Femtogram determination of ACTH by bioradioimmunoassay

International Nuclear Information System (INIS)

Bruni, G.; Dal Pra, P.; Segre, G.

1979-01-01

A bioradioimmunoassay is described for determining adrenocorticotropic hormone (ACTH) levels in biological fluids. Slices of guinea pig's adrenal gland surviving in vitro and depleted of their cortisol content were used. When challenged with ACTH, the slices release newly synthesised cortisol into the medium which is then determined by radioimmunoasssay. A log-linear relationship was evident between added ACTH and the cortisol measured in the medium. Unlike previous methods, the sensitivity of this assay allows the determination of 0.5 femtogram (10 -15 g) of ACTH. A good correlation was observed when rat plasma ACTH levels were determined by the present bioassay method and by an ACTH radioimmunoassay. Mean values of plasma ACTH determined by the present method are shown for man, child, guinea pig, rabbit, rat, and hamster. (UK)

Femtogram determination of ACTH by bioradioimmunoassay

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Bruni, G; Dal Pra, P; Segre, G [Siena Univ. (Italy). Inst. Pharmacology

1979-11-01

A bioradioimmunoassay is described for determining adrenocorticotropic hormone (ACTH) levels in biological fluids. Slices of guinea pig's adrenal gland surviving in vitro and depleted of their cortisol content were used. When challenged with ACTH, the slices release newly synthesised cortisol into the medium which is then determined by radioimmunoasssay. A log-linear relationship was evident between added ACTH and the cortisol measured in the medium. Unlike previous methods, the sensitivity of this assay allows the determination of 0.5 femtogram (10/sup -15/g) of ACTH. A good correlation was observed when rat plasma ACTH levels were determined by the present bioassay method and by an ACTH radioimmunoassay. Mean values of plasma ACTH determined by the present method are shown for man, child, guinea pig, rabbit, rat, and hamster.

Molecular interpretation of ACTH-β-endorphin coaggregation: relevance to secretory granule biogenesis.

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Srivastav Ranganathan

Full Text Available Peptide/protein hormones could be stored as non-toxic amyloid-like structures in pituitary secretory granules. ACTH and β-endorphin are two of the important peptide hormones that get co-stored in the pituitary secretory granules. Here, we study molecular interactions between ACTH and β-endorphin and their colocalization in the form of amyloid aggregates. Although ACTH is known to be a part of ACTH-β-endorphin aggregate, ACTH alone cannot aggregate into amyloid under various plausible conditions. Using all atom molecular dynamics simulation we investigate the early molecular interaction events in the ACTH-β-endorphin system, β-endorphin-only system and ACTH-only system. We find that β-endorphin and ACTH formed an interacting unit, whereas negligible interactions were observed between ACTH molecules in ACTH-only system. Our data suggest that ACTH is not only involved in interaction with β-endorphin but also enhances the stability of mixed oligomers of the entire system.

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...

Overt hypoadrenalism is uncommon in patients with stage 3 and 4 ...

African Journals Online (AJOL)

Our study aimed to determine the prevalence of primary hypoadrenalism, as defined by a subnormal cortisol response to the 250 µg adrenocorticotrophic hormone (ACTH) stimulation test, in patients with stage 3 and 4 lung cancer. Methods. Thirty patients with stage 3 and 4 bronchogenic carcinoma were prospectively ...

Acth e enzimas na supra-renal ACTH and enzymes in adrenal gland

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H. Povoa Junior

1974-01-01

Full Text Available Estudou-se a atividade da ceruloplasmina, adenosina desaminase (AD e transaminases glutâmico oxalacética (TGO e glutâmico pirúvica (TGP na supra-renal de ratos normais e injetados previamente (24 horas antes com uma injeção única, por via intraperitoneal, de ACTH em doses de 0,5 e 1,2 un. internacionais. observou-se uma elevação estatisticamente significativa das TGO e ceruloplasmina enquanto a AD sofria diminuição sensível em sua atividade.Activities of several enzymes have been studied in rat adrenal glands after ACTH injection. Activity of glutamic oxalacetic transaminase increases significantly after ACTH. The same was observed with ceruloplasmin. Adrenosine desaminase inthe same gland was decreased after administration of this hormone.

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.

Aged PROP1 deficient dwarf mice maintain ACTH production.

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Igor O Nasonkin

Full Text Available Humans with PROP1 mutations have multiple pituitary hormone deficiencies (MPHD that typically advance from growth insufficiency diagnosed in infancy to include more severe growth hormone (GH deficiency and progressive reduction in other anterior pituitary hormones, eventually including adrenocorticotropic hormone (ACTH deficiency and hypocortisolism. Congenital deficiencies of GH, prolactin, and thyroid stimulating hormone have been reported in the Prop1(null (Prop1(-/- and the Ames dwarf (Prop1(df/df mouse models, but corticotroph and pituitary adrenal axis function have not been thoroughly investigated. Here we report that the C57BL6 background sensitizes mutants to a wasting phenotype that causes approximately one third to die precipitously between weaning and adulthood, while remaining homozygotes live with no signs of illness. The wasting phenotype is associated with severe hypoglycemia. Circulating ACTH and corticosterone levels are elevated in juvenile and aged Prop1 mutants, indicating activation of the pituitary-adrenal axis. Despite this, young adult Prop1 deficient mice are capable of responding to restraint stress with further elevation of ACTH and corticosterone. Low blood glucose, an expected side effect of GH deficiency, is likely responsible for the elevated corticosterone level. These studies suggest that the mouse model differs from the human patients who display progressive hormone loss and hypocortisolism.

Blood supply to the brain and. beta. -endorphin and acth levels under the influence of thyrotrophin releasing hormone

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Mirzoyan, R.S.; Ganshina, T.S.; Mirzoyan, R.A.; Ragimov, K.S.

1985-08-01

The authors studied beta-endorphin because of its possible mediator role in terms of the cerebrovascular effects of thyrotrophin releasing hormone (TRH), and also because of data in the literature on antagonistic relations between TRH and the endogenous opioid system of the brain. Beta-endorphin was determined by radioimmunoassay; its level was determined after its separation from the beta-lipotrophin fraction. The investigation showed that TRH has a marked depressant effect on cerebrovascular vasoconstrictor refleces. Elevation of the blood ACTH level causes an increase in BP and in the tone of the cerebral vessels. An absence of correlation between the beta-endorphin and ACTH levels in the blood and CSF under the influence of TRH is shown.

Influence of heparin on radioimmunological assay of ACTH

International Nuclear Information System (INIS)

Dupouy, J.P.; Godaut, M.; Chatelain, A.

1986-01-01

1 - Heparin traps plasma ACTH, promoting the formation of aggregates with apparent high molecular weight as shown by chromatography on Sephadex G 50 fine columns. The percentage of 125 I-ACTH which appeared in the void volume of the column, increased linearly with the log. dose of heparin. 2 - Heparin at concentrations of up to 100 IU/ml does not impair ACTH adsorption on either silicic acid or Quso G 32 as well as further elution by acetic acid/acetone/water (I: 40: 59; V/V) or HCl O.I N. Silicic acid traps selectively ACTH but not heparin. 3 - Heparin interferes with direct RIA-ACTH in the plasma by decreasing 125 I-ACTH binding to the antibodies and modifying the slope of the standard curve. Unsuitable artefacts induced by heparin, as overestimation or underestimation of plasma ACTH levels by RIA, can be avoid by previous hormone extraction from heparinized plasmas. Such results emphasized the importance of the sample preparation in order to obtain consistent results [fr

Human-human and human-animal interaction

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Handlin, Linda

2010-01-01

The aim of the present thesis was to investigate hormonal and physiological effects in mothers during a breastfeeding session and in dogs and their owners in response to short-term interaction. In study one, sixty-six mothers receiving either exogenous oxytocin infusion and/or epidural analgesia (EDA) during labor or intramuscular oxytocin injection post partum were studied. Oxytocin, prolactin, adrenocorticotrophic hormone (ACTH) and cortisol levels, as well as blood pressure were measured d...

Radioimmunological determination of. cap alpha. -MSH and ACTH in the rat

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Usategui Echeverria, R; Oliver, C; Vaudry, H; Lombardi, G; Rozenberg, I; Vague, J [Centre Hospitalier Universitaire de la Timone, 13 - Marseille (France)

1975-09-01

Specific and sensitive radioimmunoassay methods for ..cap alpha..-MSH and ACTH are reported. They make possible specific measurements of each hormone in rat plasma or pituitary extracts. Endogenous ..cap alpha..-MSH and ACTH extracted from plasma or pituitary show the same immunoreactivity than synthetic ..cap alpha..-MSH and ACTH. ..cap alpha..-MSH and ACTH levels vary independently from each other in the following conditions: circadian rythm, corticoid treatment, adrenalectomy, ether stress, haloperidol injection.

Steroidogenic activity of high molecular weight forms of ACTH

International Nuclear Information System (INIS)

Gasson, J.C.

1979-01-01

The relative steroidogenic potencies of high molecular weight forms of adrenocorticotropic hormone (ACTH) were investigated using in vitro bioassays. In order to prepare pools of separated pro-ACTH/endorphin, ACTH biosynthetic intermediate and glycosylated ACTH (1-39), the protein present in serum-free tissue culture medium obtained from cultured AtT-20/D-16v mouse pituitary tumor cells was concentrated and fractionated by gel filtration. Based on sodium dodecyl sulfate polyacrylamide gel electrophoresis, over 97% of the immunoactive ACTH in each pool had the appropriate molecular weight. Suspensions of isolated rat and guinea pig adrenal cortical cells were prepared by enzymatic dissociation and mechanical dispersion. Cells were incubated in complete tissue culture medium overnight then used in a 2 hour steroid production assay. Synthetic hACTH(1-39) was used as a bioassay and immunoassay standard. The amounts of pro-ACTH/endorphin, ACTH biosynthetic intermediate and glycosylated ACTH(1-39) bioassayed were estimated by ACTH(17-24) radioimmunoassay. All three high molecular weight forms of ACTH were capable of stimulating the same maximal level of steroidogenesis, by both isolated rat and guinea pig adrenal cells, as hACTH(1-39). Glycosylated ACTH(1-39) was equipotent with hACTH(1-39); pro-ACTH/endorphin and ACTH biosynthetic intermediate were two orders of magnitude less potent than hACTH(1-39) in both bioassay systems

Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers.

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Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

2013-01-01

Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus-pituitary-adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30-64 years): a low-dose adrenocorticotrophic hormone (ACTH(1-24), Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone-corticotropin releasing hormone (DEX-CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at - 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort-reward-imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX-CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis.

Sensorimotor cortex ablation induces time-dependent response of ACTH cells in adult rats: behavioral, immunohistomorphometric and hormonal study.

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Lavrnja, Irena; Trifunovic, Svetlana; Ajdzanovic, Vladimir; Pekovic, Sanja; Bjelobaba, Ivana; Stojiljkovic, Mirjana; Milosevic, Verica

2014-02-10

Traumatic brain injury (TBI) represents a serious event with far reaching complications, including pituitary dysfunction. Pars distalis corticotropes (ACTH cells), that represent the active module of hypothalamo-pituitary-adrenocortical axis, seem to be affected as well. Since pituitary failure after TBI has been associated with neurobehavioral impairments the aim of this study was to evaluate the effects of TBI on recovery of motor functions, morphology and secretory activity of ACTH cells in the pituitary of adult rats. Wistar male rats, initially exposed to sensorimotor cortex ablation (SCA), were sacrificed at the 2nd, 7th, 14th and 30th days post-surgery (dps). A beam walking test was used to evaluate the recovery of motor functions. Pituitary glands and blood were collected for morphological and hormonal analyses. During the first two weeks post-injury increased recovery of locomotor function was detected, reaching almost the control value at day 30. SCA induces significant increase of pituitary weights compared to their time-matched controls. The volume of ACTH-immunopositive cells was reduced at the 7th dps, while at the 14th dps their volume was enlarged, in comparison to corresponding sham controls. Volume density of ACTH cells was increased only at 14th dps, while at day 30 this increase was insignificant. The plasma level of ACTH transiently increased after the injury. The most pronounced changes were observed at the 7th and 14th dps, and were followed by decrease toward control levels at the 30th dps. Thus, temporal changes in the hypothalamic-pituitary-adrenal axis after traumatic brain injury appear to correlate with the recovery process. Copyright © 2013 Elsevier Inc. All rights reserved.

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

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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.

Ectopic ACTH secretion due to a bronchopulmonary carcinoid localized by somatostatin receptor scintigraphy.

