mTc pertechnate, whereas the normal surrounding and contralateral tissue concentrate little isotopes. A toxic adenoma probably evolves gradually from a small autonomously hyperfunctioning adenoma that initially is only slightly more active than the extranodular tissue. This has been referred to as a "warm" nodule or a "compensated" adenoma. The diagnostic criterion for this designation is the persistence of detectable serum TSH maintaining some radioiodine uptake by the extranodular tissue. This "compensated" adenoma persists as long as the autonomous hormone output is not sufficient to suppress thyrotropin, i.e. to cause hyperthyroidism. The rate of development of thyrotoxicosis in patients with hyperfunctioning adenomas who are euthyroid initially is about 4% per year and depends on the size of the adenoma, iodine intake and age of the patient. No clear relationship can be establish between the nature of the TSH receptor mutations and the phenotype of the tumor.

Impact of {sup 18}F-FDG PET/CT on the management of adrenocortical carcinoma: analysis of 106 patients

Energy Technology Data Exchange (ETDEWEB)

Takeuchi, Satoshi; Macapinlac, Homer A.; Chuang, Hubert H. [The University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Balachandran, Aparna [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Habra, Mouhammed Amir [The University of Texas MD Anderson Cancer Center, Department of Endocrine Neoplasia and Hormonal Disorders, Houston, TX (United States); Phan, Alexandria T. [The University of Texas MD Anderson Cancer Center, Department of Gastrointestinal Medical Oncology, Houston, TX (United States); Bassett, Roland L. [The University of Texas MD Anderson Cancer Center, Department of Biostatistics, Houston, TX (United States)

2014-11-15

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Limited data are available about on value of {sup 18}F-FDG PET/CT in ACC. We evaluated the impact of PET/CT on the management of ACC. We performed a retrospective review in patients with ACC who had undergone PET/CT. The impact of PET/CT on the management plan was evaluated by comparing the findings on PET/CT to the findings on contrast-enhanced CT. The sensitivity, specificity, and accuracy of each form of imaging were calculated. The correlations between PET/CT parameters, including maximum standardized uptake value (SUV{sub max}), total lesion glycolysis, and decline in SUV{sub max} after chemotherapy, and clinical outcome were evaluated. Included in the analysis were 106 patients with 180 PET/CT scans. Of the 106 patients, 7 underwent PET/CT only for initial staging, 84 underwent PET/CT only for restaging, and 15 underwent PET/CT for both initial staging and restaging. PET/CT changed the management plan in 1 of 22 patients (5 %) at initial staging and 9 of 99 patients (9 %) at restaging. In 5 of the patients in whom PET/CT changed the management plan, PET/CT showed response to chemotherapy but contrast-enhanced CT showed stable disease. Sensitivity, specificity, and accuracy were 100 %, 100 %, and 100 % for PET/CT at initial staging; 92.6 %, 100 %, and 96.4 % for CT at initial staging; 98.4 %, 100 %, and 99.5 % for PET/CT at restaging; and 96.8 %, 98.6 %, and 98.0 % for CT at restaging, respectively. No PET/CT parameters were associated with survival at either initial diagnosis or recurrence. PET/CT findings could substantially change the management plan in a small proportion of patients with ACC. Although lesion detection was similar between PET/CT and CT, PET/CT may be preferred for chemotherapeutic response assessment because it may predict response before anatomic changes are detected on CT. (orig.)

Functional morphology of pituitary -thyroid and -adrenocortical axes in middle-aged male rats treated with Vitex agnus castus essential oil.

Science.gov (United States)

Šošić-Jurjević, Branka; Ajdžanović, Vladimir; Filipović, Branko; Trifunović, Svetlana; Jarić, Ivana; Ristić, Nataša; Milošević, Verica

2016-09-01

We previously reported that Vitex agnus-castus L. essential oil (VACEO), when administered to middle-aged males, exerts a bone-protective effect, induces silencing of locomotor activities and decreases pituitary prolactin immunopositivity. To further assess the putative endocrine effects of VACEO, we examined the pituitary-thyroid and -adrenocortical axes in our model. Sixteen-month-old Wistar rats were subcutaneously administered 60mg/kg of VACEO dissolved in sterile olive oil, while the control group received the same amount of vehicle alone for three weeks. Pituitaries, thyroids and adrenals were analyzed by qualitative and quantitative histological approaches. Concentration of thyroid stimulating hormone (TSH), total thyroxine and triiodothyronine (TH), adrenocorticotrophic hormone (ACTH), corticosterone in serum and in adrenal tissue were measured. In VACEO-treated rats, the relative volume density of pituitary thyrotrophs increased (p<0.001), while intensity of cytoplasmic TSHβ immunostaining decreased (p<0.001), consistent with elevated TSH in serum (p<0.01). The thyroid tissue was characterized by a micro-follicular structure, increased relative volume of follicular epithelium (p<0.05), decreased volume of luminal colloid (p<0.001) and increased basolateral expression of sodium-iodide symporter-immunopositivity (p<0.05). Serum TH also increased (p<0.01). The relative volume density of pituitary corticotrophs decreased (p<0.05), compatible with decline in circulating ACTH (p<0.05). Neither tissue nor serum corticosterone levels were affected by VACEO treatment. In conclusion, the observed changes in TSH and ACTH strongly indicate central endocrine effects of prolonged VACEO treatment. In this respect, production of ACTH decreased without impact on corticosterone production. Increase in serum concentration of both TH and TSH are not compatible with a negative feedback loop and suggest a major change in set-point regulation of the hypothalamic

The stress of being contaminated? Adrenocortical function and reproduction in relation to persistent organic pollutants in female black legged kittiwakes.

Science.gov (United States)

Tartu, Sabrina; Angelier, Frédéric; Herzke, Dorte; Moe, Børge; Bech, Claus; Gabrielsen, Geir W; Bustnes, Jan Ove; Chastel, Olivier

2014-04-01

High levels of environmental pollutants such as persistent organic pollutants (POPs) including PCB and DDT have been found in the Arctic and many of those pollutants may impair reproduction through endocrine disruption. Nevertheless, their effects on stress hormones remain poorly understood, especially in free-ranging birds. Corticosterone, the principal glucocorticoid in birds, can indirectly impair reproduction. The aim of the present study was to examine the relationships between POPs and reproduction through their potential consequences on different reproductive traits (breeding decision, egg-laying date, breeding success) and corticosterone secretion (baseline and stress-induced levels). We addressed those questions in an Arctic population of female black-legged kittiwakes during the pre-breeding stage and measured several legacy POPs (PCBs and pesticides: HCB, p,p'-DDE, CHL) in whole blood. POP levels were not related to breeding decision neither to breeding success, whereas females with high levels of pesticides laid their eggs earlier in the season. We found a negative relationship between POP levels and body condition index in non-breeding females. Black-legged kittiwakes with higher levels of PCB showed stronger adrenocortical response when subjected to a capture-handling stress protocol. We suggest that PCBs may disrupt corticosterone secretion whereas the positive relationship between pesticides and egg-laying date could either originate from a direct effect of pesticides or may be related to other confounding factors such as age or individual's quality. Although no direct negative reproduction output of POPs was found in this study, it is possible that the most contaminated individuals would be more sensitive to environmental stress and would be less able to maintain parental investment than less polluted individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

Non-invasive monitoring of adrenocortical activity in captive African Penguin (Spheniscus demersus) by measuring faecal glucocorticoid metabolites.

Science.gov (United States)

Ozella, L; Anfossi, L; Di Nardo, F; Pessani, D

2015-12-01

Measurement of faecal glucocorticoid metabolites (FGMs) has become a useful and widely-accepted method for the non-invasive evaluation of stress in vertebrates. In this study we assessed the adrenocortical activity of five captive African Penguins (Spheniscus demersus) by means of FGM evaluation following a biological stressor, i.e. capture and immobilization. In addition, we detected individual differences in secretion of FGMs during a stage of the normal biological cycle of penguins, namely the breeding period, without any external or induced causes of stress. Our results showed that FGM concentrations peaked 5.5-8h after the induced stress in all birds, and significantly decreased within 30 h. As predictable, the highest peak of FGMs (6591 ng/g) was reached by the youngest penguin, which was at its first experience with the stressor. This peak was 1.8-2.7-fold higher compared to those of the other animals habituated to the stimulus. For the breeding period, our results revealed that the increase in FGMs compared to ordinary levels, and the peaks of FGMs, varied widely depending on the age and mainly on the reproductive state of the animal. The bird which showed the lowest peak (2518 ng/g) was an old male that was not in a reproductive state at the time of the study. Higher FGM increases and peaks were reached by the two birds which were brooding (male: 5552%, 96,631 ng/g; female: 1438%, 22,846 ng/g) and by the youngest bird (1582%, 39,700 ng/g). The impact of the reproductive state on FGM levels was unexpected compared to that produced by the induced stress. The EIA used in this study to measure FGM levels proved to be a reliable tool for assessing individual and biologically-relevant changes in FGM concentrations in African Penguin. Moreover, this method allowed detection of physiological stress during the breeding period, and identification of individual differences in relation to the reproductive status. The increase in FGM levels as a response to capture and

Correlation of the secretion of insulin and C-peptide in cancer patients

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Modnikov, O P; Lomtev, N G [Kirgizskij Nauchno-Issledovatel' skij Inst. Onkologii i Radiologii, Frunze (USSR)

1983-08-01

Insulin and C-peptide levels were studied with a radioimmunoassay in the peripheral blood serum of 44 patients with gastric and cervical cancer and 22 healthy persons. Hyperfunction of the pancreatic insular apparatus was shown in cancer patients which was expressed in a statistically significant increase in the C-peptide level. In gastric cancer patients hyperfunction of the insular apparatus was accompanied by hypoinsulinemia, and in cervical cancer patients by hormoinsulinemia. An analysis has shown that the ratio insulin/C-peptide in gastric and cervical cancer patients was about the same and significantly lower than the control. A conclusion has been made that in spite of difference in the initial insulin concentration, the same phenomenon - acceleration of the metabolic clearance of insulin - occurs in patients with cancer of the above sites. The C-peptide level decreased, the ratio insulin/C-peptide increased, i.e. hyperfunction of the insular apparatus disappeared and the metabolic clearance of insulin slowed down.

Correlation of the sectetion of insulin and C-peptide in cancer patients

International Nuclear Information System (INIS)

Modnikov, O.P.; Lomtev, N.G.

1983-01-01

Insulin and C-peptide levels were studied with a radioimmunoassay in the peripheral blood serum of 44 patients with gastric and cervical cancer and 22 healthy persons. Hyperfunction of the pancreatic insular apparatus was shown in cancer patients which was expressed in a statistically significant increase in the C-peptide level. In gastric cancer patients hyperfunction of the insular apparatus was accompanied by hypoinsulinemia, and in cervical cancer patients by hormoinsulinemia. An analysis has shown that the ratio insulin/C-peptide in gastric and cervical cancer patients was about the same and significantly lower than the control. A conclusion has been made that in spite of difference in the initial insulin concentration, the same phenomenon - acceleration of the metabolic clearance of insulin - occurs in patients with cancer of the above sites. The C-peptide level decreased, the ratio insulin/C-peptide increased, i.e. hyperfunction of the insular apparatus disappeared and the metabolic clearance of insulin slowed down

Activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis at midgestation by estrogen-induced changes in placental corticosteroid metabolism

International Nuclear Information System (INIS)

Pepe, G.J.; Waddell, B.J.; Albrecht, E.D.

1990-01-01

We have hypothesized that the change in placental cortisol (F)-cortisone (E) metabolism induced by estrogen late in gestation is important to activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis, culminating in the ontogenesis of de novo F secretion by the fetal adrenal. The present study tested this hypothesis in vivo by comparing the proportion of F in the fetus derived via maternal and fetal production on day 100 (n = 7; term = day 184) and day 165 (n = 4) in untreated baboons and on day 100 in baboons (n = 9) in which 50-mg pellets of androstenedione were implanted sc in the mother in increasing numbers (i.e. two on day 70, four on day 78, six on day 86, and eight on day 94) to increase placental estrogen production. Maternal, uterine, and umbilical venous samples were collected during constant maternal infusion (120 min) of [3H]F/[14C]E, endogenous and radiolabeled F/E content was determined, and corticosteroid dynamics were quantified. The MCR and peripheral interconversion of F and E as well as the production rate of F were unaltered in the mother. However, at midgestation, androstenedione increased (P less than 0.05) estrogen by 62% and altered transuterofeto placental F-E metabolism from preferential reduction of E to preferential oxidation of F, a pattern similar to that at term. In untreated baboons, on day 100 none of the F in the fetus was due to fetal production, whereas by day 165, 49 +/- 6% was of fetal origin. In animals treated with androstenedione at midgestation, 22 +/- 4% of fetal F was derived de novo within the fetus. Thus, production of F by the fetus was negligible on day 100, increased near term in association with an increase in transplacental oxidation of F to E, and was induced at midgestation in baboons in which placental F-E metabolism was altered by an increase in estrogen production

Plasma Steroid Metabolome Profiling for Diagnosis and Subtyping Patients with Cushing Syndrome.

Science.gov (United States)

Eisenhofer, Graeme; Masjkur, Jimmy; Peitzsch, Mirko; Di Dalmazi, Guido; Bidlingmaier, Martin; Grüber, Matthias; Fazel, Julia; Osswald, Andrea; Beuschlein, Felix; Reincke, Martin

2018-03-01

Diagnosis of Cushing syndrome requires a multistep process that includes verification of hypercortisolism followed by identification of the cause of adrenocortical hyperfunction. This study assessed whether pituitary, ectopic, and adrenal subtypes of Cushing syndrome were characterized by distinct plasma steroid profiles that might assist diagnosis. In this retrospective cross-sectional study, mass spectrometric measurements of a panel of 15 plasma steroids were applied to 222 patient samples tested for Cushing syndrome. Disease was excluded in 138 and confirmed in 51 patients with pituitary Cushing syndrome, 12 with ectopic adrenocorticotropin secretion, and 21 with adrenal disease. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for comparison. Compared with patients without disease, the largest increases in plasma steroids among patients with Cushing syndrome were observed for 11-deoxycortisol (289%), 21-deoxycortisol (150%), 11-deoxycorticosterone (133%), corticosterone (124%), and cortisol (122%). Patients with ectopic disease showed the most prominent increases, but there was considerable variation for other steroids according to subtype. Patients with adrenal disease had the lowest concentrations of androgens, whereas those with ectopic and pituitary disease showed the lowest concentrations of aldosterone. Plasma 18-oxocortisol was particularly low in ectopic disease. With the use of 10 selected steroids, subjects with and without different Cushing syndrome subtypes could be discriminated nearly as closely as with the use of salivary and urinary free cortisol, dexamethasone-suppressed cortisol, and plasma adrenocorticotropin (9.5% vs 5.8% misclassification). Patients with different subtypes of Cushing syndrome show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes. © 2017 American Association for Clinical Chemistry.

Hormones in Infection. Chapter 8. Alterations in Hormone Production and Utilization during Infection,

Science.gov (United States)

1980-08-28

and ascorbic acid (Beisel and Rapoport, 1969). On the other hand, infectious illnesses can lead to acute or chronic adrenocortical insufficiency...appear hypertrophic. The likelihood of increased functional activity is reinforced by an accompanying depletion of adrenocortical cholesterol , total lipids... acid (VMA) values have sometimes been substituted as an indirect method for evaluating catecholamine metabolite output. As an example, Gruchow (1979

A parathyroid scintigraphy case study

International Nuclear Information System (INIS)

O'Leary, Desiree

2005-01-01

Background: There has been much debate concerning the most suitable protocol for parathyroid scintigraphy; the merits of various radiopharmaceuticals versus the correct imaging protocol to visualise both ectopic and anatomically placed adenomas against the various equipment choices have been debated. Aim: To demonstrate, through the use of a case study, the necessity of changing imaging protocols for parathyroid scintigraphy where a definitive imaging diagnosis is absent in the face of strong clinical suspicion. Method: Use is made of Tc99mMIBI, full field chest scintigraphy, a clearly defined imaging protocol and SPECT imaging to locate ectopic parathyroid tissue in a female patient with significant symptoms of parathyroid hyperfunction. Results: A single hyperfunctioning adenoma is located in the pre-carinal area of the mediastinum. Using a radioguided surgical technique the hyperfunctioning tissue is excised and confirmed by histopathology. Conclusion: Whilst a dramatic reduction in patient symptoms was not seen immediately in this patient, the symptoms of the illness have been subsiding since January 2003. This case study demonstrates the necessity of changing imaging protocols for parathyroid scintigraphy where a definitive imaging diagnosis is absent in the face of strong clinical suspicion

CYP2W1 is highly expressed in adrenal glands and is positively associated with the response to mitotane in adrenocortical carcinoma.

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Cristina L Ronchi

Full Text Available Adrenocortical tumors comprise frequent adenomas (ACA and rare carcinomas (ACC. Human cytochrome P450 2W1 (CYP2W1 is highly expressed in some cancers holding the potential to activate certain drugs into tumor cytotoxins.To investigate the CYP2W1 expression in adrenal samples and its relationship with clinical outcome in ACC.CYP2W1 expression was investigated by qRT-PCR in 13 normal adrenal glands, 32 ACA, 25 ACC, and 9 different non-adrenal normal tissue samples and by immunohistochemistry in 352 specimens (23 normal adrenal glands, 33 ACA, 239 ACC, 67 non-adrenal normal or neoplastic samples.CYP2W1 mRNA expression was absent/low in normal non-adrenal tissues, but high in normal and neoplastic adrenal glands (all P<0.01 vs non-adrenal normal tissues. Accordingly, CYP2W1 immunoreactivity was absent/low (H-score 0-1 in 72% of non-adrenal normal tissues, but high (H-score 2-3 in 44% of non-adrenal cancers, in 65% of normal adrenal glands, in 62% of ACAs and in 50% of ACCs (all P<0.001 vs non-adrenal normal tissues, being significantly increased in steroid-secreting compared to non-secreting tumors. In ACC patients treated with mitotane only, high CYP2W1 immunoreactivity adjusted for ENSAT stage was associated with longer overall survival and time to progression (P<0.05 and P<0.01, respectively, and with a better response to therapy both as palliative (response/stable disease in 42% vs 6%, P<0.01 or adjuvant option (absence of disease recurrence in 69% vs 45%, P<0.01.CYP2W1 is highly expressed in both normal and neoplastic adrenal glands making it a promising tool for targeted therapy in ACC. Furthermore, CYP2W1 may represent a new predictive marker for the response to mitotane treatment.

Cytosolic cholesterol ester hydrolase in adrenal cortex

OpenAIRE

Tocher, Douglas R.

1983-01-01

Cholesterol ester hydrolase (CEH) in adrenocortical cytosol was known to be phosphorylated and activated, in response to ACTH in a cAMPdependent protein kinase mediated process. The purification of CEH from bovine adrenocortical cytosol was attempted. The use of detergents to solubilise the enzyme from lipid-rich aggregates was investigated and sodium cholate was found to be effective. A purification procedure using cholate solubilised enzyme was developed. The detergent int...

Safety and clinical effect of i.v. infusion of cyclopropyl-methoxycarbonyl etomidate (ABP-700), a soft analogue of etomidate, in healthy subjects.

Science.gov (United States)

Valk, B I; Absalom, A R; Meyer, P; Meier, S; den Daas, I; van Amsterdam, K; Campagna, J A; Sweeney, S P; Struys, M M R F

2018-06-01

Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers. Five cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 μg kg -1  min -1 or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring. No serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift. Infusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern. NTR4735. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Mobile voice health monitoring using a wearable accelerometer sensor and a smartphone platform.

Science.gov (United States)

Mehta, Daryush D; Zañartu, Matías; Feng, Shengran W; Cheyne, Harold A; Hillman, Robert E

2012-11-01

Many common voice disorders are chronic or recurring conditions that are likely to result from faulty and/or abusive patterns of vocal behavior, referred to generically as vocal hyperfunction. An ongoing goal in clinical voice assessment is the development and use of noninvasively derived measures to quantify and track the daily status of vocal hyperfunction so that the diagnosis and treatment of such behaviorally based voice disorders can be improved. This paper reports on the development of a new, versatile, and cost-effective clinical tool for mobile voice monitoring that acquires the high-bandwidth signal from an accelerometer sensor placed on the neck skin above the collarbone. Using a smartphone as the data acquisition platform, the prototype device provides a user-friendly interface for voice use monitoring, daily sensor calibration, and periodic alert capabilities. Pilot data are reported from three vocally normal speakers and three subjects with voice disorders to demonstrate the potential of the device to yield standard measures of fundamental frequency and sound pressure level and model-based glottal airflow properties. The smartphone-based platform enables future clinical studies for the identification of the best set of measures for differentiating between normal and hyperfunctional patterns of voice use.

Mixture Effects of 3 Mechanistically Different Steroidogenic Disruptors (Prochloraz, Genistein, and Ketoconazole) in the H295R Cell Assay

DEFF Research Database (Denmark)

Nielsen, Frederik Knud; Hansen, Cecilie Hurup; Fey, Jennifer Anna

2015-01-01

Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β-estradiol......Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β...

Limitations of intraoperative adrenal remnant volume measurement in patients undergoing subtotal adrenalectomy.

Science.gov (United States)

Brauckhoff, Michael; Stock, Karsten; Stock, Susanne; Lorenz, Kerstin; Sekulla, Carsten; Brauckhoff, Katrin; Thanh, Phuong Nguyen; Gimm, Oliver; Spielmann, Rolf Peter; Dralle, Henning

2008-05-01

Recent studies have shown that a minimum of approximately one-third of one normal adrenal gland is required for sufficient adrenocortical stress capacity. Correlation between intraoperative measurement, determination of remnant size by computed tomography (CT), and adrenocortical stress capacity has not been examined so far. Twenty-two patients with familial pheochromocytoma (n=13), sporadic pheochromocytoma (n=3), and adrenocortical tumors (n=6) who underwent unilateral or bilateral subtotal adrenalectomy (STAE, 28 adrenal remnants) were prospectively studied. Patients were examined in a multi-slice CT to determine residual adrenal tissue and by ACTH test 4 days and 3 months postoperatively. There was a slight significant correlation between intraoperative and CT calculated volumes (r=0.77; pSTAE has limitations. CT gives larger volumes compared with intraoperative determination. For calculation of a volume-function correlation of residual adrenal tissue, in clinical practice, the determination of relative adrenal residual volume is acceptable.

Cushing's syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice.

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Isabelle Sahut-Barnola

2010-06-01

Full Text Available Carney complex (CNC is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD, a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 alpha-regulatory subunit (R1alpha of the cAMP-dependent protein kinase (PKA have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1alpha loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO. AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1alpha loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1alpha is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD.

Diagnosis and clinical genetics of Cushing syndrome in pediatrics

Science.gov (United States)

Stratakis, Constantine A.

2016-01-01

SYNOPSIS Endogenous Cushing syndrome (CS) in pediatrics is rare; it may be caused by tumors that produce corticotropin (ACTH) in the pituitary gland (this form of CS is called Cushing disease) or elsewhere (ectopic CS), tumors that produce corticotropin-releasing hormone (CRH) anywhere (mostly neuroendocrine tissues), and finally adrenocortical masses that produce cortisol, such as adrenocortical cancer (ACC) or adenomas, and bilateral adrenocortical hypeprlasia (BAHs). ACC is a very rare cause of CS in children but should be excluded first, especially among younger patients. CS in children is often caused by germline or somatic mutations in an expanding list of genes with implications for the prognosis of the patients and for their families. CS should be early recognized in children; otherwise, it can lead to significant morbidity and mortality. All patients with suspected CS should be referred to specialized clinical centers for work-up; these centers should have access to experienced endocrine and neurological surgeons. PMID:27241967

Incidental uptake of 18F-fluorocholine (FCH) in the head or in the neck of patients with prostate cancer

International Nuclear Information System (INIS)

Hodolic, Marina; Huchet, Virginie; Balogova, Sona; Michaud, Laure; Kerrou, Khaldoun; Nataf, Valérie; Cimitan, Marino; Fettich, Jure; Talbot, Jean-Noël

2014-01-01

Positron emission tomography-computed tomography (PET/CT) with 18 F-fluorocholine (FCH) is routinely performed in patients with prostate cancer. In this clinical context, foci of FCH uptake in the head or in the neck were considered as incidentalomas, except for those suggestive of multiple bone metastases. In 8 patients the incidental focus corresponded to a benign tumour. The standard of truth was histology in two cases, correlative imaging with MRI in four cases, 99m Tc-SestaMIBI scintigraphy, ultrasonography and biochemistry in one case and biochemistry including PTH assay in one case. The final diagnosis of benign tumours consisted in 3 pituitary adenomas, 2 meningiomas, 2 hyperfunctioning parathyroid glands and 1 thyroid adenoma. Malignancy was proven histologically in 2 other patients: 1 papillary carcinoma of the thyroid and 1 cerebellar metastasis. To the best of our knowledge, FCH uptake by pituitary adenomas or hyperfunctioning parathyroid glands has never been described previously. We thus discuss whether there might be a future indication for FCH PET/CT when one such tumour is already known or suspected: to detect a residual or recurrent pituitary adenoma after surgery, to guide surgery or radiotherapy of a meningioma or to localise a hyperfunctioning parathyroid gland. In these potential indications, comparative studies with reference PET tracers or with 99m Tc-sestaMIBI in case of hyperparathyroidism could be undertaken

The hyperfunctioning nodules of the thyroid

International Nuclear Information System (INIS)

Rosenthal, D.

1975-01-01

Iodine kinetic studies, using a double label ( 131 I - and T 4 -125 I), were performed on 8 patients with hot thyroid nodules, 3 diffuse toxic goiters and one normal control. This investigation was complemented by partial kinetic studies done on 62 other subjetcs, including normal controls and euthyroid or hyperthyroid patients with diffuse or nodular goiter [pt

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

Sarcoidosis Presenting Addison's Disease.

Science.gov (United States)

Takahashi, Kentaro; Kagami, Shin-Ichiro; Kawashima, Hirotoshi; Kashiwakuma, Daisuke; Suzuki, Yoshio; Iwamoto, Itsuo

2016-01-01

We herein describe a second Japanese case of sarcoidosis presenting Addison's disease. A 52-year-old man was diagnosed with sarcoidosis based on clinical and laboratory findings, including bilateral hilar lymphadenopathy and elevated levels of serum angiotensin-converting enzyme and lysozyme, as well as the presence of noncaseating epithelioid granulomas. The patient also exhibited general fatigue, pigmentation, weight loss, hypotension and hyponatremia, suggestive of chronic adrenocortical insufficiency. An endocrine examination confirmed primary adrenocortical insufficiency. This case suggests the direct involvement of sarcoid granuloma in the adrenal glands.

Evaluation of parathyroid imaging methods with 99mTc-MIBI. The comparison of planar images obtained using a pinhole collimator and a parallel-hole collimator

International Nuclear Information System (INIS)

Fujii, Hirofumi; Iwasaki, Ryuichiro; Hashimoto, Jun; Nakamura, Kayoko; Kunieda, Etsuo; Sanmiya, Toshikazu; Kubo, Atsushi; Ogawa, Koichi; Inagaki, Kazutoshi

1999-01-01

Parathyroid scintigraphy with 99m Tc-MIBI was performed using two kinds of collimators, namely, a pinhole one and a parallel-hole one, to evaluate which one was more suitable for the detection of hyperfunctioning parathyroid lesions. In the studies using 99m Tc source, the pinhole collimator showed better efficiency and spatial resolution in the distance where the parathyroid scan are actually performed. In the phantom study, the nodular activities modeling parathyroid lesions were visualized better on the images obtained using the pinhole collimator. In clinical studies for 30 patients suspicious of hyperparathyroidism, hyperfunctioning parathyroid nodules were better detected when the pinhole collimator was used. In conclusion, the pinhole collimator was thought to be more suitable for parathyroid scintigraphy with 99m Tc-MIBI than the parallel-hole collimator. (author)

Evaluation of parathyroid imaging methods with {sup 99m}Tc-MIBI. The comparison of planar images obtained using a pinhole collimator and a parallel-hole collimator

Energy Technology Data Exchange (ETDEWEB)

Fujii, Hirofumi; Iwasaki, Ryuichiro; Hashimoto, Jun; Nakamura, Kayoko; Kunieda, Etsuo; Sanmiya, Toshikazu; Kubo, Atsushi [Keio Univ., Tokyo (Japan). School of Medicine; Ogawa, Koichi; Inagaki, Kazutoshi

1999-07-01

Parathyroid scintigraphy with {sup 99m}Tc-MIBI was performed using two kinds of collimators, namely, a pinhole one and a parallel-hole one, to evaluate which one was more suitable for the detection of hyperfunctioning parathyroid lesions. In the studies using {sup 99m}Tc source, the pinhole collimator showed better efficiency and spatial resolution in the distance where the parathyroid scan are actually performed. In the phantom study, the nodular activities modeling parathyroid lesions were visualized better on the images obtained using the pinhole collimator. In clinical studies for 30 patients suspicious of hyperparathyroidism, hyperfunctioning parathyroid nodules were better detected when the pinhole collimator was used. In conclusion, the pinhole collimator was thought to be more suitable for parathyroid scintigraphy with {sup 99m}Tc-MIBI than the parallel-hole collimator. (author)

Diagnose og behandling af binyrebarkkarcinom

DEFF Research Database (Denmark)

Abildgaard, Julie; Pappot, Helle; Petersen, Peter Meidahl

2013-01-01

Adrenocortical carcinomas (ACC) are rare tumours responsible for only 0.02% of the total number of malignant diseases. However the ACC are aggressive with a mean fiveyears survival of 20-50% and are often associated with increased production of adrenocortical hormones. The effect of the treatment...... is controversial and often based on small retrospective series or expert opinions. Centralization, international attention and collaboration in the treatment of ACC are mandatory. Randomized clinical trials are needed to determine the best treatment strategy in order to increase survival in patients with ACC....

Effects of glucocorticoid hormones on cell proliferation in dimethylhydrazine-induced tumours in rat colon.

Science.gov (United States)

Tutton, P J; Barkla, D H

1981-01-01

Adrenocortical hormones have previously been shown to influence cell proliferation in many tissues. In this report, their influence on cell proliferation in the colonic crypt epithelium and in colonic adenocarcinomata is compared. Colonic tumour cell proliferation was found to be retarded following adrenalectomy and this retardation was reversible by administration of hydrocortisone, or by administration of synthetic steroids with predominantly glucocorticoid activity. Tumour cell proliferation in adrenalectomized rats was not promoted by the mineralocorticoid hormone aldosterone. Neither adrenalectomy, nor adrenocortical hormone treatment, significantly influenced colonic crypt cell proliferation.

Prosthodontic Rehabilitation of Patient with Anterior Hyper Function Syndrome

Directory of Open Access Journals (Sweden)

Vesna Korunoska-Stevkovska

2017-12-01

CONCLUSION: Anterior hyperfunction syndrome with its high incidence is a disease with the need of interdisciplinary therapy approach. Fast diagnosis, thorough clinical examination using all available diagnostic tools, and choosing the right treatment is very challenging.