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Iser, G; Pfohl, M; Dörr, U; Weiss, E M; Seif, F J

1994-11-01

We present the case of a 65-year-old woman with an adrenocorticotropic hormone (ACTH) secreting bronchopulmonary carcinoid. This patient showed the typical long history of Cushing's syndrome, including hypokaliemia, impaired glucose tolerance, high levels of ACTH and beta-endorphin, and coproduction of other peptides. At the onset of clinical symptoms in 1979 an adrenal adenoma was suspected, and left-sided adrenalectomy was performed. The symptoms soon recurred, and the diagnosis of ACTH-dependent Cushing's syndrome was made. As no ACTH-secreting tumor was found, the right adrenal was resected, and the patient was followed up regularly. Fourteen years later chest roentgenography and computed tomography revealed a para-aortic pulmonary lesion, which was suspicious for a bronchopulmonary carcinoid. ACTH and beta-endorphin were excessively, pancreatic polypeptide slightly elevated at that time. The final diagnosis was made using somatostatin receptor scintigraphy which confirmed the hormonal activity of the suspicious lesion; no additional focus was found. This method turned out to be not only a useful additional localization technique but also a promising tool for characterization and staging of a suspected ACTH-producing carcinoid. The tumor was resected curatively, and the diagnosis was confirmed histologically.

Fournier's gangrene during ACTH therapy.

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Numoto, Shingo; Kurahashi, Hirokazu; Azuma, Yoshiteru; Numaguchi, Atsushi; Nakahara, Kozaburo; Tainaka, Takahisa; Takasu, Michihiko; Yamakawa, Kiyoshi; Nago, Nozomi; Muto, Taichiro; Kitagawa, Yoshiro; Okumura, Akihisa

2017-05-01

Fournier's gangrene is an infectious necrotizing fasciitis of the perineal, genital, or perianal regions and is uncommon in children. Adrenocorticotropic hormone (ACTH) is effective for the treatment of infantile spasms; however, suppression of immune function is one of the major adverse effects of this approach. We encountered a 2-month-old boy with infantile spasms that had been treated with ACTH and had developed complicating Fournier's gangrene. Strangulation of a right inguinal hernia was observed after ACTH treatment. Although surgical repair was successful and no intestinal injuries were detected, swelling and discoloration of the right scrotum developed in association with pyrexia and a severe inflammatory response. A scrotal incision revealed pus with a putrid smell. The patient was subsequently diagnosed with Fournier's gangrene complicated by septic shock and disseminated intravascular coagulation. Extensive debridement and intensive care was performed. Enterobactor aerogenes, methicillin-resistant Staphylococcus aureus, and Enterococcus faecalis were isolated from the pus. Meropenem, teicoplanin, and clindamycin were administered to control the bacterial infection. The patient was discharged from the intensive care unit without any obvious neurological sequelae. Suppression of immune function associated with ACTH therapy may have been related to the development of Fournier's gangrene in this case. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

ACTH Regulation of Adrenal SR-B1

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Wen-Jun eShen

2016-05-01

Full Text Available The adrenal gland is one of the prominent sites for steroid hormone synthesis. Lipoprotein-derived cholesterol esters delivered via scavenger receptor, class B type 1 (SR-B1 constitute the dominant source of cholesterol for steroidogenesis, particularly in rodents. ACTH stimulates steroidogenesis through downstream actions on multiple components involved in steroidogenesis. Both acute and chronic ACTH treatment can modulate SR-B1 function including its transcription, its post transcriptional stability, its phosphorylation and dimerization status, as well as its interaction with other protein partners; all of which result in changes in the ability of SR-B1 to mediate HDL-cholesterol ester uptake and the supply of cholesterol for conversion to steroids. Here we provide a review of the recent findings on the regulation of adrenal SR-B1 function by ACTH.

The isolation and amino acid sequence of an adrenocorticotrophin from the pars distalis and a corticotrophin-like intermediate-lobe peptide from the neurointermediate lobe of the pituitary of the dogfish Squalus acanthias

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Lowry, Philip J.; Bennett, Hugh P. J.; McMartin, Colin; Scott, Alexander P.

1974-01-01

An adrenocorticotrophic hormone (ACTH) was isolated from extracts of the pars distalis of the pituitary of the dogfish Squalus acanthias by gel filtration and ion-exchange chromatography. It had 15% of the potency of human ACTH in promoting cortico-steroidogenesis in isolated rat adrenal cells. Sequence analysis revealed it to be a nonatria-contapeptide with the following primary structure: Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Met-Gly-Arg-Lys-Arg-Arg-Pro-Ile-Lys-Val-Tyr-Pro-Asn-Ser-Phe-Glu-Asp-Glu-Ser-Val-Glu-Asn-Met-Gly-Pro-Glu-Leu. The N-terminal tridecapeptide sequence was identical with the proposed structure of dogfish α-melanocyte-stimulating hormone (α-MSH). On comparison with human ACTH eleven amino acid differences were seen, nine of which are in the 20–39 region of the molecule which is not essential for the steroidogenic activity of ACTH. A peptide identical with the 18–39 portion of this new ACTH was similarly isolated from the neurointermediate lobe of the pituitary where considerable amounts of dogfish α-MSH were found. This supported our view that ACTH as well as having a distinct biological role of its own is also the precursor of α-MSH. PMID:4375977

alpha-Melanocyte-stimulating-hormone precursors in the pig pituitary

DEFF Research Database (Denmark)

Fenger, M

1986-01-01

The occurrence of intermediates from the processing of ACTH-(1-39) [adrenocorticotropic hormone-(1-39)] to alpha-melanocyte-stimulating hormone was investigated in normal pig pituitaries by the use of sensitive and specific radioimmunoassays for ACTH-(1-13), ACTH-(1-14), ACTH-(1-13)-NH2 and ACTH-(1......) were detected in lower amounts in both the intermediate lobe and the anterior lobe. ACTH-(1-17), ACTH-(1-13) and their acetylated analogues could not be detected in the anterior lobe or the intermediate lobe. The results suggest that an endopeptidase initially cleaves ACTH-(1-39) at the Lys-16-Arg-17...... bond. ACTH-(1-16) is then processed by a pituitary carboxypeptidase to ACTH-(1-14) and ACTH-(17-39) by the aminopeptidase to ACTH-(18-39)....

In vitro assay for ACTH-releasing activity using ACTH radioimmunoassay. ACTH releasing activities by various drugs

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Hashimoto, K; Takahara, J; Hosogi, H; Ofuji, N; Yasuhara, T [Okayama Univ. (Japan). School of Medicine

1976-02-01

This report deals with an in vitro assay of ACTH releasing activity utilizing pituitary incubation combined with ACTH radioimmunoassay. Half of a rat pituitary was preincubated in 2ml Krebs Ringer bicarbonate buffer containing 0.2% glucose and 0.25% BSA (KRBG-BSA) for 1.5 hr (45 min x 2). The medium was replaced by 1 ml KRBG-BSA and incubated for 30 min. Then the medium was again replaced by 1 ml KRBG-BSA or KRBG-BSA containing test materials and incubated for another 30 min. The amount of ACTH assayed by radioimmunoassay in the 2nd 30 min incubation was compared with that in the 1st 30 min incubation, and the result was expressed as a percentage. In the ACTH radioimmunoassay, anti-ACTH serum was diluted to 1:1,500-3,000. The /sup 125/I-..cap alpha../sup 1 -24/ACTH-antibody system was not affected by lysine-vasopressin (LVP), arginine-vasopressin (AVP), rat's pituitary LH, GH or prolactin. Human /sup 1 -39/ACTH was used as the ACTH standard. The dilution curve of the incubation medium was parallel to the standard curve. Reproducibility of immunoassayable ACTH within-assay was 174 +- 5.0 pg/tube (CV=2.9%). A log dose-relationship was observed between the amounts of stalk median eminence extracts (SME; NIAMDD) added to the incubation medium and its ACTH releasing activities. The sensitivity of this assay method was at least 0.1 SME or 10 mU of LVP and AVP. Using this method, it was found that LVP, AVP, norepinephrine (100 ng/ml--200 ng/ml) and 5-hydroxytryptophane (1 ..mu..g/ml) had ACTH releasing activities, but LH-RH, TRH, glucagon, dopamine, phentolamine, propranolol, haloperidol, prostaglandin E/sub 1/ and indomethacin did not affect the release of ACTH.

Clinical study on postoperative steroid hormon replacement for preclinical Cushing's syndrome

International Nuclear Information System (INIS)

Furuta, Nozomu; Koide, Haruhisa; Sasaki, Hiroshi; Miki, Jun; Kimura, Takahiro; Egawa, Shin

2009-01-01

Diagnostic criteria for preclinical Cushing's syndrome (PCS) were reported in 1996. However, requirement of postoperative steroid hormone replacement is still controversial issue. In this study, we observed recent surgical cases retrospectively and evaluate the use of postoperative steroid hormone replacement. Eighteen patients with PCS underwent surgery from 1997 to 2007 in Jikei University Hospital. Thirteen of them received postoperative steroid hormone replacement. We investigated preoperative hormone activity by 131 I-adosterol scintigraphy and suppression of adrenocorticotropic hormone (ACTH) and evaluated the requirement of postoperative steroid hormone replacement. Preoperative serum cortisol was normal range in all patients. Serum ACTH was suppressed in 10 of them (56%). In 131 I-adosterol scintigraphy, accumulation in ipsilateral side was observed in all patients. Accumulation in contralateral side was observed in 13 patients whose serum ACTH had tendency to be suppressed. Mean period of steroid hormone replacement was 19.8 weeks. Patients with lower preoperative ACTH tended to require longer period until withdrawal of steroid hormone replacement. In addition, patients received steroid hormone replacement with higher starting dose significantly required longer period. Three of them had complications during tapering of steroid hormone. Postoperative adrenal insufficiency is important issue as postoperative management of PCS patients whose function of contralateral adrenal or pituitary gland is suppressed. 131 I-adosterol scintigraphy and preoperative serum ACTH were important factors to evaluate the requirement of postoperative steroid hormone replacement. Especially, patients with low preoperative serum ACTH tended to require long duration of postoperative steroid hormone replacement. On the other hand, patients with accumulation of contralateral side in 131 I-adosterol scintigraphy and without suppression of serum ACTH may not require steroid hormone

Severe Hypoglycemia due to Isolated ACTH Deficiency in Children: A New Case Report and Review of the Literature

OpenAIRE

Torchinsky, Michael Y.; Wineman, Robert; Moll, George W.

2011-01-01

Isolated ACTH deficiency causes life-threatening severe hypoglycemia. A 7-year-old girl with hypoglycemia due to this rare disorder is described. Our patient had undetectable plasma ACTH repeatedly and cortisol 0 mcg/dl before and after ACTH 1-24 stimulation. There was no evidence of other pituitary hormone deficiency. Glucocorticoid replacement therapy resulted in resolution of all symptoms and normalization of blood glucose. Previously published data on isolated ACTH deficiency in children ...

The response of the pituitary-adrenal and pituitary-thyroidal axes to the plasma glucose perturbations in Babesia canis rossi babesiosis

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J.P. Schoeman

2007-06-01

Full Text Available This prospective, cross-sectional, interventional study was designed to determine the association between the hormones of the pituitary-adrenal and pituitary-thyroid axes and other clinical parameters with the blood glucose perturbations in dogs with naturally occurring Babesia canis rossi babesiosis. Thirty-six dogs with canine babesiosis were studied. Blood samples were obtained from the jugular vein in each dog prior to treatment at admission to hospital and serum endogenous adrenocorticotrophic hormone(ACTH, pre-ACTH cortisol, thyroxine, free thyroxine and TSH concentrations were measured. Immediately thereafter each dog was injected intravenously with 5 µg/kg of ACTH (tetracosactrin. A 2nd blood sample was taken 1 hour later for serumpost-ACTHcortisol measurement. Three patient groups were recruited: hypoglycaemic dogs (glucose 5.5 mmol/ℓ, n = 12. Basal and post-ACTH serum cortisol concentrations were significantly higher in hypoglycaemic dogs, whereas body temperature, serum thyroxine and free thyroxine were significantly lower in hypoglycaemic dogs. Haematocrit was significantly lower in both hypo-and hyperglycaemic dogs compared with normoglycaemic dogs. Low blood glucose concentrations were significantly associated with high basal and post-ACTH cortisol concentrations and with low serum thyroxine and free thyroxine concentrations in dogs suffering from B. canis rossi babesiosis.

Effects of ACTH on corticosteroid and progesterone levels in female baboons depending on the phase of the menstrual cycle

International Nuclear Information System (INIS)

Todua, T.N.; Goncharov, N.P.; Katsiya, G.V.; Lapin, B.A.; Vorontsov, V.I.

1986-01-01

To study the effect of ACTH on the endocrine function of steroid producing glands depending on the level of sex hormones in the body, a comparative study of the dynamics of steroid hormones in the follicular and luteal phases of the menstrual cycle in response to a standard does of ACTH was undertaken in experiments on hamadryad baboons. Concentrations of corticosterone, 11-deoxycortisol, and progesterone were determined in duplicate samples of plasma by radioimmunoassay. It is shown that the sensitivity of the adrenals to a single injection of ACTH is independent of the phase of the menstrual cycle and the inhibitory effects of ACTH on progesterone secretion is exhibited only in the presence of an actively functioning corpus luteus of the ovary

Effects of ACTH on corticosteroid and progesterone levels in female baboons depending on the phase of the menstrual cycle

Energy Technology Data Exchange (ETDEWEB)

Todua, T.N.; Goncharov, N.P.; Katsiya, G.V.; Lapin, B.A.; Vorontsov, V.I.

1986-01-01

To study the effect of ACTH on the endocrine function of steroid producing glands depending on the level of sex hormones in the body, a comparative study of the dynamics of steroid hormones in the follicular and luteal phases of the menstrual cycle in response to a standard does of ACTH was undertaken in experiments on hamadryad baboons. Concentrations of corticosterone, 11-deoxycortisol, and progesterone were determined in duplicate samples of plasma by radioimmunoassay. It is shown that the sensitivity of the adrenals to a single injection of ACTH is independent of the phase of the menstrual cycle and the inhibitory effects of ACTH on progesterone secretion is exhibited only in the presence of an actively functioning corpus luteus of the ovary.

The Role of Uron and Chlorobenzene Derivatives, as Potential Endocrine Disrupting Compounds, in the Secretion of ACTH and PRL

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Krisztian Sepp

2018-01-01

Full Text Available Uron herbicides polluting the environment represent a serious concern for environmental health and may be regarded as endocrine-disrupting compounds (EDCs, which influence the regulation of human homeostasis. We aimed to investigate the effect of EDC urons (phenuron: PU, monuron: MU, and diuron: DU and chlorobenzenes on the basal release of the adrenocorticotropic hormone (ACTH, which is a part of the adenohypophysis-adrenocortical axis. Hormone secretion in the presence of EDC was studied in two cell types: normal adenohypophysis cells (AdH and cells of prolactinomas (PRLOMA. PRLOMA was induced in female Wistar rats by subcutaneously injecting them with estrone acetate for 6 months. AdH and PRLOMA were separated from treated and untreated experimental animals, dissociated enzymatically and mechanically in order to create monolayer cell cultures, which served as an experimental in vitro model. We investigated the effects of ED agents separately and in combination on ACTH and prolactin (PRL release through the hypophyseal-adrenal axis. Hormone determination was carried out by the luminescent immunoassay and the radioimmunoassay methods. Our results showed that (1 uron agents separately did not change ACTH and PRL release in AdH culture; (2 ACTH secretion in arginine vasopressin- (AVP- activated AdH cells was significantly increased by EDC treatment; (3 ED agents increased the basal hormone release (ACTH, PRL in PRLOMA cells; and (4 EDC exposure increased ACTH release in AVP-activated PRLOMA cells. We conclude that the herbicides PU, MU, and DU carry EDC effects and show human toxicity potential.

Selenium-75-cholesterol imaging and computed tomography of the adrenal glands in differentiating the cause of Cushing's syndrome

International Nuclear Information System (INIS)

Miller, J.L.; Smith, J.A.; Mervis, B.; Roman, T.

1983-01-01

Measurement of 75 Se-cholesterol (Scintadren) uptake and computed tomography (CT) of the adrenal glands were compared as a means of differentiating the cause of Cushing's syndrome in 11 patients over a 2-year period. Quantitative Scintadren imaging differentiated adrenocorticotrophic hormone (ACTH)-dependent disease from local adrenocortical lesions as the cause of Cushing's syndrome in all the patients studied. CT of the adrenal glands rapidly and accurately detected the adrenal mass lesions in 2 cases and was effective in documenting bilateral hyperplasia due to ectopic ACTH-dependent disease. However, in entopic ACTH (pituitary)-dependent disease the adrenal glands were of normal thickness in all but 2 patients, who had bilateral hyperplasia. Scintadren imaging and CT are useful non-invasive procedures for differentiating local adrenal disease from ACTH-dependent disease as the cause of Cushing's syndrome and should be the initial investigations once a firm clinical and biochemical diagnosis of Cushing's syndrome has been made

The role of ACTH and glucocorticoids in nonenzymatic fibrinolysis during immobilization stress in animals

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Kudryashov, B. A.; Shapiro, F. B.; Lomovskaya, E. G.; Lyapina, L. A.

1980-01-01

The role of the altered hormonal status of an organism in the activation of the anticoagulative system during stress is investigated. The 30 minute immobilization stress was shown to raise significantly the nonenzymatic fibrinolytic activity of blood in rats. Combined with adrenocorticotropin (ACTH) the effect is still greater. Intravenous administration of 0.2 m1 0.01 percent solution of protamine sulphate prevented the nonenzymatic fibrinolysis induced by the stress. Administration of ACTH after protomine sulphate again raised the fibrinolysis. This suggests that ACTH stimulates the release of heparin.

ACTH antagonists

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Adrian John Clark

2016-08-01

Full Text Available ACTH acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1 Cushing’s disease and ectopic ACTH syndrome – especially whilst preparing for definitive treatment of a causative tumour, or in refractory cases, or (2 congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role.

ACTH Prevents Deficits in Fear Extinction Associated with Early Life Seizures

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Andrew T Massey

2016-05-01

Full Text Available Early life seizures are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of early life seizures (ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action. We found that while rats with a history of ELS were able to acquire a conditioned fear learning paradigm as well as controls, these rats had significant deficits in their ability to extinguish fearful memories. ACTH treatment did not alter any seizure parameters but nevertheless was able to significantly improve this fear extinction, while dexamethasone treatment during the same period did not. This ACTH effect was specific for fear extinction deficits and not for spatial learning deficits in a water maze. Additionally, ACTH did not alter seizure latency or duration suggesting that cognitive and seizure outcomes may be dissociable. Expression levels of melanocortin receptors, which bind ACTH, were found to be significantly lower in animals that had experienced ELS than in control animals, potentially implicating central melanocortin receptor dysregulation in the effects of ELS and suggesting a mechanism of action for ACTH. Taken together, these data suggest that early treatment with ACTH can have significant long-term consequences for cognition in animals with a history of ELS independently of seizure cessation, and may act in part through a CNS melanocortin receptor pathway.

Detection of brain atrophy due to ACTH or corticosteroid therapy with computed tomography

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Tamai, Isamu; Takei, Tadao; Oota, Hideomi; Maekawa, Kihei.

1981-01-01

Adrenocorticotropic hormone (ACTH) or corticosteroids seemed to cause brain atrophy in intants. We studied the atrophy which was caused by these drugs with computed tomography (CT). 1) Nine cases of infantile spasms examined before, during and after ACTH therepy with CT. Brain atrophy on CT was observed immediately after the completion of ACTH therapy. The brain atrophy receded slightly after several months. It was more marked in younger patients, in cases treated by hight doses of ACTH and in cases where brain atrophy had already been obserbed before ACTH therapy. 2) Twenty cases of infantile spasms or Lennox Gastaut syndrome were examined after ACTH therapy with CT. Brain atrophy was observed in twelve cases. Main features of brain atrophy were the enlargement of sylvian fissure and the widening of subarachnoid space at the frontal or temporal region. Mental retardation was observed in eighteen cases. 3) Two cases of nephrotic syndrome were treated with pulse therapy of prednisolone. CT was carried out before and after treatment. Atrophy of cerebrum was observed in these cases. 4) A case of infantile spasms treated with anticonvulsants without ACTH was studied by electroencephalography (EEG) and CT. The abnormal pattern of EEG was markedly corrected, while brain atrophy on CT was not observed after the therapy. Because of these observations the use of ACTH has to be reconsidered. ACTH should be the drug of second choice for the therapy of infantile spasms and should be used in case other anticonvulsants have no effect. ACTH should be used at lower dosages and for shorter periods of time. (author)

Detection of brain atrophy due to ACTH or corticosteroid therapy with computed tomography

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Tamai, I.; Takei, T. (National Sagamihara Hospital, Kanagawa (Japan)); Oota, H.; Maekawa, K.

1981-07-01

Adrenocorticotropic hormone (ACTH) or corticosteroids seemed to cause brain atrophy in infants. We studied the atrophy which was caused by these drugs with computed tomography (CT). 1) Nine cases of infantile spasms examined before, during and after ACTH therapy with CT. Brain atrophy on CT was observed immediately after the completion of ACTH therapy. The brain atrophy receded slightly after several months. It was more marked in younger patients, in cases treated by high doses of ACTH and in cases where brain atrophy had already been observed before ACTH therapy. 2) Twenty cases of infantile spasms or Lennox Gastaut syndrome were examined after ACTH therapy with CT. Brain atrophy was observed in twelve cases. Main features of brain atrophy were the enlargement of sylvian fissure and the widening of subarachnoid space at the frontal or temporal region. Mental retardation was observed in eighteen cases. 3) Two cases of nephrotic syndrome were treated with pulse therapy of prednisolone. CT was carried out before and after treatment. Atrophy of cerebrum was observed in these cases. 4) A case of infantile spasms treated with anticonvulsants without ACTH was studied by electroencephalography (EEG) and CT. The abnormal pattern of EEG was markedly corrected, while brain atrophy on CT was not observed after the therapy. Because of these observations the use of ACTH has to be reconsidered. ACTH should be the drug of second choice for the therapy of infantile spasms and should be used in case other anticonvulsants have no effect. ACTH should be used at lower dosages and for shorter periods of time.

Ectopic ACTH and CRH co-secreting tumor localized by 68Ga-DOTA-TATE PET/CT

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Papadakis, Georgios Z.; Bagci, Ulas; Sadowski, Samira M.; Patronas, Nicholas J.; Stratakis, Constantine A.

2015-01-01

Diagnosis of ectopic adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) co-secreting tumors causing Cushing syndrome (CS) is challenging, since these tumors are rare and their diagnosis is frequently confused with Cushing disease (CD), due to the effect of CRH on the pituitary. We report a case of a 21-year-old male who was referred to our institution with persistent hypercortisolemia and CS after undergoing unnecessary transsphenoidal surgery (TSS). 68Ga-DOTA-TATE PET/CT revealed increased tracer uptake in the thymus which was histologically proved to be neuroendocrine tumor (NET) staining positive for ACTH and CRH. Imaging with 18F-FDG PET/CT was not diagnostic. PMID:26018709

Severe Hypoglycemia due to Isolated ACTH Deficiency in Children: A New Case Report and Review of the Literature

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Michael Y. Torchinsky

2011-01-01

Full Text Available Isolated ACTH deficiency causes life-threatening severe hypoglycemia. A 7-year-old girl with hypoglycemia due to this rare disorder is described. Our patient had undetectable plasma ACTH repeatedly and cortisol 0 mcg/dl before and after ACTH 1-24 stimulation. There was no evidence of other pituitary hormone deficiency. Glucocorticoid replacement therapy resulted in resolution of all symptoms and normalization of blood glucose. Previously published data on isolated ACTH deficiency in children is summarized. Review of the literature showed that the prevalence of this condition could be underestimated in the neonatal period and in Prader-Willi syndrome. Isolated ACTH deficiency occurs in older children as well as in neonates.

Release of β-endorphin, adrenocorticotropic hormone and cortisol in response to machine milking of dairy cows

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E. Fazio

2015-03-01

Full Text Available Aim: The present study was undertaken with the objective to obtain insight into the dynamics of the release of β-endorphin, adrenocorticotrophic hormone (ACTH and cortisol in response to machine milking in dairy cows. Materials and Methods: A total of 10 healthy multiparous lactating Italian Friesian dairy cows were used in the study. Animals were at the 4th-5th month of pregnancy and were submitted to machine milking 2 times daily. Blood samples were collected in the morning: In baseline conditions, immediately before milking and after milking; and in the early afternoon: In baseline conditions, before milking and after milking, for 2 consecutive days. Endocrine variables were measured in duplicate, using a commercial radioimmunoassay for circulating β-endorphin and ACTH concentrations and a competitive enzyme-linked immunoassay for cortisol concentration. Results: Data obtained showed a similar biphasic cortisol secretion of lactating dairy cows, with a significant increase of cortisol concentration after morning machine milking, at both the 1st and the 2nd day (p<0.05, and a decrease after afternoon machine milking at the 2nd day (p<0.01. One-way RM ANOVA showed significant effects of the machine milking on the cortisol changes, at both morning (f=22.96; p<0.001 and afternoon (f=15.10; p<0.01 milking, respectively. Two-way RM ANOVA showed a significant interaction between cortisol changes at the 1st and the 2nd day (f=7.94; p<0.0002, and between the sampling times (f=6.09; p<0.001. Conversely, no significant effects of the machine milking were observed on β-endorphin and ACTH changes, but only a moderate positive correlation (r=0.94; p<0.06 after milking stimuli. Conclusions: A wide range of cortisol concentrations reported in this study showed the complex dynamic patterns of the homeostatic mechanisms involved during machine milking in dairy cows, suggesting that β-endorphin and ACTH were not the main factors that caused the

Radioimmunoassay of polypeptide hormones and enzymes

International Nuclear Information System (INIS)

Felber, J.P.