Experience with surgical treatment for primary malignant adrenal tumors

Directory of Open Access Journals (Sweden)

V. R. Latypov

2016-01-01

Full Text Available Background. Adrenal tumors occur in 3–10 % of the population and are mostly benign adrenal cortical tumors. Adrenocortical carcinoma is a very rare tumor and has an annual incidence of 1–2 cases per million people. The U.S. National Cancer Data Base registered 4275 patients with adrenocortical carcinoma in 1985 to 2007. It is extremely difficult to assess Russia’s epidemiological data, as reports on adrenocortical carcinoma are not presented separately.Materials and methods. A total of 133 patients (49 men and 84 women (1:1.7 with adrenal tumors were operated on at the clinics of the Siberian State Medical University in the period December 1998 to March 2015. The patients’ mean age was 51.3 (16–80 years (median age 51.0 years. The right and left adrenal glands were affected in 49 (36.9 % and 77 (57.9 % patients, respectively; both adrenal glands were involved in 7 (5.3 %. A group of 21 (15.8 % people with primary malignant adrenal tumors was identified among all the patients. The clinical manifestations of the disease were evaluated from the presence of hormonal activity, gastrointestinal symptoms, pain syndrome, and hypertension. All the patients were operated on under endotracheal anesthesia. The data were statistically processed using the program package Statistica 6.0. Survival rates were analyzed by the Kaplan–Meier method. The Gehan–Wilcoxon test was used to compare the groups.Results. The investigation analyzed treatment results in 21 (15.8 % patients with primary malignant adrenal lesions (Group 1. The most common morphological form was adrenocortical carcinoma in 15 (11.3 % patients (5 men and 10 women (1:2; their mean age was 48.1 years. The right, left, and both adrenal glands were affected in 4, 9, and 2 cases, respectively. In Group 2, other malignant adrenal involvements were identified from 1 case of rare malignant adrenal tumors: malignant pheochromocytoma, sarcoma, melanoma, squamous cell

Stages of Adrenocortical Carcinoma

Science.gov (United States)

... the adrenal gland is the adrenal medulla . Enlarge Anatomy of the adrenal gland. There are two adrenal ... spleen , or liver ) or to large blood vessels ( renal vein or vena cava ) and may have spread ...

Use of radiofrequency ablation in benign thyroid nodules: a literature review and updates.

Science.gov (United States)

Wong, Kai-Pun; Lang, Brian Hung-Hin

2013-01-01

Successful thermal ablation using radiofrequency has been reported in various tumors including liver or kidney tumors. Nonsurgical minimally invasive ablative therapy such as radiofrequency ablation (RFA) has been reported to be a safe and efficient treatment option in managing symptomatic cold thyroid nodules or hyperfunctioning thyroid nodules. Pressure and cosmetic symptoms have been shown to be significantly improved both in the short and long terms after RFA. For hyperfunctioning thyroid nodules, RFA is indicated for whom surgery or radioiodine are not indicated or ineffective or for those who refuse surgery or radio-iodine. Improvement of thyroid function with decreased need for antithyroid medications has been reported. Complication rate is relatively low. By reviewing the current literature, we reported its efficacy and complications and compared the efficacy of RFA relative to other ablative options such as ethanol ablation and laser ablation.

Use of Radiofrequency Ablation in Benign Thyroid Nodules: A Literature Review and Updates

Directory of Open Access Journals (Sweden)

Kai-Pun Wong

2013-01-01

Full Text Available Successful thermal ablation using radiofrequency has been reported in various tumors including liver or kidney tumors. Nonsurgical minimally invasive ablative therapy such as radiofrequency ablation (RFA has been reported to be a safe and efficient treatment option in managing symptomatic cold thyroid nodules or hyperfunctioning thyroid nodules. Pressure and cosmetic symptoms have been shown to be significantly improved both in the short and long terms after RFA. For hyperfunctioning thyroid nodules, RFA is indicated for whom surgery or radioiodine are not indicated or ineffective or for those who refuse surgery or radio-iodine. Improvement of thyroid function with decreased need for antithyroid medications has been reported. Complication rate is relatively low. By reviewing the current literature, we reported its efficacy and complications and compared the efficacy of RFA relative to other ablative options such as ethanol ablation and laser ablation.

The 5-HT₁A receptor CG polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

NARCIS (Netherlands)

Janssen, Paddy K C; van Schaik, R; Zwinderman, Aeilko H; Olivier, Berend|info:eu-repo/dai/nl/073067199; Waldinger, Marcel D|info:eu-repo/dai/nl/163958564

INTRODUCTION: Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 min, and has been postulated as a neurobiological dysfunction related to diminished serotonergic neurotransmission with 5-HT₁A receptor hyperfunction and

The 5-HT₁A receptor CG polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

NARCIS (Netherlands)

Janssen, Paddy K. C.; van Schaik, R.; Zwinderman, Aeilko H.; Olivier, Berend; Waldinger, Marcel D.

2014-01-01

Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 min, and has been postulated as a neurobiological dysfunction related to diminished serotonergic neurotransmission with 5-HT₁A receptor hyperfunction and 5-HT₂C

Noradrenergic enhancement of amygdala responses to fear

NARCIS (Netherlands)

Onur, Oezguer A; Walter, Henrik; Schlaepfer, Thomas E; Rehme, Anne K; Schmidt, Christoph; Keysers, Christian; Maier, Wolfgang; Hurlemann, René

Multiple lines of evidence implicate the basolateral amygdala (BLA) and the noradrenergic (norepinephrine, NE) system in responding to stressful stimuli such as fear signals, suggesting hyperfunction of both in the development of stress-related pathologies including anxiety disorders. However, no

Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic Acid animal model of autism

DEFF Research Database (Denmark)

Rinaldi, Tania; Perrodin, Catherine; Markram, Henry

2008-01-01

of synapses. The microcircuit alterations found in the prefrontal cortex are therefore similar to the alterations previously found in the somatosensory cortex. Hyper-connectivity and hyper-plasticity in the prefrontal cortex implies hyper-functionality of one of the highest order processing regions...

Free thyroxine in needle washout after fine needle aspiration biopsy of toxic thyroid nodules.

Science.gov (United States)

Raikov, Nikolai; Nonchev, Boyan; Chaushev, Borislav; Vjagova, Diyana; Todorov, Svetoslav; Bocheva, Yana; Malceva, Daniela; Vicheva, Snejinka; Raikova, Asyia; Argatska, Antoaneta; Raikov, Miroslav

2016-01-01

The main diagnostic tool for toxic adenomas (TA) is radionuclide imaging indicated in patients with evidence of thyroid nodules in combination with thyrotoxic syndrome. Thyroid ultrasound and fine-needle aspiration biopsy (FNAB) are widely used for the valuation of thyroid masses. There is no literature data concerning the utility of FNAB and related tests for the diagnosis of hyperfunctioning thyroid nodules. The purpose of this study is to determine the levels of free thyroxine (FT4) in the needle washout after FNAB of hot thyroid nodules. The results of our study show that the FT4 levels in needle washout from TA were significantly higher than the surrounding parenchyma and correlated with the hormonal changes in patients with thyroid hyperfunctioning nodules. Further studies on a large number of patients are needed to refine the diagnostic value of this method and evaluate its importance in quantitative risk assessment of thyroid autonomy.

Contribution of the TP53 R337H mutation to the cancer burden in southern Brazil: Insights from the study of 55 families of children with adrenocortical tumors.

Science.gov (United States)

Mastellaro, Maria J; Seidinger, Ana L; Kang, Guolian; Abrahão, Renata; Miranda, Eliana C M; Pounds, Stanley B; Cardinalli, Izilda A; Aguiar, Simone S; Figueiredo, Bonald C; Rodriguez-Galindo, Carlos; Brandalise, Silvia R; Yunes, José A; Barros-Filho, Antônio de A; Ribeiro, Raul C

2017-08-15

The tumor protein p53 (TP53) arginine-to-histidine mutation at codon 337 (R337H) predisposes children to adrenocortical tumors (ACTs) and, rarely, to other childhood tumors, but its impact on adult cancer remains undetermined. The objective of this study was to investigate the frequency and types of cancer in relatives of children with ACT who carry the TP53 R337H mutation. TP53 R337H testing was offered to relatives of probands with ACT. The parental lineage segregating the R337H mutation was identified in all families. The frequency and distribution of cancer types were compared according to R337H status. The authors' data also were compared with those publicly available for children with TP53 mutations other than R337H. The mean and median follow-up times for the probands with ACT were 11.2 years and 9.7 years (range, 3-32 years), respectively. During this time, cancer was diagnosed in 12 of 81 first-degree relatives (14.8%) carrying the R337H mutation but in only 1 of 94 noncarriers (1.1%; P = .0022). At age 45 years, the cumulative risk of cancer was 21% (95% confidence interval, 5%-33%) in carriers and 2% (95% confidence interval, 0%-4%) in noncarriers (P = .008). The frequency of cancer was higher in the R337H segregating lineages than in the nonsegregating lineages (249 of 1410 vs 66 of 984 individuals; P cancer were the most common types. TP53 R337H carriers have a lifelong predisposition to cancer with a bimodal age distribution: 1 peak, represented by ACT, occurs in the first decade of life, and another peak of diverse cancer types occurs in the fifth decade. The current findings have implications for genetic counseling and surveillance of R337H carriers. Cancer 2017;123:3150-58. © 2017 American Cancer Society. © 2017 American Cancer Society.

Selenium supplementation for patients with Graves’ hyperthyroidism (the GRASS trial)

DEFF Research Database (Denmark)

Watt, Torquil; Cramon, Per; Bjorner, Jakob Bue

2013-01-01

Graves' hyperthyroidism is an autoimmune disease causing hyperfunction of the thyroid gland. The concentration of selenium is high in the thyroid gland and two important groups of enzymes within the thyroid are selenoproteins, that is, they depend on selenium. Selenium may have beneficial effects...

Case of hyperparathyroidism associated with radiation to the head and neck area

International Nuclear Information System (INIS)

Rosen, I.B.; Strawbridge, H.G.; Bain, J.

1975-01-01

Hyperparathyroidism due to a hyperfunctioning parathyroid adenoma developed in a 57-year-old woman exposed to radiation for facial hirsutism, in whom other tumors of the head and neck had occurred. The details of history and the implications of causal relationship are presented. (auth)

Cytomorphologic significance of marginal vacuoles in diffuse thyroid enlargements

Directory of Open Access Journals (Sweden)

Anshu Gupta

2013-01-01

Conclusions: A significant association was found between abundant MVs and a hyperthyroid state. Moderate/absent MVs in diffuse goiters were not found to correlate with thyroid function. Thus, all diffuse goiters with prominent MVs require hormonal evaluation to rule out hyperfunction of the thyroid.

Neuromodulators: available agents, physiology, and anatomy.

Science.gov (United States)

Nettar, Kartik; Maas, Corey

2011-12-01

Neuromodulators have risen to the forefront of aesthetic medicine. By reversibly relaxing target muscles, neuromodulators exhibit their effect by softening hyperfunctional lines. An understanding of their physiology, relevant facial anatomy, and current agents is imperative for a successful aesthetic practice. © Thieme Medical Publishers.

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

Science.gov (United States)

Pomara, G; Cappello, F; Barzon, L; Morelli, G; Rappa, F; Benvegna, L; Giannarini, G; Palù, G; Selli, C

2006-01-01

We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV) DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry). Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV) and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

Directory of Open Access Journals (Sweden)

G Pomara

2009-06-01

Full Text Available We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry. Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

Effect of Home Cage Bedding in the Induction Chamber on Serum Cortisol and Corticosterone Levels in Response to Isoflurane-induced Anesthesia in C57BL/6J Mice.

Science.gov (United States)

Reiter, Cara P; Christy, Amanda C; Olsen, Cara H; Bentzel, David E

2017-03-01

Mice are routinely anesthetized with isoflurane in an induction chamber. The AVMA Guidelines for the Euthanasia of Animals states that distress should be minimized during euthanasia but does not address this point in regard to induction of anesthesia. Here we evaluated the potential for familiar surroundings to reduce the adrenocortical response of mice during anesthesia induction with isoflurane. However, adding bedding from the animals' home cage to the induction chamber failed to significantly reduce serum cortisol or corticosterone levels in male and female C57BL/6J mice. These results indicate that familiar surroundings do not appear sufficient to reduce the adrenocortical response of mice during anesthesia induction with isoflurane.

Vocal Fold Phase Asymmetries in Patients with Voice Disorders: A Study across Visualization Techniques

Science.gov (United States)

Bonilha, Heather Shaw; Deliyski, Dimitar D.; Whiteside, Joanna Piasecki; Gerlach, Terri Treman

2012-01-01

Purpose: To examine differences in vocal fold vibratory phase asymmetry judged from stroboscopy, high-speed videoendoscopy (HSV), and the HSV-derived playbacks of mucosal wave kymography, digital kymography, and a static medial digital kymography image of persons with hypofunctional and hyperfunctional voice disorders. Differences between the…

PRIMARY HYPERPARATHYROIDISM - CASE REPORT OF A FEMALE PATIENT WITH ADVANCED DISEASE

Directory of Open Access Journals (Sweden)

Predrag Grubor

2009-04-01

Full Text Available Primary hyperparathyroidism is a result of increased and uncontrolled function of the parathyroid hormone caused by hyperfunction of one or more parathyroid glands.The cause of hyperfunction of the parathyroid glands could be adenoma, hyperplasia, carcinoma. The leading sign of disease is hypercalcemia due to higher resorption of calcium from bones, decreased urinary elimination of calcium, and higher absorption of calcium in the bowels.The paper presents the case report of a 41-year-old female patient treated in our hospital in February, 2003. She came to hospital in poor general condition with suspicion of multiple bone metastases. She explained that she felt unwell last four years.After clinical, laboratory and radiological examination we found adenoma of the left parathyroid gland which was operated. Histologically, adenoma was confirmed.After supportive and symptomatic therapy, one year after surgical treatment, the patient was back to normal daily activities without any signs of disease.

Differentiated thyroid carcinoma with functional autonomy.

Science.gov (United States)

Yaturu, Subhashini; Fowler, Marjorie R

2002-01-01

To present a case of papillary carcinoma in an autonomously hyperfunctioning thyroid nodule. We chronicle the clinical and laboratory findings in a patient with a painless neck mass, with a particular focus on the pathologic findings after surgical removal of the right thyroid lobe. A 39-year-old woman had an enlarging nodule of the right thyroid lobe. Results of thyroid function tests suggested subclinical hyperthyroidism. Two months later, the patient complained of increasing swelling in the neck (but still had no symptoms suggestive of hyperthyroidism). Thus, resection of the right thyroid lobe was performed. Pathologic analysis disclosed low-grade papillary thyroid carcinoma within the nodule, with a small rim of compressed inactive-appearing thyroid tissue surrounding the nodule. Subsequently, she underwent total thyroidectomy and follow-up care for thyroid carcinoma. Although solitary hyperfunctioning nodules of the thyroid gland are usually considered benign, the current case suggests that the diagnosis of autonomous thyroid nodules does not preclude thyroid carcinoma in a functioning nodule.

A comparative assessment of the adrenotoxic effects of cadmium in two teleost species, rainbow trout, Oncorhynchus mykiss, and yellow perch, Perca flavescens

Energy Technology Data Exchange (ETDEWEB)

Lacroix, Alexandra; Hontela, Alice

2004-03-30

Rainbow trout (Oncorhynchus mykiss) and yellow perch (Perca flavescens) have a different sensitivity to cadmium (Cd) in vivo (troutadrenocortical cells in both species. The purpose of the present study was to assess in vitro the effect of Cd on cortisol secretion by adrenocortical cells of trout and perch, to compare the sensitivity of adrenal steroidogenesis in these two teleosts. Adrenocortical cells were exposed to Cd for 60 min, then stimulated with ACTH, dbcAMP or with pregnenolone, a cortisol precursor. Cd inhibited ACTH-stimulated cortisol secretion in a dose-dependent manner in both fish species, however, the EC50s (concentration resulting in 50% inhibition of cortisol secretion) was significantly lower in trout (EC50=0.09 mM) than perch (EC50=0.26 mM). To test the specificity of Cd to act as an endocrine disrupter, the LC50 (concentration that kills 50% of the cells) was also evaluated to determine the LC50/EC50 ratio (LC50/EC50{sub O.mykiss}=175.6>LC50/EC50{sub P.flavescens}=37.7). Adrenocortical cells of trout were more sensitive than those of perch and Cd had a higher endocrine-disrupting potential and specificity in trout than in perch. However, in both species, Cd had the same effect on ACTH, dbcAMP and pregnenolone-stimulated cortisol secretion, with pregnenolone maintaining cortisol secretion until cell viability was impaired. These results confirm that for both species, Cd interferes in the signalling pathway of cortisol synthesis in a step prior to the pregnenolone formation. Data provided by the present study revealed important differences in vulnerability of adrenal steroidogenesis between rainbow trout and yellow perch.

Hyperthyreoidie, radioactief jodium en daarna.

NARCIS (Netherlands)

Grient, Anton Jacobus van der

1969-01-01

The cause of hyperthyroidism is unknown. The methods available for treating this disease are thus limited to decreasing the hyperfunction of the gland by drugs, or eliminating a large pan of the gland by surgical removal or radiation. From 1959 to 1967 268 cases of hyperthyroidism were treated with

Effects of Pro-Gly-Pro tripeptide on the dopamine system.

Science.gov (United States)

Meshavkin, V K; Batishcheva, E Yu; Kost, N V; Sokolov, O Yu; Trufanova, A V; Samonina, G E

2011-08-01

Tripeptide Pro-Gly-Pro interacted with dopamine receptors in vitro and reduced behavioral manifestations of apomorphine-induced hyperfunction of the dopamine system in verticalization, stereotypy, and yawning tests. Presumably, the behavioral effects of Pro-Gly-Pro tripeptide were mediated through post- and presynaptic D(2)and D(3)receptors.

[Hyperthyroidism and carcinoma of the thyroid gland].

Science.gov (United States)

Ardito, G; Mantovani, M; Vincenzoni, C; Guidi, M L; Corsello, S; Rabitti, C; Fadda, G; Di Giovanni, V

1997-01-01

The incidence of thyroid carcinoma in hyperthyroidism varies considerably from as low as 0.3% to as high as 16.6% with a higher rate in toxic nodular goiters. Occult thyroid carcinoma (thyroid carcinoma was 5.6% (23 cases). In detail, a neoplasm occurred in 5 cases of Graves' disease (specific incidence: 3.8%), in 13 cases of toxic nodular goiter (12.5%) and in 5 cases of hyperfunctioning adenomas (2.8%). 19 cancers were papillary (12 in toxic nodular goiter, 3 in Graves' disease, 4 in hyperfunctioning adenomas), three were follicular (1 in Graves' disease, 1 in toxic nodular goiter, 1 in hyperfunctioning adenomas) and 1 medullary in Graves' disease. A papillary carcinoma was diagnosed preoperatively on fine needle aspiration with ultrasonography in only two patients with Graves' disease and confirmed by postoperative histological examination on permanent section. We do not believe in the frozen-section examination intraoperatively because it's not diagnostical for follicular lesions and evaluates rarely capsular invasion. Twenty patients received total thyroidectomy and four of them also lymphoadenectomy. Three patients received emithyroidectomy: in two cases for occult papillary carcinoma and in the last case for local cancer invasion (T4N0M0). Twenty patients are alive and with no evidence of cancer recurrence. Mean follow-up is 59.6 months. Our retrospective study shows a progressive increase of the incidence of coexisting thyroid malignancy and hyperthyroidism especially in toxic nodular goiter, probably related to extended surgical indications. Our findings do confirm that, even in the presence of hyperthyroidism, all thyroid nodules require careful diagnostics for exclusion of malignancy.

Autoimmune Addison's disease - An update on pathogenesis.

Science.gov (United States)

Hellesen, Alexander; Bratland, Eirik; Husebye, Eystein S

2018-06-01

Autoimmunity against the adrenal cortex is the leading cause of Addison's disease in industrialized countries, with prevalence estimates ranging from 93-220 per million in Europe. The immune-mediated attack on adrenocortical cells cripples their ability to synthesize vital steroid hormones and necessitates life-long hormone replacement therapy. The autoimmune disease etiology is multifactorial involving variants in immune genes and environmental factors. Recently, we have come to appreciate that the adrenocortical cell itself is an active player in the autoimmune process. Here we summarize the complex interplay between the immune system and the adrenal cortex and highlight unanswered questions and gaps in our current understanding of the disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Treatment Option Overview (Adrenocortical Carcinoma)

Science.gov (United States)

... affect the prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

General Information about Adrenocortical Carcinoma

Science.gov (United States)

... the adrenal gland is the adrenal medulla . Enlarge Anatomy of the adrenal gland. There are two adrenal ... spleen , or liver ) or to large blood vessels ( renal vein or vena cava ) and may have spread ...

21 CFR 862.1025 - Adrenocorticotropic hormone (ACTH) test system.

Science.gov (United States)

2010-04-01

... and serum. ACTH measurements are used in the differential diagnosis and treatment of certain disorders of the adrenal glands such as Cushing's syndrome, adrenocortical insufficiency, and the ectopic ACTH...

Die verband tussen persoonlikheid en stemhiperfunksie by 'n ...

African Journals Online (AJOL)

Due to the close relationship between personality and voice it is important to investigate personality factors that may have an influence on the development of vocal hyperfunction. The aim of this study was to determine whether similar personality characteristics occur in a group of speakers with vocal fold nodules and to ...

The hypofunctioning thyroid nodule: Radiography, computed tomography (CT) and magnetic resonance imaging (MRI)

International Nuclear Information System (INIS)

Dorn, R.; Wagner-Manslau, C.

1992-01-01

The hyperfunctioning thyroid nodule is a scintigraphic diagnosis by definition. Its dignity is assessed by fine needle aspiration biopsy. Radiographic methods and magnetic resonance imaging (MRI) are no primary tools in diagnosis of the hypofunctioning thyroid nodule but may reveal additional information, especially in cases of retrosternal goiter and thyroid malignomas. (orig.) [de

Improvement of Astatikopsia (Riddoch’s phenomenonafter correction of bivertebral stenoses with angioplasty

Directory of Open Access Journals (Sweden)

Yamille Vidal

2012-01-01

Full Text Available Visual perception disorder detection may be challenging with several dozen different syndromes identifiable. These may range from hypofunction to hyperfunction in the topological as well as hodological dimensions of cerebral structure. We report here a case of a 61- year-old white man presented with dizziness and visual impairment.

Stress and stereotypic behaviour in mink (Mustela vison)

DEFF Research Database (Denmark)

Malmkvist, Jens; Jeppesen, Leif Lau; Palme, R.

2011-01-01

We examined whether female mink with low (LS) and high (HS) occurrence of stereotypic behaviour differ in their adrenocortical activity in baseline conditions or in response to immobilisation (Experiment 1), handling, adrenocorticotropic hormone (ACTH) challenge (Experiment 2) and excretion...... 4-20 h after the handling (P = 0.001). In Experiment 3 (n = 16), the excretion of infused (3)H-cortisol did not differ between LS and HS mink. Stereotypic behaviour is concurrent with higher baseline concentrations of FCM, which cannot be explained by a greater adrenocortical reactivity...... or a different excretion of the circulating cortisol. Instead, we conclude that mink with a high level of stereotypic behaviour have a greater perception of stress, or increased sensitivity to stressors at the pituitary level....

Clinical discussion of adrenal scan by 131I-adosterol

International Nuclear Information System (INIS)

Kubo, Atsushi

1976-01-01

131 I-adosterol adrenal scan was conducted to 31 patients. Clear positive images were obtained at the adrenal gland at the side of cortical adenoma on scintigram in all of 5 patients with primary aldosteronism and 5 patients with Cushing's syndrome. It was found that the quantitative measurements of 131 I-adosterol % uptake and of right-to-left uptake ratio do not only make a regional diagnosis of adrenocortical tumor more positive, but also they make the state of adrenocortical function known to an extent. Adrenal scan is easy to be used, and is non-invasive to patients. The obtained results are diagnostically valuable. It is considered that 131 I-Adosterol is an excellent radiopharmaceutical having the sufficient efficacy for adrenal diseases. (Ichikawa, K.)

Adrenal neoplasms: Effectiveness and safety of CT-guided ablation of 23 tumors in 22 patients

Energy Technology Data Exchange (ETDEWEB)

Wolf, Farrah J.; Dupuy, Damian E.; Machan, Jason T. [Department of Diagnostic Imaging and the Office of Research Administration, Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903 (United States); Mayo-Smith, William W., E-mail: wmayo-smith@lifespan.org [Department of Diagnostic Imaging and the Office of Research Administration, Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903 (United States)

2012-08-15

Purpose: To retrospectively evaluate the effectiveness and safety of image-guided ablation of adrenal tumors. Materials and methods: : This HIPAA-compliant study was IRB approved and informed consent was waived. From 5/1999-6/2008, 20 consecutive adrenal metastases (mean diameter 4.2 cm; range, 2-8) and 3 hormonally active primary adrenal tumors (mean diameter 2.3 cm; range, 1-4), including an aldosteronoma and 2 pheochromocytomas in 22 patients (14 men, 8 women; mean age 61 years; range 40-84) were ablated in 23 sessions. Bilateral metastases were treated in a single patient. Radiofrequency ablation was used to treat 16 adrenal metastases and the 3 hyperfunctioning tumors. Microwave ablation was used to treat 4 metastases. Successful treatment was defined as a lack of both enhancement on follow-up contrast enhanced CT and/or up-take on FDG PET-CT and for functioning tumors, resolution of biochemical abnormalities. Results: Technical success was achieved in all sessions. Mean follow-up was 45.1 months (range, 1-91) Local tumor progression (focal enhancement at ablation site {>=}1 cm in short axis) was detected in 4 of 23 tumors, two of which were identified bilaterally in a single patient prompting re-treatment. Of 19 patients with metastatic disease, 16 had fatal extra-adrenal disease progression, and 3 remain alive. Two of the 3 patients who underwent ablation of hyperfunctioning tumors remain alive, including the patient with an aldosteronoma who had recurrent symptoms 91 months post ablation. Intra-ablative hypertension occurred in 9% (2/23) of sessions and was successfully treated pharmacologically. Conclusion: Ablation of metastatic and hyperfunctioning adrenal tumors is safe and may provide local control and treatment of pathologic biochemical activity.

Adrenal neoplasms: Effectiveness and safety of CT-guided ablation of 23 tumors in 22 patients

International Nuclear Information System (INIS)

Wolf, Farrah J.; Dupuy, Damian E.; Machan, Jason T.; Mayo-Smith, William W.

2012-01-01

Purpose: To retrospectively evaluate the effectiveness and safety of image-guided ablation of adrenal tumors. Materials and methods: : This HIPAA-compliant study was IRB approved and informed consent was waived. From 5/1999-6/2008, 20 consecutive adrenal metastases (mean diameter 4.2 cm; range, 2–8) and 3 hormonally active primary adrenal tumors (mean diameter 2.3 cm; range, 1–4), including an aldosteronoma and 2 pheochromocytomas in 22 patients (14 men, 8 women; mean age 61 years; range 40–84) were ablated in 23 sessions. Bilateral metastases were treated in a single patient. Radiofrequency ablation was used to treat 16 adrenal metastases and the 3 hyperfunctioning tumors. Microwave ablation was used to treat 4 metastases. Successful treatment was defined as a lack of both enhancement on follow-up contrast enhanced CT and/or up-take on FDG PET-CT and for functioning tumors, resolution of biochemical abnormalities. Results: Technical success was achieved in all sessions. Mean follow-up was 45.1 months (range, 1–91) Local tumor progression (focal enhancement at ablation site ≥1 cm in short axis) was detected in 4 of 23 tumors, two of which were identified bilaterally in a single patient prompting re-treatment. Of 19 patients with metastatic disease, 16 had fatal extra-adrenal disease progression, and 3 remain alive. Two of the 3 patients who underwent ablation of hyperfunctioning tumors remain alive, including the patient with an aldosteronoma who had recurrent symptoms 91 months post ablation. Intra-ablative hypertension occurred in 9% (2/23) of sessions and was successfully treated pharmacologically. Conclusion: Ablation of metastatic and hyperfunctioning adrenal tumors is safe and may provide local control and treatment of pathologic biochemical activity.

Thyroid tissue: US-guided percutaneous laser thermal ablation.

Science.gov (United States)

Pacella, Claudio Maurizio; Bizzarri, Giancarlo; Spiezia, Stefano; Bianchini, Antonio; Guglielmi, Rinaldo; Crescenzi, Anna; Pacella, Sara; Toscano, Vincenzo; Papini, Enrico

2004-07-01

To evaluate in vivo the safety and effectiveness of percutaneous laser thermal ablation (LTA) in the debulking of thyroid lesions. Twenty-five adult patients at poor surgical risk with cold nodules (n = 8), autonomously hyperfunctioning thyroid nodules (n = 16), or anaplastic carcinoma (n = 1) underwent LTA. One to four 21-gauge spinal needles were inserted with ultrasonographic (US) guidance into the thyroid lesions. A 300-microm-diameter quartz optical fiber was advanced through the sheath of the needle. Nd:YAG laser was used with output power of 3-5 W. Side effects, complications, and clinical and hormonal changes were evaluated at the end of LTA and during follow-up. Linear regression analysis was used to investigate the correlation between energy delivered and reduction in nodule volume. Volume of induced necrosis and reduction in nodule volume were assessed with US or computed tomography. LTA was performed without difficulties in 76 LTA sessions. After treatment with 5 W, two patients experienced mild dysphonia, which resolved after 48 hours and 2 months. Improvement of local compression symptoms was experienced by 12 of 14 (86%) patients. Thyroid-stimulating hormone (TSH) was detectable in five of 16 (31%) patients with hyperfunctioning nodules at 6 months after LTA. Volume of induced necrosis ranged from 0.8 to 3.9 mL per session. Anaplastic carcinoma treated with four fibers yielded 32.0 mL of necrosis. Echo structure and baseline volume did not influence response. Energy load and reduction in nodule volume were significantly correlated (r(2) =.75, P nodule volume reduction at 6 months in hyperfunctioning nodules was 3.3 mL +/- 2.8 (62% +/- 21.4 [SD]) and in cold nodules was 7.7 mL +/- 7.5 (63% +/- 13.8). LTA may be a therapeutic tool for highly selected problems in the treatment of thyroid lesions. Copyright RSNA, 2004

Cancer risk and clinicopathological characteristics of thyroid nodules harboring thyroid-stimulating hormone receptor gene mutations.

Science.gov (United States)

Mon, Sann Y; Riedlinger, Gregory; Abbott, Collette E; Seethala, Raja; Ohori, N Paul; Nikiforova, Marina N; Nikiforov, Yuri E; Hodak, Steven P

2018-05-01

Thyroid-stimulating hormone receptor (TSHR) gene mutations play a critical role in thyroid cell proliferation and function. They are found in 20%-82% of hyperfunctioning nodules, hyperfunctioning follicular thyroid cancers (FTC), and papillary thyroid cancers (PTC). The diagnostic importance of TSHR mutation testing in fine needle aspiration (FNA) specimens remains unstudied. To examine the association of TSHR mutations with the functional status and surgical outcomes of thyroid nodules, we evaluated 703 consecutive thyroid FNA samples with indeterminate cytology for TSHR mutations using next-generation sequencing. Testing for EZH1 mutations was performed in selected cases. The molecular diagnostic testing was done as part of standard of care treatment, and did not require informed consent. TSHR mutations were detected in 31 (4.4%) nodules and were located in exons 281-640, with codon 486 being the most common. Allelic frequency ranged from 3% to 45%. Of 16 cases (12 benign, 3 FTC, 1 PTC) with surgical correlation, 15 had solitary TSHR mutations and 1 PTC had comutation with BRAF V600E. Hyperthyroidism was confirmed in all 3 FTC (2 overt, 1 subclinical). Of 5 nodules with solitary TSHR mutations detected at high allelic frequency, 3 (60%) were FTC. Those at low allelic frequency (3%-22%) were benign. EZH1 mutations were detected in 2 of 4 TSHR-mutant malignant nodules and neither of 2 benign nodules. We report that TSHR mutations occur in ∼5% thyroid nodules in a large consecutive series with indeterminate cytology. TSHR mutations may be associated with an increased cancer risk when present at high allelic frequency, even when the nodule is hyperfunctioning. Benign nodules were however most strongly correlated with TSHR mutations at low allelic frequency. © 2018 Wiley Periodicals, Inc.

Hyperthyroidism

OpenAIRE

Sharma, Mala; Aronow, Wilbert S.; Patel, Laxesh; Gandhi, Kaushang; Desai, Harit

2011-01-01

Summary Hyperthyroidism is a pathological syndrome in which tissue is exposed to excessive amounts of circulating thyroid hormone. The most common cause of this syndrome is Graves? disease, followed by toxic multinodular goitre, and solitary hyperfunctioning nodules. Autoimmune postpartum and subacute thyroiditis, tumors that secrete thyrotropin, and drug-induced thyroid dysfunction, are also important causes.