1974-01-01

General principles of radioimmunoassay are reviewed. Detailed procedures are reviewed for the following hormones: insulin, pituitary hormones, gonadotropins, parathyroid hormone, ACTH, glucagon, gastrin, and peptide hormones. Radioimmunoassay of enzymes is also discussed. (U.S.)

Analysis of the brain ACTH-immunoreactive peptide spectrum in inbred mice

International Nuclear Information System (INIS)

Fedoseev, Yu.L.; Blednov, Yu.A.; Seredenin, S.B.

1987-01-01

Mice of the BALB/c (C) and C57BL/6 (B6) strains, characterized by high and low emotionality respectively in open field tests, have been shown to differ considerably in both the initial level and the time course of changes in the plasma ACTH concentration after exposure to stress in an open field and after administration of a benzodiazepine tranquilizer. The ACTH concentration in the pituitary gland of animals of these lines also differs. The ACTH molecule is known to contain regions with neurotropic activity. It can therefore be postulated that differences in the level of this hormone and the products of its bioconversion in the brain are an essential factor in the mechanisms of formation of the hereditary features of emotional behavior. In this first stage of this investigation, represented in this paper and undertaken to test this hypothesis, spectra of ACTH-immunoreactive peptides were studied in chromatographic fractions of an acid brain extract as well as in the blood plasma of mice belonging to B6 and C lines and their hybrids. The peptides were determined by radioimmunoassay

Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome

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Sarma, Asha; Shyn, Paul B.; Vivian, Mark A.; Ng, Ju-Mei; Tuncali, Kemal; Lorch, Jorchen H.; Zaheer, Sarah N.; Gordon, Michael S.; Silverman, Stuart G.

2015-01-01

Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements

Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome

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Sarma, Asha, E-mail: ashasarma@gmail.com; Shyn, Paul B., E-mail: pshyn@partners.org [Brigham and Women’s Hospital, Department of Radiology (United States); Vivian, Mark A. [University of Manitoba, Department of Radiology (Canada); Ng, Ju-Mei [Brigham and Women’s Hospital, Department of Anesthesiology (United States); Tuncali, Kemal [Brigham and Women’s Hospital, Department of Radiology (United States); Lorch, Jorchen H. [Dana Farber Cancer Institute, Department of Medicine (United States); Zaheer, Sarah N.; Gordon, Michael S. [Brigham and Women’s Hospital, Department of Endocrinology (United States); Silverman, Stuart G. [Brigham and Women’s Hospital, Department of Radiology (United States)

2015-10-15

Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.

Radioactive probes for adrenocorticotropic hormone receptors

International Nuclear Information System (INIS)

Hofmann, K.; Romovacek, H.; Stehle, C.J.; Finn, F.M.; Bothner-By, A.A.; Mishra, P.K.

1986-01-01

Our attempts to develop adrenocorticotropic hormone (ACTH) analogues that can be employed for ACTH receptor identification and isolation began with the synthesis of ACTH fragments containing N epsilon-(dethiobiotinyl)lysine (dethiobiocytin) amide in position 25 to be used for affinity chromatographic purification of hormone-receptor complexes on Sepharose-immobilized avidin resins. Because labeling ACTH or ACTH fragments by conventional iodination techniques destroys biological activity due to oxidation of Met4 and incorporation of iodine into Tyr2, we have prepared [Phe2,Nle4]ACTH1-24, [Phe2,Nle4,biocytin25]ACTH1-25 amide, and [Phe2,Nle4,dethiobiocytin25]ACTH1-25 amide by conventional synthetic techniques. The HPLC profiles and amino acid analyses of the final products indicate that the materials are of a high degree of purity. The amount of tertiary butylation of the Trp residue in the peptides was assessed by NMR and was found to be less than 0.5%. All three peptides are equipotent with the standard ACTH1-24 as concerns their ability to stimulate steroidogenesis and cAMP formation in bovine adrenal cortical cells. Iodination of [Phe2,Nle4]ACTH1-24, with iodogen as the oxidizing agent, has been accomplished without any detectable loss of biological activity. The mono- and diiodo derivatives of [Phe2,Nle4]ACTH1-24 have been prepared, separated by HPLC, and assayed for biological activity. Both peptides have the full capacity to stimulate steroidogenesis and cAMP production in bovine adrenal cortical cells

Cushing's syndrome: from physiological principles to diagnosis and clinical care

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Raff, Hershel; Carroll, Ty

2015-01-01

The physiological control of cortisol synthesis in the adrenal cortex involves stimulation of adrenocorticotrophic hormone (ACTH) by hypothalamic corticotrophin-releasing hormone (CRH) and then stimulation of the adrenal by ACTH. The control loop of the hypothalamic–pituitary–adrenal (HPA) axis is closed by negative feedback of cortisol on the hypothalamus and pituitary. Understanding this system is required to master the diagnosis, differential diagnosis and treatment of endogenous hypercortisolism – Cushing's syndrome. Endogenous Cushing's syndrome is caused either by excess ACTH secretion or by autonomous cortisol release from the adrenal cortex. Diagnosis of cortisol excess exploits three physiological principles: failure to achieve the normal nadir in the cortisol diurnal rhythm, loss of sensitivity of ACTH-secreting tumours to cortisol negative feedback, and increased excretion of free cortisol in the urine. Differentiating a pituitary source of excess ACTH (Cushing's disease) from an ectopic source is accomplished by imaging the pituitary and sampling for ACTH in the venous drainage of the pituitary. With surgical removal of ACTH or cortisol-secreting tumours, secondary adrenal insufficiency ensues because of the prior suppression of the HPA axis by glucocorticoid negative feedback. Medical therapy is targeted to the anatomical location of the dysregulated component of the HPA axis. Future research will focus on new diagnostics and treatments of Cushing's syndrome. These are elegant examples of translational research: understanding basic physiology informs the development of new approaches to diagnosis and treatment. Appreciating pathophysiology generates new areas for inquiry of basic physiological and biochemical mechanisms. PMID:25480800

A Case of Paraneoplastic Cushing Syndrome Presenting as Hyperglycemic Hyperosmolar Nonketotic Syndrome

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Christina E. Brzezniak

2017-04-01

Full Text Available Carcinoid tumors are neuroendocrine tumors that mainly arise in the gastrointestinal tract, lungs, and bronchi. Bronchopulmonary carcinoids have been associated with Cushing syndrome, which results from ectopic adrenocorticotrophic hormone (ACTH secretion. We report the case of a 65-year-old man, a colonel in the US Air Force, with metastatic bronchopulmonary carcinoid tumors treated on a clinical trial who was hospitalized for complaints of increasing thirst, polydipsia, polyuria, weakness, and visual changes. Decompensated hyperglycemia suggested a diagnosis of hyperglycemic hyperosmolar nonketotic syndrome (HHNS. Additional findings, which included hypokalemia, hypernatremia, hypertension, metabolic alkalosis, moon facies, and striae, raised a red flag for an ectopic ACTH syndrome. Elevated ACTH levels confirmed Cushing syndrome. Treatment with a fluid replacement and insulin drip resulted in immediate symptomatic improvement. Cushing syndrome should be considered in carcinoid patients with physical stigmata such as moon facies and striae. HHNS may be the presenting clinical feature in patients with impaired glucose metabolism.

Sphenoid sinus carcinoid tumour causing ectopic ACTH syndrome.

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Perera, Sanjaya; Taha, Ahmad

2017-05-01

A thirty-eight year old patient presented with a gradual increase in weight and Cushingoid facies of two years duration. He also had orbital congestion, with puffy eyelids and corkscrew conjunctival vessels, associated with painful eye movements. An endocrine evaluation revealed raised cortisol and ACTH. Head imaging was performed which showed an enhancing tumour arising from the sphenoid sinus, with osseous erosion of the sphenoid sinus, extending to the nasopharynx, sellar and a small amount extending intracranially. He underwent an endoscopic endonasal resection of the tumour and histology revealed a low-grade carcinoid tumour with ACTH staining. The patient also underwent radiotherapy for the intracranial extension. He is currently in his fourth year of follow-up and imaging has showed a small, stable intracranial remnant. His anterior pituitary hormonal profile remains normal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of ACTH, capture, and short term confinement on glucocorticoid concentrations in harlequin ducks (Histrionicus histrionicus)

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Nilsson, P.B.; Hollmén, Tuula E.; Atkinson, S.; Mashburn, K.L.; Tuomi, P.A.; Esler, Daniel N.; Mulcahy, D.M.; Rizzolo, D.J.

2008-01-01

Little is known about baseline concentrations of adrenal hormones and hormonal responses to stress in sea ducks, although significant population declines documented in several species suggest that sea ducks are exposed to increased levels of environmental stress. Such declines have been observed in geographically distinct harlequin duck populations. We performed an adrenocorticotropic hormone (ACTH) challenge to evaluate adrenal function and characterize corticosterone concentrations in captive harlequin ducks and investigated the effects of capture, surgery, and short term confinement on corticosterone concentrations in wild harlequin ducks. Harlequin ducks responded to the ACTH challenge with an average three-fold increase in serum corticosterone concentration approximately 90 min post injection, and a four- to five-fold increase in fecal glucocorticoid concentration 2 to 4 h post injection. Serum corticosterone concentrations in wild harlequin ducks increased within min of capture and elevated levels were found for several hours post capture, indicating that surgery and confinement maintain elevated corticosterone concentrations in this species. Mean corticosterone concentrations in wild harlequin ducks held in temporary captivity were similar to the maximum response levels during the ACTH challenge in captive birds. However, large variation among individuals was observed in responses of wild birds, and we found additional evidence suggesting that corticosterone responses varied between hatch year and after hatch year birds.

Ectopic ACTH syndrome complicated by multiple opportunistic infections treated with percutaneous ablation of the adrenal glands.

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Chan, Chrystal; Roberts, James Mark

2017-11-14

Ectopic adrenocorticotropic hormone (ACTH)-related Cushing's syndrome can lead to multiple complications including severe immunosuppression. If the ACTH-secreting tumour cannot be found, definitive treatment is surgical adrenalectomy, typically followed by glucocorticoid replacement. Here, we present a case of fulminant respiratory failure secondary to coinfection with Pneumocystis jirovecii and cytomegalovirus in a patient with ectopic ACTH-dependent Cushing's syndrome with occult primary. Due to significant deconditioning, she was unable to undergo definitive adrenalectomy and instead underwent percutaneous microwave ablation of the adrenal glands. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Second-line tests in the differential diagnosis of ACTH-dependent Cushing's syndrome.

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Barbot, Mattia; Trementino, Laura; Zilio, Marialuisa; Ceccato, Filippo; Albiger, Nora; Daniele, Andrea; Frigo, Anna Chiara; Mardari, Rodica; Rolma, Giuseppe; Boscaro, Marco; Arnaldi, Giorgio; Scaroni, Carla

2016-10-01

Diagnosing Cushing's syndrome (CS) can be a challenge, especially in ACTH-dependent CS, when it comes to detecting the origin of ACTH secretion. Retrospective data were collected on 170 patients with ACTH-dependent CS (149 CD, 21 EAS) referring to two endocrinology units, focusing on three non-invasive tests: dexamethasone 8 mg overnight challenge (HDDST); corticotrophin-releasing hormone (CRH) assay and the desmopressin (DDAVP) test. Patients with EAS were slightly older and had higher ACTH, serum and urinary cortisol levels than patients with CD (p 52.7 % below the basal level suggested a pituitary origin with a SE of 88 % (95 % CI 81-93) and a SP of 90 % (95 % CI 68-99). There were no cases of EAS with positive responses to both these tests. Increases in ACTH and cortisol levels after the DDAVP test were also higher in CD than in EAS (p < 0.01), though the SE and SP were lower. Patients with CD showed a stronger response to HDDST and CRH, and the adopted cut-offs showed a good SE and SP in discriminating them from patients with EAS. Concordant tests indicated CD when positive, whereas no response to either test was highly suggestive of EAS. The DDAVP test was of limited utility in the diagnostic phase. In conclusion, the choice of tests may play an important part in the differential diagnosis of ACTH-dependent CS.

Cushing's syndrome in infancy due to ectopic ACTH secretion by a sacro-coccygeal teratoma.

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Rydzewska, Marta; Krawczuk-Rybak, Maryna; Zajkowska, Adrianna; Jurczuk, Natalia; Polnik, Dariusz; Szalecki, Mieczysław; Moszczyńska, Elżbieta; Savage, Martin O; Bossowski, Artur

2017-04-01

Adenocorticotropic hormone (ACTH)-dependent Cushing's syndrome in infancy is extremely rare. We describe the case of a sacro-coccygeal ectopic ACTH-secreting immature teratoma in an infant who also presented the triad of defects characteristic of Currarino syndrome. A girl was born with a large immature teratoma in the sacro-coccygeal region associated with anal atresia. At the age of 7 days, the concentration of α-fetoprotein (AFP) was above the age-specific normal range. Two non-radical surgical excisions of the tumour were performed. At the age of 7 months, she developed polyphagia, acne, hirsutism, hypertension and hypokalemia with elevated ACTH and absence of serum cortisol circadian rhythm. Immunostaining of tumour tissue showed ACTH-immunoreactive cells. Due to unsuccessful therapy with ketoconazole and resistance to antihypertensive medications [blood pressure (BP) 210/160 mmHg], metyrapone was administered, which controlled her ACTH and cortisol levels in the normal range. Following further removal of tumour bulk after three operations during the first year of life, there was a decrease of BP to normal values. A rare case of ectopic ACTH syndrome causing Cushing's syndrome in infancy in the context of Currarino syndrome is reported. Radical surgery has resulted in excision of the tumour and current control of Cushing's syndrome.

ACTH blood test

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... thyroid, or pancreas) making too much ACTH ( ectopic Cushing syndrome ) A lower-than-normal level of ACTH may ... Disease Read more Adrenal Gland Disorders Read more Cushing's Syndrome Read more A.D.A.M., Inc. is ...

A Miniaturized Impedimetric Immunosensor for the Competitive Detection of Adrenocorticotropic Hormone

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Nan Li

2017-12-01

Full Text Available Adrenocorticotropic hormone (ACTH plays an essential role in regulating corticosteroid hormone production, which has important functions in a myriad of critical physiological functions. In this proof-of-concept study, a miniaturized immunosensor was developed for the highly sensitive detection of ACTH using electrochemical impedance spectroscopy (EIS in connection with disposable screen-printed gold electrodes (SPGEs. A film of 3,3′-dithiobis[sulfosuccinimidylpropionate] (DTSSP was prepared to immobilize anti-ACTH antibodies covalently on the nanostructured SPGE surface. The surface-immobilized anti-ACTH antibodies captured the biotinylated ACTH (biotin-ACTH and non-labelled ACTH for the competitive immunoassay. After coupling of a streptavidin-alkaline phosphatase conjugate (Streptavidin-ALP, the bio-catalysed precipitation of an insoluble and insulating product onto the sensing interface changed the charge transfer resistance (Rct characteristics significantly. The detection limit of 100 fg/mL was determined for ACTH in a 5 μL sample volume, which indicated that this versatile platform can be easily adapted for miniaturized electrochemical immunosensing of cancer marker biomolecules. High selectivity and sensitivity of our immunoassay to detect ACTH in real samples demonstrated its promising potential for future development and applications using clinical samples.

The effect of X-rays and hypothermia on basal and stress levels of circulatory adrenocorticotropic hormone (ACTH) in rats

International Nuclear Information System (INIS)

Demajo, M.; Ivanisevic-Milovanovic, O.

1995-01-01

Basal and stress values of plasma ACTH were studied in: 1. normal controls (N), 2. hypothermic controls (NH), 3. Irradiated with 9.6 Gy of X-rays in the head region (9.6 Gy) and 4. hypothermic irradiated with 9.6 Gy (9.6 GyH). A lower basal level of ACTH (p<0.05) was detected in 9.6 Gy animals compared to the other groups, between which there was no significant difference (p<0.05). The stress response of ACTH in relation to the basal level was highest in N (323.92%), the lowest in 9.6 Gy animals (67.41%). The significant increase of ACTH stress response (p<0.001) was detected in the group 9.6 GyH (118.83%) compared to 9.6 Gy. In conclusion, a single dose of X-rays significantly reduced ACTH i circulation, while hypothermia shows a significant protective effect. (author)

Effect of deafferentation of the rat tongue on plasma corticosterone, aldosterone, angiotensin and ACTH levels

International Nuclear Information System (INIS)

Polyntsev, Yu.V.; Serova, O.N.

1987-01-01

The effect of deafferentation of the tongue on the plasma level of hormones involved in regulation of the sodium ion level -- aldosterone, corticosterone, ACTH, and angiotensin -- was studied. Plasma hormone levels were determined by radioimmunoassay. The results indicate the important role of orosensory and taste perception in the processes of regulation of the sodium balance in the body. The experiments in this study were conducted on rats

Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing’s Disease to Pituitary Carcinoma

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Clarissa Groberio Borba

2015-01-01

Full Text Available Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH. It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushing’s disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15% and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge.

Subspecies-specific response to ACTH challenge test in the house mouse (Mus musculus)

Czech Academy of Sciences Publication Activity Database

Daniszová, Kristina; Mikula, O.; Macholán, M.; Pospíšilová, I.; Vošlajerová Bímová, Barbora; Hiadlovská, Z.

2017-01-01

Roč. 252, October (2017), s. 186-192 ISSN 0016-6480 R&D Projects: GA ČR GAP506/11/1792 Institutional support: RVO:68081766 Keywords : ACTH challenge * Endocrine activity * Corticosterone * Hormone metabolites * Mouse * Noninvasive monitoring Subject RIV: EG - Zoology OBOR OECD: Zoology Impact factor: 2.585, year: 2016

A hormone map of human immune cells showing the presence of adrenocorticotropic hormone, triiodothyronine and endorphin in immunophenotyped white blood cells

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Pállinger, Éva; Csaba, György

2008-01-01

The amounts of adrenocorticotropic hormone (ACTH), endorphin and triiodothyronine (T3) in twenty-six blood samples from men and women who were healthy or had non-haematological diseases were determined by flow cytometry. Lymphocytes were immunophenotyped using monoclonal antibodies against cell surface antigens, and monocytes and granulocytes were separated by their size and granularity (using forward-scatter versus side-scatter dot plots). Each hormone was found in each cell type. The hormone content of lymphocytes was balanced, but the concentration of ACTH was significantly lower in activated T cells, that of endorphin was significantly lower in natural killer (NK) cells, and that of T3 was lower in both cell types compared with values for all lymphocytes. Monocytes and granulocytes contained very significantly more hormones than lymphocytes or monocytes. The concentration of endorphin was an order of magnitude higher in granulocytes than in monocytes or lymphocytes, reflecting the pain-relieving role of granulocytes during inflammation. Compared with monocytes, in granulocytes there was a higher concentration of ACTH and a lower concentration of T3, which suggests selective hormone production by these cells. PMID:18005034

Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

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Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko [Osaka City General Hospital (Japan)] (and others)

2002-06-01

A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 {mu}g corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

International Nuclear Information System (INIS)

Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko

2002-01-01

A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 μg corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

Attenuated stress response to acute restraint and forced swimming stress in arginine vasopressin 1b receptor subtype (Avpr1b) receptor knockout mice and wild-type mice treated with a novel Avpr1b receptor antagonist.

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Roper, J A; Craighead, M; O'Carroll, A-M; Lolait, S J

2010-11-01

Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors. © 2010 The Authors. Journal of Neuroendocrinology © 2010 Blackwell Publishing Ltd.

The role of intrа- and postoperative ACTH and cortisol levels measurement in patients with Cushing’s disease as an early predictors of remission

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Elena Y. Nadezhdina

2017-07-01

Full Text Available Objectives. The aim of this research was to study the dynamic changes of intra- and early postoperative hormonal parameters (ACTH and cortisol as predictors of hypercorticism remission. Material and methods. 50 patients with confirmed Cushing`s disease (CD were sampled for this research. The patients were divided into 3 groups depending on the outcome of the operation. The first group – patients with secondary adrenal insufficiency confirmed by clinical picture and the level of cortisol less than 50 nmol/l; the second group – with normalization of levels of ACTH and cortisol; the third – with the persistence of the CD. The results of intraoperative studies during the transnasal adenomectomy were then studied. The group sample consisted of 38 women and 12 men, aged 15–66 years. To assess the levels of ACTH and cortisol blood sampling was performed from a peripheral vein. The first sample was taken during the incision of the Dura mater, the second – immediately after removal of the tumor and the last – 20 minutes after the removal of the adenoma. Then, 1 day after the surgery the hormones mentioned above were studied in all patients. The levels of ACTH and cortisol were measured by immunochemiluminescent analysis on the automated system Cobas 6000 (Roche, France. Reference intervals ACTH 0–30 ng/ml, cortisol123–626 nmol/l. Results. The analysis of the obtained data did not suggest a relationship between the changes of intraoperative indicators of hormonal status and the likelihood of disease remission (p > 0.125. In the postoperative period, of the 50 patients, 41 (82% developed adrenal insufficiency, 5 (10% showed normalization and in 4 patients (8% adrenal insufficiency was not observed. The results of the hormonal research after 1 day had a correlation with the frequency of postoperative remission (p < 0.125. Conclusion. Intraoperative measurement of levels of ACTH and cortisol is not appropriate and cannot serve as guidance for

Dopamine-regulated adrenocorticotropic hormone secretion in lactating rats: functional plasticity of melanotropes.

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Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E; Nagy, Gyorgy M; Vecsernyés, Miklós

2009-01-01

Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and beta-lipotropin in corticotropes of the anterior lobe, and to alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D(2) type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence alpha-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E(2))-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in alpha-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by alpha-methyl-p-tyrosine (alphaMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma alpha-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E(2) animals. In lactating mothers, BRC was able to block ACTH responses induced by both alphaMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is

ACTH overexpressing pituitary hyperplasia in a patient with ectopic ACTH-syndrome due to carcinoid of the lung

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Larisa Konstantinovna Dzeranova

2015-01-01

Full Text Available Ectopic ACTH-syndrome is the most diagnostically challenging  variant of endogenous hypercortisolism. Particularly difficult differential diagnosis of this syndrome is from Cushing's disease (CD, as currently there is no single test sufficiently accurate to differentiate accurately ectopic ACTH production from the pituitary. The main functional tests are based on the fact that the vast majority of ectopic ACTH production is autonomous and suppresses one from pituitary. But in some cases this is not observed, and then the data obtained all necessary laboratory and instrumental research evidence in favor of central genesis of CD in a patient with ACTH ectopic secretion, which can lead to inappropriate treatment. If you confirm the ectopic ACTH-syndrome, it may take quite a long time of searching for the pathological focus, as there is no sufficiently precise imaging and diagnostic method for determining the localization of ectopic source of ACTH production. Thus, the differential diagnosis of ACTH-dependent hypercortisolism and localization of the ectopic tumor is the cornerstone of early and radical treatment of patients. We present a difficult clinical case of a patient having a pituitary hyperplasia with excessive ACTH expression with primary ectopic ACTH syndrome caused by lung carcinoid.

ACTH, corticosterone, and beta-endorphin in rat blood plasma after prolonged immobilization stress

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Kiyatkin, E.A.; Amiragova, M.G.; Kushlinskii, N.E.; Polyntsev, Yu. V.

1986-01-01

To assess functional relations between changes in ACTH, beta-endorphin (BE), and corticosterone (CS) levels, plasma concentrations of these hormones were studied in rats during the development of prolonged immobilization stress. Plasma hormone concentrations were determined by radioimmunoassay. The results were analyzed by standard statistical methods on a microcomputer. A particular feature about the kit used to determine BE was the presence of 50% cross-reactivity of the antiserum against beta-lipotrophin. To determine CS a highly specific antiserum produced by a laboratory was used.

The utility of preoperative acth/cortisol ratio for the diagnosis and prognosis of cushing's disease

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Alev Selek

2018-01-01

Full Text Available Purpose: Cushing's syndrome (CS is a rare disease having diagnostic difficulties. Many diagnostic tests have been defined but none of these are diagnostic alone. Determination of the cause is another problem which sometimes requires more sophisticated and invasive procedures. Therefore, we aimed to evaluate the utility of pretreatment plasma adrenocorticotropic hormone (ACTH/cortisol ratios in patients with confirmed endogenous CS for the diagnosis and differential diagnosis of CS. Materials and Methods: This retrospective evaluation included 145 patients with the diagnosis of CS, 119 patients with Cushing's disease (CD, and 26 patients with ACTH-independent CS (AICS, in a university hospital. Furthermore, 114 individuals in whom CS diagnosis was excluded with at least one negative screening test were enrolled to the study as control group. The clinical, laboratory, imaging, postsurgical pathologic records and also clinical follow-up data of all patients were evaluated. Results: The median basal ACTH/cortisol ratio of the patients with CD was significantly higher than AICS and controls. A cutoff ACTH/cortisol ratio >2.5 was found to be diagnostic for CD with 82% specificity and 63% sensitivity. Among CD group, patients with recurrent disease had higher preoperative ACTH levels and ACTH/cortisol ratio than patients with sustained remission. Furthermore, these patients had more invasive, atypical, and larger tumors. Conclusion: An ACTH/cortisol ratio >2.5 would be beneficial to diagnose CD together with other diagnostic tests. It is a simple test with no additional cost. Higher ratios might be related with larger, invasive, and atypical adenoma and also might be helpful to predict recurrence.