Dysphonia in extremely preterm children: A longitudinal observation.

Science.gov (United States)

Reynolds, Victoria; Meldrum, Suzanne; Simmer, Karen; Vijayasekaran, Shyan; French, Noel

2016-12-01

Dysphonia is a potential long-term complication of preterm birth. Childhood voice disorders caused by vocal hyperfunction resolve with pubertal changes to the vocal mechanism in many cases. In extremely preterm children, whose voice quality is affected by supraglottic hyperfunction adapted secondary to underlying structural laryngeal pathology sustained during neonatal intubation, the prognosis is unknown. A pilot study was conducted to assess the incidence and severity of dysphonia in children born at dysphonia severity scores were significantly lower on repeat assessment, but no differences were observed in objective or quality of life scores. Individual variation was observed: the difference in CAPE-V scores ranged from -36 to + 1. No participant presented with normal voice quality on repeat assessment. Analysis of group data masked individual variability in this series. Mechanisms underlying such individual variation are currently unknown. These data suggest that dysphonia is persistent in extremely preterm children. Further investigation is warranted to elucidate the progression of voice disorders in extremely preterm children, to inform prognostic predictors and treatment decisions.

Carcinoma in hyperfunctioning thyroid nodule in recurrent hyperthyroidism

International Nuclear Information System (INIS)

Hoving, J.; Piers, D.A.; Vermey, A.; Oosterhuis, J.W.

1981-01-01

A patient with an invasive thyroid carcinoma located within a hot thyroid nodule is reported. Only four similar cases have been described in the literature. It is emphasized that a hot thyroid nodule per se should not be used as an argument against the diagnosis of thyroid carcinoma. (orig.) [de

Sexual dimorphism in cortisol secretion starts after age 10 in healthy children: urinary cortisol metabolite excretion rates during growth.

Science.gov (United States)

Wudy, Stefan A; Hartmann, Michaela F; Remer, Thomas

2007-10-01

Detailed data on the physiological pattern of adrenocortical activity during normal growth are lacking. An established method to determine adrenocortical glucocorticoid secretion is the measurement of 24-h excretion rates of major urinary cortisol metabolites (C21). To test the hypothesis that the frequently reported higher cortisol secretion in men than in women develops during puberty, we examined C21 together with excretions of combined urinary free and conjugated cortisol (F(comb)) in 400 healthy boys and girls aged 3-18 yr using GC-MS. Daily excretion rates of C21, F(comb), and body surface area (BSA)-corrected F(comb) significantly increased with age in both sexes. In contrast, C21/BSA (microgxm(-2).day(-1)) declined from the age of 3-4 yr to 7-8 yr in boys and girls (P activity (allotetrahydrocortisol/tetrahydrocortisol) in females compared with males. Our results demonstrate dynamic changes in adrenocortical activity in healthy children resulting in an emerging sexual dimorphism in cortisol secretion after age 11. The latter can be explained, at least partly, by diverging 5alpha-reductase activities in boys and girls. F(comb), a frequently analyzed GC-MS parameter, proved not to reflect dynamic changes in cortisol secretion. In conclusion, the varying metabolic need for cortisol during normal growth may have implications for future improvements in glucocorticoid replacement therapy.

Targeted Molecular Imaging in Adrenal Disease—An Emerging Role for Metomidate PET-CT

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Iosif A. Mendichovszky

2016-11-01

Full Text Available Adrenal lesions present a significant diagnostic burden for both radiologists and endocrinologists, especially with the increasing number of adrenal ‘incidentalomas’ detected on modern computed tomography (CT or magnetic resonance imaging (MRI. A key objective is the reliable distinction of benign disease from either primary adrenal malignancy (e.g., adrenocortical carcinoma or malignant forms of pheochromocytoma/paraganglioma (PPGL or metastases (e.g., bronchial, renal. Benign lesions may still be associated with adverse sequelae through autonomous hormone hypersecretion (e.g., primary aldosteronism, Cushing’s syndrome, phaeochromocytoma. Here, identifying a causative lesion, or lateralising the disease to a single adrenal gland, is key to effective management, as unilateral adrenalectomy may offer the potential for curing conditions that are typically associated with significant excess morbidity and mortality. This review considers the evolving role of positron emission tomography (PET imaging in addressing the limitations of traditional cross-sectional imaging and adjunctive techniques, such as venous sampling, in the management of adrenal disorders. We review the development of targeted molecular imaging to the adrenocortical enzymes CYP11B1 and CYP11B2 with different radiolabeled metomidate compounds. Particular consideration is given to iodo-metomidate PET tracers for the diagnosis and management of adrenocortical carcinoma, and the increasingly recognized utility of 11C-metomidate PET-CT in primary aldosteronism.

Positron emission tomography imaging of adrenal masses: 18F-fluorodeoxyglucose and the 11β-hydroxylase tracer 11C-metomidate

International Nuclear Information System (INIS)

Zettinig, Georg; Becherer, Alexander; Pirich, Christian; Dudczak, Robert; Mitterhauser, Markus; Wadsak, Wolfgang; Kletter, Kurt; Vierhapper, Heinrich; Niederle, Bruno

2004-01-01

11 C-metomidate (MTO), a marker of 11β-hydroxylase, has been suggested as a novel positron emission tomography (PET) tracer for adrenocortical imaging. Up to now, experience with this very new tracer is limited. The aims of this study were (1) to evaluate this novel tracer, (2) to point out possible advantages in comparison with 18 F-fluorodeoxyglucose (FDG) and (3) to investigate in vivo the expression of 11β-hydroxylase in patients with primary aldosteronism. Sixteen patients with adrenal masses were investigated using both MTO and FDG PET imaging. All patients except one were operated on. Five patients had non-functioning adrenal masses, while 11 had functioning tumours(Cushing's syndrome, n=4; Conn's syndrome, n=5; phaeochromocytoma, n=2). Thirteen patients had benign disease, whereas in three cases the adrenal mass was malignant (adrenocortical cancer, n=1; malignant phaeochromocytoma, n=1; adrenal metastasis of renal cancer, n=1). MTO imaging clearly distinguished cortical from non-cortical adrenal masses (median standardised uptake values of 18.6 and 1.9, respectively, p<0.01). MTO uptake was slightly lower in patients with Cushing's syndrome than in those with Conn's syndrome, but the difference did not reach statistical significance. The expression of 11β-hydroxylase was not suppressed in the contralateral gland of patients with Conn's syndrome, whereas in Cushing's syndrome this was clearly the case. The single patient with adrenocortical carcinoma had MTO uptake in the lower range. MTO could not definitely distinguish between benign and malignant disease. FDG PET, however, identified clearly all three study patients with malignant adrenal lesions. We conclude: (1) MTO is an excellent imaging tool to distinguish adrenocortical and non-cortical lesions; (2) the in vivo expression of 11β-hydroxylase is lower in Cushing's syndrome than in Conn's syndrome, and there is no suppression of the contralateral gland in primary aldosteronism; (3) for the purpose

Positron emission tomography imaging of adrenal masses: {sup 18}F-fluorodeoxyglucose and the 11{beta}-hydroxylase tracer {sup 11}C-metomidate

Energy Technology Data Exchange (ETDEWEB)

Zettinig, Georg; Becherer, Alexander; Pirich, Christian; Dudczak, Robert [Department of Nuclear Medicine, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Ludwig Boltzmann Institute for Nuclear Medicine, University of Vienna, Vienna (Austria); Mitterhauser, Markus [Department of Nuclear Medicine, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Department of Pharmaceutic Technology and Biopharmaceutics, University of Vienna, Vienna (Austria); Wadsak, Wolfgang; Kletter, Kurt [Department of Nuclear Medicine, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Vierhapper, Heinrich [Department of Internal Medicine III, University of Vienna, Vienna (Austria); Niederle, Bruno [Department of Surgery, University of Vienna, Vienna (Austria)

2004-09-01

{sup 11}C-metomidate (MTO), a marker of 11{beta}-hydroxylase, has been suggested as a novel positron emission tomography (PET) tracer for adrenocortical imaging. Up to now, experience with this very new tracer is limited. The aims of this study were (1) to evaluate this novel tracer, (2) to point out possible advantages in comparison with{sup 18}F-fluorodeoxyglucose (FDG) and (3) to investigate in vivo the expression of 11{beta}-hydroxylase in patients with primary aldosteronism. Sixteen patients with adrenal masses were investigated using both MTO and FDG PET imaging. All patients except one were operated on. Five patients had non-functioning adrenal masses, while 11 had functioning tumours(Cushing's syndrome, n=4; Conn's syndrome, n=5; phaeochromocytoma, n=2). Thirteen patients had benign disease, whereas in three cases the adrenal mass was malignant (adrenocortical cancer, n=1; malignant phaeochromocytoma, n=1; adrenal metastasis of renal cancer, n=1). MTO imaging clearly distinguished cortical from non-cortical adrenal masses (median standardised uptake values of 18.6 and 1.9, respectively, p<0.01). MTO uptake was slightly lower in patients with Cushing's syndrome than in those with Conn's syndrome, but the difference did not reach statistical significance. The expression of 11{beta}-hydroxylase was not suppressed in the contralateral gland of patients with Conn's syndrome, whereas in Cushing's syndrome this was clearly the case. The single patient with adrenocortical carcinoma had MTO uptake in the lower range. MTO could not definitely distinguish between benign and malignant disease. FDG PET, however, identified clearly all three study patients with malignant adrenal lesions. We conclude: (1) MTO is an excellent imaging tool to distinguish adrenocortical and non-cortical lesions; (2) the in vivo expression of 11{beta}-hydroxylase is lower in Cushing's syndrome than in Conn's syndrome, and there is no suppression of the

Adrenal Gland Cancer

Science.gov (United States)

... either benign or malignant. Benign tumors aren't cancer. Malignant ones are. Most adrenal gland tumors are ... and may not require treatment. Malignant adrenal gland cancers are uncommon. Types of tumors include Adrenocortical carcinoma - ...

What is the optimal bone-preserving strategy for patients with Addison's disease?

Science.gov (United States)

Lee, Paul; Greenfield, Jerry R

2015-08-01

Addison's disease is associated with low bone mineral density and increased risk of hip fractures. Causes are multifactorial, contributed by underlying adrenocortical hormonal deficiency, associated autoimmune endocrinopathies, electrolyte disturbances and, in some patients, supraphysiologic glucocorticoid replacement. Recent realization of physiologic cortisol production rate has revised downwards glucocorticoid replacement dosages. Meanwhile, new research has emerged suggesting complex interplay between sodium and calcium homoeostasis under the influence of mineralocorticoid and parathyroid hormone that may impact bone health. As the prevalence of Addison's disease is rising, and osteoporosis and fractures are associated with significant morbidity and increased mortality, attention to bone preservation in Addison's disease is of clinical relevance and importance. We suggest an approach to bone health in Addison's disease integrating physiologic adrenocortical hormonal replacement with electrolyte and mineral homoeostasis optimization. © 2015 John Wiley & Sons Ltd.

Effects of bisphenol A-related diphenylalkanes on vitellogenin production in male carp (Cyprinus carpio) hepatocytes and aromatase (CYP19) activity in human H295r adrenocortical carcinoma cells

International Nuclear Information System (INIS)

Letcher, Robert J.; Sanderson, J. Thomas; Bokkers, Abraham; Giesy, John P.; Berg, Martin van den

2005-01-01

The present study investigated the effects of the known xenoestrogen bisphenol A (BPA) relative to eight BPA-related diphenylalkanes on estrogen receptor (ER)-mediated vitellogenin (vtg) production in hepatocytes from male carp (Cyprinus carpio), and on aromatase (CYP19) activity in the human adrenocortical H295R carcinoma cell line. Of the eight diphenylalkanes, only 4,4'-(hexafluoropropylidene)diphenol (BHF) and 2,2'-bis(4-hydroxy-3-methylphenyl)propane (BPRO) induced vtg, i.e., to a maximum of 3% to 4% (at 100 μM) compared with 8% for BPA relative to the maximum induction by 17β-estradiol (E2, 1 μM). Bisphenol A diglycidyl ether (BADGE) was a potent antagonist of vtg production with an IC50 of 5.5 μM, virtually 100% inhibition of vtg at 20 μM, and an inhibitive (IC50) potency about one-tenth that of the known ER antagonist tamoxifen (IC50, 0.6 μM). 2,2'-Diallyl bisphenol A, 4,4'-(1,4-phenylene-diisopropylidene)bisphenol, BPRO, and BHF were much less inhibitory with IC50 concentrations of 20-70 μM, and relative potencies of 0.03 and 0.009 with tamoxifen. Bisphenol ethoxylate showed no anti-estrogenicity (up to 100 μM), and 4,4'-isopropylidene-diphenol diacetate was only antagonistic at 100 μM. When comparing the (anti)estrogenic potencies of these bisphenol A analogues/diphenylalkanes, anti-estrogenicity occurred at lower concentrations than estrogenicity. 4,4'-Isopropylidenebis(2,6-dimethylphenol) (IC50, 2.0 μM) reduced E2-induced (EC50, 100 nM) vtg production due to concentration-dependent cytotoxicity as indicated by a parallel decrease in MTT activity and vtg, whereas the remaining diphenylalkanes did not cause any cytotoxicity relative to controls. None of the diphenylalkanes (up to 100 μM) induced EROD activity indicating that concentration-dependent, CYP1A enzyme-mediated metabolism of E2, or any Ah-receptor-mediated interaction with the ER, was not a likely explanation for the observed anti-estrogenic effects. At concentrations as great as 100

A rare cause of acromegaly: McCune-Albright syndrome

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Erdal Bodakçi

2015-06-01

Full Text Available McCune-Albright syndrome is characterized by polyostatic fibrous dysplasia, brown spots on the skin (café au lait pigmentation and autonomous endocrine hyperfunction. Early puberty and other endocrinological manifestations, such as acromegaly, gigantism and hypercortisolism are widely observed in the syndrome. Acromegaly is seen in 20% of patients. We report a case of acromegaly accompanied with this syndrome.

Hypoadrenia following adrenal venography in Cushing's disease

International Nuclear Information System (INIS)

Goth, M.; Szilagy, G.; Irsy, G.; Szabolcs, I.; Berentey, E.; Molnar, F.; Magyar, E.

1984-01-01

Three patients with Cushing's disease are reported. In two patients the hyperfunction of the adrenal glands creased following selective adrenal venography, moreover hypoadrenia has developed. In the third case necrosis following venography was proved by surgery and confirmed by histology. Regarding the therapeutic possibilities of Cushing's diesease the use of this diagnostic procedure is taken into consideration but not recommended. (orig.)

Percutaneous ethanol injection therapy of autonomous (toxic) thyroid nodules

International Nuclear Information System (INIS)

Dieter Erich Apitzsch, M. D.; Staedtische Paracelsusklinik

2005-01-01

In Europe, 9-10% of hyperfunctioning thyroid glands have toxic, autonomous thyroid nodules (ATN). Since 1994, in the Municipal hospital of Marl, Germany, 186 patients have performed percutaneous ethanol ablation of toxic thyroid nodules with very good or at least sufficient results. In this article, the ablation technique is described in detail and the costs of therapy of ATN are given.(authors)

The relationship between the population size and the postirradiation mortality of mice with respect to individual differences in stress reactivity

International Nuclear Information System (INIS)

Pospisil, M.; Pipalova, I.; Netikova, J.

1976-01-01

Differences in radiosensitivity, expressed by the death rate up to the 30th day after irradiation by single whole-body exposures in the region of LD 50 , were followed in mice caged in groups by five, 15 and 25 individuals. No marked differences in the whole-group mortality of differently sized collectives were detected. Preirradiation as well as postirradiation leucocyte counts (after a sublethal irradiation) exhibit, however, differences, which correspond to an assumed different degree of the adrenocortical activity in differently sized collectives. Also the follow-up of the stress reactivity of the animals by measuring the Na/K ratio in 24-hour-samples of urine prior to irradiation demonstrated marked differences between the groups with low number and high number of animals in a cage. By correlating values of this indirect indicator of the adrenocortical activity with manifestations of the individual radiosensitivity it was found that the extremely hyporeactive animals (belonging to groups with five animals per cage) and the extremely hyperreactive ones (belonging to groups with 25 animals per cage) exhibit a markedly higher mortality. The absence of differences in the whole-group mortality of differently sized collectives can be explained by the existence of nonlinear 'U'-shaped relations between the adrenocortical activity and the individuals' radiosensitivity. The results support the conception on the unfavorable prognostic significance of unbalanced reactions of homeostatic functions of system regulation under conditions of radiation syndrome. (orig.) [de

Glucocorticoids and relapse of major depression (dexamethasone/corticotropin-releasing hormone test in relation to relapse of major depression)

NARCIS (Netherlands)

Appelhof, Bente C.; Huyser, Jochanan; Verweij, Mijke; Brouwer, Jantien P.; van Dyck, Richard; Fliers, Eric; Hoogendijk, Witte J. G.; Tijssen, Jan G. P.; Wiersinga, Wilmar M.; Schene, Aart H.

2006-01-01

BACKGROUND: Knowledge of pathogenic mechanisms and predictors of relapse in major depressive disorder is still limited. Hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation is thought to be related to the development and course of depression. METHODS: We investigated whether

Endocrine correlates of musth in free-ranging Asian elephants (Elephas maximus determined by non-invasive faecal steroid hormone metabolite measurements.

Directory of Open Access Journals (Sweden)

Ratna Ghosal

Full Text Available The occurrence of musth, a period of elevated levels of androgens and heightened sexual activity, has been well documented for the male Asian elephant (Elephas maximus. However, the relationship between androgen-dependent musth and adrenocortical function in this species is unclear. The current study is the first assessment of testicular and adrenocortical function in free-ranging male Asian elephants by measuring levels of testosterone (androgen and cortisol (glucocorticoid--a physiological indicator of stress metabolites in faeces. During musth, males expectedly showed significant elevation in faecal testosterone metabolite levels. Interestingly, glucocorticoid metabolite concentrations remained unchanged between musth and non-musth periods. This observation is contrary to that observed with wild and captive African elephant bulls and captive Asian bull elephants. Our results show that musth may not necessarily represent a stressful condition in free-ranging male Asian elephants.

[Potentialities of computed tomography and ultrasound in diagnosis of hormonally active adrenal diseases: results of comparison CT and US with operative adn histological data].

Science.gov (United States)

Denisova, L B; Vorontsova, S V; Emel'ianova, L N

2000-01-01

The data given in the paper suggest that X-ray computed tomography (CT) is highly effective in detecting all types of hormonally active adrenal abnormalities. CT used in hormonally active adrenal diseases yielded data on major quantitative and qualitative (primarily densitometric) criteria that could be used in assessing the images of the adrenal area in these patients. Ultrasound study (USS) made at the first stage of topical diagnostic searches was of informative value in detecting adrenal tumor lesions, the technique being highly sensitive in the diagnosis of adrenal pheochromocytomas and adenocarcinomas, but less informative in the detection of hormonally active adrenocortical adenomas (aldesterone-producing ones in particular) than CT. The diagnosis of various adrenocortical hyperplasies and the differentiation of hyperplastic and tumor forms of hypercorticoidism are a prerogative of CT that substantially supplements USS findings in such cases.

Ping-pong champion with adrenal insufficiency

Science.gov (United States)

Arima, Hiroshi; Imamine, Rui; Oiso, Yutaka

2009-01-01

A 62-year-old Japanese man, a bronze medal winner in the World Championship of table tennis when in his 20s, was diagnosed with secondary adrenocortical insufficiency due to isolated adrenocorticotropic hormone (ACTH) deficiency, and steroid administration was started. About 1 year after the diagnosis, he took part in a table tennis championship which was open to those 40 years or older. He took 10 mg hydrocortisone after breakfast as usual, played 10 matches, each of which took 20–30 min, and won the championship in about 8 h. Since the man could not always win the gruelling competition even when in his 50s, it is suggested that extra steroid hormone is not necessary for patients with adrenocortical insufficiency due to ACTH deficiency in order to successfully engage in sports requiring such intensity and endurance. PMID:21686433

Multiple osteoblastomas in a child with Cushing syndrome due to bilateral adrenal micronodular hyperplasias

Directory of Open Access Journals (Sweden)

Hyeoh Won Yu

2016-03-01

Full Text Available Adrenocorticotropin-independent adrenal hyperplasias are rare diseases, which are classified into macronodular (>1 cm and micronodular (≤1 cm hyperplasia. Micronodular adrenal hyperplasia is subdivided into primary pigmented adrenocortical disease and a limited or nonpigmented form 'micronodular adrenocortical disease (MAD', although considerable morphological and genetic overlap is observed between the 2 groups. We present an unusual case of a 44-month-old girl who was diagnosed with Cushing syndrome due to MAD. She had presented with spotty pigmentation on her oral mucosa, lips and conjunctivae and was diagnosed with multiple bone tumors in her femur, pelvis and skull base at the age of 8 years. Her bone tumor biopsies were compatible with osteoblastoma. This case highlights the importance of verifying the clinicopathologic correlation in Cushing syndrome and careful follow-up and screening for associated diseases.

Treatment Options by Stage (Adrenocortical Carcinoma)

Science.gov (United States)

... affect the prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

The role of the sympathetic nervous system in radiation-induced apoptosis in jejunal crypt cells of spontaneously hypertensive rats

International Nuclear Information System (INIS)

Matsuu, Mutsumi; Shichijo; Kazuko; Nakamura, Yasuko; Ikeda, Yuji; Naito, Shinji; Ito, Masahiro; Okaichi, Kumio; Sekine, Ichiro

2000-01-01

To evaluate the effect of the sympathetic nervous system on radiation-induced apoptosis in jejunal crypt cells, apoptosis levels were compared in spontaneously hypertensive rats (SHR), animals which are a genetic hyperfunction model of the sympathetic nervous system, and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were exposed to whole body X-ray irradiation at doses from 0.5 to 2 Gy. The apoptotic index in jejunal crypt cells was significantly greater in SHR than in WKY at each time point after irradiation and at each dose. WKY and SHR were treated with reserpine to induce sympathetic dysfunction, and were subsequently exposed to irradiation. Reserpine administration to SHR or WKY resulted in a significant suppression of apoptosis. p53 accumulation was detected in the jejunum in both WKY and SHR after irradiation by Western blotting analysis. There were no significant differences in the levels of p53 accumulation in irradiated intestine between WKY and SHR. These findings suggested that hyperfunction of the sympathetic nervous system is involved in the mechanism of high susceptibility to radiation-induced apoptosis of the jejunal crypt cells. (author)

Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic acid animal model of autism

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Tania Rinaldi

2008-10-01

Full Text Available The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. These excitatory connections are more plastic displaying enhanced long-term potentiation of the strength of synapses. The microcircuit alterations found in the prefrontal cortex are therefore similar to the alterations previously found in the somatosensory cortex. Hyper-connectivity and hyper-plasticity in the prefrontal cortex implies hyper-functionality of one of the highest order processing regions in the brain, and stands in contrast to the hypo-functionality that is normally proposed in this region to explain some of the autistic symptoms. We propose that a number of deficits in autism such as sociability, attention, multi-tasking and repetitive behaviours, should be re-interpreted in the light of a hyper-functional prefrontal cortex.

Large Multinodular Toxic Goiter: Is Surgery Always Necessary?

Directory of Open Access Journals (Sweden)

Roberto Negro

2016-01-01

Full Text Available Patients suffering from multinodular toxic goiter (MNTG are candidates to thyroidectomy or radioiodine 131I (131I therapy. Thyroidectomy may be preferable especially when the volume of hyperfunctioning tissue is so large that a single administration of 131I is unlikely to cure the patient in terms of nodule’s volume reduction and thyroid function. We describe the case of a 71-year-old man suffering from thyrotoxic state for the presence of two large hyperfunctioning thyroid nodules. As the patient refused surgery, at first we administered 600 MBq dose of 131I, which was unable to solve hyperthyroidism and local compressive symptoms. Then, before administering another 131I dose, the patient underwent a laser ablation treatment (LAT in both nodules. After a significant shrinkage due to LAT, the patient received 400 MBq 131I. This procedure was able to definitely cure hyperthyroidism, to induce a significant reduction of nodules’ volume, and to render the patient asymptomatic for compressive symptoms. This case demonstrates that 131I preceded by LAT represents a valid alternative strategy to surgery, even in the presence of two large coexistent hot nodules.

Percutaneous laser ablation of benign and malignant thyroid nodules.

Science.gov (United States)

Papini, Enrico; Bizzarri, Giancarlo; Pacella, Claudio M

2008-10-01

Percutaneous image-guided procedures, largely based on thermal ablation, are at present under investigation for achieving a nonsurgical targeted cytoreduction in benign and malignant thyroid lesions. In several uncontrolled clinical trials and in two randomized clinical trials, laser ablation has demonstrated a good efficacy and safety for the shrinkage of benign cold thyroid nodules. In hyperfunctioning nodules, laser ablation induced a nearly 50% volume reduction with a variable frequency of normalization of thyroid-stimulating hormone levels. Laser ablation has been tested for the palliative treatment of poorly differentiated thyroid carcinomas, local recurrences or distant metastases. Laser ablation therapy is indicated for the shrinkage of benign cold nodules in patients with local pressure symptoms who are at high surgical risk. The treatment should be performed only by well trained operators and after a careful cytological evaluation. Laser ablation does not seem to be consistently effective in the long-term control of hyperfunctioning thyroid nodules and is not an alternative treatment to 131I therapy. Laser ablation may be considered for the cytoreduction of tumor tissue prior to external radiation therapy or chemotherapy of local or distant recurrences of thyroid malignancy that are not amenable to surgical or radioiodine treatment.

Signs of testicular insufficiency in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy: a retrospective study

NARCIS (Netherlands)

Assies, J.; Gooren, L. J.; van Geel, B.; Barth, P. G.

1997-01-01

X-linked adrenoleukodystrophy (X-ALD) is characterized by central nervous system demyelination, and impaired steroidogenesis in the adrenal cortex and testis. Most patients develop adrenocortical insufficiency. We studied retrospectively the frequency and severity of testicular dysfunction in 26 men

Histologic and Immunohistochemical classification of 41 bovine adrenal gland neoplasms

DEFF Research Database (Denmark)

Grossi, Anette Blak; Leifsson, Páll S.; Jensen, Henrik Elvang

2013-01-01

. An immunohistochemistry panel consisting of antibodies against melan A, synaptophysin, and CNPase was considered most useful to classify bovine adrenal tumors. However, the distinction between benign and malignant adrenocortical tumors was based on histologic features as in human medicine....

Genetics of Beckwith-Wiedemann syndrome-associated tumors: common genetic pathways

NARCIS (Netherlands)

Steenman, M.; Westerveld, A.; Mannens, M.

2000-01-01

A specific subset of solid childhood tumors-Wilms' tumor, adrenocortical carcinoma, rhabdomyosarcoma, and hepatoblastoma-is characterized by its association with Beckwith-Wiedemann syndrome. Genetic abnormalities found in these tumors affect the same chromosome region (11p15), which has been

Behavioural and physiological responses of heifer calves to acute stressors : Long-term consistency and relationship with adult reactivity to milking

NARCIS (Netherlands)

Van Reenen, Cornelis G.; Van der Werf, Jozef T. N.; O'Connell, Niamh E.; Heutinck, Leonie F. M.; Spoolder, Hans A. M.; Jones, R. Bryan; Koolhaas, Jaap M.; Blokhuis, Harry J.; O’Connell, Niamh E.

The present study investigated the long-term consistency of individual differences in dairy cattles' responses in tests of behavioural and hypothalamo-pituitary-adrenocortical (HPA) axis reactivity, as well as the relationship between responsiveness in behavioural tests and the reaction to first

Behavioural and physiological responses of heifer calves to acute stressors: Long-term consistency and relationship with adult reactivity to milking

NARCIS (Netherlands)

Reenen, van C.G.; Werf, van der J.T.N.; O'Connell, N.E.; Heutinck, L.F.M.; Spoolder, H.A.M.; Jones, R.B.; Koolhaas, J.M.; Blokhuis, H.J.

2013-01-01

The present study investigated the long-term consistency of individual differences in dairy cattles’ responses in tests of behavioural and hypothalamo–pituitary–adrenocortical (HPA) axis reactivity, as well as the relationship between responsiveness in behavioural tests and the reaction to first

Changes in Plasma Corticosterone and Catecholamine Contents Induced by Low Doses of Deltamethrin in Rats

NARCIS (Netherlands)

Boer, Sietse F. de; Gugten, Jan van der; Slangen, Jef. L.; Hijzen, Theo H.

1988-01-01

The effects of low doses of (S)-α-cyano-3-phenoxybenzyl (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (Roussel UCLAF, Paris, France), (deltamethrin) upon sympathetic-adrenomedullary and pituitary-adrenocortical activity were investigated in rats by measuring plasma noradrenaline

Vocal therapy of hyperkinetic dysphonia

OpenAIRE

Mumović Gordana; Veselinović Mila; Arbutina Tanja; Škrbić Renata

2014-01-01

Introduction. Hyperkinetic (hyperfunctional) dysphonia is a common pathology. The disorder is often found in vocal professionals faced with high vocal requirements. Objective. The objective of this study was to evaluate the effects of vocal therapy on voice condition characterized by hyperkinetic dysphonia with prenodular lesions and soft nodules. Methods. The study included 100 adult patients and 27 children aged 4-16 years with prenodular lesions and soft...

The clinical evaluation of combining radionuclide imaging with radioimmunoassay for hashimoto's thyroiditis

International Nuclear Information System (INIS)

Huang Chenggang; Chen Xiaoyan; Deng Yan

2003-01-01

By analysing nuclide image characteristics and radioimmunoassay data of 61 cases with Hashimoto's thyroiditis (HT), HT can be classified five types as below: uneven distribution, diffusion, with hyperfunction, with nodules, nearly normal. The results of radionuclide imaging and the radioimmunoassay of all the types indicate that HT can be preliminarily diagnosed by conscientiously analysing nuclide image characteristics and radioimmunoassay data and linking clinical symptoms and signs

Enabling minimal invasive parathyroidectomy for patients with primary hyperparathyroidism using Tc-99m-sestamibi SPECT–CT, ultrasound and first results of {sup 18}F-fluorocholine PET–CT

Energy Technology Data Exchange (ETDEWEB)

Kluijfhout, Wouter P., E-mail: WPKluijfhout@gmail.com [Department of Endocrine Surgery, University Medical Center Utrecht, Utrecht (Netherlands); Vorselaars, Wessel M.C.M., E-mail: W.M.Vorselaars@umcutrecht.nl [Department of Endocrine Surgery, University Medical Center Utrecht, Utrecht (Netherlands); Vriens, Menno R., E-mail: mvriens@umcutrecht.nl [Department of Endocrine Surgery, University Medical Center Utrecht, Utrecht (Netherlands); Borel Rinkes, Inne H.M., E-mail: I.H.M.BorelRinkes@umcutrecht.nl [Department of Endocrine Surgery, University Medical Center Utrecht, Utrecht (Netherlands); Valk, Gerlof D., E-mail: G.D.Valk@umcutrecht.nl [Department of Endocrinology, University Medical Center Utrecht, Utrecht (Netherlands); Keizer, Bart de, E-mail: B.deKeizer@umcutrecht.nl [Department of Nuclear Medicine and Radiology, University Medical Center Utrecht, Utrecht (Netherlands)

2015-09-15

Highlights: • We examined an optimal pre-operative imaging strategy. • Goal was to perform minimal invasive parathyroidectomy. • Ultrasound significantly decreased the PPV when added to SPECT–CT. • {sup 18}F-fluorocholine was positive in 4/5 cases with negative conventional imaging. - Abstract: Objective: Assessment of the diagnostic value of ultrasound (US), single photon-emission computed tomography–computed tomography (SPECT–CT) and {sup 18}F-fluorocholine (FCH) PET–CT for preoperative localization of hyper-functioning parathyroid(s) in order to create a more efficient diagnostic pathway and enable minimal invasive parathyroidectomy (MIP) in patients with biochemical proven non-familial primary hyperparathyroidism (pHPT). Methods: A single-institution retrospective study of 63 consecutive patients with a biochemical diagnosis of non-familial pHPT who received a Tc-99m-sestamibi SPECT–CT and neck ultrasound. Surgical findings were used in calculating the sensitivity and the positive predictive value (PPV) of both imaging modalities. Furthermore we present 5 cases who received additional FCH PET–CT. Results: A total of 42 (66.7%) patients underwent MIP. The PPV and sensitivity of SPECT–CT, 93.0% and 80.3%, were significantly higher than those of US with 78.3% and 63.2%, respectively. Adding US to SPECT–CT for initial pre-operative localization did not significantly increase sensitivity but did significantly decrease PPV. Performance of US was significantly better when performed after SPECT–CT. {sup 18}F-fluorocholine PET–CT localized the hyper-functioning parathyroid gland in 4/5 cases with discordant conventional imaging, enabling MIP. Conclusion: SPECT–CT is the imaging modality of choice for initial pre-operative localization of hyper-functioning parathyroid gland(s) in patients with biochemical pHPT. Ultrasound should be performed after SPECT–CT for confirmation of positive SPECT–CT findings and for pre-operative marking

Unilateral nodular adrenal hyperplasia: Case series | Kot | African ...