Comparison of 68Ga-DOTANOC PET/CT and contrast-enhanced CT in localisation of tumours in ectopic ACTH syndrome

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Jadhav, Swati S; Lila, Anurag R; Kasaliwal, Rajeev; Khare, Shruti; Yerawar, Chaitanya G; Hira, Priya; Phadke, Uday; Shah, Hina; Lele, Vikram R; Malhotra, Gaurav; Bandgar, Tushar; Shah, Nalini S

2016-01-01

Background Localising ectopic adrenocorticotrophic hormone (ACTH) syndrome (EAS) tumour source is challenging. Somatostatin receptor-based PET imaging has shown promising results, but the data is limited to case reports and small case series. We reviewed here the performance of 68Ga-DOTANOC positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) in our cohort of 12 consecutive EAS patients. Materials and methods Retrospective data analysis of 12 consecutive patients of EAS presenting to a single tertiary care centre in a period between January 2013 and December 2014 was done. CECT and 68Ga-DOTANOC PET/CT were reported (blinded) by an experienced radiologist and a nuclear medicine physician, respectively. The performance of CECT and 68Ga-DOTANOC PET/CT was compared. Results Tumours could be localised in 11 out of 12 patients at initial presentation (overt cases), whereas in one patient, tumour remained occult. Thirteen lesions were identified in 11 patients as EAS source (true positives). CECT localised 12 out of these 13 lesions (sensitivity 92.3%) and identified five false-positive lesions (positive predictive value (PPV) 70.5%). Compared with false-positive lesions, true-positive lesions had greater mean contrast enhancement at 60s (33.2 vs 5.6 Hounsfield units (HU)). 68Ga-DOTANOC PET/CT was able to identify 9 out of 13 lesions (sensitivity 69.2%) and reported no false-positive lesions (PPV 100%). Conclusion CECT remains the first-line investigation in localisation of EAS. The contrast enhancement pattern on CECT can further aid in characterisation of the lesions. 68Ga-DOTANOC PET/CT can be added to CECT, to enhance positive prediction of the suggestive lesions. PMID:27006371

Plasma-Glucocorticoids and ACTH Levels During Different Periods of Activity in the European Beaver (Castor fiber L.).

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Czerwińska, Joanna; Chojnowska, Katarzyna; Kamiński, Tadeusz; Bogacka, Iwona; Panasiewicz, Grzegorz; Smolińska, Nina; Kamińska, Barbara

2015-01-01

Glucocorticoids (GCs) and adrenocorticotropic hormone (ACTH) are major components of the classic endocrine stress response. Free-living vertebrates are characterized by circannual changes in the baseline and/or stress-induced secretion of GCs and ACTH. In mammalian species, GC and ACTH levels vary seasonally but there is no consensus to the season in which animals have elevated GC and ACTH levels. The aim of our study was to determine, for the first time, the type and amount of glucocorticoids produced in free-living beaver (Castor fiber L.)--the largest rodent in Eurasia, and to find out whether stress-induced plasma GC and ACTH levels show seasonal variations. Blood samples were obtained from animals under general anesthesia in April (pregnancy in females), July (offspring rearing) and November (preparing for the winter). The adrenals of beavers produce both cortisol and corticosterone, and plasma cortisol levels were higher than corticosterone. In the current experiment, plasma cortisol concentrations in beavers were affected by the season. The highest stress-associated cortisol levels were noted in males in July during offspring rearing. Corticosterone and ACTH concentrations in beavers remained generally constant, regardless of the season and sex. In conclusion, seasonal changes were observed only in relation to stress-induced plasma cortisol levels in the beaver.

Subspecies-specific response to ACTH challenge test in the house mouse (Mus musculus)

Czech Academy of Sciences Publication Activity Database

Daniszová, K.; Mikula, Ondřej; Macholán, Miloš; Pospíšilová, I.; Vošlajerová Bímová, Barbora; Hiadlovská, Zuzana

2017-01-01

Roč. 252, October (2017), s. 186-192 ISSN 0016-6480 R&D Projects: GA ČR GAP506/11/1792 Institutional support: RVO:67985904 Keywords : ACTH challenge * endocrine activity * corticosterone * hormone metabolities * mouse * noninvasive monitoring Subject RIV: EA - Cell Biology OBOR OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology Impact factor: 2.585, year: 2016

Rare case of Cushing's disease due to double ACTH-producing adenomas, one located in the pituitary gland and one into the stalk.

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Mendola, Marco; Dolci, Alessia; Piscopello, Lanfranco; Tomei, Giustino; Bauer, Dario; Corbetta, Sabrina; Ambrosi, Bruno

2014-01-01

We describe a patient affected by Cushing's disease due to the presence of double pituitary adenomas, one located within the anterior pituitary and the other in the infundibulum associated with a remnant of Rakthe's pouch. Cure was achieved only after the infundibulum lesion was surgically removed. A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia. Hormonal studies indicated Cushing's disease and MRI showed an enlarged pituitary gland with a marked and homogeneous enhancement after injection of gadolinium and an enlarged infundibulum with a maximum diameter of 8 mm. As a venous sampling of the inferior petrosal sinus after 10 μg iv desmopressin stimulation revealed a central to peripheral ACTH ratio consistent with a pituitary ACTH-secreting tumor, transphenoidal explorative surgery was performed and a 4-mm pituitary adenoma immunopositive for ACTH was disclosed and removed. Since postoperative hormonal evaluation showed persistent hypercortisolism, confirmed by dynamic tests, the patient again underwent surgery by transcranial access and the infundibulum mass was removed. Histology and immunochemistry were consistent with an ACTH-secreting adenoma. A few months after the second operation, cushingoid features were significantly reverted and symptoms improved. Although Cushing's patients bearing multiple adenomas have already been documented, the presence of two adenomas both immunohistochemically positive for ACTH is a very rare cause of Cushing's disease and this is the first report of a case of double ACTH-producing adenomas, one located in the pituitary gland and one attached to the stalk.

Exercise training alters effect of high-fat feeding on the ACTH stress response in pigs.

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Jankord, Ryan; Ganjam, Venkataseshu K; Turk, James R; Hamilton, Marc T; Laughlin, M Harold

2008-06-01

Eating and physical activity behaviors influence neuroendocrine output. The purpose of this study was to test, in an animal model of diet-induced cardiovascular disease, the effects of high-fat feeding and exercise training on hypothalamo-pituitary-adrenocortical (HPA) axis activity. We hypothesized that a high-fat diet would increase circulating free fatty acids (FFAs) and decrease the adrenocorticotropic hormone (ACTH) and cortisol response to an acute stressor. We also hypothesized that exercise training would reverse the high-fat diet-induced changes in FFAs and thereby restore the ACTH and cortisol response. Pigs were placed in 1 of 4 groups (normal diet, sedentary; normal diet, exercise training; high-fat diet, sedentary; high-fat diet, exercise training; n = 8/group). Animals were placed on their respective dietary and activity treatments for 16-20 weeks. After completion of the treatments animals were anesthetized and underwent surgical intubation. Blood samples were collected after surgery and the ACTH and cortisol response to surgery was determined and the circulating concentrations of FFAs, glucose, cholesterol, insulin, and IGF-1 were measured. Consistent with our hypothesis, high-fat feeding increased FFAs by 200% and decreased the ACTH stress response by 40%. In exercise-trained animals, the high-fat diet also increased FFA; however, the increase in FFA in exercise-trained pigs was accompanied by a 60% increase in the ACTH response. The divergent effect of high-fat feeding on ACTH response was not expected, as exercise training alone had no effect on the ACTH response. Results demonstrate a significant interaction between diet and exercise and their effect on the ACTH response. The divergent effects of high-fat diet could not be explained by changes in weight gain, blood glucose, insulin, or IGF-1, as these were altered by high-fat feeding, but unaffected by exercise training. Thus, the increase in FFA with high-fat feeding may explain the blunted

Exercise induced asthma and endogenous opioids.

Science.gov (United States)

Gaillard, R C; Bachman, M; Rochat, T; Egger, D; de Haller, R; Junod, A F

1986-01-01

Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV1 was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV1; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, beta endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma. PMID:2944240

Internal jugular vein: Peripheral vein adrenocorticotropic hormone ratio in patients with adrenocorticotropic hormone-dependent Cushing′s syndrome: Ratio calculated from one adrenocorticotropic hormone sample each from right and left internal jugular vein during corticotrophin releasing hormone stimulation test

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Sachin Chittawar

2013-01-01

Full Text Available Background: Demonstration of central: Peripheral adrenocorticotropic hormone (ACTH gradient is important for diagnosis of Cushing′s disease. Aim: The aim was to assess the utility of internal jugular vein (IJV: Peripheral vein ACTH ratio for diagnosis of Cushing′s disease. Materials and Methods: Patients with ACTH-dependent Cushing′s syndrome (CS patients were the subjects for this study. One blood sample each was collected from right and left IJV following intravenous hCRH at 3 and 5 min, respectively. A simultaneous peripheral vein sample was also collected with each IJV sample for calculation of IJV: Peripheral vein ACTH ratio. IJV sample collection was done under ultrasound guidance. ACTH was assayed using electrochemiluminescence immunoassay (ECLIA. Results: Thirty-two patients participated in this study. The IJV: Peripheral vein ACTH ratio ranged from 1.07 to 6.99 ( n = 32. It was more than 1.6 in 23 patients. Cushing′s disease could be confirmed in 20 of the 23 cases with IJV: Peripheral vein ratio more than 1.6. Four patients with Cushing′s disease and 2 patients with ectopic ACTH syndrome had IJV: Peripheral vein ACTH ratio less than 1.6. Six cases with unknown ACTH source were excluded for calculation of sensitivity and specificity of the test. Conclusion: IJV: Peripheral vein ACTH ratio calculated from a single sample from each IJV obtained after hCRH had 83% sensitivity and 100% specificity for diagnosis of CD.

An unusual case of ectopic ACTH syndrome.

Science.gov (United States)

Willhauck, M J; Pöpperl, G; Rachinger, W; Giese, A; Auernhammer, C J; Spitzweg, C

2012-02-01

Ectopic ACTH-syndrome is a rare cause of Cushing's disease. Despite extensive diagnostic procedures the source of ACTH secretion often remains occult. This case describes a 45-year old woman with an ectopic Cushing's syndrome. Extensive imaging procedures including CT scan of chest and abdomen, octreotide scan and MRI of the chest and pituitary did not reveal the source of ACTH secretion. In consideration of an occult source of ACTH secretion we started a therapeutic trial with cabergoline (0.5 mg/d), a dopamine receptor agonist, which has been shown to be effective in ectopic Cushing's syndrome. 2 months after cabergoline treatment had been initiated, ACTH and cortisol levels normalized in association with significant improvement of the clinical symptoms. During follow-up a [(68)Ga-DOTA-dPhe(1), Tyr(3)]-octreotate ([(68)Ga-DOTA]-TATE) PET-CT was performed revealing a somatostatin receptor positive lesion in the right sphenoidal sinus suggesting the source of ACTH secretion. The patient was cured by transnasal resection of the polypoid lesion, which was immunohistochemically characterized as an ACTH-positive neuroendocrine tumor. This case report demonstrates the management of ectopic ACTH-syndrome by molecularly -targeted therapy with dopamine receptor -agonists as well as improved detection of the ectopic ACTH source by novel imaging modalities, such as [(68)Ga-DOTA]-TATE PET specifically targeting somatostatin receptor subtype-2 with high affinity. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Exposure to retrieval cues improves retention performance and induces changes in ACTH and corticosterone release.

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Gisquet-Verrier, Pascale; Botreau, Fanny; Venero, Cesar; Sandi, Carmen

2004-05-01

Memory retrieval can be facilitated by pretest exposure to cues associated with the original training. The present series of experiments was aimed at investigating whether the effectiveness of the retrieval cues might be due to their emotional value and thus be associated to a particular pattern of activation of stress systems. Therefore, the effects of exposing rats to different cueing conditions were investigated both on retention performance and on the level of different stress hormones (ACTH, corticosterone and glucose; the latter as an indirect index of adrenergic/sympathetic nervous system activation). Rats trained in a brightness avoidance discrimination task exhibited an enhancement of the retention performance following exposure to the light discriminative stimulus when delivered 1-day after training and not after 21 days, while exposure to contextual cues led to opposite effects on the retention performance, confirming our previous results. Analyses of the level of stress hormones at the time of testing indicated that when the retrieval cues were effective at the behavioral level, cued rats exhibited higher ACTH plasmatic levels than controls, but did not differ in their glucose or corticosterone levels. Further experiments showed that one day after training, both ACTH and corticosterone levels were elevated in light-cued rats if hormone samples were taken 15 min after cueing. These results show that exposure to an effective retrieval cue is accompanied by the activation of the hypothalamus-pituitary-adrenal axis. The possible involvement of the Corticotropin Releasing Factor at the level of the hypothalamus and amygdala (particularly the central nucleus) on the facilitating effect on retention performance following exposure to aversive training-associated cues is discussed. The present results strengthen the notion that emotion can interact with retrieval processes.

ACTH has beneficial effects on stuttering in ADHD and ASD patients with ESES: A retrospective study.

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Altunel, Attila; Sever, Ali; Altunel, Emine Özlem

2017-02-01

Etiology of stuttering remains unknown and no pharmacologic intervention has been approved for treatment. We aimed to evaluate EEG parameters and the effect of adrenocorticotropic hormone (ACTH) therapy in stuttering. In this retrospective study, 25 patients with attention deficit and hyperactivity (ADHD) or autism spectrum disorder (ASD), and comorbid stuttering were followed and treated with ACTH for electrical status epilepticus in sleep (ESES). Sleep EEGs were recorded at referral and follow-up visits and short courses of ACTH were administered when spike-wave index (SWI) was ⩾15%. The assessment of treatment effectiveness was based on reduction in SWI, and the clinician-reported improvement in stuttering, and ADHD or ASD. Statistical analyses were conducted in order to investigate the relationship between the clinical and EEG parameters. Following treatment with ACTH, a reduction in SWI in all the patients was accompanied by a 72% improvement in ADHD or ASD, and 83.8% improvement in stuttering. Twelve of the 25 patients with stuttering showed complete treatment response. Linear regressions established that SWI at final visit significantly predicted improvement in ADHD or ASD, and in stuttering. If symptoms had recurred, improvement was once again achieved with repeated ACTH therapies. Stuttering always improved prior to, and recurred following ADHD or ASD. The underlying etiology leading to ESES may play a significant role in the pathophysiology of stuttering and connect stuttering to other developmental disorders. ACTH therapy has beneficial effects on stuttering and improves EEG parameters. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

A case of insulin and ACTH co-secretion by a neuroendocrine tumour.

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Solomou, S; Khan, R; Propper, D; Berney, D; Druce, M

2014-01-01

A 33-year-old male was diagnosed with a metastatic neuroendocrine carcinoma of uncertain primary. He defaulted from follow-up without therapy and some months later developed episodic severe hypoglycaemia, which was found to be associated with inappropriately elevated insulin and C-peptide levels. It was considered likely that the neuroendocrine tumour was the source of the insulin secretion. Diazoxide and somatostatin analogue were used to control hypoglycaemia. Much later in the course of the disease, he developed metabolic derangement, increased skin pigmentation and psychological disturbance, without frankly Cushingoid physical findings. Investigations revealed highly elevated cortisol levels (the levels having previously been normal) with markedly raised ACTH levels, consistent with the co-secretion of ACTH and insulin by the tumour. Treatment with metyrapone improved his psychological state and electrolyte imbalance. Unfortunately, despite several cycles of first-, second- and third-line chemotherapy from the start of the first hormonal presentation onwards, imaging revealed widespread progressive metastatic disease and the patient eventually passed away. This case highlights the importance of keeping in mind the biochemical heterogeneity of endocrine tumours during their treatment. The clinical presentation of insulin-secreting tumours includes symptoms of neuroglycopaenia and sympathetic overstimulation.Tumour-associated hypoglycaemia can be due to pancreatic insulinomas, and although ectopic hormone production occurs in a number of tumours, ectopic secretion of insulin is rare.A possible switch in the type of hormone produced can occur during the growth and progression of neuroendocrine tumours and, when treating neuroendocrine tumours, it is important to keep in mind their biochemical heterogeneity.

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.

Circulatory Immune Cells in Cushing Syndrome: Bystanders or Active Contributors to Atherometabolic Injury? A Study of Adhesion and Activation of Cell Surface Markers

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Gloria Aranda

2017-01-01

Full Text Available Glucocorticoids (GC induce cardiometabolic risk while atherosclerosis is a chronic inflammation involving immunity. GC are immune suppressors, and the adrenocorticotrophic hormone (ACTH has immune modulator activities. Both may act in atherothrombotic inflammation involving immune cells (IMNC. Aim. To investigate adhesion and activation surface cell markers (CDs of peripheral IMNC in endogenous Cushing syndrome (CS and the immune modulator role of ACTH. Material and Methods. 16 ACTH-dependent CS (ACTH-D, 10 ACTH-independent (ACTH-ID CS, and 16 healthy controls (C were included. Leukocytes (Leuc, monocytes (MN, lymphocytes (Lym, and neutrophils (N were analyzed by flow cytometry for atherosclerosis previously associated with CDs. Results. Leuc, N, and MN correlated with CS (p<0.05, WC (p<0.001, WHR (p=0.003, BMI (p<0.001, and hs-CRP (p<0.001. CD14++CD16+ (p=0.047; CD14+CD16++ (p=0.053 MN; CD15+ (p=0.027; CD15+CD16+ (p=0.008 N; and NK-Lym (p=0.019 were higher in CS. CD14+CD16++ MN were higher in ACTH-ID (8.9 ± 3.5% versus ACTH-D CS (4.2 ± 1.9% versus C (4.9 ± 2.3%. NK-Lym correlated with c-LDL (r = 0.433, p=0.039 and CD15+ N with hs-CRP (r = 0.446, p=0.037. In multivariate analysis, Leuc, N, and MN depended on BMI (p=0.021, WC (p=0.002, and WHR (p=0.014, while CD15+ and CD15+CD16+ N on hypercortisolism and CS (p=0.035. Conclusion. In CS, IMNC present changes in activation and adhesion CDs implicated in atherothrombotic inflammation. ACTH-IDCS presents a particular IMNC phenotype, possibly due to the absence of the immune modulator effect of ACTH.

Long-term outcomes of tissue-based ACTH-antibody assay-guided transsphenoidal resection of pituitary adenomas in Cushing disease.

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Erfe, J Mark; Perry, Avital; McClaskey, John; Inzucchi, Silvio E; James, Whitney Sheen; Eid, Tore; Bronen, Richard A; Mahajan, Amit; Huttner, Anita; Santos, Florecita; Spencer, Dennis

2017-10-13

OBJECTIVE Cushing disease is caused by a pituitary micro- or macroadenoma that hypersecretes adrenocorticotropic hormone (ACTH), resulting in hypercortisolemia. For decades, transsphenoidal resection (TSR) has been an efficacious treatment but with certain limitations, namely precise tumor localization and complete excision. The authors evaluated the novel use of a double-antibody sandwich assay for the real-time quantitation of ACTH in resected pituitary specimens with the goals of augmenting pathological diagnosis and ultimately improving long-term patient outcome. METHODS This study involved a retrospective review of records and an analysis of assay values, pathology slides, and MRI studies of patients with Cushing disease who had undergone TSR in the period from 2009 to 2014 and had at least 1 year of follow-up in coordination with an endocrinologist. In the operating room, biopsy specimens from the patients had been analyzed for tissue ACTH concentration. Additional samples were simultaneously sent for frozen-section pathological analysis. The ACTH assay performance was compared against pathology assessments of surgical tumor samples using receiver operating characteristic (ROC) analysis and against pre- and postoperative MRI studies. RESULTS Fourteen patients underwent TSR with guidance by ACTH-antibody assay and pathological assessment of 127 biopsy samples and were followed up for an average of 3 years. The ACTH threshold for discriminating adenomatous from normal tissue was 290,000 pg/mg of tissue, based on jointly maximized sensitivity (95.0%) and specificity (71.3%). Lateralization discordance between preoperative MRI studies and surgical visualization was noted in 3 patients, confirming the impression that MRI alone may not achieve optimal localization. A majority of the patients (85.7%) attained long-term disease remission based on urinary free cortisol levels, plasma cortisol levels, and long-term corticosteroid therapy. Comparisons of patient

Positive gallium scan in the syndrome of opsoclonus-myoclonus treated with adrenocorticotropic hormone

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Gumbinas, M.; Gratz, E.S.; Johnston, G.S.; Schwartz, A.D.

1984-01-01

The syndrome of opsoclonus and myoclonus may be the first presenting symptom of neuroblastoma. The disorder is often controlled by treatment with adrenocorticotropic hormone (ACTH). A child with this disorder and treated with ACTH gel had abnormal uptake of 67 Ga in both adrenal glands during studies to attempt to detect an occult neuroblastoma. Repeat 67 Ga scans proved to be normal once the ACTH was discontinued and the patient was treated with prednisone. It is concluded that ACTH stimulation of normal adrenal tissue was responsible for these abnormal findings

Refractory Post-Herpetic Neuralgia As An Initial Presentation Of Olfactory Neuroblastoma-Related Ectopic ACTH Syndrome

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Hsiang-Hung Lin

2009-03-01

Full Text Available We report a woman aged 64 years with ectopic adrenocorticotropic hormone (ACTH syndrome caused by olfactory neuroblastoma as an initial presentation of refractory post-herpetic neuralgia. The manifestations such as cushingoid appearance and endocrine abnormalities are compatible with Cushing's syndrome. Brain computed tomography revealed a sellar mass. A biopsy revealed olfactory neuroblastoma. Immunohistochemical staining further defined the tumor as an ACTH-secreting neuroblastoma. Subsequent opportunistic infections by Candida glabrata fungemia and multiple drug-resistant Acinetobacter baumannii pneumonia occurred during hospitalization as a complication of severe hypercortisolism. Before any therapy for Cushing's syndrome and neuroblastoma could be initiated, the patient died from sepsis and multiorgan failure. We propose that Cushing's syndrome is more complex than what clinicians thought, and that meticulous cerebral imaging studies are crucial.

Brain sites mediating corticosteroid feedback inhibition of stimulated ACTH secretion

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Jacobson, L.

1989-01-01

There is substantial evidence that the brain mediates stress-induced and circadian increases in ACTH secretion and that corticosteroid concentrations which normalize basal plasma ACTH are insufficient to normalize ACTH responses to circadian or stressful stimuli in adrenalectomized rats. To identify brain sites mediating corticosteroid inhibition of stimulated ACTH secretion, two approaches were used. The first compared brain [ 14 C]-2-deoxyglucose uptake in rats with differential ACTH responses to stress. Relative to sham-adrenalectomized (SHAM) rats, adrenalectomized rats replaced with low, constant corticosterone levels via a subcutaneous corticosterone pellet (B-PELLET) exhibited elevated and prolonged ACTH responses to a variety of stimuli. Adrenalectomized rate given a circadian corticosterone rhythm via corticosterone in their drinking water exhibited elevated ACTH levels immediately after stress, but unlike B-PELLET rats, terminated stress induced ACTH secretion normally relative to SHAMS. Therefore, the abnormal ACTH responses to stress in B-PELLET rats were due to the lack of both circadian variations and stress-induced increases in corticosterone. Hypoxia was selected as a standardized stimulus for correlating brain [ 14 C]-2-deoxyglucose uptake with ACTH secretion. In intact rats, increases in plasma ACTH and decreases in arterial PO 2 correlated with the severity of hypoxia at arterial PCO 2 below 60 mm Hg. Hypoxia PELLET vs. SHAM rats. However, in preliminary experiments, although hypoxia increased brain 2-deoxyglucose uptake in most brain regions, plasma ACTH correlated poorly with 2-deoxyglucose uptake at 12% and 10% O 2

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.