African Journals Online (AJOL)

Introduction: Nodular adrenal hyperplasia is one of rare causes of adrenocortical hyperplasia. The disease usually presents bilaterally. Few publications discussed the possibility of unilateral disease, in association with hyperaldosteronism or Cushing syndrome. Case series: We are reporting 3 cases of radiologically ...

Unilateral nodular adrenal hyperplasia: Case series

African Journals Online (AJOL)

A.F. Kotb

2016-07-26

Jul 26, 2016 ... Abstract. Introduction: Nodular adrenal hyperplasia is one of rare causes of adrenocortical hyperplasia. The disease usually presents bilaterally. Few publications discussed the possibility of unilateral disease, in association with hyperaldosteronism or Cushing syndrome. Case series: We are reporting 3 ...

Luteinizing hormone (LH)-responsive Cushing's syndrome: the demonstration of LH receptor messenger ribonucleic acid in hyperplastic adrenal cells, which respond to chorionic gonadotropin and serotonin agonists in vitro

NARCIS (Netherlands)

R.A. Feelders (Richard); W.W. de Herder (Wouter); S.W.J. Lamberts (Steven); L.J. Hofland (Leo); P.M. van Koetsveld (Peter); M. Verhoef-Post (Miriam); A.P.N. Themmen (Axel); F.H. de Jong (Frank); H.J. Bonjer (Jaap); A.J. Clark (Adrian); A-J. van der Lely (Aart-Jan)

2003-01-01

textabstractIn a substantial part of adrenal adenomas and hyperplasias from patients with Cushing's syndrome, cortisol production is controlled by the expression of aberrant hormone receptors on adrenocortical cells. We present in vivo and in vitro data of two patients with a

The short-term effects of effort-reward imbalance : Daily and within-day psychological and physiological measurements

NARCIS (Netherlands)

Hanson, E.K.S.

2000-01-01

In the present thesis, the short-term effects of Effort-Reward Imbalance (ERI) are studied by measuring indices of vagal control, hypothalamo-pituitary-adrenocortical (HPAC) activity and affect. The studies provide an illustration of recent developments in the field. Primarily, Ecological Momentary

Thyroid carcinoma masquerading as a solitary benign hyperfunctioning nodule

Energy Technology Data Exchange (ETDEWEB)

Sandler, M.P.; Fellmeth, B.; Salhany, K.E.; Patton, J.A.

1988-06-01

Focal hot nodules on iodine thyroid images are associated with an exceedingly low incidence of malignancy. Most previously reported hot carcinomas represent the coexistence of small malignancies in or adjacent to a benign hot lesion. Described here is a 3-cm papillary carcinoma that fulfilled the criteria for benignancy on Tc-99m and I-123 imaging. Coincidental carcinoma within a benign lesion was excluded by detailed scintigraphic-pathologic correlation of the tumor. The implications of this case on the management of the solitary hot nodule are discussed and the literature reviewed.

Thyroid carcinoma masquerading as a solitary benign hyperfunctioning nodule

International Nuclear Information System (INIS)

Sandler, M.P.; Fellmeth, B.; Salhany, K.E.; Patton, J.A.

1988-01-01

Focal hot nodules on iodine thyroid images are associated with an exceedingly low incidence of malignancy. Most previously reported hot carcinomas represent the coexistence of small malignancies in or adjacent to a benign hot lesion. Described here is a 3-cm papillary carcinoma that fulfilled the criteria for benignancy on Tc-99m and I-123 imaging. Coincidental carcinoma within a benign lesion was excluded by detailed scintigraphic-pathologic correlation of the tumor. The implications of this case on the management of the solitary hot nodule are discussed and the literature reviewed

Hyperfunctioning Solid/Trabecular Follicular Carcinoma of the Thyroid Gland

OpenAIRE

Luca Giovanella; Fabrizio Fasolini; Sergio Suriano; Luca Mazzucchelli

2010-01-01

A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the 9 9 m T c -pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissu...

Journal of Endocrinology, Metabolism and Diabetes of South Africa ...

African Journals Online (AJOL)

Adrenocortical function in hospitalised patients with active pulmonary tuberculosis receiving a rifampicin-based regimen - a pilot study · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. WD Francois Venter, Vanessa R Panz, Charles Feldman, Barry I Joffe, 16-21.

Pure red cell aplasia following irradiation of an asymptomatic thymoma

International Nuclear Information System (INIS)

Shibata, Kazuo; Masaoka, Akira; Mizuno, Takeo; Ichimura, Hideki

1982-01-01

An unusual case of pure red-cell aplasia (PRCA) developed sixteen days after irradiation of an asymptomatic thymoma. After removal of the encapsulated thymoma there was no improvement in the anemia, and no response to adrenocortical and anabolic steroid hormones or immunosuppressive agents. (author)

Plasma aldosterone concentrations and plasma renin activity in healthy dogs and dogs with hyperadrenocorticism

NARCIS (Netherlands)

Javadi, S; Mol, JA; Boer, P; Boer, WH; Runberk, A

2003-01-01

The mean (se) basal plasma aldosterone concentrations were significantly lower in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH) (75 [9] pmol/litre) than in 12 healthy dogs (118 [14] pmol/litre), whereas in five dogs with hyperadrenocorticism due to an adrenocortical tumour they were

a note on the effects of maternal or foetal injection of flumethasone ...

African Journals Online (AJOL)

Pregnancy has been successfully terminated in sheep using potent corticosteroids (Skinner,.Jochl6 & Nel, 1970). Furthermore, van Rensburg (1970) reported on the role of adrenal corticosteroids during pregnancy on the incidence of abortion in Angora goat does. Since an antagonism exists between adrenocortical and ...

Inhibition and Exuberance in Preschool Classrooms: Associations with Peer Social Experiences and Changes in Cortisol across the Preschool Year

Science.gov (United States)

Tarullo, Amanda R.; Mliner, Shanna; Gunnar, Megan R.

2011-01-01

Associations between behavioral inhibition and activity of the hypothalamic-pituitary-adrenocortical (HPA) system, a stress-sensitive neuroendocrine system indexed by salivary cortisol, have varied widely across studies. In the current study, we examined the role of peer social experiences in moderating patterns of association between…

Auditory-Perceptual Evaluation of Dysphonia: A Comparison Between Narrow and Broad Terminology Systems

DEFF Research Database (Denmark)

Iwarsson, Jenny

2017-01-01

of the terminology used in the multiparameter Danish Dysphonia Assessment (DDA) approach into the five-parameter GRBAS system. Methods. Voice samples illustrating type and grade of the voice qualities included in DDA were rated by five speech language pathologists using the GRBAS system with the aim of estimating...... terms and antagonists, reflecting muscular hypo- and hyperfunction. Key Words: Auditory-perceptual voice analysis–Dysphonia–GRBAS–Listening test–Voice ratings....

Radioimmunological diagnostics of endocrine disorders in radiotherapy of cervical carcinoma

International Nuclear Information System (INIS)

Modnikov, O.P.

1986-01-01

In 117 patients with cervical carcinoma and 57 healthy women of the same age a radioimmunologic investigation of the systems hypophysis-adrenal glands and hypophysis-ovaries was carried out. Functional disorders in these systems were detected already before irradiation (hyperfunction of adrenal glands, diminished production of estradiol). The function of the systems hypophysis-adrenal glands and hypophysis-ovaries was diminished in patients with cervical carcinoma under radiotherapy. (author)

Polyostotic fibrous dysplasia with gigantism and huge pelvic tumor: a rare case of McCune-Albright syndrome.

Science.gov (United States)

Sakayama, Kenshi; Sugawara, Yoshifumi; Kidani, Teruki; Fujibuchi, Taketsugu; Kito, Katsumi; Tanji, Nozomu; Nakamura, Atsushi

2011-06-01

We report a rare case of polyostotic fibrous dysplasia on endocrine hyperfunction with elevated human growth hormone and normal serum level of prolactin. There were some differential points of gender, gigantism, endocrine function, and GNAS gene from McCune-Albright syndrome. Malignant transformation was suspected in the pelvic tumor from imaging because rapid growth of the tumor by imaging was observed; however, no malignant change occurred in this case.

Thyroid carcinoma mimicking a toxic adenoma

International Nuclear Information System (INIS)

De Rosa, G.; Testa, A.; Satta, M.A.; Maurizi, M.; Aimoni, C.; Artuso, A.; Silvestri, E.; Rufini, V.; Troncone, L.

1990-01-01

A young woman with a thyroid papillary carcinoma behaving as an autonomously hyperfunctioning nodule is described. Only 17 similar patients have been seen in the past 25 years. It is emphasized that hyperthyroidism does not exclude malignant disease in hot nodules. This possibility suggests that all thyroid nodules, either cold or hot, require careful management. Therefore, in 'at risk' cases, surgery could be the most useful treatment. (orig.)

Are birds stressed during long-term flights? A wind-tunnel study on circulating corticosterone in the red knot

NARCIS (Netherlands)

Jenni-Eiermann, Susanne; Hasselquist, Dennis; Lindstrom, Ake; Koolhaas, Anita; Piersma, Theunis; Lindström, Åke

2009-01-01

During endurance flight most birds do not feed and have to rely on their body reserves. Fat and protein is catabolised to meet the high energetic demands. Even though the hormonal regulation of migration is complex and not yet fully understood. the adrenocortical hormone corticosterone crystallizes

Rare endocrine cancers have novel genetic alterations

Science.gov (United States)

A molecular characterization of adrenocortical carcinoma, a rare cancer of the adrenal cortex, analyzed 91 cases for alterations in the tumor genomes and identified several novel genetic mutations as likely mechanisms driving the disease as well as whole genome doubling as a probable driver of the disease.

21 CFR 522.535 - Desoxycorticosterone pivalate.

Science.gov (United States)

2010-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522... variable and must be individualized on the basis of the response of the patient to therapy. Initial dose of... as replacement therapy for the mineralocorticoid deficit in dogs with primary adrenocortical...

Flow Glottogram and Subglottal Pressure Relationship in Singers and Untrained Voices.

Science.gov (United States)

Sundberg, Johan

2018-01-01

This article combines results from three earlier investigations of the glottal voice source during phonation at varying degrees of vocal loudness (1) in five classically trained baritone singers (Sundberg et al., 1999), (2) in 15 female and 14 male untrained voices (Sundberg et al., 2005), and (3) in voices rated as hyperfunctional by an expert panel (Millgård et al., 2015). Voice source data were obtained by inverse filtering. Associated subglottal pressures were estimated from oral pressure during the occlusion for the consonant /p/. Five flow glottogram parameters, (1) maximum flow declination rate (MFDR), (2) peak-to-peak pulse amplitude, (3) level difference between the first and the second harmonics of the voice source, (4) closed quotient, and (5) normalized amplitude quotient, were averaged across the singer subjects and related to associated MFDR values. Strong, quantitative relations, expressed as equations, are found between subglottal pressure and MFDR and between MFDR and each of the other flow glottogram parameters. The values for the untrained voices, as well as those for the voices rated as hyperfunctional, deviate systematically from the values derived from the equations. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

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.

Local blockage of EMMPRIN impedes pressure ulcers healing in a rat model

OpenAIRE

Zhao, Xi-Lan; Luo, Xiao; Wang, Ze-Xin; Yang, Guo-Li; Liu, Ji-Zhong; Liu, Ya-Qiong; Li, Ming; Chen, Min; Xia, Yong-Mei; Liu, Jun-Jie; Qiu, Shu-Ping; Gong, Xiao-Qing

2015-01-01

Excessive extracellular matrix degradation caused by the hyperfunction of matrix metalloproteinases (MMPs) has been implicated in the failure of pressure ulcers healing. EMMPRIN, as a widely expressed protein, has emerged as an important regulator of MMP activity. We hypothesize that EMMPRIN affects the process of pressure ulcer healing by modulating MMP activity. In the rat pressure ulcer model, the expression of EMMPRIN in ulcers detected by Western blot was elevated compared with that obse...

Recurrent transient thyrotoxicosis in multinodular goitre.

OpenAIRE

Arem, R.

1990-01-01

A patient initially presented with an autonomously functioning right thyroid nodule and transient hyperthyroidism which lasted for a few months. Several months after resolution of thyrotoxicosis, the patient had a recurrent episode of hyperthyroidism and was found to have a left hot nodule. The right hyperfunctioning nodule had become cold on scintigraphy, and its aspiration revealed haemorrhagic fluid suggesting haemorrhagic infarction as the mechanism of resolution of the first episode of h...

Parathyromatosis: Critical Diagnosis Regarding Surgery and Pathologic Evaluation

OpenAIRE

Aksoy-Altinboga, Ayşegül; Akder Sari, Ayşegül; Rezanko, Türkan; Haciyanli, Mehmet; Orgen Calli, Aylin

2012-01-01

Parathyromatosis, in which several nodules of hyperfunctioning parathyroid tissue form in the neck and mediastinum, is a rare cause of recurrent hyperparathyroidism. However, there are some theories regarding the origin of parathyromatosis, and seeding after rupture of the parathyroid gland capsule during surgical removal of a parathyroid lesions is the most regarded one. Herein, we report a 41-year-old man who presented with multiple parathyroid nodules in and around the left thyroid lobe 5 ...

Child Care and Cortisol across Early Childhood: Context Matters

Science.gov (United States)

Berry, Daniel; Blair, Clancy; Ursache, Alexandra; Wiloughy, Michael; Garrett-Peters, Patricia; Veron-Feagans, Lynne; Bratsch-Hines, Mary; Mills-Koonce, W. Roger; Granger, Douglas A.

2014-01-01

A considerable body of literature suggests that children's child-care experiences may impact adrenocortical functioning in early childhood. Yet emerging findings also suggest that the magnitude and sometimes the direction of child-care effects on development may be markedly different for children from higher risk contexts. Using data from a large…

Fluconazole inhibits human adrenocortical steroidogenesis in vitro

NARCIS (Netherlands)

R. van der Pas (Rob); L.J. Hofland (Leo); J. Hofland (Johannes); A.E. Taylor (A.); W. Arlt (Wiebke); J. Steenbergen (Jacobie); P.M. van Koetsveld (Peter); W.W. de Herder (Wouter); F.H. de Jong (Frank); R.A. Feelders (Richard)

2012-01-01

textabstractThe antifungal agent ketoconazole is often used to suppress cortisol production in patients with Cushing's syndrome (CS). However, ketoconazole has serious side effects and is hepatotoxic. Here, the in vitro effects of ketoconazole and fluconazole, which might be less toxic, on human

Late recurrent adrenocortical carcinoma presenting radiologically as ...

African Journals Online (AJOL)

A. Beltagy

2016-07-01

Jul 1, 2016 ... malignancy with an estimated incidence of 1–2 per million peo- ple [2]. There are 3 .... scopic features of a tumour composed of solid sheets of eosinophilic cells with vesicular .... World J Surg 2001;25:891–7. [14] Hermsen GC ...

Bilateral spontaneous adrenal haemorrhage complicating acute pancreatitis

International Nuclear Information System (INIS)

Pianta, M.; Varma, D. K.

2007-01-01

Bilateral adrenal haemorrhage is an event that mandates prompt diagnosis and treatment to prevent primary adrenocortical insufficiency and potential death. Presentation can be non-specific and incidentally diagnosed with imaging alone, primarily CT. We present a case of acute pancreatitis with spontaneous bilateral adrenal haemorrhage and briefly discuss imaging and treatment implications

Multiglandular primary hyperparathyroidism with a hyperfunctional intrathyroid gland. Case report

International Nuclear Information System (INIS)

Goni E, Ignacio; Campusano M, Claudia; Gejman E, Roger; Orellana B, Pilar

2011-01-01

We report a 56 years old female, admitted to the hospital for the study of general weakness, constipation, a recent radial fracture, hypercalcemia of 18 mg/dl, hypophosphataemia of 1.2 meq/dl and a serum parathormone (PTH) of 995 pg/ml. A thyroid ultrasound disclosed a nodule of 6 cm diameter. Following emergency management and normalization of the hypercalcemia, that patient was subjected to a total thyroidectomy and parathyroidectomy. The pathological study of the surgical piece showed a multiglandular hyperplasia of the parathyroid glands. One of these was located inside the left thyroid lobe

Study of organic acids in Schisandrae Chinensis Fructus after vinegar processing.

Science.gov (United States)

Yin, Fangzhou; Dai, Hui; Li, Lin; Lu, Tuling; Li, Weidong; Cai, Baochang; Yin, Wu

2017-10-01

The ripened fruit of Schisandrae Chinensis Fructus has unique medical properties in Chinese medicine. It is commonly used after vinegar steaming. Vinegar steaming changes the color of Schisandrae Chinensis Fructus from red to black and enhances its acidic and astringent properties. Lignans are the well-investigated components in this herb. However, Schisandrae Chinensis Fructus is acidic in the theory of Chinese medicine, and whether vinegar processing changes its organic acid components remains largely unknown. In this study, the organic acids in this herb were derived by the method of methyl esterification, and further analyzed by gas chromatography with mass spectrometry. A total of 39 organic acid compounds were identified. Interestingly, Schisandrae Chinensis Fructus after vinegar processing showed a significant increase in the content of levulinic acid as compared to the unprocessed ones. Pharmacological experiments demonstrated that levulinic acid inhibited the contractility of isolated intestine and had an inhibitory effect on the excessive hyperfunction of small intestinal propulsion. Moreover, the extracts of vinegar-processed Schisandrae Chinensis Fructus had a stronger inhibitory on the excessive hyperfunction of small intestinal propulsion than that of unprocessed ones. Taken together, this study offers novel insight into the effect of Schisandrae Chinensis Fructus after vinegar processing. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prolactin induces adrenal hypertrophy

Directory of Open Access Journals (Sweden)

E.J. Silva

2004-02-01

Full Text Available Although adrenocorticotropic hormone is generally considered to play a major role in the regulation of adrenal glucocorticoid secretion, several reports have suggested that other pituitary hormones (e.g., prolactin also play a significant role in the regulation of adrenal function. The aim of the present study was to measure the adrenocortical cell area and to determine the effects of the transition from the prepubertal to the postpubertal period on the hyperprolactinemic state induced by domperidone (4.0 mg kg-1 day-1, sc. In hyperprolactinemic adult and young rats, the adrenals were heavier, as determined at necropsy, than in the respective controls: adults (30 days: 0.16 ± 0.008 and 0.11 ± 0.007; 46 days: 0.17 ± 0.006 and 0.12 ± 0.008, and 61 days: 0.17 ± 0.008 and 0.10 ± 0.004 mg for treated and control animals, respectively; P < 0.05, and young rats (30 days: 0.19 ± 0.003 and 0.16 ± 0.007, and 60 days: 0.16 ± 0.006 and 0.13 ± 0.009 mg; P < 0.05. We selected randomly a circular area in which we counted the nuclei of adrenocortical cells. The area of zona fasciculata cells was increased in hyperprolactinemic adult and young rats compared to controls: adults: (61 days: 524.90 ± 47.85 and 244.84 ± 9.03 µm² for treated and control animals, respectively; P < 0.05, and young rats: (15 days: 462.30 ± 16.24 and 414.28 ± 18.19; 60 days: 640.51 ± 12.91 and 480.24 ± 22.79 µm²; P < 0.05. Based on these data we conclude that the increase in adrenal weight observed in the hyperprolactinemic animals may be due to prolactin-induced adrenocortical cell hypertrophy.

PRKAR1A-negative familial Cushing's syndrome: two case reports.

Science.gov (United States)

Lim, Lee Ling; Kitan, Normayah; Paramasivam, Sharmila Sunita; Ratnasingam, Jeyakantha; Ibrahim, Luqman; Chan, Siew Pheng; Tan, Alexander Tong Boon; Vethakkan, Shireene Ratna

2015-12-01

Determining the etiology of Cushing's syndrome is very challenging to endocrinologists, with most of the difficulty arising from subtype differentiation of adrenocorticotropic hormone-dependent Cushing's syndrome. We present the pitfalls of evaluating a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome in the transition period between adolescence and adulthood. A sibling pair with familial isolated primary pigmented nodular adrenocortical disease is described. The index case, a 20-year-old Chinese woman, presented with premenopausal osteoporosis with T12 compression fracture and young hypertension. Biochemical analysis confirmed adrenocorticotropic hormone-independent Cushing's syndrome (elevated 0800 h plasma cortisol 808 nmol/L with suppressed adrenocorticotropic hormone level Cushing's syndrome at age 18 years, with typical cushingoid habitus, but no osteoporosis or hypertension. His adrenal computed tomographic scans showed micronodularities over bilateral adrenal glands. He was successfully treated with bilateral adrenalectomy. Screening for Carney's complex and PRKAR1A gene mutation was negative. Signs and symptoms of Cushing's syndrome resolved after bilateral adrenalectomy for both patients. They were placed on lifelong glucocorticoid and mineralocorticoid replacement therapy and long-term surveillance for Carney's complex. The cases of these two patients illustrate the difficulties involved in diagnosing primary pigmented nodular adrenocortical disease, a variant of adrenocorticotropic hormone-independent Cushing's syndrome that is managed with bilateral adrenalectomy. A high index of suspicion for this disease is needed, especially in adolescents with adrenocorticotropic hormone-independent Cushing's syndrome who have a significant family history, features of Carney's complex, and no resolution of Cushing's syndrome after unilateral adrenalectomy. Patients with primary pigmented nodular adrenocortical disease can either have

Novel somatic mutations in the catalytic subunit of the protein kinase A as a cause of adrenal Cushing's syndrome: a European multicentric study.

Science.gov (United States)

Di Dalmazi, Guido; Kisker, Caroline; Calebiro, Davide; Mannelli, Massimo; Canu, Letizia; Arnaldi, Giorgio; Quinkler, Marcus; Rayes, Nada; Tabarin, Antoine; Laure Jullié, Marie; Mantero, Franco; Rubin, Beatrice; Waldmann, Jens; Bartsch, Detlef K; Pasquali, Renato; Lohse, Martin; Allolio, Bruno; Fassnacht, Martin; Beuschlein, Felix; Reincke, Martin

2014-10-01

Somatic mutations in PRKACA gene, encoding the catalytic subunit of protein kinase A (PKA), have been recently found in a high proportion of sporadic adenomas associated with Cushing's syndrome. The aim was to analyze the PRKACA mutation in a large cohort of patients with adrenocortical masses. Samples from nine European centers were included (Germany, n = 4; Italy, n = 4; France, n = 1). Samples were drawn from 149 patients with nonsecreting adenomas (n = 32 + 2 peritumoral), subclinical hypercortisolism (n = 36), Cushing's syndrome (n = 64 + 2 peritumoral), androgen-producing tumors (n = 4), adrenocortical carcinomas (n = 5 + 2 peritumoral), and primary bilateral macronodular adrenal hyperplasias (n = 8). Blood samples were available from patients with nonsecreting adenomas (n = 15), subclinical hypercortisolism (n = 10), and Cushing's syndrome (n = 35). Clinical and hormonal data were collected. DNA amplification by PCR of exons 6 and 7 of the PRKACA gene and direct sequencing were performed. PRKACA heterozygous mutations were found in 22/64 samples of Cushing's syndrome patients (34%). No mutations were found in peritumoral tissue and blood samples or in other tumors examined. The c.617A>C (p.Leu206Arg) occurred in 18/22 patients. Furthermore, two novel mutations were identified: c.600_601insGTG/p.Cys200_Gly201insVal in three patients and c.639C>G+c.638_640insATTATCCTGAGG/p.Ser213Arg+p.Leu212_Lys214insIle-Ile-Leu-Arg) in one. All the mutations involved a region implicated in interaction between PKA regulatory and catalytic subunits. Patients with somatic PRKACA mutations showed higher levels of cortisol after dexamethasone test and a smaller adenoma size, compared with nonmutated subjects. These data confirm and extend previous observations that somatic PRKACA mutations are specific for adrenocortical adenomas causing Cushing's syndrome.

Testosterone-secreting adrenal adenoma in a peripubertal girl

International Nuclear Information System (INIS)

Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.; Hoursanidis, A.; Panageas, S.; Yiannatos, J.

1987-01-01

A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-β-[ 75 Se] selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor

Cell-to-cell communication in bilateral macronodular adrenal hyperplasia causing hypercortisolism

Directory of Open Access Journals (Sweden)

Herve eLefebvre

2015-04-01

Full Text Available It has been well established that, in the human adrenal gland, cortisol secretion is not only controlled by circulating corticotropin but is also influenced by a wide variety of bioactive signals, including conventional neurotransmitters and neuropeptides, released within the cortex by various cell types such as chromaffin cells, neurons, cells of the immune system, adipocytes and endothelial cells. These different types of cells are present in bilateral macronodular adrenal hyperplasia, a rare etiology of primary adrenal Cushing’s syndrome, where they appear intermingled with adrenocortical cells in the hyperplastic cortex. In addition, the genetic events which cause the disease favor abnormal adrenal differenciation that results in illicit expression of paracrine regulatory factors and their receptors in adrenocortical cells. All these defects constitute the molecular basis for aberrant autocrine/paracrine regulatory mechanisms which are likely to play a role in the pathophysiology of bilateral macronodular adrenal hyperplasia-associated hypercortisolism. The present review summarizes the current knowledge on this topic as well as the therapeutic perspectives offered by this new pathophysiological concept.

Testosterone-secreting adrenal adenoma in a peripubertal girl

Energy Technology Data Exchange (ETDEWEB)

Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.; Hoursanidis, A.; Panageas, S.; Yiannatos, J.

1987-11-13

A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-..beta..-(/sup 75/Se) selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor.

Screening for Cushing's syndrome in obese patients

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Ozay Tiryakioglu

2010-01-01

Full Text Available OBJECTIVES: The aim of this study was to examine the frequency of Cushing's syndrome (CS in obese patients devoid of specific clinical symptoms of Cushing's syndrome. METHODS: A total of 150 obese patients (129 female, 21 male; mean age 44.41 ± 13.34 yr; mean BMI 35.76 ± 7.13 were included in the study. As a first screening step, we measured 24-h urinary free cortisol (UFC. An overnight 1-mg dexamethasone suppression test was also performed on all patients. Urinary free cortisol levels above 100 μg/24 h were considered to be abnormal. Suppression of serum cortisol 100 μg/24 h were recorded in 37 patients (24%. Cushing's syndrome was diagnosed in 14 of the 150 patients (9.33%. Etiologic reasons for Cushing's syndrome were pituitary microadenoma (9 patients, adrenocortical adenoma (3 patients, and adrenocortical carcinoma (1 patient. CONCLUSION: A significant proportion (9.33% of patients with simple obesity were found to have Cushing's syndrome. These findings argue that obese patients should be routinely screened for Cushing's syndrome.

Primary hyperparathyroidism with classic and severe skeletal involvement

OpenAIRE

Sandoval, Mark Anthony S; Paz-Pacheco, Elizabeth

2010-01-01

A 63-year-old woman has had multiple repeated fractures. A diagnosis of primary hyperparathyroidism (PHPT) was made after she was found to be hypercalcaemic with an elevated level of intact parathyroid hormone (iPTH). Radiographs revealed classic and severe bone findings in PHPT, features which were common in the past but are thought to be rare at this modern age. She also had nephrolithiasis and osteoporosis. An enlarged parathyroid gland was seen on ultrasound and CT scan, and hyperfunction...

Hansen′s disease with McCune-Albright syndrome

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KVS Hari Kumar

2012-01-01

Full Text Available McCune-Albright syndrome (MAS comprises a triad of fibrous dysplasia of bone, cafι-au-lait macule, and endocrinopathy. The disease is due to activating mutation of G protein-coupled receptor leading to hyperfunction of glands. Hansen′s disease is caused by infection with Mycobacterium leprae and is seen with underlying immunosuppressed conditions in genetically predisposed individuals. We recently encountered a patient with Hansen′s disease along with underlying MAS and report the same in this report.

Nonfunctioning parathyromatosis after endoscopic thyroid lobectomy via an axillo-breast approach: A case report

Energy Technology Data Exchange (ETDEWEB)

Park, Jong Chun; Jeong, Young Ju [School of Medicine, Catholic University of Daegu, Daegu (Korea, Republic of)

2015-04-15

Parathyromatosis is characterized by multiple lesions of benign hyperfunctioning parathyroid tissue in the neck or mediastinum. Parathyromatosis is caused by proliferation of embryonic remnant or seeding of parathyroid tissue after parathyroidectomy. Parathyromatosis is rare but is the common cause of recurrent hyperparathyroidism. We describe a unique case of non-functional parathyromatosis in a 16-year-old girl with a history of right thyroid lobectomy via an axillo-breast approach for a nonfunctioning parathyroid adenoma in the right side of the neck.

The advent of ultrasound-guided ablation techniques in nodular thyroid disease

DEFF Research Database (Denmark)

Papini, Enrico; Pacella, Claudio M; Misischi, Irene

2014-01-01

non-functioning thyroid nodules that grow or become symptomatic, trained operators may safely induce, with a single session of laser ablation treatment or radiofrequency ablation, a 50% volume decrease and, in parallel, improve local symptoms. In contrast, hyperfunctioning nodules remain best treated...... minimally invasive treatments, directed towards office-based management of symptomatic nodules, without requiring general anaesthesia, and with negligible damage to the skin and cervical tissues, have been proposed during the past two decades. Today, ultrasound-guided percutaneous ethanol injection...

Scintigraphy of the functioning thyroid nodule

International Nuclear Information System (INIS)

Mahlstedt, J.

2008-01-01

The evaluation of functioning thyroid nodules is achieved by use of several Iodine isotopes, while in clinical routine 99m Tc-Pertechnetate is dominating. For classification the terms hyperfunctional, isofunctional (normal) and hypofunctional are useful in comparison to the surrounding normally functioning thyroid tissue, which can be stimulated or suppressed. Therefore, autonomous functioning thyroid nodules can vary the scintigraphic appearance. For precise description the terms 'compensation' and 'decompensation' have to be used in relation to scintigraphy or thyroidal metabolism (regulation). (orig.)

Assessment of the relationship between melatonin, hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes, and osteoprotegerin and its ligand sRANKL in girls with anorexia nervosa

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Zofia Ostrowska

2013-05-01

Full Text Available Background: It has been suggested that disturbances in melatonin (MEL secretion might play a role in osteoporosis development in females with anorexia nervosa (AN. It might be hypothesized that changes in the levels of hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes might mediate the potential relationship between MEL and bone tissue.Aim: We investigated whether a relationship existed between MEL and LH, FSH-E2, TSH-FT3, FT4 and ACTH-cortisol axes in girls with AN. We also aimed to establish whether such a relationship might adversely affect the balance of the OPG/sRANKL system.Material/Methods: Eighty-six girls with AN and 21 healthy subjects aged 12.6 to 18.2 years participated in the study. The serum levels of hormones as well as OPG and sRANKL were determined by radioimmunoassay (RIA, immunoradiometric assay (IRMA or enzyme-linked immunosorbent assay (ELISA methods.Discussion: Our study participants with AN showed a significant reduction in body mass and body mass index (BMI, a decrease in LH, E2 and FT3 concentrations, increased MEL concentration at 02.00 hours and increased amplitude between its nocturnal and morning levels (Δ MEL2.00/9.00 as well as an increase in cortisol concentration. These changes were associated with a significant increase of OPG and sRANKL levels and a decrease in the OPG/sRANKL ratio. BMI values correlated positively with LH, FSH, E2, FT3 and the OPG/sRANKL ratio while the correlation between BMI and cortisol was negative. Δ MEL2.00/9.00 correlated positively with cortisol and negatively with LH, FSH, E2, FT3 concentrations and the OPG/sRANKL ratio. A positive correlation was observed between LH, E2 and the OPG/sRANKL ratio as well as between cortisol and sRANKL while the correlation between LH and OPG as well as between cortisol and the OPG/sRANKL ratio was negative. E2 and LH were shown to be significant and independent predictors of Δ MEL2.00/9.00. LH turned out to be a

Giant adrenal tumor presenting as Cushing's syndrome and pheochromocytoma: A case report

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Puskal Kumar Bagchi

2015-07-01

Full Text Available We report a case of a 35-year-old lady who presented with Cushingoid features and associated raised urinary metanephrine. The patient underwent open adrenelectomy. Histopathological examination revealed adreno-cortical carcinoma with microscopic lymphovascular invasion. Postoperative period was uneventful and is on follow-up for the last one year and is doing well.

On angularly perturbed Laplace equations in the unit ball of IR{sup n+2} and their distributional boundary values

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Massopust, P.R.

1997-08-01

All solutions of an in its angular coordinates continuously perturbed Laplace-Beltrami equation in the open unit ball IB{sup n+2} {contained_in} IR{sup n+2}, n {ge} 1, are characterized. Moreover, it is shown that such pertubations yield distributional boundary values which are different from, but algebraically and topologically equivalent to, the hyperfunctions of Lions & Magenes. This is different from the case of radially perturbed Laplace-Beltrami operators (cf. [7]) where one has stability of distributional boundary values under such perturbations.

Update: Systemic Diseases and the Cardiovascular System (II). The endocrine system and the heart: a review.

Science.gov (United States)

Rhee, Soo S; Pearce, Elizabeth N

2011-03-01

Normal endocrine function is essential for cardiovascular health. Disorders of the endocrine system, consisting of hormone hyperfunction and hypofunction, have multiple effects on the cardiovascular system. In this review, we discuss the epidemiology, diagnosis, and management of disorders of the pituitary, thyroid, parathyroid, and adrenal glands, with respect to the impact of endocrine dysfunction on the cardiovascular system. We also review the cardiovascular benefits of restoring normal endocrine function. Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Myopathy in Addison's disease.

OpenAIRE

Mor, F; Green, P; Wysenbeek, A J

1987-01-01

Since the first description of primary adrenocortical insufficiency by Thomas Addison in 1855 several large series of patients with Addison's disease have been published. The common signs and symptoms include: weakness, hyperpigmentation, weight loss, gastrointestinal complaints, and hypotension. It is rare for patients with Addison's disease to present with musculoskeletal symptoms including flexion contractures, hyperkalaemic neuromyopathy, Guillain-Barré syndrome, migratory myalgia, sciati...

The Presence of a Best Friend Buffers the Effects of Negative Experiences

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Adams, Ryan E.; Santo, Jonathan Bruce; Bukowski, William M.

2011-01-01

The goal of the current study was to examine how the presence of a best friend might serve as protection against the effect of negative experiences on global self-worth and the hypothalamic-pituitary-adrenocortical axis (HPA axis). A total of 103 English-speaking male (n = 55) and female (n = 48) participants from Grade 5 (M = 10.27 years) and…

Pheochromocytoma and Adrenocortical Adenoma in the Same Gland

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Wei-Ren Hwang

2007-07-01

Full Text Available A right adrenal tumor was found incidentally during abdominal computed tomography exam in a 51-year-old female patient, who had had diabetes and hypertension for more than 10 years. The computed tomography scan was arranged for possible pancreatic lesion by a neurologist. Norepinephrine level was high in the plasma and urine. Vanillylmandelic acid level was elevated in the urine. Diurnal cortisol rhythm, plasma adrenocorticotropic hormone and urine free cortisol were all normal, but the plasma cortisol concentration could not be suppressed after a standard low-dose dexamethasone suppression test. Therefore, adrenal cortical adenoma with subclinical Cushing's syndrome was highly suspected; however, further imaging studies, including magnetic resonance image and 131I-6β-iodomethylnorcholesterol adrenal scintigraphy failed to discriminate an additional tumor. After right adrenalectomy, a small adrenal cortical adenoma and a large pheochromocytoma were noted. This is an extremely rare case of an adrenal incidentaloma consisting of both medullary and cortical tumors in the same gland.

Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition.

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Blagosklonny, Mikhail V

2006-09-01

While ruling out programmed aging, evolutionary theory predicts a quasi-program for aging, a continuation of the developmental program that is not turned off, is constantly on, becoming hyper-functional and damaging, causing diseases of aging. Could it be switched off pharmacologically? This would require identification of a molecular target involved in cell senescence, organism aging and diseases of aging. Notably, cell senescence is associated with activation of the TOR (target of rapamycin) nutrient- and mitogen-sensing pathway, which promotes cell growth, even though cell cycle is blocked. Is TOR involved in organism aging? In fact, in yeast (where the cell is the organism), caloric restriction, rapamycin and mutations that inhibit TOR all slow down aging. In animals from worms to mammals caloric restrictions, life-extending agents, and numerous mutations that increase longevity all converge on the TOR pathway. And, in humans, cell hypertrophy, hyper-function and hyperplasia, typically associated with activation of TOR, contribute to diseases of aging. Theoretical and clinical considerations suggest that rapamycin may be effective against atherosclerosis, hypertension and hyper-coagulation (thus, preventing myocardial infarction and stroke), osteoporosis, cancer, autoimmune diseases and arthritis, obesity, diabetes, macula-degeneration, Alzheimer's and Parkinson's diseases. Finally, I discuss that extended life span will reveal new causes for aging (e.g., ROS, 'wear and tear', Hayflick limit, stem cell exhaustion) that play a limited role now, when quasi-programmed senescence kills us first.

A model for treating voice disorders in school-age children within a video gaming environment.

Science.gov (United States)

King, Suzanne N; Davis, Larry; Lehman, Jeffrey J; Ruddy, Bari Hoffman

2012-09-01

Clinicians use a variety of approaches to motivate children with hyperfunctional voice disorders to comply with voice therapy in a therapeutic session and improve the motivation of children to practice home-based exercises. Utilization of current entertainment technology in such approaches may improve participation and motivation in voice therapy. The purpose of this study is to test the feasibility of using an entertainment video game as a therapy device. Prospective cohort and case-control study. Three levels of game testing were conducted to an existing entertainment video game for use as a voice therapy protocol. The game was tested by two computer programmers and five normal participants. The third level of testing was a case study with a child diagnosed with a hyperfunctional voice disorder. Modifications to the game were made after each feasibility test. Errors with the video game performance were modified, including the addition of a time stamp directory and game controller. Resonance voice exercises were modified to accommodate the gaming environment and unique competitive situation, including speech rate, acoustic parameters, game speed, and point allocations. The development of video games for voice therapeutic purposes attempt to replicate the high levels of engagement and motivation attained with entertainment video games, stimulating a more productive means of learning while doing. This case study found that a purely entertainment video game can be implemented as a voice therapeutic protocol based on information obtained from the case study. Copyright © 2012 The Voice Foundation. All rights reserved.

Interstitial laser photocoagulation for benign thyroid nodules: time to treat large nodules.

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Amabile, Gerardo; Rotondi, Mario; Pirali, Barbara; Dionisio, Rosa; Agozzino, Lucio; Lanza, Michele; Buonanno, Luciano; Di Filippo, Bruno; Fonte, Rodolfo; Chiovato, Luca

2011-09-01

Interstitial laser photocoagulation (ILP) is a new therapeutic option for the ablation of non-functioning and hyper-functioning benign thyroid nodules. Amelioration of the ablation procedure currently allows treating large nodules. Aim of this study was to evaluate the therapeutic efficacy of ILP, performed according to a modified protocol of ablation, in patients with large functioning and non-functioning thyroid nodules and to identify the best parameters for predicting successful outcome in hyperthyroid patients. Fifty-one patients with non-functioning thyroid nodules (group 1) and 26 patients with hyperfunctioning thyroid nodules (group 2) were enrolled. All patients had a nodular volume ≥40 ml. Patients were addressed to 1-3 cycles of ILP. A cycle consisted of three ILP sessions, each lasting 5-10 minutes repeated at an interval of 1 month. After each cycle of ILP patients underwent thyroid evaluation. A nodule volume reduction, expressed as percentage of the basal volume, significantly occurred in both groups (F = 190.4; P nodule volume; (iii) total amount of energy delivered expressed in Joule. ROC curves identified the percentage of volume reduction as the best parameter predicting a normalized serum TSH (area under the curve 0.962; P thyroid nodules, both in terms of nodule size reduction and cure of hyperthyroidism (87% of cured patients after the last ILP cycle). ILP should not be limited to patients refusing or being ineligible for surgery and/or radioiodine. Copyright © 2011 Wiley-Liss, Inc.

Bipolar radiofrequency ablation of benign thyroid nodules using a multiple overlapping shot technique in a 3-month follow-up.

Science.gov (United States)

Kohlhase, Konstantin David; Korkusuz, Yücel; Gröner, Daniel; Erbelding, Christian; Happel, Christian; Luboldt, Wolfgang; Grünwald, Frank

2016-08-01

Purpose The aim of this study was to evaluate the decrease of benign thyroid nodules after bipolar radiofrequency ablation (RFA) in a 3-month follow-up using a multiple overlapping shot technique ('MOST'). Methods A total of 18 patients with 20 symptomatic benign thyroid nodules (17 cold nodules, 3 hyperfunctioning nodules) were treated in one single session by bipolar RFA. Bipolar ablation was performed using MOST. The nodule volumes were measured prior to ablation and 3 months after the procedure using ultrasound. The population consisted of either solid (>80% solid tissue within the volume of interest), complex, or cystic nodules (nodule volume (ΔV), median 5.3 mL (range 0.13-43.1 mL), corresponding to a relative reduction in mean of 56 ± 17.9%. Median initial volume was 8 mL (range 0.48-62 mL); 3 months after ablation a median volume of 2.3 mL (range 0.3-32 mL) was measured. Nodule growth ≥50% occurred in 70% (14 nodules). At the follow-up no complications such as infections, persisting pain, nerve injuries or immunogen stimulation occurred. Patients with cold nodules (15) remained euthyroid, with hyperfunctioning nodules either euthyroid (2) or latent hypofunctional (1). Conclusion The use of bipolar RFA is an effective, safe and suitable thermoablative technique to treat benign thyroid nodules. Combined with the multiple overlapping shot technique it allows sufficient ablation.

Autoimmune Addison's disease.

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Napier, Catherine; Pearce, Simon H S

2012-12-01

Addison's disease is a rare autoimmune disorder. In the developed world, autoimmune adrenalitis is the commonest cause of primary adrenal insufficiency, where the majority of patients have circulating antibodies against the key steroidogenic enzyme 21-hydroxylase. A complex interplay of genetic, immunological and environmental factors culminates in symptomatic adrenocortical insufficiency, with symptoms typically developing over months to years. Biochemical evaluation and further targeted investigations must confirm primary adrenal failure and establish the underlying aetiology. The diagnosis of adrenocortical insufficiency will necessitate lifelong glucocorticoid and mineralocorticoid replacement therapy, aiming to emulate physiological patterns of hormone secretion to achieve well-being and good quality of life. Education of patients and healthcare professionals is essential to minimise the risk of a life-threatening adrenal crisis, which must be promptly recognised and aggressively managed when it does occur. This article provides an overview of our current understanding of the natural history and underlying genetic and immunological basis of this condition. Future research may reveal novel therapeutic strategies for patient management. Until then, optimisation of pharmacological intervention and continued emphasis on education and empowerment of patients should underpin the management of individuals with autoimmune Addison's disease. Copyright © 2012. Published by Elsevier Masson SAS.

Umbilical Cord Blood-Derived Stem Cells Improve Heat Tolerance and Hypothalamic Damage in Heat Stressed Mice

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Ling-Shu Tseng

2014-01-01

Full Text Available Heatstroke is characterized by excessive hyperthermia associated with systemic inflammatory responses, which leads to multiple organ failure, in which brain disorders predominate. This definition can be almost fulfilled by a mouse model of heatstroke used in the present study. Unanesthetized mice were exposed to whole body heating (41.2°C for 1 hour and then returned to room temperature (26°C for recovery. Immediately after termination of whole body heating, heated mice displayed excessive hyperthermia (body core temperature ~42.5°C. Four hours after termination of heat stress, heated mice displayed (i systemic inflammation; (ii ischemic, hypoxic, and oxidative damage to the hypothalamus; (iii hypothalamo-pituitary-adrenocortical axis impairment (reflected by plasma levels of both adrenocorticotrophic-hormone and corticosterone; (iv decreased fractional survival; and (v thermoregulatory deficits (e.g., they became hypothermia when they were exposed to room temperature. These heatstroke reactions can be significantly attenuated by human umbilical cord blood-derived CD34+ cells therapy. Our data suggest that human umbilical cord blood-derived stem cells therapy may improve outcomes of heatstroke in mice by reducing systemic inflammation as well as hypothalamo-pituitary-adrenocortical axis impairment.

SLC26A4 Variations Among Graves’ Hyper-Functioning Thyroid Gland

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Hassen Hadj-Kacem

2010-01-01

Full Text Available Deleterious mutations of SLC26A4 cause Pendred syndrome (PS, an autosomal recessive disorder comprising goitre and deafness with enlarged vestibular aqueducts (EVA, and nonsyndromic hearing loss (NSHL. However, the SLC26A4 hyperactivity was recently associated with the emergence of autoimmune thyroid diseases (AITD and asthma among human and mouse model. Here, by direct sequencing, we investigate the sequences of the 20 coding exons (2 to 21 of SLC26A4 and their flanking intron-exon junctions among patients affected with Graves' disease (GD hyperthyroidism. Ten mono-allelic variants were identified, seven of which are intronic and previously unreported. Two, c.898A>C (p.I300L and c.1061T>C (p.F354S, of the three exonic variants are non synonymous. The p.F354S variant is already described to be involved in PS or NSHL inheritances. The exploration by PCR-RFLP of p.I300L and p.F354S variants among 132 GD patients, 105 Hashimoto thyroiditis (HT, 206 Healthy subjects and 102 families with NSHL have shown the presence of both variants. The p.F354S variation was identified both among patients (1~HT and 3 GD and healthy subjects (n=5. Whereas, the p.I300L variant was identified only in GD patients (n=3. Our studies provide evidence of the importance of systematic analysis of SLC26A4 gene sequences on models other than deafness. This approach allows the identification of new variants and the review of the pathogenic effects of certain mono-allelic variants reported responsible for PS and NSHL development.

The Assessment Methods of Laryngeal Muscle Activity in Muscle Tension Dysphonia: A Review

Science.gov (United States)

Khoddami, Seyyedeh Maryam; Nakhostin Ansari, Noureddin; Izadi, Farzad; Talebian Moghadam, Saeed

2013-01-01

The purpose of this paper is to review the methods used for the assessment of muscular tension dysphonia (MTD). The MTD is a functional voice disorder associated with abnormal laryngeal muscle activity. Various assessment methods are available in the literature to evaluate the laryngeal hyperfunction. The case history, laryngoscopy, and palpation are clinical methods for the assessment of patients with MTD. Radiography and surface electromyography (EMG) are objective methods to provide physiological information about MTD. Recent studies show that surface EMG can be an effective tool for assessing muscular tension in MTD. PMID:24319372

Radionuclide investigations of the hormonal reflection of warm stress in cancer patients under whole body guided hyperthermia

International Nuclear Information System (INIS)

Prokhorova, V.I.; Zhavrid, Eh.A.; Fradkin, S.Z.; Tsyrus', T.P.; Shitikov, B.D.; Kosheleva, M.I.

1991-01-01

The results of the radioimmunoassay of ACTH, ST, hydrocortisone, glucagon, C-peptide, insulin and cyclic nucleotides in 180 patients with advanced and metastatic melanomas, soft tissue sarcomas, lung cancers and renal cell carcinomas testify to the development of the syndrome of endocrine hyperfunction in patients under whole-body guided hyperthermia and artificial hyperglycemia as well as of functional pancreas insufficiency. The data presented form a biochemical basis for working out measures to optimally carry out whole-body hyperthermia and artificial hyperglycemia treatment, aimed at increasing the range of indications for its use in clinical oncology

Incomplete McCune-Albright Syndrome: A Case Report

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Nagehan Aslan

2014-08-01

Full Text Available Fibrous dysplasia of bone is a genetic, non-inheritable disease that can cause bone pain, bone deformities and fracture. It has a large clinic spectrum from benign monostotic fibrous dysplasia to McCune-Albright syndrome. Rare McCune-Albright syndrome is characterized by precocious puberty, cafe au lait spots and fibrous dysplasia. Herein we presented a case who was preferred to hospital with pathological fractures and diagnosed with Incomplet McCune Albright syndrome because of the lack of endocrine hyperfunction and developed early puberty at clinical course.

Follicular thyroid carcinoma masquerading as subacute thyroiditis diagnosis using ultrasonography and radionuclide thyroid angiography

International Nuclear Information System (INIS)

Prakash, R.; Jayaram, G.

1991-01-01

The rare presentation of a follicular thyroid carcinoma mimicking the clinical and radionuclide features of subacute thyroiditis is described. Granulomatous thyroiditis was initially suspected on the clinical basis. Repeat fine needle aspiration cytology was suggestive of acinar proliferation with hyperfunction. Ultrasonography revealed a solid nodule with a peripheral sonolucent halo. Radionuclide angiography showed intense arterial flow of Tc-99m pertechnetate through the right lobe thyroid enlargement suggestive of malignant thyroid pathology. Surgical excision and histopathological examination revealed a follicular carcinoma involving the right lobe. 31 refs., 4 figs

Radionuclide investigations of the hormonal reflection of warm stress in cancer patients under whole body guided hyperthermia. Radionuklidnye issledovaniya gormonal'nykh proyavlenij teplovogo stressa u onkologicheskikh bol'nykh pri obshchej upravlyaemoj gipertermii

Energy Technology Data Exchange (ETDEWEB)

Prokhorova, V I; Zhavrid, Eh A; Fradkin, S Z; Tsyrus' , T P; Shitikov, B D; Kosheleva, M I

1991-01-01

The results of the radioimmunoassay of ACTH, ST, hydrocortisone, glucagon, C-peptide, insulin and cyclic nucleotides in 180 patients with advanced and metastatic melanomas, soft tissue sarcomas, lung cancers and renal cell carcinomas testify to the development of the syndrome of endocrine hyperfunction in patients under whole-body guided hyperthermia and artificial hyperglycemia as well as of functional pancreas insufficiency. The data presented form a biochemical basis for working out measures to optimally carry out whole-body hyperthermia and artificial hyperglycemia treatment, aimed at increasing the range of indications for its use in clinical oncology.

Change of Oral to Topical Corticosteroid Therapy Exacerbated Glucose Tolerance in a Patient with Plaque Psoriasis

OpenAIRE

Hongo, Yui; Ashida, Kenji; Ohe, Kenji; Enjoji, Munechika; Yamaguchi, Miyuki; Kurata, Tsuyoshi; Emoto, Akiko; Yamanouchi, Hiroko; Takagi, Satoko; Mori, Hitoe; Kawata, Nozomi; Hisata, Yoshio; Sakanishi, Yuta; Izumi, Kenichi; Sugioka, Takashi

2017-01-01

Patient: Male, 80 Final Diagnosis: Plaque psoriasis• drug induced diabetes Symptoms: Hyperglycemia• adrenocortical dysfunction Medication: Oral steroid• Topical steroid• Insulin Clinical Procedure: Changing route and strength of steroid administration Specialty: Endocrinology• Dermatology Objective: Rare disease Background: Psoriasis is known as the most frequent disease treated by long-term topical steroids. It is also known that patients with thick, chronic plaques require the highest poten...

The adrenal gland and the patient with pulmonary tuberculosis infected with human immunodeficiency virus

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Ifedayo Adeola Odeniyi

2017-01-01

Full Text Available Background: The adrenal gland is not spared from the involvement by tuberculosis. One of the recognized causes of adrenal insufficiency (AI is tuberculosis. AI, mostly at the subclinical level, is common in persons with pulmonary tuberculosis (PTB infection, occurring in about 23% of patients. Coinfection with PTB and human immunodeficiency virus (HIV may compromise adrenocortical function and produce significant adrenocortical insufficiency. Objective: To determine if coinfection with tuberculosis and HIV have a compound effect on adrenocortical function in persons with HIV and PTB coinfection. Materials and Methods: Persons with sputum-positive PTB, treatment naive, who met our inclusion criteria, were selected. All the recruited patients were screened for HIV and those positive for HIV infection had confirmatory test. A baseline blood samples for cortisol, fasting plasma glucose, full blood count, and electrolytes were collected between 8.00 h and 9.00 h immediately before administration of adrenocorticotropic hormone (ACTH. The persons received an intravenous bolus injection of 1 μg ACTH (Alliance Pharmaceuticals Ltd., Chippenham, Wiltshire SN15 2BB and blood sample was drawn for cortisol level at 30 min. Results: Forty-four people with PTB infection and forty people with PTB and HIV coinfection met the inclusion criteria of the study. The adrenal response to 1 μg ACTH stimulation in participants with PTB and PTB and HIV coinfection showed that the mean basal cortisol level in the 2 groups was not statistically significant; however, 30-min post-ACTH stimulation cortisol level was 630.84 ± 372.17 and 980.36 ± 344.82 nmol/L (P < 0.001 and increment was 367.79 ± 334.87 and 740.77 ± 317.97 nmol/L (P < 0.001, respectively. Fourteen persons (31.8% with PTB has subnormal adrenal response to ACTH stimulation while only 2 (5% persons with PTB and HIV coinfection has subnormal response. Conclusion: AI, at subclinical level, was less frequent in

Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test

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René Rodríguez-Gutiérrez

2016-01-01

Full Text Available Background. Multidrug-resistant tuberculosis (MDR-TB is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction that if not diagnosed could seriously jeopardize patients’ health. Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 μg ACTH stimulation test at baseline and at 6–12 months of follow-up after antituberculosis treatment and culture conversion. Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 μg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment. Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2% of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3% alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2±3.6 months adrenocortical function was restored in all cases. Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical

Invasive fungal infections in endogenous Cushing's syndrome

Science.gov (United States)

Scheffel, Rafael Selbach; Dora, José Miguel; Weinert, Letícia Schwerz; Aquino, Valério; Maia, Ana Luiza; Canani, Luis Henrique; Goldani, Luciano Z.

2010-01-01

Cushing's syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing's original description of the disease. We describe here a patient with endogenous Cushing's syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease. PMID:24470886

131I-19-iodocholesterol scintigraphy and suprarenal pathology

International Nuclear Information System (INIS)

Leger, F.A.; Baulieu, J.L.; Plouin, P.F.

The methods used and results obtained by 131 I-19-iodocholesterol scintigraphy (dose 2mCi) are given for 24 patients with various kinds of suprarenal hyperactivity (primary hyperaldosteronism, Cushing's syndrome, malignant adrenocortical tumour, pheochromocytoma). The morphological and quantitative aspects of suprarenal scintigraphy are examined. A technique to determine the iodocholesterol uptake ratio of the two adrenal glands, considered more important than the fixation rate of each is described [fr

Immunologic Storm Simulating Systemic Lupus Erythematosus Following Parvovirus B19 Infection

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Roxana González-Mazarío

2015-02-01

Full Text Available Background: The appearance of symptoms compatible with systemic autoimmune diseases has been described in relation to several viral infections like HIV, cytomegalovirus and especially PVB19, depending on the evolution of the immunological condition of the host and their age. We present a young immunocompetent male patient, with clinical manifestations simulating systemic lupus erythematosus (SLE with important activation of cytokines. Methods: For quantification of the different cytokines in plasma, a commercially available multiplex bead immunoassay, based on the Luminex platform (Cat # HSCYTO-60SK-08, Milliplex® MAP High Sensitivity, Millipore, was used according to the manufacturer’s instructions. All samples were run in duplicate and the data (mean fluorescence intensity were analyzed using a Luminex reader. The mean concentration was calculated using a standard curve. Results: The clinical evolution was favourable without the need for any specific treatment, showing complete recovery after two months. Whilst the symptoms and viral charge were disappearing, the anti-DNA continued to increase and we demonstrate important activation of IL-10, IL-6 and TNFα cytokines as a result of a hyperstimulating response by an immunocompetent hyperfunctional system, which persists after clinical improvement. We should emphasize the behaviour of two cytokines: IL-12p70 and IL-2, which showed opposite tendencies. Conclusions: Viral infections, especially PVB19, can produce or simulate several autoimmune diseases as a hyperstimulation response from an immunocompetent hyperfunctional system. Consequently, a persistent increase of autoantobodies and important activation of cytokines, even after clinical improvement and seroconversion, can be demonstrated.

Discriminatory power of MRI for differentiation of adrenal non-adenomas vs adenomas evaluated by means of ROC analysis: Can biopsy be obviated?

Energy Technology Data Exchange (ETDEWEB)

Slapa, R.Z.; Jakubowski, W.; Krolicki, L. [Department of Imaging, Warsaw Medical School (Poland); Januszewicz, A. [Department of Hypertension, National Institute of Cardiology, Warsaw (Poland); Kasperlik-Zaluska, A.A. [Department of Endocrinology, Center for Postgraduate Medical Education, Warsaw (Poland); Dabrowska, E.; Feltynowski, T. [Department of Hypertension, Warsaw Medical School, Warsaw (Poland); Fijuth, J. [Department of Teleradiotherapy, Institute of Oncology, Warsaw (Poland); Tarnawski, R. [Department of Radiotherapy, Institute of Oncology, Gliwice Branch, Gliwice (Poland)

2000-01-01

The purpose of our study was to evaluate the discriminatory power of MRI in high-field magnet (1.5 T) for differentiation of adrenal non-adenomas vs adenomas assessing the following parameters separately and in combination: mean diameter of adrenal mass; previously described and new ratios as well as index calculated from signal intensity (SI) on SE T2-weighted images, chemical shift imaging (CSI), and Gd-DTPA-enhanced dynamic studies. One hundred eight adrenal masses (36 non-hyperfunctioning adenomas, 27 pheochromocytomas, 23 aldosterone-secreting adenomas, 20 malignant masses and 2 cortisol-secreting adenomas) in 95 patients were evaluated with SE sequences, CSI and Gd-DTPA dynamic studies. Indices and ratios of SI for all examined MRI methods were calculated and examined retrospectively for significance of differences between the groups with calculation of sensitivity and specificity. Receiver operating characteristics (ROC) analysis of calculated parameters in combination was performed. The multifactorial analysis of all four parameters, including size of the tumor, T2{sub liver} index, CSI ratio reflecting lipid content in the tumor and Wo{sub max/last} ratio reflecting maximal washout of contrast agent from the tumor had 100 % sensitivity and 100 % specificity in characterization of adrenal non-adenoma. The best performance of combination of mean tumor diameter with single MRI SI parameter was achieved in combination with T2{sub liver} index for all adrenal masses (area under ROC 0.987) and CSI ratio for non-hyperfunctioning adrenal masses (area under ROC 0.991). Magnetic resonance imaging enables sensitive and specific diagnosis of adrenal non-adenoma. (orig.)

Marine-Lenhart syndrome with papillary thyroid carcinoma

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Hulusi Atmaca

2015-01-01

Full Text Available Graves′ disease with accompanying functioning nodules is known as Marine-Lenhart syndrome. Autonomously functioning thyroid nodules (AFTNs also within Graves′ thyroid tissue are almost always bening in nature. A 45-year-old man developed hyperthyroidism due to the coexistence of Graves′ disease and AFTN. Total thyroidectomy was performed. The hyperfunctioning nodule with centrally hypoactive foci detected by technetium-99m thyroid scanning was histologically diagnosed as papillary thyroid carcinoma that was 2.5 cm in diameter. We report the presence of papillary thyroid carcinoma within AFTN in patients with Marine-Lenhart syndrome, which has not been reported so far.

Unusual cause for recurrent Cushing syndrome and its diagnosis by computed tomography and NP-59 radiocholesterol scanning

International Nuclear Information System (INIS)

Harris, R.D.; Herwig, K.R.

1990-01-01

Cushing syndrome can recur following an adrenalectomy. One of the primary causes is recurrence of adrenal carcinoma either locally or from metastases. Hyperplasia and hyperfunction of adrenal remnants may also occur if there is pituitary stimulation. We have a patient in whom recurrent Cushing syndrome developed from small nonmalignant deposits of adrenal tissue in the perirenal adipose tissue following adrenalectomy of a benign adenoma. These deposits were identifiable by computed tomography. A false-negative NP-59 iodocholesterol scan was instructive in pointing out some problems in the interpretation of this type of scan for adrenal tissue

Marine-Lenhart syndrome with papillary thyroid carcinoma.

Science.gov (United States)

Atmaca, Hulusi; Çolak, Ramis; Yazici, Zihni Acar; Kefeli, Mehmet; Tosun, Fevziye Canbaz

2015-04-01

Graves' disease with accompanying functioning nodules is known as Marine-Lenhart syndrome. Autonomously functioning thyroid nodules (AFTNs) also within Graves' thyroid tissue are almost always bening in nature. A 45-year-old man developed hyperthyroidism due to the coexistence of Graves' disease and AFTN. Total thyroidectomy was performed. The hyperfunctioning nodule with centrally hypoactive foci detected by technetium-99m thyroid scanning was histologically diagnosed as papillary thyroid carcinoma that was 2.5 cm in diameter. We report the presence of papillary thyroid carcinoma within AFTN in patients with Marine-Lenhart syndrome, which has not been reported so far.

Thyroid carcinoma presenting as a pertechnetate ''Hot'' nodule, but with 131I uptake: case report

International Nuclear Information System (INIS)

Turner, J.W.; Spencer, R.P.

1976-01-01

A 24-year-old woman presented with a mass on the right side of the neck; this proved to be a hyperfunctioning or hot nodule on /sup 99m/Tc-scan. Because of the firmness of the area, the study was repeated with 131 I, but the region did not accumulate radioiodide. The tissue showing this discrepant handling of pertechnetate and radioiodide was surgically removed and identified as a follicular carcinoma with papillary foci. A brief review of the literature data on the disassociation of thyroid trapping and organification functions, and hence of possible discrepancies between pertechnetate and radioiodide uptake, is given

Thyroid nodule

International Nuclear Information System (INIS)

McKenney, J.F.

1975-01-01

A palpable mass or nodule may represent any one of a large and diverse group of conditions that involve the thyroid. Whether the patient is euthyroid, hypothyroid, or hyperthyroid can be assessed, and the cause of hypofunction or hyperfunction can usually be determined. Scintiscanning provides important information on the anatomic structure of thyroid nodules. A hot nodule should be ablated by either radioiodine or surgery. A warm nodule usually responds to suppression therapy; if regression does not occur, the problem should be reevaluated. A cold nodule should be surgically excised, as microscopic study of such a lesion is mandatory

Radioiodine treatment in McCune-Albright syndrome with hyperthyroidism

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Dhritiman Chakraborty

2012-01-01

Full Text Available McCune-Albright syndrome (MAS is a sporadic disease characterized by polyostotic fibrous dysplasia, "café-au-lait" spots and hyperfunctional endocrinopathies. Pathophysiological basis is activating mutation of the gene that encodes the alpha subunit of Gs membrane protein that stimulates the intracellular production of cAMP, conferring autonomous secretion of the gland in particular. One of the uncommon endocrine manifestations is hyperthyroidism. We present a patient who had café-au-lait spots, polyostotic fibrous dysplasia and hyperthyroidism. She was treated with radioactive iodine for the symptoms of hyperthyroidism and subsequently relieved from hyperthyroid features.

A case of isolated adrenocorticotropic hormone deficiency: a rare but possible cause of hypercalcemia

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Harano Y

2015-03-01

Full Text Available Yumi Harano,1 Atsuko Kitano,2 Yurika Akiyama,1 Lisa Kotajima,1 Kazufumi Honda,1 Hiroko Arioka11Department of General Internal Medicine, 2Department of Medical Oncology, St Luke’s International Medical Center, Tokyo, JapanAbstract: A 52-year-old woman presented with an 8-month history of epigastric pain, nausea, and weight loss. One year before, she was diagnosed with breast cancer. During the postoperative chemotherapy, she developed epigastric pain and nausea. As a result, she gradually lost 12 kg of her body weight. We performed upper gastrointestinal endoscopy, which revealed mild erosive gastritis. After the treatment with a proton pump inhibitor, her symptoms persisted. Before the admission, mild hypercalcemia was pointed out. Fluid replacement didn't improve hypercalcemia. We assessed adrenocortical function, which showed that her serum cortisol and adrenocorticotropic hormone were decreased. Through loading tests, we established diagnosis of isolated adrenocorticotropic hormone deficiency. She was treated with hydrocortisone. Soon after the treatment, her serum calcium level returned to normal and her symptoms improved. In a case of hypercalcemia unresponsive to fluid replacement, we recommend ruling out adrenal insufficiency after excluding more common diseases which induce hypercalcemia.Keywords: hypercalcemia, breast cancer, chemotherapy, adrenocorticotropic hormone deficiency, adrenocortical insufficiency

Cell proliferation, movement and differentiation during maintenance of the adult mouse adrenal cortex.

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Su-Ping Chang

Full Text Available Appropriate maintenance and regeneration of adult endocrine organs is important in both normal physiology and disease. We investigated cell proliferation, movement and differentiation in the adult mouse adrenal cortex, using different 5-bromo-2'-deoxyuridine (BrdU labelling regimens and immunostaining for phenotypic steroidogenic cell markers. Pulse-labelling showed that cell division was largely confined to the outer cortex, with most cells moving inwards towards the medulla at around 13-20 µm per day, though a distinct labelled cell population remained in the outer 10% of the cortex. Pulse-chase-labelling coupled with phenotypic immunostaining showed that, unlike cells in the inner cortex, most BrdU-positive outer cortical cells did not express steroidogenic markers, while co-staining for BrdU and Ki67 revealed that some outer cortical BrdU-positive cells were induced to proliferate following acute adrenocorticotropic hormone (ACTH treatment. Extended pulse-chase-labelling identified cells in the outer cortex which retained BrdU label for up to 18-23 weeks. Together, these observations are consistent with the location of both slow-cycling stem/progenitor and transiently amplifying cell populations in the outer cortex. Understanding the relationships between these distinct adrenocortical cell populations will be crucial to clarify mechanisms underpinning adrenocortical maintenance and long-term adaptation to pathophysiological states.

Neurobehavioral endocrine regulation of small mammal populations

International Nuclear Information System (INIS)

Christian, J.J.

1978-01-01

A brief review is given of the hypothesis that density-dependent behavioral-endocrine negative feedbacks can regulate and often limit the growth of populations of many species of small mammals. Recent laboratory studies are summarized that show how stress, particularly psychogenic, which results in increased adrenocortical secretion also alters gonadotropin secretion and inhibits reproduction. Chronic stress due to crowding, immobilization, et al. inhibits the release of LH and FSH, particularly by abolishing the pulsatile release of LH, and also causes a rise in prolactin (at least acutely). Stimulation of the hypothalamo-pituitary-adrenocortical system is accompanied by an inversely proportional inhibition of growth hormone secretion. Decreasing photoperiod enhances the sensitivity of the hypothalamus to inhibition of gonadotropin secretion by androgens and estrogens. Other endocrine responses to increased density or subordinate social rank also are summarized. How these facts fit into the negative feedback scheme is discussed, including the greatly prolonged effects of diminished lactation. The changed quality of the animals associated with changes in density discussed by Lidicker also can be explained by the above responses to density. Data on changes in growth and reproductive function which are consistent with the behavioral-endocrine feedback hypothesis are presented for several populations of small mammals, including some previously unpublished data for Microtus pennsylvanicus

Renal tubular acidosis complicated with hyponatremia due to cortisol insufficiency

OpenAIRE

Izumi, Yuichiro; Nakayama, Yushi; Onoue, Tomoaki; Inoue, Hideki; Mukoyama, Masashi

2015-01-01

Adrenocortical insufficiency such as occurs in Addison's disease causes hyponatremia and renal tubular acidosis (RTA). Hyponatremia results from both aldosterone and cortisol insufficiency. RTA is due to aldosterone insufficiency. The involvement of cortisol in RTA is unclear. Here, we report a woman in her 70s who was admitted to our hospital with severe hyponatremia (106 mEq/l) and RTA. The patient exhibited low plasma cortisol levels with little response to rapid adrenocorticotropic hormon...

Longitudinal measurement of cortisol in association with mental health and experience of domestic violence and abuse: study protocol

OpenAIRE

Lokhmatkina, Natalia V; Feder, Gene; Blake, Sarah; Morris, Richard; Powers, Victoria; Lightman, Stafford

2013-01-01

Background Domestic violence and abuse is threatening behavior, violence/abuse used by one person to control the other within an intimate or family-type relationship. Women experience more severe physical and sexual domestic violence and abuse and more mental health consequences than men. The current study aims at exploring of the role of hypothalamic-pituitary-adrenocortical axis activity in abuse impact on women's mental health. Study objectives: 1) To evaluate diurnal cortisol slope, corti...

Dicty_cDB: SSK827 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available |pid:none) Xenopus laevis achalasia, adrenoco... 80 8e-14 BC067671_1( BC067671 |pid:none) Danio rerio achalasia...222509_1( AK222509 |pid:none) Homo sapiens mRNA for achalasia, a... 65 2e-09 (Q9NRG9) RecName: Full=Aladin; ... cl... 65 3e-09 BC120418_1( BC120418 |pid:none) Bos taurus achalasia, adrenocortic... 63 7e-09 AK087134_1( A

The Contribution of Serine 194 Phosphorylation to Steroidogenic Acute Regulatory Protein Function

OpenAIRE

Sasaki, Goro; Zubair, Mohamad; Ishii, Tomohiro; Mitsui, Toshikatsu; Hasegawa, Tomonobu; Auchus, Richard J.

2014-01-01

The steroidogenic acute regulatory protein (StAR) facilitates the delivery of cholesterol to the inner mitochondrial membrane, where the cholesterol side-chain cleavage enzyme catalyzes the initial step of steroid hormone biosynthesis. StAR was initially identified in adrenocortical cells as a phosphoprotein, the expression and phosphorylation of which were stimulated by corticotropin. A number of in vitro studies have implicated cAMP-dependent phosphorylation at serine 194 (S194, S195 in hum...

Clinical and prognostic aspects of adrenocortical neoplasms in childhood.

Science.gov (United States)

Teinturier, C; Pauchard, M S; Brugières, L; Landais, P; Chaussain, J L; Bougnères, P F

1999-02-01

A retrospective study of 54 children was undertaken to define the clinical presentation and secretory patterns of adrenal tumors and to evaluate the outcome of surgical resection and medical therapy. Different factors were studied in univariate and multivariate analysis by using the Cox proportional hazard model. Median age at diagnosis was 4 years. Boys and girls were affected equally. The disease was revealed by virilization (61%) or by a palpable mass (39%) with a 0.1-5.5 year delay from initial symptoms. At initial examination, we found that 76% of children were virilized. Ninety-four percent of the tested tumors secreted androgens, which were associated with glucocorticoids in 36%. Adrenal tumors in children were smaller than in adults. Half of them measured less than 10 cm. There were recurrences in 40% of children. The survival rate at 5 years was 49%, 70% if resection was microscopically complete and 7% if not (P < 0.001). In children, rare adrenal tumors have different diagnostic and prognostic characteristics than in adults; however, recurrences remain frequent. The efficacy of chemotherapy, mainly o,p'-DDD (Mitotane), remains to be evaluated in comparative trials.

Treatment of hyperfunctioning thyroid nodules with percutaneous ethanol injection: Eight years' experience.

Science.gov (United States)

Monzani, F; Caraccio, N; Goletti, O; Casolaro, A; Lippolis, P V; Cavina, E; Miccoli, P

1998-01-01

The aim of our study was to define the long-term efficacy and safety of percutaneous ethanol injection (PEI) for the treatment of autonomous thyroid nodule (ATN), and to optimise the clinical usefulness of such a therapy. We treated 132 patients with ATN (30 M and 102 F, aged 47.5+/-12.9 years; mean+/-SD), in case other established treatments were refused or contraindicated. Eighty-five patients were affected by toxic adenoma and 47 suffered from pre-toxic nodules. Ethanol was administered weekly under sonographic control, in 7 sessions (range 2-16). During PEI treatment, 26 toxic elderly patients were treated with methimazole and propranolol. Three possible outcomes were identified for statistical analysis: failure (persistent suppression of extra nodular tissue uptake, along with elevated free thyroid hormone and undetectable TSH levels); partial cure (normal free thyroid hormone and low/undetectable TSH levels); complete cure (normal thyroid hormone and TSH levels; restored extra nodular uptake). The patients were followed for up to 8.5 years (median 76 months). PEI therapy was well tolerated by all patients though a mild to moderate local pain occurred in about 30% of sessions. Complete cure was achieved in all pre-toxic patients and in 60 (70.6%) patients with toxic adenoma, while partial cure was observed in 11 cases (12.9%) and failure in 14 (16.5%). A significant shrinkage of nodule volume was observed in all patients (p = 0.0001), while those with toxic nodules larger than 30 mL showed a significantly lower response rate to PEI (p thyroid adenoma where therapy is least necessary- despite the nodule volume. Though ethanol injection therapy of toxic thyroid nodules may be troublesome for the need of multiple sessions, it appears an effective alternative procedure in patients at poor surgical risk, and in younger patients in whom radioiodine is contraindicated. Since a special technical skill in intervention procedures is required, PEI therapy may be suitable only for patients living nearby a trained centre.

Autoimmune polyendocrine syndrome type 1 – a case report from Bangladesh

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Tahniyah Haq

2016-01-01

Full Text Available We describe a case of a 26 years old man who presented with adrenocortical insufficiency followed by hypoparathyroidism and subsequently mucocutaneous candidiasis. He also had nail dystrophy, cataract and alopecia, but no other endocrinopathies. He was diagnosed as a case of autoimmune polyendocrine syndrome type 1(APS 1. APS1 is a rare endocrine disorder and only a few cases have been reported from Bangladesh. IMC J Med Sci 2016; 10(1: 33-35

Invasive fungal infections in endogenous Cushing’s syndrome

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Rafael Selbach Scheffel

2010-06-01

Full Text Available Cushing’s syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing’s original description of the disease. We describe here a patient with endo-genous Cushing’s syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease.

Dicty_cDB: CFG838 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available iscoideum chromosom... 390 e-107 BC077988_1( BC077988 |pid:none) Xenopus laevis achalasia..., adrenoco... 81 9e-14 BC067671_1( BC067671 |pid:none) Danio rerio achalasia, adrenocorti... 68 6e-1...e) Homo sapiens mRNA for achalasia, a... 62 3e-08 (Q9NRG9) RecName: Full=Aladin; AltName: Full=Adracalin; &A... BC120418 |pid:none) Bos taurus achalasia, adrenocortic... 60 1e-07 AK087134_1( A

Neuropsychology of trauma-exposure: emotional learning, stress responsivity and the glucocorticoid receptor

OpenAIRE

Liebscher, Claudia

2010-01-01

In the present dissertation the aim was to identify correlates of trauma-exposure in persons who developed symptoms of a posttraumatic stress disorder and in those who were trauma-exposed but do not suffer from PTSD as well as in persons without trauma-exposure. In the first part of the dissertation, mechanisms of context conditioning and the release of glucocorticoids by the Hypothalamus-pituitary-adrenocortical axis were investigated in trauma-exposed and non-exposed persons. In the second ...

The Intense World Theory – A Unifying Theory of the Neurobiology of Autism

Science.gov (United States)

Markram, Kamila; Markram, Henry

2010-01-01

Autism covers a wide spectrum of disorders for which there are many views, hypotheses and theories. Here we propose a unifying theory of autism, the Intense World Theory. The proposed neuropathology is hyper-functioning of local neural microcircuits, best characterized by hyper-reactivity and hyper-plasticity. Such hyper-functional microcircuits are speculated to become autonomous and memory trapped leading to the core cognitive consequences of hyper-perception, hyper-attention, hyper-memory and hyper-emotionality. The theory is centered on the neocortex and the amygdala, but could potentially be applied to all brain regions. The severity on each axis depends on the severity of the molecular syndrome expressed in different brain regions, which could uniquely shape the repertoire of symptoms of an autistic child. The progression of the disorder is proposed to be driven by overly strong reactions to experiences that drive the brain to a hyper-preference and overly selective state, which becomes more extreme with each new experience and may be particularly accelerated by emotionally charged experiences and trauma. This may lead to obsessively detailed information processing of fragments of the world and an involuntarily and systematic decoupling of the autist from what becomes a painfully intense world. The autistic is proposed to become trapped in a limited, but highly secure internal world with minimal extremes and surprises. We present the key studies that support this theory of autism, show how this theory can better explain past findings, and how it could resolve apparently conflicting data and interpretations. The theory also makes further predictions from the molecular to the behavioral levels, provides a treatment strategy and presents its own falsifying hypothesis. PMID:21191475

11C-methionine PET/CT in 99mTc-sestamibi-negative hyperparathyroidism in patients with renal failure on chronic haemodialysis

International Nuclear Information System (INIS)

Rubello, Domenico; Fanti, Stefano; Nanni, Cristina; Farsad, Mohsen; Castellucci, Paolo; Boschi, Stefano; Franchi, Roberto; Mariani, Giuliano; Fig, Lorraine M.; Gross, Milton D.

2006-01-01

Scintigraphic localisation of parathyroid glands is often unsuccessful in patients with renal failure on chronic haemodialysis who have secondary hyperparathyroidism (HPT). The purpose of this study was to investigate the use of 11 C-methionine PET/CT to detect hyperfunctioning parathyroid glands in patients with renal failure on chronic haemodialysis who had 99m Tc-sestamibi-negative HPT. 11 C-methionine PET/CT was performed in 18 patients (11 women and 7 men, aged 42-79 years; mean age 57.8 years) on haemodialysis for renal failure (2-14 years' duration), with normo-, hypo- or hypercalcaemia and HPT not localised by either dual-tracer 99m Tc-pertechnetate/ 99m Tc-sestamibi subtraction scans or dual-phase 99m Tc-sestamibi scans. In three of ten patients with normo- or hypocalcaemic HPT there was increased 11 C-methionine accumulation in one gland. Seven of eight patients with hypercalcaemic HPT showed increased uptake: in five of these patients increased 11 C-methionine accumulation was present in one gland, while in two it was demonstrated in two glands. All patients also had high-resolution ultrasound of the neck and were treated with subtotal parathyroidectomy, leaving a remnant of the smallest of the four glands. Regardless of their size, all glands with abnormal 11 C-methionine parathyroid uptake were removed, and all demonstrated parathyroid hyperplasia. All patients developed post-parathyroidectomy hypoparathyroidism and one patient with normocalcaemic HPT relapsed 8 months after surgery. These data suggest that 11 C-methionine PET/CT may be used to identify hyperfunctioning parathyroid glands in non-primary HPT, and especially hypercalcaemic HPT, when conventional 99m Tc-sestamibi imaging is non-localising. (orig.)

Primary hyperparathyroidism with classic and severe skeletal involvement.

Science.gov (United States)

Sandoval, Mark Anthony S; Paz-Pacheco, Elizabeth

2010-08-26

A 63-year-old woman has had multiple repeated fractures. A diagnosis of primary hyperparathyroidism (PHPT) was made after she was found to be hypercalcaemic with an elevated level of intact parathyroid hormone (iPTH). Radiographs revealed classic and severe bone findings in PHPT, features which were common in the past but are thought to be rare at this modern age. She also had nephrolithiasis and osteoporosis. An enlarged parathyroid gland was seen on ultrasound and CT scan, and hyperfunction was demonstrated by scintigraphy. Parathyroidectomy was performed. Histopathologic analysis revealed a parathyroid adenoma. She developed the hungry-bone syndrome 7 days postoperatively, which resolved with with administration of calcium and calcitriol.

Vocal characteristics of congenital anterior glottic webs in children: A case report.

Science.gov (United States)

Shah, Jay; White, Katherine; Dohar, Joseph

2015-06-01

This case report describes a 5-year-old girl with chronic dysphonia and high-pitched voice since birth. Vocal quality was noted to be harsh. Videostroboscopy revealed significant hyperfunction and a Type II congenital anterior glottic web. Endoscopic division of the anterior glottic web was performed with significant improvement in vocal quality and quality of life. This paper describes methods of analyzing, diagnosing, and treating anterior glottic web with a focus on quality of life. Also, unique acoustic and aerodynamic voice features are identified. No other descriptions of a voice characteristic for anterior glottic web currently exist in the literature. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Answering the ultimate question "what is the proximal cause of aging?".

Science.gov (United States)

Blagosklonny, Mikhail V

2012-12-01

Recent discoveries suggest that aging is neither driven by accumulation of molecular damage of any cause, nor by random damage of any kind. Some predictions of a new theory, quasi-programmed hyperfunction, have already been confirmed and a clinically-available drug slows aging and delays diseases in animals. The relationship between diseases and aging becomes easily apparent. Yet, the essence of aging turns out to be so startling that the theory cannot be instantly accepted and any possible arguments are raised for its disposal. I discuss that these arguments actually support a new theory. Are any questions remaining? And might accumulation of molecular damage still play a peculiar role in aging?

[Adrenal hormones in the formation of atherosclerotic precursors in adolescents with primary arterial hypertension].

Science.gov (United States)

Bogmat, L F

1993-01-01

The components of blood lipid spectrum (total cholesterol, triglycerides and high density lipoprotein cholesterol) were studied in 131 adolescents (12-18 years old) with primary arterial hypertension at various levels of adrenal hormones (hydrocortisone and aldosterone) and blood plasma renin activity. The optimal ratio of lipid components in blood was detected if concentrations of adrenal hormones and blood plasma renin activity were low. Hyperfunction of the adrenal cortex in teen-agers contributed both to the development of hypertension and to atherosclerotic changes in vessels. This suggests that definite forms of hypertension occurred in adults, with specific impairments in the metabolism of blood serum lipids, were developed during the juvenile age.

M(o)TOR of aging: MTOR as a universal molecular hypothalamus.

Science.gov (United States)

Blagosklonny, Mikhail V

2013-07-01

A recent ground-breaking publication described hypothalamus-driven programmatic aging. As a Russian proverb goes "everything new is well-forgotten old". In 1958, Dilman proposed that aging and its related diseases are programmed by the hypothalamus. This theory, supported by beautiful experiments, remained unnoticed just to be re-discovered recently. Yet, it does not explain all manifestations of aging. And would organism age without hypothalamus? Do sensing pathways such as MTOR (mechanistic Target of Rapamycin) and IKK-beta play a role of a "molecular hypothalamus" in every cell? Are hypothalamus-driven alterations simply a part of quasi-programmed aging manifested by hyperfunction and secondary signal-resistance? Here are some answers.

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome

Science.gov (United States)

Lecoq, Anne-Lise; Stratakis, Constantine A.; Viengchareun, Say; Chaligné, Ronan; Tosca, Lucie; Hage, Mirella; Berthon, Annabel; Faucz, Fabio R.; Hanna, Patrick; Boyer, Hadrien-Gaël; Servant, Nicolas; Salenave, Sylvie; Tachdjian, Gérard; Adam, Clovis; Benhamo, Vanessa; Clauser, Eric; Guiochon-Mantel, Anne; Young, Jacques; Lombès, Marc; Bourdeau, Isabelle; Maiter, Dominique; Tabarin, Antoine; Bertherat, Jérôme; Lefebvre, Hervé; Louiset, Estelle; Lacroix, André; Bouligand, Jérôme; Kamenický, Peter

2017-01-01

GIP-dependent Cushing’s syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing’s syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing’s syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations. PMID:28931750

Endogenous Cushing’s Syndrome with Precocious Puberty in an 8-Year-Old Boy due to a Large Unilateral Adrenal Adenoma

Directory of Open Access Journals (Sweden)

Muhammad Rajib Hossain

2013-01-01

Full Text Available Adrenocortical tumors (ACTs causing Cushing’s syndrome are extremely rare in children and adolescents. Bilateral macronodular adrenocortical disease which is a component of the McCune-Albright syndrome is the most common cause of endogenous Cushing’s syndrome. We report the case of a boy with Cushing’s syndrome who presented with obesity and growth retardation. The child was hypertensive. The biochemical evaluation revealed that his serum cortisol levels were 25.80 g/dL, with a concomitant plasma ACTH level of 10.0 pg/mL and nonsuppressed serum cortisol on high-dose dexamethasone suppression test (HDDST to be 20.38 g/dL. Computed tomography of the abdomen demonstrated a 8 × 6 × 5 cm left adrenal mass with internal calcifications. Following preoperative stabilization, laparotomy was carried out which revealed a lobulated left adrenal mass with intact capsule weighing 120 grams. Histopathological examination revealed a benign cortical neoplastic lesion, suggestive of adrenal adenoma; composed of large polygonal cells with centrally placed nuclei and prominent nucleoli without capsular and vascular invasion. On the seventh postoperative day, cortisol levels were within normal range indicating biochemical remission of Cushing’s syndrome. On followup after three months, the patient showed significant clinical improvement and had lost moderate amount of weight and adrenal imaging was found to be normal.

A Prospective Study of Expectant Observation as Primary Therapy for Neuroblastoma in Young Infants, a Children’s Oncology Group Study

Science.gov (United States)

Nuchtern, Jed G.; London, Wendy B.; Barnewolt, Carol E.; Naranjo, Arlene; McGrady, Patrick W.; Geiger, James D.; Diller, Lisa; Schmidt, Mary Lou; Maris, John M.; Cohn, Susan L.; Shamberger, Robert C.

2015-01-01

Structured Abstract OBJECTIVE To demonstrate that expectant observation of young infants with small adrenal masses would result in excellent event-free and overall survival (EFS and OS). SUMMARY BACKGROUND DATA Neuroblastoma is the most common malignant tumor in infants, and in young infants, 90% are located in the adrenal gland. Although surgical resection is standard therapy, multiple observations suggest that expectant observation could be a safe alternative for infants 2 were referred for surgical resection. RESULTS 87 eligible patients were enrolled, 83 elected observation and 4 chose immediate surgery. 16 observation patients ultimately had surgery; 8 had INSS stage 1 neuroblastoma, 2 had higher stage neuroblastoma (2B and 4S), 2 had low grade adrenocortical neoplasm, 2 had adrenal hemorrhage and 2 had extralobar pulmonary sequestration. The two patients with adrenocortical tumors were resected because of a >50% increase in tumor volume. The 3-year EFS for a neuroblastoma event was 97.7±2.2% within the entire cohort of patients (n=87). The 3-year overall survival was 100% with median follow-up of 3.2 years. 81% of patients on the observation arm were spared resection. CONCLUSIONS Expectant observation of infants <6 months old with small adrenal masses led to excellent EFS and OS while avoiding surgical intervention in a large majority of the patients. PMID:22964741

[Arterial hypertension during pregnancy: Always preeclampsia?

Science.gov (United States)

Torres-Courchoud, I; Alastrue-Del Castaño, V; Cebollada-Del Hoyo, J; Bielsa-Rodrigo, M A; Sancho-Serrano, M A

Cushing's syndrome is a rare condition during pregnancy, but it is associated with serious maternal and fetal complications. The most common etiology during pregnancy is the presence of an adrenocortical adenoma. Urinary free cortisol over 3 times the upper limit of normal usually indicates Cushing's syndrome during pregnancy. The treatment of choice is surgical, and the ideal time for surgery is before the third trimester. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Long-term follow-up of autonomous hyperfunctioning thyroid nodules treated with 131I

International Nuclear Information System (INIS)

Zhou Qian

1990-01-01

30 cases of hyperthyroidism caused by solitary autonomous functioning thyroid nodules (AFTN) and treated with 131 I 4 to 24 years earlier (mean, 14.13 years) were studied. In comparison, a control group of 15 cases with AFTN, trated surgically 4 to 22 years ago (mean, 8.66 years), was also examined. The results showed that: (1) Thyroid scintigraphy is not only the determinant criterion for the diagnosis of AFTN, but also the most reliable measure for evaluating the effect of treatment and prognosis. Disappearance of the hot nodule and restoration of the function of suppressed thyroid tissue indicate cure of the disease. (2) Solitary toxic thyroid nodules are frequently polyclonal and occur in nodular goiters with scattered small multifocal hot areas. Therefore, recurrence of the disease is unavoidable either after 131 I therapy or partial thyroidectomy. (3) After treatment of this disease, an absent or low response to TRH test dose not indicate ineffective cure, and an exaggerated response also dose not predict hypothyroidims. (4) Use 131 I and surgery are almost equally effective for the treatment of this disease. All the patients are clinically euthyroid. According to the scintigraphic pattern, all the surgically treated patients are cured, but there are 1 recurrent and 1 with persistent hot nodule in the 131 I therapy group. (5) The 131 I dose calculated individually is more reasonable than a standard does

Autonomously hyperfunctioning cystic nodule harbouring thyroid carcinoma – Case report and literature review

OpenAIRE

Lima, Maria João; Soares, Virgínia; Koch, Pedro; Silva, Artur; Taveira-Gomes, António

2018-01-01

Introduction: Hyperthyroidism is rarely associated with malignancy, but it cannot rule out thyroid cancer. Although there is published data describing this coexistence, thyroid carcinomas inside autonomously functioning nodules are uncommon. Presentation of case: A 49-year-old woman presented with a cervical mass, unexplained weight loss and anxiousness, sweating and insomnia. On physical examination, she had a palpable left thyroid nodule. Thyroid function tests showed suppressed TSH (

Adrenocortical Carcinoma: False Positive in an I-123 Metaiodobenzylguanidine Scan

Energy Technology Data Exchange (ETDEWEB)

Rey, Cristina Rodriguez; Candil, Aida Ortega; Galvan, Eliseo Vano; Martin, Maria Nieves Cabrera; Delgado, Jose Luis Carreras [Clinico San Carlos Hospital, Madrid (Spain)

2016-06-15

A 55-year-old man with a personal his history of left pheochromocytoma 2 years previously presented with an abdominal ultrasound showed a large left upper quadrant solid mass (calipers), with heterogeneous echogenicity and central cystic degeneration areas or necrosis. F-18 Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT was performed as ACC was suspected. ACC is an uncommon malignant neoplasm of unknown cause; however, smoking and oral contraceptives may be risk factors. Patients usually present with advanced-stage disease and have poor prognosis, with a 2-year recurrence rate that ranges form 73 to 86 %. An MIBG scan was performed after injection of 185 MBq of I-123 MIBG intravenously. Single photon emission tomography (SPECT)/CT scan showed abnormal isotope accumulation in the tumor region. The patient underwent total resection of the tumor. The histology was of ACC, with areas of necrosis and cystic areas, so the result of the MIBG scan was a false positive. Authors divided false-positive MIBG studies into three categories. The first category is neuroendocrine lesions other than pheochromocytomas (tumors of the APUD series). the second category consists in adrenal lesions other than pheochromocytomas (adenomas, ACC) the reasons for this abnormal uptake are unclear. The third category consists of tracer uptake adjacent to the adrenal due to abnormalities in the route of excretion.

Evaluation of adrenocortical function in Florida manatees (Trichechus manatus latirostris)

Science.gov (United States)

Tripp, K.M.; Verstegen, J.P.; Deutsch, C.; Bonde, Robert K.; de Wit, M.; Manire, Charles A.; Gaspard, J.; Harr, K.E.

2011-01-01

The study objectives were to determine the predominant manatee glucocorticoid; validate assays to measure this glucocorticoid and adrenocorticotropic hormone (ACTH); determine diagnostic thresholds to distinguish physiological vs. pathological concentrations; identify differences associated with sex, age class, female reproductive status, capture time, and lactate; and determine the best methods for manatee biologists and clinicians to diagnose stress. Cortisol is the predominant manatee glucocorticoid. IMMULITE 1000 assays for cortisol and ACTH were validated. Precision yielded intra- and inter-assay coefficients of variation for serum cortisol: ≤23.5 and ≤16.7%; and ACTH: ≤6.9 and ≤8.5%. Accuracy resulted in a mean adjusted R(2)≥0.87 for serum cortisol and ≥0.96 for ACTH. Assay analytical sensitivities for cortisol (0.1 µg/dl) and ACTH (10.0 pg/ml) were verified. Methods were highly correlated with another IMMULITE 1000 for serum cortisol (r=0.97) and ACTH (r=0.98). There was no significant variation in cortisol or ACTH with sex or age class and no correlation with female progesterone concentrations. Cortisol concentrations were highest in unhealthy manatees, chronically stressed by disease or injury. ACTH was greatest in healthy free-ranging or short-term rehabilitating individuals, peracutely stressed by capture and handling. Cortisol concentrations ≥1.0 µg/dl were diagnostic of chronic stress; ACTH concentrations ≥87.5 pg/ml were diagnostic of peracute stress. In healthy long-term captive manatees, cortisol (0.4±0.2 µg/dl) and ACTH (47.7±15.9 pg/ml) concentrations were lower than healthy free-ranging, short-term rehabilitated or unhealthy manatees. Capture time was not significantly correlated with cortisol; ACTH correlation was borderline significant. Cortisol and ACTH were positively correlated with lactate.

Bilateral primary adrenocortical carcinoma complicated by Addisonian crisis: case report

International Nuclear Information System (INIS)

Foster, M.; Nolan, R.L.; Hong, H.H.

2001-01-01

Primary adrenal carcinoma is a rare malignancy. Primary adrenal insufficiency (i.e. Addison's disease) is a rare complication of bilateral infiltration. We report a case of primary bilateral adrenal carcinoma complicated by an episode of primary adrenal insufficiency. (author)

The adrenocortical response of tufted puffin chicks to nutritional deficits

Science.gov (United States)

Kitaysky, A.S.; Romano, Marc D.; Piatt, John F.; Wingfield, J.C.; Kikuchi, M.

2005-01-01

In several seabirds, nutritional state of a nest-bound chick is negatively correlated with the activity of its hypothalamus-pituitary-adrenal (HPA) axis. Increased corticosterone (cort) secretion has been shown to facilitate changes in behavior that allow hungry chicks to obtain more food from parents. However, if parents are not willing/able to buffer their young from temporary food shortages, increased cort secretion could be detrimental to undernourished chicks. In a system where parents are insensitive to chick demands, low benefits and high costs of activation of the HPA-axis in hungry chicks should lead to a disassociation of the nutritional state of the young and the activity of its HPA-axis. We tested this novel hypothesis for the tufted puffin (Fratercula cirrhata), a seabird with intermittent provisioning of a nest-bound semi-precocial chick. We examined the HPA-axis activity of captive chicks exposed to the following: (1) a short-term (24 h) food deprivation; and (2) an array of prolonged (3 weeks) restrictions in feeding regimens. We found that in response to a short-term food deprivation chicks decreased baseline levels of cort and thyroid hormones. In response to prolonged restrictions, food-limited chicks exhibited signs of nutritional deficit: they had lower body mass, endogenous lipid reserves, and thyroid hormone titers compared to chicks fed ad libitum. However, baseline and maximum acute stress-induced levels of cort were also lower in food-restricted chicks compared to those of chicks fed ad libitum. These results support a major prediction of the study hypothesis that puffin chicks suppress HPA-axis activity in response to short- and long-term nutritional deficits. This physiological adaptation may allow a chick to extend its development in the nest, while eluding detrimental effects of chronic cort elevation. 

Miectomía con cauterización de los extremos versus visualización directa Myectomy with cauterization of the extremitates versus direct visualization

Directory of Open Access Journals (Sweden)

Rosa M. Naranjo Fernández

2004-12-01

Full Text Available Se realizó un estudio descriptivo, retrospectivo de 71 pacientes con hiperfunción de oblicuo inferior bilateral que acudieron al Servicio de Oftalmología Pediátrica y Estrabismo del Hospital Oftalmológico Docente "Ramón Pando Ferrer", de ellos 26 intervenidos con la técnica quirúrgica de miectomía con cauterización de los extremos y un segundo grupo donde se aplicó la técnica de miectomía bajo visualización directa con 45 pacientes, que fueron operados desde enero de 1998 hasta enero de 2003. A todos se les realizó una valoración preoperatoria y posoperatoria de la hiperfunción del oblicuo inferior. El 72 % se agrupó en un rango de edad de 1 a 10 años, el 55 % tenía diagnóstico de esotropía con hipertopía; no hubo recidiva en los pacientes intervenidos de miectomía con cauterización de los extremos bajo visualización directa.A descriptive and retrospective study of 71 patients with hyperfunction of the bilateral inferior oblique that received attention at the Service of Pediatric Ophthalmology and Strabismus of "Ramón Pando Ferrer" Ophthalmological Hospital was conducted. 26 of them underwent myectomy with cauterization of the extremitates, whereas in the other 45 myectomy under direct visualization was performed. They were operated on from January 1998 to January 2003. A preoperative and postoperative assessment of the hyperfunction of the inferior oblique was made. 72 % were grouped in an age range from 1 to 10 years old, and 55 % had a diagnosis of esotropia with hypertropia. No relapse was observed in the patients that underwent myectomy with cauterization of the extremitates under direct visualization.

Influence of haloperidol on the /sup 3/H-leucine incorporation in incretory organs of the mouse

Energy Technology Data Exchange (ETDEWEB)

Lange, E; Hackenberg, P [Bezirksnervenklinik, Schwerin (German Democratic Republic)

1978-01-01

The /sup 3/H-leucine incorporation in proteins of incretory organs of the mouse, the exocrine pancreas, and the renal tubuli was studied autoradiographically after administration of therapylike doses of the neuroleptic drug Haloperidol. With exception of the pancreas, a dosage dependent increase of the /sup 3/H-leucine incorporation was observed in the treated animals. The results reveal an activation of the hypothalamus-hypophysis-adrenocortical system due to a 10-days administration of Haloperidol. These results are in conformity with former ones in brain and liver.

Influence of haloperidol on the 3H-leucine incorporation in incretory organs of the mouse

International Nuclear Information System (INIS)

Lange, E.; Hackenberg, P.

1978-01-01

The 3 H-leucine incorporation in proteins of incretory organs of the mouse, the exocrine pancreas, and the renal tubuli was studied autoradiographically after administration of therapylike doses of the neuroleptic drug Haloperidol. With exception of the pancreas, a dosage dependent increase of the 3 H-leucine incorporation was observed in the treated animals. The results reveal an activation of the hypothalamus-hypophysis-adrenocortical system due to a 10-days administration of Haloperidol. These results are in conformity with former ones in brain and liver. (author)

Autoimmune polyglandular syndrome in a 13-year old girl

DEFF Research Database (Denmark)

Borgwardt, L.; Pedersen, P.; Peitersen, B.

2008-01-01

Autoimmune polyglandular syndrome (APS) is an entity, defined by autoimmunity towards two or more endocrine organs. APS is classified in 3 subgroups (type-1, type-2a, type-2b), according to the organs involved. A case is presented of a 13-year old girl referred to the Department of Paediatrics...... with hypothyroidism, subsequently diagnosed adrenocortical insufficiency and impending Addison crisis, typical for APS-type 2a. In the paper we discuss the need for more attention to APS in clinical work Udgivelsesdato: 2008/9/29...

Cushing's syndrome associated with a bronchial adenoma. Possible periodic hormonogenesis.

Science.gov (United States)

Shapiro, M S; Gutman, A; Bruderman, I; Myers, B; Griffel, W B

1975-09-01

Diagnostic and therapeutic problems in a patient with ectopic ACTH syndrome caused by a malignant bronchial adenoma are discussed. Persistent Cushing's syndrome was present following apparent total adrenalectomy, but radioactive scanning with 131I-19-iodocholesterol showed the presence of residual adrenal tissue in the right suprarenal bed. Amelioration of the hypercortisolism occurred after removal of the bronchial adenoma. A paradoxical elevation of adrenocortical activity followed administration of dexamethasone and data are presented which suggest that periodic secretion of ACTH accounted for this phenomenon.

Dicty_cDB: AFH742 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available AC115581 |pid:none) Dictyostelium discoideum chromosom... 477 e-133 BC077988_1( BC077988 |pid:none) Xenopus laevis achalasia...lus 2 days neonate thymus... 84 3e-17 BC067671_1( BC067671 |pid:none) Danio rerio achalasia, adrenocorti... ... |pid:none) Homo sapiens mRNA for achalasia, a... 79 4e-16 (Q9NRG9) RecName: Full...0826 fis, cl... 79 5e-16 BC120418_1( BC120418 |pid:none) Bos taurus achalasia, adrenocortic... 80 6e-16 EF14

Autonomous Functioning Thyroid Nodule in a 4-year-old Male Child Treated with Radioiodine (I-131)

International Nuclear Information System (INIS)

Khare, Abhishek; Bhutani, Puneet; Chauhan, Suneel

2013-01-01

Autonomous functioning thyroid nodules that cause toxic manifestations (toxic adenomas) are benign monoclonal tumors characterized by their capacity to grow and produce thyroxine (T4) and triiodothyronine (T3) autonomously, i.e. in the absence of thyrotropin thyroid stimulating hormone. Toxic adenomas are a rare presentation of hyperthyroidism in the pediatric population. Radioiodine (I-131) has been widely used for therapy of patients with toxic adenomas and is now accepted as a safe and effective treatment even in the pediatric age group. The authors here present a case of a 4-year-old boy with a solitary hyperfunctioning thyroid nodule, who was successfully treated with radioiodine (I-131) and is presently on follow-up

Answering the ultimate question “What is the Proximal Cause of Aging?”

Science.gov (United States)

Blagosklonny, Mikhail V.

2012-01-01

Recent discoveries suggest that aging is neither driven by accumulation of molecular damage of any cause, nor by random damage of any kind. Some predictions of a new theory, quasi-programmed hyperfunction, have already been confirmed and a clinically-available drug slows aging and delays diseases in animals. The relationship between diseases and aging becomes easily apparent. Yet, the essence of aging turns out to be so startling that the theory cannot be instantly accepted and any possible arguments are raised for its disposal. I discuss that these arguments actually support a new theory. Are any questions remaining? And might accumulation of molecular damage still play a peculiar role in aging? PMID:23425777

Bone Health in Adrenal Disorders

Directory of Open Access Journals (Sweden)

Beom-Jun Kim

2018-03-01

Full Text Available Secondary osteoporosis resulting from specific clinical disorders may be potentially reversible, and thus continuous efforts to find and adequately treat the secondary causes of skeletal fragility are critical to ameliorate fracture risk and to avoid unnecessary treatment with anti-osteoporotic drugs. Among the hyperfunctional adrenal masses, Cushing's syndrome, pheochromocytoma, and primary aldosteronism are receiving particularly great attention due to their high morbidity and mortality mainly by increasing cardiovascular risk. Interestingly, there is accumulating experimental and clinical evidence that adrenal hormones may have direct detrimental effects on bone metabolism as well. Thus, the present review discusses the possibility of adrenal disorders, especially focusing on pheochromocytoma and primary aldosteronism, as secondary causes of osteoporosis.

Micromethod for determination of cortisol in peripheral blood

International Nuclear Information System (INIS)

Maleeva, A.; Mileva, Zh.; Kekhajova, M.

1982-01-01

The micromethod for determination of cortisol in peripheral blood is based on the classical radiommunologic method for its determination. A drop of peripheral blood is applied on filter paper, used for detection of phenyketonuria. A 7 mm disk of this paper is then cut with a perforator and placed in the tube instead of 50 microliters blood plasma. The classical radiommunoassay and the micromethod were used in parallel for determining peripheral blood cortisol concentrations in 26 sexually mature persons, in 12 children and in 40 patients with thyroid hyperfunction. In all tested 78 persons no statistically significant difference (P>0.5) was found in cortisol concentrations, determined by the two methods. (authors)

Parathyromatosis: critical diagnosis regarding surgery and pathologic evaluation.

Science.gov (United States)

Aksoy-Altinboga, Ayşegül; Akder Sari, Ayşegül; Rezanko, Türkan; Haciyanli, Mehmet; Orgen Calli, Aylin

2012-04-01

Parathyromatosis, in which several nodules of hyperfunctioning parathyroid tissue form in the neck and mediastinum, is a rare cause of recurrent hyperparathyroidism. However, there are some theories regarding the origin of parathyromatosis, and seeding after rupture of the parathyroid gland capsule during surgical removal of a parathyroid lesions is the most regarded one. Herein, we report a 41-year-old man who presented with multiple parathyroid nodules in and around the left thyroid lobe 5 years after parathyroid surgery for secondary hyperparathyroidism that was finally diagnosed as parathyromatosis. We discuss the differential diagnosis of parathyromatosis from other parathyroid tumors, particularly from parathyroid carcinoma, which is important in the management of a suspected lesion.

Localization of primary hyperparathyroidism using 99mTc-MIBI scintigraphy

International Nuclear Information System (INIS)

Yane, Katsunari; Emoto, Mie; Okamoto, Hideyuki; Yuki, Kazue; Hosoi, Hiroshi; Miyahara, Hiroshi

2003-01-01

To determine the clinical utility of 99mTc-MIBI scintigraphy (MIBI) in the localization of hyperfunctioning parathyroid lesions, detection of lesions in 14 patients with primary hyperparathyroidism was compared between MIBI, ultrasonography and computed tomography (CT). MIBI (85.7%) and ultrasonography (78.5%) demonstrated higher detection rates than CT (50%). Furthermore, combination of MIBI and ultrasonography (92.8%) increased the detection rate. One case of ectopic parathyroid adenoma was detected only on MIBI. The smallest parathyroid lesion detected using MIBI was a parathyroid adenoma weighing 300 mg. A combination of MIBI and ultrasonography is therefore useful for the localization of primary hyperparathyroidism, and MIBI is particularly useful for detecting ectopic lesions. (author)

Effects of mild cold stress on the survival of seawater-adapted mallard ducks (Anas platyrhynchos) maintained on food contaminated with petroleum

Science.gov (United States)

Holmes, W.N.; Gorsline, J.; Cronshaw, J.

1979-01-01

(1) Seawater-adapted Mallard ducks maintained in the laboratory will freely consume food that has been contaminated with either any one of a variety of crude oils or a petroleum derivative such as No. 2 fuel oil. (2) During a 100-day experimental period total masses of petroleum equivalent to 50% of the mean body weight were consumed by some birds and many showed no apparent symptoms of distress. (3) The consumption of petroleum-contaminated food was frequently accompanied by a persistent hyperphagia but no clear patterns of change in body weight were associated with this condition. (4) Among those birds that survived the 100-day experimental period only small changes in mean body weight were observed between successive weighings and in most instances these represented less than 10% of the previously recorded weight. (5) In all groups, including those maintained on uncontaminated food, most of the mortality occurred following exposure to continuous mild cold stress. The total number of deaths in the groups given petroleum-contaminated food, however, was always higher than that among birds given uncontaminated food. (6) The spate of mortality that occurred in groups given petroleum-contaminated food usually occurred earlier, lasted longer, and involved more birds than it did among groups fed uncontaminated food. (7) The pattern of each episode of mortality was sometimes quantitatively related to the concentration of petroleum in the food and a striking range of relative toxicities were observed among the crude oils from different geographic regions. (8) Throughout the experiment, the mean body weight of the birds that died was always significantly less than that of the survivors in the same group; in all instances most of the loss in weight occurred during the 2 weeks preceding death. (9) Autopsy revealed that adrenal hypertrophy and lymphoepithelial involution were characteristic in all of the birds that died, suggesting that a high level of adrenocortical

Seasonal variation in hormonal responses of timber rattlesnakes (Crotalus horridus) to reproductive and environmental stressors.

Science.gov (United States)

Lutterschmidt, William I; Lutterschmidt, Deborah I; Mason, Robert T; Reinert, Howard K

2009-08-01

Data addressing adrenocortical modulation across taxonomic groups are limited, especially with regard to how female reproductive condition influences the sensitivity of the hypothalamus-pituitary-adrenal axis. We investigated seasonal and reproductive variation in basal and stress-induced hormone profiles in a population of free-ranging timber rattlesnakes (Crotalus horridus) in north-central Pennsylvania during spring (i.e., May), summer (i.e., July), and early fall (i.e., September). Baseline corticosterone concentrations varied seasonally and were significantly lower during the summer sampling period in July. We observed a significant negative relationship between baseline corticosterone and testosterone in male snakes, while baseline corticosterone and estradiol tended to be positively correlated in females. Treatment of snakes with 1 h of capture stress significantly increased corticosterone across all seasons. However, there was a significant interaction between corticosterone responses to capture stress and season, suggesting that adrenocortical function is modulated seasonally. Because elevated corticosterone may be associated with reproduction, we asked whether hormonal stress responses vary with female reproductive condition. Although sample sizes are low, reproductive snakes had significantly higher baseline and stress-induced corticosterone concentrations than non-reproductive or post-parturient females. Further, despite similar baseline corticosterone concentrations between non-reproductive and post-parturient rattlesnakes, post-parturient females responded to capture stress with a significantly higher increase in corticosterone. Collectively, these data suggest that the sensitivity of the hypothalamus-pituitary-adrenal axis varies both seasonally and with changing reproductive states.

Immunoreactive cortisone in droppings reflect stress levels, diet and growth rate of gull-billed tern chicks.

Science.gov (United States)

Albano, Noelia; Santiago-Quesada, Francisco; Masero, José A; Sánchez-Guzmán, Juan M; Möstl, Erich

2015-03-01

Blood levels of corticosterone have been traditionally analyzed to assess stress levels in birds; however, measuring steroid hormone metabolites in feces and droppings has gained much interest as a noninvasive technique successfully used for such purposed in vertebrates. Diet may affect these fecal metabolite levels (e.g., due to nutritional stress), however, this variable has not been taken into account in studies with chicks despite the great dietary flexibility of many avian species. In this study, we addressed for the first time this key issue and validated the technique in wild gull-billed tern chicks (Gelochelidon nilotica). Several enzyme immunoassays were used to determine the most appropriate test to measure the stress response. Subsequently, we performed an experiment in captivity to assess adrenocortical activity in gull-billed tern chicks fed with two diets: piscivorous vs. insectivorous. Finally, the relation between the chicks' growth rate and excreted immunoreactive glucocorticoid metabolites (EGMs) was also evaluated. We found the immunoreactive cortisone metabolites to be a good index of stress (as being an index of adrenocortical reactivity) in chicks of this species. Fish-fed chicks had higher levels of cortisone metabolites when comparing both concentration and total daily excreted metabolites. Within each treatment diet, cortisone metabolite levels and growth rates were negatively correlated. These findings suggest that the diet should be considered when using this technique for comparative purposes and highlight the trade-off between stress levels and chicks growth rates. Copyright © 2015 Elsevier Inc. All rights reserved.

Pathways and processes of risk in associations among maternal antisocial personality symptoms, interparental aggression, and preschooler's psychopathology.

Science.gov (United States)

Davies, Patrick T; Sturge-Apple, Melissa L; Cicchetti, Dante; Manning, Liviah G; Vonhold, Sara E

2012-08-01

Two studies examined the nature and processes underlying the joint role of interparental aggression and maternal antisocial personality as predictors of children's disruptive behavior problems. Participants for both studies included a high-risk sample of 201 mothers and their 2-year-old children in a longitudinal, multimethod design. Addressing the form of the interplay between interparental aggression and maternal antisocial personality as risk factors for concurrent and prospective levels of child disruptive problems, the Study 1 findings indicated that maternal antisocial personality was a predictor of the initial levels of preschooler's disruptive problems independent of the effects of interparental violence, comorbid forms of maternal psychopathology, and socioeconomic factors. In attesting to the salience of interparental aggression in the lives of young children, latent difference score analyses further revealed that interparental aggression mediated the link between maternal antisocial personality and subsequent changes in child disruptive problems over a 1-year period. To identify the family mechanisms that account for the two forms of intergenerational transmission of disruptive problems identified in Study 1, Study 2 explored the role of children's difficult temperament, emotional reactivity to interparental conflict, adrenocortical reactivity in a challenging parent-child task, and experiences with maternal parenting as mediating processes. Analyses identified child emotional reactivity to conflict and maternal unresponsiveness as mediators in pathways between interparental aggression and preschooler's disruptive problems. The findings further supported the role of blunted adrenocortical reactivity as an allostatic mediator of the associations between parental unresponsiveness and child disruptive problems.

A case of Addison's disease accompanied with bilateral adrenal calcification on CT

International Nuclear Information System (INIS)

Lee, Li-Chik; Fujita, Naohisa; Ohba, Yachiyo

1985-01-01

A 62-year-old woman was admitted to our hospital with complaints of general malaise and hyperpigmentation. We diagnosed her case as primary adrenocortical insufficiency (Addison's disease) by endocrinological studies. CT demonstrated dense calcification in both adrenal beds without evidence of normal glandular remnants. Calcified adrenal is not specific to tuberculosis, but some points of CT findings are useful for pathogenetic approach. Recently, there have been several reports that ACTH producing pituitary tumors develop in patients treated with conventional corticosteroid replacement. Corticosteroid should be administered by monitoring of plasma cortisol and ACTH concentrations. (author)

The α4β2 nicotine acetylcholine receptor agonist ispronicline induces c-Fos expression in selective regions of the rat forebrain

DEFF Research Database (Denmark)

Jacobsen, Julie; Hansen, Henrik H; Kiss, Alexander

2012-01-01

The dominant nicotine acetylcholine receptor (nAChR) subtype in the brain is the pentameric receptor containing both α4 and β2 subunits (α4β2). Due to the lack of selective agonists it has not been ruled out what neuronal circuits that are stimulated after systemic administration with nicotine. We...... or indirectly involved in acute stress regulation after a single dose of ispronicline, supports earlier studies that the α4β2 receptors are strongly involved in nicotine-dependent activation of the hypothalamo-pituitary adrenocortical axis....

Infection and twiddler syndrome in a dog with addison's disease, complete heart block, and wandering artificial pacemakers

International Nuclear Information System (INIS)

Hill, R.C.; Buchanan, J.W.

1990-01-01

Third degree heart block developed in an obese, 10-year-old Labrador retriever with adrenocortical failure. A permanent transthoracic pacemaker was fitted, but the pulse generator migrated 2 years later, to the ventral part of the flank, where an abscess formed. A new pacemaker was fitted, but also migrated and rotated and a syndrome analogous to Twiddler's syndrome in man developed. After a further 2 years the second pacemaker was located, encapsulated within the right pleural cavity. Culture of the brownish exudate around the pulse generator yielded Pseudomonas sp

Dicty_cDB: Contig-U08780-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Y4) RecName: Full=Uncharacterized protein DDB_G0276777; &A... 138 5e-31 BC077988_1( BC077988 |pid:none) Xenopus laevis achalasia...s... 84 1e-17 BC067671_1( BC067671 |pid:none) Danio rerio achalasia, adrenocorti... 82 4e-17 AY891872_1( AY8...509 |pid:none) Homo sapiens mRNA for achalasia, a... 79 2e-16 (Q9NRG9) RecName: Full=Aladin; AltName: Full=A... BC120418_1( BC120418 |pid:none) Bos taurus achalasia, adrenocortic... 80 3e-16 E

Oncology of the ferret (Mustela putorius furo)

International Nuclear Information System (INIS)

Bunel Le Coz, Bertrand Jacques Thierry

2006-01-01

Ferret oncology is in full evolution. Many types of tumors are mentioned. They affect all the systems of the organism: the endocrine, hemo-lymphatic, integument, digestive, reproductive, musculoskeletal, cardiovascular, nervous, urinary or respiratory systems. Insulinoma, adrenocortical tumors and lymphoma are the three mostly seen tumors. Complementary examination have been developed too. CBC, biochemistry, radiography and ultrasonography can now be completed by cytology, immunohistochemistry, endoscopies, scan, I.R.M. or scintigraphy. Treatments such as surgery, chemotherapy or radiotherapy can be associated. They allow recovery or, if not a palliative solution. (author) [fr

Autonomous thyroid nodules in adolescents: clinical characteristics and results of TRH testing

International Nuclear Information System (INIS)

Osburne, R.C.; Goren, E.N.; Bybee, D.E.; Johnsonbaugh, R.E.

1982-01-01

Seven adolescents with autonomous thyroid nodules were evaluated over a three-year period. They had hyperfunctioning nodules on radionuclide scan which failed to suppress with exogenous administration of thyroid hormone. They were clinically euthyroid and had normal T4, free T4, and basal TSH values. However, as a group they had elevated total serum T3 concentrations, blunted TSH response to TRH, and accelerated closure of cranial sutures, all of which suggested subtle hyperthyroidism. These patients have been followed for one to five years. Four have undergone partial thyroidectomy because of persistent elevation in the serum T3 concentration or enlargement of the nodule. The clinical presentation and laboratory findings in this group are similar to those found in adults with autonomous nodules

Autonomous thyroid nodules in adolescents: clinical characteristics and results of TRH testing

Energy Technology Data Exchange (ETDEWEB)

Osburne, R.C.; Goren, E.N.; Bybee, D.E.; Johnsonbaugh, R.E.

1982-03-01

Seven adolescents with autonomous thyroid nodules were evaluated over a three-year period. They had hyperfunctioning nodules on radionuclide scan which failed to suppress with exogenous administration of thyroid hormone. They were clinically euthyroid and had normal T4, free T4, and basal TSH values. However, as a group they had elevated total serum T3 concentrations, blunted TSH response to TRH, and accelerated closure of cranial sutures, all of which suggested subtle hyperthyroidism. These patients have been followed for one to five years. Four have undergone partial thyroidectomy because of persistent elevation in the serum T3 concentration or enlargement of the nodule. The clinical presentation and laboratory findings in this group are similar to those found in adults with autonomous nodules.

Coincidence of scintigraphic false positive and false negative findings in parathyroid and thyroid adenomas (case report)

Energy Technology Data Exchange (ETDEWEB)

Mana, O.; Zatta, G.; Boccolari, S.; Barbesti, S.; Tarolo, G.L.

1987-04-01

The subtractive double tracer scintigraphy with /sup 201/Tl and /sup 99m/Tc is a useful technique in studying parathyroid nodules; nevertheless, this method can give misleading informations especially in presence of thyroid nodules with false positive and false negative findings. In this case report the technique was applied in studying a patient with three nodules (two thyroid adenomas and one parathyroid adenoma), where both scintigraphic and echographic methods provided misleading informations. The selective uptake of /sup 201/Tl in the upper region of the right thyroid lobe gave a false positive finding, while the increased uptake of /sup 99m/Tc in a hyperfunctioning thyroid adenoma of left lobe masked the parathyroid adenoma laying below, giving a false negative finding.

Malignancy in solitary nodular lesions of thyroid : a review

International Nuclear Information System (INIS)

Padmanabhan, V.; Ramachandran, M.; Poulose, K.P.; Das, K.V.K.

1980-01-01

Out of the cases seen for thyroid disorders, 150 cases with solitary nodule were studied to find out the correlation between the histopathological features and the functional status of the nodules. 35-45 μCs of sup(131)I was given orally and thyroid uptake was measured at 2,4,24 and 48 hours after administration and thyroid scan was done at the end of 24 hours. On the basis of sup(131)I concentration found in the nodules, single nodules were classified as hyperfunctioning, functioning, hypofunctioning and nonfunctioning. The incidence of malignancy was high in nonfunctioning and hypofunctioning nodules, while no malingnancy was found in the functioning types of nodules. These results are compared with those of other such studies. (M.G.B.)

Impact of endocrine hyperfunction and phosphate wasting on bone in McCune-Albright syndrome.

Science.gov (United States)

Lala, R; Matarazzo, P; Andreo, M; Defilippi, C; de Sanctis, C

2002-01-01

Skin dysplasia, as café-au-lait spots, bone fibrous dysplasia and peripheral endocrinopathies are the main clinical features of McCune-Albright syndrome (MAS). This illness is due to activating mutations of the Gsalpha protein and is spread with a mosaic pattern in affected tissues that consist of intermixed areas of normal and mutated cells. Peripheral endocrine secretion, free of hypothalamic pituitary control, is the hallmark of the endocrine syndromes: precocious puberty, Cushing's syndrome, hyperthyroidism and gigantism/acromegaly. In addition, phosphate wasting as hyperphosphaturia is often present. The impact of hormonal hypersecretion and phosphate loss on the bones of patients with MAS is poorly understood both in normal and fibrous bone tissue. As hypercortisolism and hyperthyroidism increase bone resorption, hyperestrogenism and growth hormone hypersecretion stimulate bone growth and mineralization, and phosphate wasting reduces bone mineral content. All these actions can be exerted at varying times and degrees in a single patient on lesional and non-lesional bones. Sonographic evidence of multiple diffused hyperechogenic spots in the testes of patients with MAS do not seem to be related to alterations in calcium-phosphate metabolism but rather to zonal dysplasia/hyperplasia of testicular tissue.

Residual manifestations of hypercortisolemia following surgical treatment in a patient with Cushing syndrome.

Science.gov (United States)

Bartz, Sara K; Karaviti, Lefkothea P; Brandt, Mary L; Lopez, Monica E; Masand, Prakash; Devaraj, Sridevi; Hicks, John; Anderson, Lauren; Lodish, Maya; Keil, Meg; Stratakis, Constantine A

2015-01-01

Cushing Syndrome is difficult to diagnose, and the comorbidities and persistent late effects of hypercortisolemia after treatment of the primary disease are challenging for the patient and the endocrinologist. To report the case of a girl with obesity and hypertension, ultimately diagnosed with Cushing syndrome due to primary pigmented nodular adrenocortical disease. In this case, the complications of hypercortisolism persisted short term despite surgical intervention. A 4 year old morbidly obese African-American girl with developmental delay presented with hypertensive emergency in the ER and 18-month history of progressive weight gain. Her previous history included premature adrenarche, hypertension, seizures and a random high cortisol with suppressed ACTH. She was subsequently stabilized, and a diagnostic work-up persistently demonstrated elevated cortisol and suppressed ACTH. An abdominal MRI showed bilateral adrenal multinodular disease, consistent with multinodular hyperplasia of the adrenal glands. Based on these findings the patient underwent a bilateral adrenalectomy, which confirmed primary pigmented nodular adrenocortical disease. The patient had a complicated, protracted post-operative course requiring adjustment of therapy for persistent hypertension. Two months after surgery, she was readmitted to the Emergency Department with hyperpyrexia and hypertension and succumbed to the complications of sepsis. This case highlights the significant diagnostic and therapeutic challenges in treating children with Cushing syndrome. Resolution of the source of hypercortisolemia does not imply regression of hypertension or recovery of the immune system. Although the child underwent bilateral adrenalectomy, persistent consequences of prolonged severe hypercortisolism contributed to her death two months later.

Adolescent environmental enrichment prevents behavioral and physiological sequelae of adolescent chronic stress in female (but not male) rats.

Science.gov (United States)

Smith, Brittany L; Morano, Rachel L; Ulrich-Lai, Yvonne M; Myers, Brent; Solomon, Matia B; Herman, James P

2017-11-22

The late adolescent period is characterized by marked neurodevelopmental and endocrine fluctuations in the transition to early adulthood. Adolescents are highly responsive to the external environment, which enhances their ability to adapt and recover from challenges when given nurturing influences, but also makes them vulnerable to aberrant development when exposed to prolonged adverse situations. Female rats are particularly sensitive to the effects of chronic stress in adolescence, which manifests as passive coping strategies and blunted hypothalamo-pituitary adrenocortical (HPA) stress responses in adulthood. We sought to intervene by exposing adolescent rats to environmental enrichment (EE) immediately prior to and during chronic stress, hypothesizing that EE would minimize or prevent the long-term effects of stress that emerge in adult females. To test this, we exposed male and female rats to EE on postnatal days (PND) 33-60 and implemented chronic variable stress (CVS) on PND 40-60. CVS consisted of twice-daily unpredictable stressors. Experimental groups included: CVS/unenriched, unstressed/EE, CVS/EE and unstressed/unenriched (n = 10 of each sex/group). In adulthood, we measured behavior in the open field test and forced swim test (FST) and collected blood samples following the FST. We found that environmental enrichment given during the adolescent period prevented the chronic stress-induced transition to passive coping in the FST and reversed decreases in peak adrenocortical responsiveness observed in adult females. Adolescent enrichment had little to no effect on males or unstressed females tested in adulthood, indicating that beneficial effects are specific to females that were exposed to chronic stress.

Clinicopathological correlates of adrenal Cushing's syndrome.

Science.gov (United States)

Duan, Kai; Gomez Hernandez, Karen; Mete, Ozgur

2015-03-01

Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical Characteristics of Endogenous Cushing's Syndrome at a Medical Center in Southern Taiwan

Science.gov (United States)

Tung, Shih-Chen; Wang, Pei-Wen; Liu, Rue-Tsuan; Chen, Jung-Fu; Hsieh, Ching-Jung; Kuo, Ming-Chun; Yang, Joseph W.; Lee, Wei-Ching; Cheng, Min-Hsiung; Lee, Tao-Chen

2013-01-01

From January 1987 to December 2011, over a total of 25 years, 84 patients with Cushing's syndrome (CS) were identified at a medical center in southern Taiwan. We observed a higher incidence of ACTH-independent CS (75%) than ACTH-dependent CS (25%). A higher incidence of adrenocortical adenoma (58.3%) than Cushing's disease (CD, 21.4%) was also found. The sensitivity of the definitive diagnostic tests for CS, including loss of plasma cortisol circadian rhythm, a baseline 24 h urinary free cortisol (UFC) value >80 μg, and overnight and 2-day low-dose dexamethasone suppression test, was between 94.4% and 100%. For the 2-day high-dose dexamethasone suppression test for the differential diagnosis of CD, the sensitivity of 0800 h plasma cortisol and 24 h UFC was 44.4% and 85.7%, respectively. For the differential diagnosis of adrenal CS, the sensitivities of the 0800 h plasma cortisol and 24 h UFC were 95.5% and 88.9%, respectively. In patients with ACTH-independent CS and ACTH-dependent CS, the baseline plasma ACTH levels were all below 29 pg/mL and above 37 pg/mL, respectively. The postsurgical hospitalization stay following retroperitoneoscopic adrenalectomy was shorter than that observed for transabdominal adrenalectomy (4.3 ± 1.6 versus 8.8 ± 3.7 days, P < 0.001). It was easy to develop retroperitoneal and peritoneal seeding of adrenocortical carcinoma via laparoscopic adrenalectomy. PMID:24062770

Clinical Characteristics of Endogenous Cushing’s Syndrome at a Medical Center in Southern Taiwan

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Shih-Chen Tung

2013-01-01

Full Text Available From January 1987 to December 2011, over a total of 25 years, 84 patients with Cushing’s syndrome (CS were identified at a medical center in southern Taiwan. We observed a higher incidence of ACTH-independent CS (75% than ACTH-dependent CS (25%. A higher incidence of adrenocortical adenoma (58.3% than Cushing’s disease (CD, 21.4% was also found. The sensitivity of the definitive diagnostic tests for CS, including loss of plasma cortisol circadian rhythm, a baseline 24 h urinary free cortisol (UFC value >80 μg, and overnight and 2-day low-dose dexamethasone suppression test, was between 94.4% and 100%. For the 2-day high-dose dexamethasone suppression test for the differential diagnosis of CD, the sensitivity of 0800 h plasma cortisol and 24 h UFC was 44.4% and 85.7%, respectively. For the differential diagnosis of adrenal CS, the sensitivities of the 0800 h plasma cortisol and 24 h UFC were 95.5% and 88.9%, respectively. In patients with ACTH-independent CS and ACTH-dependent CS, the baseline plasma ACTH levels were all below 29 pg/mL and above 37 pg/mL, respectively. The postsurgical hospitalization stay following retroperitoneoscopic adrenalectomy was shorter than that observed for transabdominal adrenalectomy (4.3 ± 1.6 versus 8.8 ± 3.7 days, P<0.001. It was easy to develop retroperitoneal and peritoneal seeding of adrenocortical carcinoma via laparoscopic adrenalectomy.

The Role of gsp Mutations on the Development of Adrenal Cortical Tumors and Adrenal Hyperplasias

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Maria Candida Barisson Villares Fragoso

2016-07-01

Full Text Available Somatic GNAS point mutations, commonly known as gsp mutations, are involved in the pathogenesis of McCune Albright syndrome and have also been described in autonomous hormone-producing tumors, such as somatotropinoma, corticotrophoma, thyroid cancer, ovarian and testicular Leydig cell tumors and primary macronodular adrenocortical hyperplasia (PMAH. [1-3]The involvement of gsp mutations in adrenal tumors was first described by Lyons et al. in 1990. Since then, several studies have detected the presence of gsp mutations in adrenal tumors, but none of them could explain its presence along or the mechanism that leads to tumor formation and hormone hypersecretion. As a result, the molecular pathogenesis of the majority of sporadic adrenocortical tumors remains unclear. [3] PMAH has also been reported with gsp somatic mutations in a few cases. Fragoso et al. in 2003 identified two distinct gsp somatic mutations affecting arginine residues on codon 201 of GNAS in a few patients with PMAH who lacked any features or manifestations of McCune Albright syndrome. Followed by this discovery, other studies have continued looking for gsp mutations based on strong prior evidence demonstrating that increased cAMP signaling is sufficient for cell proliferation and cortisol production. [2, 4] With consideration for the previously reported findings, we conjecture that although somatic activating mutations in GNAS are a rare molecular event, these mutations could probably be sufficient to induce the development of macronodule hyperplasia and variable cortisol secretion.In this manuscript, we revised the presence of gsp mutations associated with adrenal cortical tumors and hyperplasia.

POD-1/Tcf21 overexpression reduces endogenous SF-1 and StAR expression in rat adrenal cells

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M. M. França

2015-12-01

Full Text Available During gonad and adrenal development, the POD-1/capsulin/TCF21transcription factor negatively regulates SF-1/NR5A1expression, with higher SF-1 levels being associated with increased adrenal cell proliferation and tumorigenesis. In adrenocortical tumor cells, POD-1 binds to the SF-1 E-box promoter region, decreasing SF-1 expression. However, the modulation of SF-1 expression by POD-1 has not previously been described in normal adrenal cells. Here, we analyzed the basal expression of Pod-1 and Sf-1 in primary cultures of glomerulosa (G and fasciculata/reticularis (F/R cells isolated from male Sprague-Dawley rats, and investigated whether POD-1 overexpression modulates the expression of endogenous Sf-1 and its target genes in these cells. POD-1 overexpression, following the transfection of pCMVMycPod-1, significantly decreased the endogenous levels of Sf-1 mRNA and protein in F/R cells, but not in G cells, and also decreased the expression of the SF-1 target StAR in F/R cells. In G cells overexpressing POD-1, no modulation of the expression of SF-1 targets, StAR and CYP11B2, was observed. Our data showing that G and F/R cells respond differently to ectopic POD-1 expression emphasize the functional differences between the outer and inner zones of the adrenal cortex, and support the hypothesis that SF-1 is regulated by POD-1/Tcf21 in normal adrenocortical cells lacking the alterations in cellular physiology found in tumor cells.

Percutaneous computed tomography-guided ethanol injection in aldosterone-producing adrenocortical adenoma

International Nuclear Information System (INIS)

Rossi, R.; Savastano, S.; Tommaselli, A.P.

1995-01-01

The feasibility, safety and effectiveness of percutaneous computed tomography-guided ethanol injection (PEI-CT) was investigated in a patient affected by aldosterone-producing adenoma (APA). A 42-year-old male patient with typical features of hyperaldosteronism presented a solitary left adrenal adenoma measuring 2 cm, with a normal contralateral gland, evidenced by both CT scan and adrenal [ 75 Se-19]-nor-cholesterol scintigraphy. After normalization of potassium plasma levels, 4 ml of sterile 95% ethanol with 0.5 ml of 80% iothalamate sodium was injected. The procedure was completed in about 30 min. No severe pain or local complication was noted. Five hour after PEI, a fourfold and a twofold increase in aldosterone and cortisol plasma levels were observed, respectively. After 11 days on a normal sodium and potassium diet, normal potassium plasma levels and reduced aldosterone plasma levels were present, with reappearance of an aldosterone postural response. Plasma renin activity and aldosterone plasma levels normalized 1 month later, with reappearance also of a plasma renin activity postural response and maintenance of normal potassium plasma levels on a high sodium and normal potassium diet. The patient has remained hypertensive, although lower antihypertensive drug dosages have been employed. After 17 months, normal biochemical, hormonal and morphological findings were present. The authors suggested PEI-CT as a further alternative approach to surgery in the management of carefully selected patients with APA. 15 refs., 2 figs., 1 tab

Addison disease in patients treated with glucocorticoid therapy.

LENUS (Irish Health Repository)

Cronin, C C

2012-02-03

Acute adrenal crisis in patients with unrecognized chronic adrenocortical failure is difficult to diagnose and potentially fatal. We describe 2 patients with acute adrenal crisis whose diagnoses were hindered because of concomitant glucocorticoid treatment. Acute adrenal insufficiency is primarily a state of mineralocorticoid deficiency. Prednisolone and prednisone, the most frequently prescribed anti-inflammatory corticosteroid agents, have minimal mineralocorticoid activity. Several conditions that may be treated with pharmacological glucocorticoids are associated with an increased risk of Addison disease. An acute adrenal crisis, against which concurrent glucocorticoid therapy does not confer adequate protection, may develop in such patients.

Effect of radon inhalations on certain oxyda-reductive enzymes in adrenols of white rats

International Nuclear Information System (INIS)

Robaczynski, J.; Kaplonska, J.; Lozinska, E.

1974-01-01

Histochemical investigations were carried out on adrenals of white rats after radon inhalations from inhalers in Swieradow-spa. Increased reactions of oxydo-reductive enzymes: NAD tetrazolium reductase, succinic dehydrogenase and glucose-6-phosphate dehydrogenase were observed in the adrenal cortex, particularly in the zona reticularis which was hypertrophied. Raised activity of oxydo-reductive enzymes in the cells of adrenal cortex evidences increased metabolism in these cells which may reflect increased production of hormones. Finding of stimulation of adrenocortical cells after radon inhalations is of essential importance for explanation of the biological mechanism of action of radon used in balneotherapy. (author)

Nonislet Cell Tumor Hypoglycemia in a Patient with Adrenal Cortical Carcinoma

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Se Won Kim

2016-01-01

Full Text Available Nonislet cell tumor hypoglycemia (NICTH is a rare but serious paraneoplastic syndrome in which a tumor secretes incompletely processed precursors of insulin-like growth factor-II (IGF-II, causing hypoglycemia. Here, we report an exceptional case of NICTH caused by nonfunctioning adrenocortical carcinoma in a 39-year-old male with recurrent hypoglycemia. The patient’s serum IGF-II/IGF-I ratio had increased to 27.8. The serum level of the IGF-II/IGF-I ratio was normalized after removal of the tumor, and the hypoglycemic attacks no longer occurred after the operation.

Modifications in adrenal hormones response to ethanol by prior ethanol dependence.

Science.gov (United States)

Guaza, C; Borrell, S

1985-03-01

Ethanol was administered to rats by means of a liquid diet for 16 days; after an ethanol-free interval of four weeks, animals received a test (IP) dose of ethanol (2 g/kg), and the adrenocortical and adrenomedullary responses were evaluated. Chronically ethanol-exposed animals showed tolerance to the stimulatory effect of ethanol in the pituitary-adrenal axis. Likewise, previously dependent rats showed tolerance to the increase in the activity of the adrenomedullary function induced by acute administration of the drug. Our results indicate that chronic ethanol ingestion can induce persistent changes after complete alcohol abstinence.

Dicty_cDB: AFI409 [Dicty_cDB

Lifescience Database Archive (English)

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Clinical impact of SPECT-CT in the diagnosis and surgical management of hyper-parathyroidism.

Science.gov (United States)

Tokmak, Handan; Demirkol, Mehmet Onur; Alagöl, Faruk; Tezelman, Serdar; Terzioglu, Tarik

2014-01-01

Hyper-functioning parathyroid glands with autonomous overproduction of PTH is the most frequent cause of hypercalcemia in outpatient populations with primary hyper-parathyroidism. It is generally caused by a solitary adenoma in 80%-90% of patients. Despite the various methodologies that are available for preoperative localization of parathyroid lesions, there is still no certain preoperative imaging algorithm to guide a surgical approach prior to the management of primary hyper-parathyroidism (P-HPT). Minimally invasive surgery has replaced the traditional bilateral neck exploration (BNE) as the initial approach in parathyroidectomy at many referral hospitals worldwide. In our study, we investigated diagnostic contributions of SPECT-CT combined with conventional planar scintigraphy in the detection of hyper-functioning parathyroid gland localization, since planar imaging has limitations. We also evaluated the efficacy of preoperative USG in adding to initial diagnostic imaging algorithms to localize a parathyroid adenoma. A total of 256 consecutive surgically naive patients with hyper-parathyroidism diagnosis were included in the following preoperative localization study. The study consisted of 256 consecutive patients with HPT, with a selected 154 patients who had neck surgery with definitive histology reports. All patients had 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) double-phase scintigraphy. The SPECT-CT procedure, combined with standard 99mTc-MIBI planar parathyroid scintigraphy with a pinhole and parallel-hole collimator to evaluate whether the SPECT-CT procedure was able to provide additional information in the localization of the pathology, caused hyper-parathyroidism in both P-HPT and S-HPT. In the 154 P-HPT patients, 168 lesions (142 adenomas including 2 intrathyroidal and 2 double adenoma, 2 carcinoma, and 22 hyperplastic glands (four patients had MEN I, each with four hyperplastic glands)), were found at surgery. SPECT-CT detected more lesions than

Role of 99mTc-sestamibi SPECT in accurate selection of primary hyperparathyroid patients for minimally invasive radio-guided surgery

International Nuclear Information System (INIS)

Rubello, Domenico; Massaro, Arianna; Cittadin, Silvia; Rampin, Lucia; Al-Nahhas, Adil; Boni, Giuseppe; Mariani, Giuliano; Pelizzo, Maria R.

2006-01-01

A prerequisite for optimum minimally invasive radio-guided surgery (MIRS) for primary hyperparathyroidism (PHPT) is the demonstration of significant uptake of 99m Tc-sestamibi in a parathyroid adenoma (PA). The aim of this study was to evaluate the clinical role or 99m Tc-sestamibi SPECT in selecting patients for this procedure. Fifty-four consecutive PHPT patients were evaluated by single-session 99m Tc-pertechnetate/ 99m Tc-sestamibi planar subtraction scintigraphy, followed by 99m Tc-sestamibi SPECT acquisition to localise hyperfunctioning PAs and assist in planning the surgical approach. Scintigraphy showed the presence of a solitary PA in 47/54 patients (87%) and two or more PAs in four patients (7.4%); it was negative in the remaining three patients (5.6%). The overall sensitivity of 99m Tc-sestamibi scintigraphy was 94.6%. In 7/54 patients, the PA was located deep in the para-oesophageal/paratracheal space. So far, 22 patients with scintigraphic evidence of a solitary PA (in four of whom the PA was located deep in the neck) have undergone successful MIRS using the low 37 MBq (1 mCi) 99m Tc-sestamibi dose protocol. Intraoperative quick parathyroid hormone (QPTH) assay demonstrated a fall in all 22 patients, thus confirming successful removal of the hyperfunctioning PA. No major surgical complications were observed. After a period of follow-up ranging between 6 and 27 months (median 13 months), no case of persistent/recurrent PHPT was recorded. When comparing the parathyroid to background (P/B) ratio measured at planar and SPECT preoperative scintigraphy with that measured intraoperatively with the gamma probe, a good linear correlation was found between the SPECT and the intraoperative gamma probe measurements (r=0.89; p 99m Tc-sestamibi SPECT is more accurate in predicting the intraoperative measurements with the gamma probe. In this respect, a preoperative 99m Tc-sestamibi SPECT acquisition should be recommended for better selection of PHPT patients in whom

Psicopatologia della Teoria della Mente: riflessioni evoluzionistiche

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Alfonso Troisi

2015-08-01

Full Text Available Psychopathology of Theory of Mind: Evolutionary Reflections - In medicine, the study of pathology can often help to get a better understanding of physiology. Based on this premise and adopting an evolutionary perspective, the present commentary analyzes some conditions characterized by an abnormal functioning of the Theory of Mind (ToM. It has been hypothesized that ToM dysfunctions include not only deficit syndromes (e.g., childhood autism but also disorders involving a hyper-function of social cognition (e.g., psychosis. ToM dysfunction may also consists of a dissociation of its cognitive and affective components, as in the case of primary psychopathy. An evolutionary analysis of the adaptive function of ToM is crucial to explain the origin of these statistically-deviant conditions and to decide if they are pathological or not.

Radio-guided surgery for removal of a giant parathyroid cyst related to hyperthyroidism

International Nuclear Information System (INIS)

Fuentes Valdes, Edelberto; Escarpanter Gonzalez, Julio C; Lopez Diaz, Adlin; Alfonso Trujillo, Yiovanni; Infante Amoros, Adalberto; Dominguez lvarez, Carlos A; Palau San Pedro, Aley

2009-01-01

Among present advances of surgical treatment of hyperthyroidism is the preoperative localization of hyper-functioning glands by preoperative and intraoperative scan, this later one by a special gamma probe. By the other hand, parathyroid cysts are rare; may be of functioning type or not, as well as the findings of 99mTc-MIBI, and the intraoperative use of gamma probe to assess all the possible sites where could be hyperproductive glands of parathyroid hormone. We describe features of management, safety, and administration of radiological agent during the immediate preoperative period, as well as use of gamma probe during intervention. Evolution over follow-up is reported. This case represents the third patient operated on from hyperthyroidism by radio-guided surgery in our center, which introduced this technique in our country. (Author)

Detection of synchronous parathyroid adenoma and breast cancer with {sup 18}F-fluorocholine PET-CT

Energy Technology Data Exchange (ETDEWEB)

Vorselaars, Wessel MCM; Kluijfthout, Wiuter P.; Vriens, Menno R; Van der Pol, Carmen C.; Rinkes, Inne HM Borel; Valk, Gerlof D.; De Keizer, Bart [University Medical Center Utrecht, Utrecht (Netherlands)

2016-06-15

A 71-year-old woman was referred to our tertiary care center for evaluation of asymptomatic recurrence of primary hyperparathyroidism. As per our protocol, the patient underwent neck/mediastinum {sup 18}F-fluorocholine (FCH) positron emission tomography-computed tomography (PET-CT) for localization. In our institution, FCH PET-CT is performed in patients with hyperparathyroidism and negative conventional imaging. FCH PET-CT is a promising new imaging modality for detection of hyperfunctioning parathyroid glands. As can be seen in the case presented, high FCH uptake was seen in a small breast cancer. Due to its favorable half-life and wide availability by its use as a localization technique for patients with prostate cancer and complicated hyperparathyroidism, FCH PET-CT may be a new promising modality in the imaging of breast cancer.

Proliferative signaling initiated in ACTH receptors

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C.F.P. Lotfi

2000-10-01

Full Text Available This article reviews recent results of studies aiming to elucidate modes of integrating signals initiated in ACTH receptors and FGF2 receptors, within the network system of signal transduction found in Y1 adrenocortical cells. These modes of signal integration should be central to the mechanisms underlying the regulation of the G0->G1->S transition in the adrenal cell cycle. FGF2 elicits a strong mitogenic response in G0/G1-arrested Y1 adrenocortical cells, that includes a rapid and transient activation of extracellular signal-regulated kinases-mitogen-activated protein kinases (ERK-MAPK (2 to 10 min, b transcription activation of c-fos, c-jun and c-myc genes (10 to 30 min, c induction of c-Fos and c-Myc proteins by 1 h and cyclin D1 protein by 5 h, and d onset of DNA synthesis stimulation within 8 h. ACTH, itself a weak mitogen, interacts with FGF2 in a complex manner, blocking the FGF2 mitogenic response during the early and middle G1 phase, keeping ERK-MAPK activation and c-Fos and cyclin D1 induction at maximal levels, but post-transcriptionally inhibiting c-Myc expression. c-Fos and c-Jun proteins are mediators in both the strong and the weak mitogenic responses respectively triggered by FGF2 and ACTH. Induction of c-Fos and stimulation of DNA synthesis by ACTH are independent of PKA and are inhibited by the PKC inhibitor GF109203X. In addition, ACTH is a poor activator of ERK-MAPK, but c-Fos induction and DNA synthesis stimulation by ACTH are strongly inhibited by the inhibitor of MEK1 PD98059.

A Longitudinal Follow-up of Autoimmune Polyendocrine Syndrome Type 1

Science.gov (United States)

Bruserud, Øyvind; Oftedal, Bergithe E.; Landegren, Nils; Erichsen, Martina M.; Bratland, Eirik; Lima, Kari; Jørgensen, Anders P.; Myhre, Anne G.; Svartberg, Johan; Fougner, Kristian J.; Bakke, Åsne; Nedrebø, Bjørn G.; Mella, Bjarne; Breivik, Lars; Viken, Marte K.; Knappskog, Per M.; Marthinussen, Mihaela C.; Løvås, Kristian; Kämpe, Olle; Wolff, Anette B.

2016-01-01

Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insufficiency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse. Objective: To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator (AIRE) mutations during extended follow-up (1996–2016). Patients: All known Norwegian patients with APS1. Results: Fifty-two patients from 34 families were identified. The majority presented with one of the major disease components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent components. With age, most patients presented three to five disease manifestations, although some had milder phenotypes diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were deceased siblings with a high probability of undisclosed APS1. All except three had interferon-ω) autoantibodies, and all had organ-specific autoantibodies. The most common AIRE mutation was c.967_979del13, found in homozygosity in 15 patients. A mild phenotype was associated with the splice mutation c.879+1G>A. Primary adrenocortical insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes. Conclusions: Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon-ω) and AIRE sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured follow-up should be performed in a specialized center. PMID:27253668

Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease.

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Molnár, Ágnes; Kövesdi, Annamária; Szücs, Nikolette; Tóth, Miklós; Igaz, Péter; Rácz, Károly; Patócs, Attila

2016-08-01

Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease. 68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR. The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone. The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients. © 2016 John Wiley & Sons Ltd.

The expression of the ACTH receptor

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L.L.K. Elias

2000-10-01

Full Text Available Adrenal glucocorticoid secretion is regulated by adrenocorticotropic hormone (ACTH acting through a specific cell membrane receptor (ACTH-R. The ACTH-R is a member of the G protein superfamily-coupled receptors and belongs to the subfamily of melanocortin receptors. The ACTH-R is mainly expressed in the adrenocortical cells showing a restricted tissue specificity, although ACTH is recognized by the other four melanocortin receptors. The cloning of the ACTH-R was followed by the study of this gene in human diseases such as familial glucocorticoid deficiency (FGD and adrenocortical tumors. FGD is a rare autosomal recessive disease characterized by glucocorticoid deficiency, elevated plasma ACTH levels and preserved renin/aldosterone secretion. This disorder has been ascribed to an impaired adrenal responsiveness to ACTH due to a defective ACTH-R, a defect in intracellular signal transduction or an abnormality in adrenal cortical development. Mutations of the ACTH-R have been described in patients with FGD in segregation with the disease. The functional characterization of these mutations has been prevented by difficulties in expressing human ACTH-R in cells that lack endogenous melanocortin receptor activity. To overcome these difficulties we used Y6 cells, a mutant variant of the Y1 cell line, which possesses a non-expressed ACTH-R gene allowing the functional study without any background activity. Our results demonstrated that the several mutations of the ACTH-R found in FGD result in an impaired cAMP response or loss of sensitivity to ACTH stimulation. An ACTH-binding study showed an impairment of ligand binding with loss of the high affinity site in most of the mutations studied.

Interleukin-1β causes fluoxetine resistance in an animal model of epilepsy-associated depression.

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Pineda, Eduardo A; Hensler, Julie G; Sankar, Raman; Shin, Don; Burke, Teresa F; Mazarati, Andréy M

2012-04-01

Depression represents a common comorbidity of epilepsy and is frequently resistant to selective serotonin reuptake inhibitors (SSRI). We tested the hypothesis that the SSRI resistance in epilepsy associated depression may be a result of a pathologically enhanced interleukin-1β (IL1-β) signaling, and consequently that the blockade of IL1-β may restore the effectiveness of SSRI. Epilepsy and concurrent depression-like impairments were induced in Wistar rats by pilocarpine status epilepticus (SE). The effects of the 2-week long treatment with fluoxetine, interleukin-1 receptor antagonist (IL-1ra), and their combination were examined using behavioral, biochemical, neuroendocrine, and autoradiographic assays. In post-SE rats, depression-like impairments included behavioral deficits indicative of hopelessness and anhedonia; the hyperactivity of the hypothalamo-pituitary-adrenocortical axis; the diminished serotonin output from raphe nucleus; and the upregulation of presynaptic serotonin 1-A (5-HT1A) receptors. Fluoxetine monotherapy exerted no antidepressant effects, whereas the treatment with IL-1ra led to the complete reversal of anhedonia and to a partial improvement of all other depressive impairments. Combined administration of fluoxetine and IL-1ra completely abolished all hallmarks of epilepsy-associated depressive abnormalities, with the exception of the hyperactivity of the hypothalamo-pituitary-adrenocortical axis, the latter remaining only partially improved. We propose that in certain forms of depression, including but not limited to depression associated with epilepsy, the resistance to SSRI may be driven by the pathologically enhanced interleukin-1β signaling and by the subsequent upregulation of presynaptic 5-HT1A receptors. In such forms of depression, the use of interleukin-1β blockers in conjunction with SSRI may represent an effective therapeutic approach.

Dietary restriction causes chronic elevation of corticosterone and enhances stress response in red-legged kittiwake chicks

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Kitaysky, A.S.; Kitaiskaia, E.V.; Wingfield, J.C.; Piatt, John F.

2001-01-01

Release of corticosterone in hungry kittiwake chicks facilitates begging and allows them to restore depleted energy reserves by increasing parental food provisioning. However, in order to avoid detrimental effects of chronic elevation of corticosterone, chicks might suppress adrenocortical activity in response to prolonged food shortages. In this study we examined temporal dynamics of corticosterone release in red-legged kittiwake (Rissa brevirostris) chicks exposed to prolonged restrictions in energy content and/or nutritional quality (low versus high lipid content) of their food. Starting at the age of 15 days, chicks were fed either high- or low-lipid fish at 40%, 65%, and 100% of ad libitum energy intake. Body mass measurements and baseline plasma samples were taken on a weekly basis after beginning of the treatment. After 3 weeks of treatment, chicks were exposed to a standardized acute handling and restraint stress protocol, where in addition to a baseline sample, three plasma samples were taken at intervals up to 50 min. We found that food-restricted chicks had lower body mass, chronically (during 2-3 weeks) elevated baseline and higher acute stress-induced levels of corticosterone compared to chicks fed ad libitum. Low lipid content of food further exacerbated these effects. An increase in baseline levels of corticosterone was observed within a week after energy requirements of food-restricted chicks exceeded their daily energy intake. A tendency for suppression of adrenocortical activity was observed in treatments fed low-lipid diets only at the end of the experiment. We suggest that nest-bound chicks, if food-stressed, might suffer deleterious effects of chronic elevation of corticosterone.

Developmental programming of adult adrenal structure and steroidogenesis: effects of fetal glucocorticoid excess and postnatal dietary omega-3 fatty acids.

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Waddell, Brendan J; Bollen, Maike; Wyrwoll, Caitlin S; Mori, Trevor A; Mark, Peter J

2010-05-01

Fetal glucocorticoid excess programs a range of detrimental outcomes in the adult phenotype, at least some of which may be due to altered adult adrenocortical function. In this study, we determined the effects of maternal dexamethasone treatment on offspring adrenal morphology and function, as well as the interactive effects of postnatal dietary omega-3 (n-3) fatty acids. This postnatal dietary intervention has been shown to alleviate many of the programming outcomes in this model, but whether this is via the effects on adrenal function is unknown. Dexamethasone acetate was administered to pregnant rats (0.75 microg/ml drinking water) from day 13 to term. Cross-fostered offspring were raised on either a standard or high-n-3 diet. Adrenal weight (relative to body weight) at 6 months of age was unaffected by prenatal dexamethasone, regardless of postnatal diet, and stereological analysis showed no effect of dexamethasone on the volumes of adrenal components (zona glomerulosa, zona fasciculata/reticularis or adrenal medulla). Expression of key steroidogenic genes (Cyp11a1 and Star) was unaffected by either prenatal dexamethasone or postnatal diet. In contrast, adrenal expression of Mc2r mRNA, which encodes the ACTH receptor, was higher in offspring of dexamethasone-treated mothers, an effect partially attenuated by the Hn3 diet. Moreover, stress-induced levels of plasma and urinary corticosterone and urinary aldosterone were elevated in offspring of dexamethasone-treated mothers, indicative of enhanced adrenal responsiveness. In conclusion, this study shows that prenatal exposure to dexamethasone does not increase basal adrenocortical activity but does result in a more stress-responsive adrenal phenotype, possibly via increased Mc2r expression.

The influence of social hierarchy on primate health.

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Sapolsky, Robert M

2005-04-29

Dominance hierarchies occur in numerous social species, and rank within them can greatly influence the quality of life of an animal. In this review, I consider how rank can also influence physiology and health. I first consider whether it is high- or low-ranking animals that are most stressed in a dominance hierarchy; this turns out to vary as a function of the social organization in different species and populations. I then review how the stressful characteristics of social rank have adverse adrenocortical, cardiovascular, reproductive, immunological, and neurobiological consequences. Finally, I consider how these findings apply to the human realm of health, disease, and socioeconomic status.

Mortality in Patients with Endogenous Cushing's Syndrome.

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Javanmard, Pedram; Duan, Daisy; Geer, Eliza B

2018-06-01

Cushing's syndrome is associated with increased morbidity and mortality. Cardiovascular events, sepsis, and thromboembolism are the leading causes of mortality. Patient's with Cushing's due to a pituitary adenoma and those with Cushing's due to benign adrenal adenoma have relatively good survival outcomes often mirroring that of the general population. Persistent or recurrent disease is associated with high mortality risk. Ectopic Cushing's syndrome and Cushing's due to adrenocortical carcinoma confer the highest mortality risk among Cushing's etiologies. Prompt diagnosis and treatment, and specific monitoring for and treatment of associated comorbidities are essential to decrease the burden of mortality from Cushing's. Copyright © 2018 Elsevier Inc. All rights reserved.

Adrenal Surgery for Cushing's Syndrome: An Update.

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Di Dalmazi, Guido; Reincke, Martin

2018-06-01

Recent advances in the molecular pathogenesis and the natural history of Cushing's syndrome have improved the understanding of the management of this disease. The long-term efficacy of several cortisol-lowering medical treatments is currently under evaluation. However, adrenalectomy is a safe option for the treatment of patients affected by Cushing's syndrome. Unilateral adrenalectomy is the gold standard for treatment of adrenocortical adenomas associated with hypercortisolism. Bilateral adrenalectomy has been widely used in the past as definitive treatment of bilateral macronodular hyperplasia and persistent or recurrent Cushing's disease. The indication and the potential applications of this technique have been recently critically analyzed. Copyright © 2018 Elsevier Inc. All rights reserved.

Adrenal scintigraphy

International Nuclear Information System (INIS)

Veen, E.A. van der.

1978-01-01

The visualization of functioning adrenocortical tissue by scintigraphy became possible with the introduction of radioiodinated cholesterol derivatives. According to the literature, there is evidence that one of these iodinated cholesterols, 6-β-iodomethyl-nor-cholesterol, concentrates in the adrenal cortex to a much greater extent than 131 I-19-odocholesterol. Results comparing both radiopharmaceuticals are described. The authors investigated the possibility of increasing the uptake of iodinated cholesterol using simultaneous ACTH and the 'cholesterol side-chain cleavage enzymeblocker': aminoglutethimide. The results of adrenal scintigraphy performed in 37 patients are described. Finally, the literature on adrenal scintigraphy is reviewed, and results reported in various studies are compared. (Auth.)

Aldosterone and cortisol co-secreting bifunctional adrenal cortical carcinoma: A rare event

Directory of Open Access Journals (Sweden)

Puskar Shyam Chowdhury

2014-01-01

Full Text Available Adrenocortical carcinoma (ACC co-secreting aldosterone and cortisol is extremely rare. We report the case of a 37-yearold female who presented with paresis and facial puffiness. Evaluation revealed hypertension, hyperglycemia, severe hypokalemia and hyperaldosteronemia with elevated plasma aldosterone to renin ratio (ARR. Urinary free cortisol estimation showed elevated levels. Computed tomography scan revealed a right adrenal mass. Radical adrenalectomy specimen revealed ACC (T3N1. Post-operatively, the patient became normotensive and euglycemic with normalization of urinary cortisol and ARR. This case highlights the need for a complete evaluation in patients of hyperaldosteronism if overlapping symptoms of hypercortisolism are encountered, to avoid post-operative adrenal crisis.

Microencapsulation Of Living Cells

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Chang, Manchium; Kendall, James M.; Wang, Taylor G.

1989-01-01

In experimental technique, living cells and other biological materials encapsulated within submillimeter-diameter liquid-filled spheres. Sphere material biocompatible, tough, and compliant. Semipermeable, permitting relatively small molecules to move into and out of sphere core but preventing passage of large molecules. New technique promises to make such spherical capsules at high rates and in uniform, controllable sizes. Capsules injected into patient through ordinary hypodermic needle. Promising application for technique in treatment of diabetes. Also used to encapsulate pituitary cells and thyroid hormone adrenocortical cells for treatment of other hormonal disorders, to encapsulate other secreting cells for transplantation, and to package variety of pharmaceutical products and agricultural chemicals for controlled release.

Neonatal Cushing Syndrome: A Rare but Potentially Devastating Disease.

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Tatsi, Christina; Stratakis, Constantine A

2018-03-01

Neonatal Cushing syndrome (CS) is most commonly caused by exogenous administration of glucocorticoids and rarely by endogenous hypercortisolemia. CS owing to adrenal lesions is the most common cause of endogenous CS in neonates and infants, and adrenocortical tumors (ACTs) represent most cases. Many ACTs develop in the context of a TP53 gene mutation, which causes Li-Fraumeni syndrome. More rarely, neonatal CS presents as part of other syndromes such as McCune-Albright syndrome or Beckwith-Wiedemann syndrome. Management usually includes resection of the primary tumor with or without additional medical treatment, but manifestations may persist after resolution of hypercortisolemia. Published by Elsevier Inc.