Clinical study on the relationship between FENG syndrome and pituitary-adrenal axis hormones at the onset of acute cerebral infarction

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Guan Shaoxia; Chen Jianfei; Ma Yaling

2002-01-01

Objective: To find the relationship between FENG syndrome and pituitary-adrenal axis hormones (adrenocorticotropic hormone ACTH, corticosteroid CS) at the onset of acute cerebral infarction (ACI). Methods: Using the table of syndrome quantitative diagnosis formulated according to the experiences of apoplectic experts to score the patient at the onset for 151 cases, the patients were divided into two groups: those of FENG syndrome (score ≥ 7 n=77) and NON-FENG syndrome (score<7 n=74). Levels of plasma ACTH and CS in there two groups and 60 healthy subject were determined with RIA. Results: 1) The levels of plasma ACTH and CS in the FENG group were very significantly higher than those in the NON-FENG group (p<0.001); the same result existed between patients and healthy subjects (p<0.001). 2) Highly positive cor-relationship existed between the scores of 77 FENG syndrome cases and the levels of plasma ACTH (r=0.89, t=14.61); moderately positive cor-relationship existed between the scores of FENG syndrome cases and the levels of plasma CS (r=0.53, t=4.83). Conclusion: There is a positive cor-relationship between FENG syndrome and pituitary adrenal axis hormones (ACTH, CS), the levels of plasma ACTH and CS can be regarded as index to differentiate FENG syndrome from NON-FENG syndrome

Internal jugular vein adrenocorticotropic hormone estimation for diagnosis of adrenocorticotropic hormone-dependent Cushing′s syndrome: Ultrasound-guided direct jugular vein sample collection

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Jaya Prakash Sahoo

2012-01-01

Full Text Available Aim of Study: To assess the utility of internal jugular vein (IJV / peripheral adrenocorticotropic hormone (ACTH gradient in determining the etiology of ACTH- dependent Cushing′s syndrome. Materials and Methods: Patients with ACTH-dependent Cushing′s syndrome, (except children less than 12 years, had IJV blood collection under ultrasound guidance using a linear 7 MHZ probe. Blood was collected with a 21 G needle at the level of mandible with the patient in supine position. Six ml of blood was collected sequentially from right and left internal jugular veins for ACTH and prolactin estimation. Peripheral blood for ACTH and prolactin was taken from a previously placed IV cannula in the antecubital vein. Results: Thirty patients (20 F, 10 M, age 14 to 50 yrs were enrolled for this study. Source of ACTH excess was pituitary in 22, ectopic ACTH in 4, and unknown in 4 cases. Using an IJV: Peripheral ACTH ratio of ≥ 1.6, 15 out of 22 Cushing′s disease patients were correctly identified. However, 1 out of 4 ectopic Cushing also had IJV: Peripheral ratio ≥ 1.6. Overall, it had sensitivity of 68% with specificity of 75% while MRI pituitary and HDDST had sensitivity of 86% and 59%, respectively, with specificity of 100% each. Conclusion: IJV: Peripheral ACTH gradient was observed in 68% of patients with Cushing′s disease. Simultaneous IJV and peripheral sample collection with CRH stimulation may improve sensitivity and specificity of this test.

Chronic food restriction and the circadian rhythms of pituitary-adrenal hormones, growth hormone and thyroid-stimulating hormone.

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Armario, A; Montero, J L; Jolin, T

1987-01-01

Adult male Sprague-Dawley rats were subjected to food restriction so that they ate 65% of food ingested by control rats. While control rats had free access to food over the 24-hour period, food-restricted rats were provided with food daily at 10 a.m. The experimental period lasted for 34 days. On day 35, rats from both experimental groups were killed at 08.00, 11.00, 14.00, 24.00 and 02.00 h. Food restriction modified the circadian rhythms of ACTH and corticosterone. In addition, total circulating corticosterone throughout the day was higher in food-restricted than in control rats. In contrast, food restriction resulted in depressed secretion of thyroid-stimulating hormone and growth hormone. The results indicate that time of food availability entrained circadian corticosterone rhythm but not thyroid-stimulating hormone and growth hormone rhythms.

Treatment of idiopathic FSGS with adrenocorticotropic hormone gel.

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Hogan, Jonathan; Bomback, Andrew S; Mehta, Kshama; Canetta, Pietro A; Rao, Maya K; Appel, Gerald B; Radhakrishnan, Jai; Lafayette, Richard A

2013-12-01

Adrenocorticotropic hormone (ACTH) has shown efficacy as primary and secondary therapy for nephrotic syndrome due to membranous nephropathy. The data on using ACTH to treat idiopathic FSGS are limited. This report describes our experience using ACTH for nephrotic syndrome due to idiopathic FSGS in the United States. Twenty-four patients with nephrotic syndrome from idiopathic FSGS were treated with ACTH gel at two academic medical centers between 2009 and 2012, either as part of investigator-initiated pilot studies (n=16) or by prescription for treatment-resistant FSGS (n=8). The primary outcome was remission of proteinuria. The median dose of ACTH was 80 units injected subcutaneously twice weekly. Treatment durations were not uniform. Twenty-two patients had received immunosuppression (mean, 2.2 medications) before ACTH therapy. Six patients had steroid-dependent and 15 had steroid-resistant FSGS. At the time of ACTH initiation, the median serum creatinine (interquartile range) was 2.0 (1.1-2.7) mg/dl, estimated GFR was 36 (28-78) ml/min per 1.73 m(2), and urine protein-to-creatinine ratio was 4595 (2200-8020) mg/g. At the end of ACTH therapy, 7 of 24 patients (29%) experienced remission (n=2 complete remissions, n=5 partial remissions). All remitters had steroid-resistant (n=5) or steroid-dependent (n=2) FSGS. Two responders relapsed during the follow-up period (mean ± SD, 70±31 weeks). Adverse events occurred in 21 of 24 patients, including one episode of new-onset diabetes that resolved after stopping ACTH and two episodes of AKI. Response to ACTH treatment among steroid-resistant or steroid-dependent patients with FSGS is low, but ACTH gel may be a viable treatment option for some patients with resistant nephrotic syndrome due to idiopathic FSGS. Further research is necessary to determine which patients will respond to therapy.

Omnigen-AF reduces basal plasma cortisol, AWA cortisol release to adrencocorticotropic hormone or corticotrophin releasing hormone & vasopressin in lactating dairy cows under thermoneutral or acute heat stress conditions.

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Differences in the adrenal cortisol response of OmniGen-AF (OG) supplemented dairy cows to a corticotrophin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 1...

Adrenal Incidentalomas with Supraphysiologic Response to ACTH Stimulus: A Case Report

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Marianna Antonopoulou

2012-01-01

Full Text Available We present the diagnostic approach of a patient with adrenal incidentalomas. A 72-year-old African American male had a CT scan of the abdomen showing right and left adrenal masses measuring and , respectively. The patient had negative hormonal workup. The radiologist insisted that the CT findings are consistent with adrenal hyperplasia, and therefore he underwent ACTH stimulation to rule out late-onset congenital adrenal hyperplasia (CAH. The stimulation test revealed that 17-hydroxyprogesterone and 11-deoxycortisol increased to levels high enough to confirm CAH, but cortisol had exaggerated response as well, thus making the diagnosis of CAH unlikely where metabolism is shifted to precursors. Subsequently, the patient underwent screening for Cushing's syndrome (CS with a dexamethasone suppression test. Patient failed the suppresion test, raising the issue for subclinical CS (SCS, likely due to ACTH-independent macronodular adrenal hyperplasia. Our patient had been diagnosed with MGUS and so far there are only 3 case reports of extramedullary plasmacytoma arising from the adrenals. One was bilateral and one had functional abnormalities. Our differential diagnosis includes subclinical CS with aberrant receptors versus a functioning extramedullary plasmacytoma.

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

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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

[Behavior of circadian rhythm of ACTH and cortisol in 16 normal subjects after a balanced normocaloric diet and after a high protein diet (Cosinor mean method)].

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Sellini, M; Giovannini, C; Manzo, G; Barletta, C; Borboni, P

1983-01-31

In 16 normal subjects the circadian rhythm of ACTH has been studied during normal calories diet and after a 15 days period of high protein content diet (2 g/Kg body weight). The statistical study, according Cosinor method, has shown a significant increase of the mesor and of the amplitude, but has not shown any change of the ACTH and Cortisol rhythm, after hyperproteic diet. Data advise the increase of the tonic and fasic secretion of both hormones and shown the mantained acrophase. The action of the protein on the ACTH and Cortisol secretion does not seem related to mechanism like stress, neither to the probable mediation of intestinal like-ACTH messengers. On the contrary it seems related to a direct stimulus on the diencephalo-pituitary axis; it is possible that some amino-acids (tryptophan, arginine) act as a mediator, even if data concern just the effect of the over mentioned amino-acid in large doses.

Ectopic adrenocorticotropic hormone syndrome presenting as hypokalemic metabolic alkalosis and hypertension

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Mansoor C Abdulla

2016-01-01

Full Text Available The ectopic adrenocorticotropic hormone (ACTH syndrome is an uncommon cause of hypercortisolism, which should be considered in patients with hypokalemic metabolic alkalosis and hypertension in the context of lung neoplasm. We report a 60-year-old male patient with severe hypertension, metabolic alkalosis, and hypokalemia as the initial manifestations of an ACTH-secreting small cell lung carcinoma. Ectopic Cushing's syndrome should always be ruled out in patients with severe hypertension and hypokalemia.

Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism.

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Wang, Wen-Bo; She, Fei; Xie, Li-Fang; Yan, Wen-Hua; Ouyang, Jin-Zhi; Wang, Bao-An; Ma, Hang-Yun; Zang, Li; Mu, Yi-Ming

2016-05-20

Prolonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism (IHH) may produce adverse effects on the endocrine homeostasis and metabolism. This study aimed to compare basal serum adrenocorticotropic hormone (ACTH) and cortisol levels between male IHH patients and healthy controls. Moreover, this study compared the basal hypothalamic-pituitary-adrenal (HPA) axis in patients with and without nonalcoholic fatty liver disease (NAFLD), and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients. This was a retrospective case-control study involving 75 Chinese male IHH patients (mean age 21.4 ± 3.8 years, range 17-30 years) and 135 healthy controls after matching for gender and age. All subjects underwent physical examination and blood testing for serum testosterone, luteinizing hormone, follicle-stimulating hormone, ACTH, and cortisol and biochemical tests. Higher basal serum ACTH levels (8.25 ± 3.78 pmol/L vs. 6.97 ± 2.81 pmol/L) and lower cortisol levels (366.70 ± 142.48 nmol/L vs. 452.82 ± 141.53 nmol/L) were observed in male IHH patients than healthy subjects (all pIHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD (34.9% vs. 4.4%) than the controls (all P IHH patients with NAFLD than those without NAFLD (all P IHH patients. Furthermore, NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis. The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.

Relationships between the pituitary-adrenal hormones, insulin, and glucose in middle-aged men: moderating influence of psychosocial stress.

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Keltikangas-Järvinen, L; Ravaja, N; Räikkönen, K; Hautanen, A; Adlercreutz, H

1998-12-01

We examined whether the relationships between the pituitary-adrenal hormones (corticotropin [ACTH) and cortisol), insulin, and glucose differ as a function of psychosocial stress defined in terms of vital exhaustion (VE) and depressive behavior (DB). The participants were 69 normotensive and 21 unmedicated borderline hypertensive (BH) middle-aged men whose work is stressful. Hormonal and metabolic variables were measured during an oral glucose tolerance test (OGTT), and the cortisol response to dexamethasone (DXM) suppression and intravenous ACTH stimulation was also measured. We found that the basal ACTH level during the OGTT was positively associated with the cortisol response to ACTH at 60 minutes, the fasting insulin level, and the insulin to glucose ratio among exhausted and high DB men, while the reverse was true for nonexhausted and low DB men. Also, a high cortisol response to ACTH, a low cortisol level during the OGTT, and a high ratio of these cortisol determinations (cortisol ratio) were associated with high fasting insulin and glucose levels, the summed insulin values, and the insulin to glucose ratio only among nonexhausted and low DB men; among exhausted and high DB men, these associations were less pronounced, absent, or in the opposite direction. The findings suggest that VE and DB have a moderating influence on the relationships among the hormonal and metabolic parameters studied. Psychosocial stress may affect the pituitary-adrenocortical system in complex ways, contributing thereby to insulin resistance, hyperinsulinemia, and coronary heart disease (CHD) risk.

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.

Adrenocorticotropic hormone-producing pheochromocytoma: analysis of clinical cases

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Evgeniya Ivanovna Marova

2015-04-01

Full Text Available Ectopic secretion of ACTH from non-pituitary tumors, referred to as ectopic ACTH syndrome (EAS, accounts for about 10–20% of Cushing’s syndrome (CS. Ectopic hormone-secreting pheochromocytomas (Pheo are rare. The first publication of association between pheochromocytoma and Cushing’s syndrome by Roux is dated 1955. Pheochromocytoma represents a rare cause of hypercortisolism, accounting for less than 5 % of ectopic Cushing’s syndrome while less than 1 % of pheochromocytomas is accompanied by Cushing’s syndrome. We are reporting 4 cases of ACTH-secreting pheochromocytoma presenting as Cushing’s syndrome. Data from 4 patients were analysed. There were 4 women from 50 to 63 years old. All patients had a clinical presentation of hypercorticoidism. Their levels of adrenocorticotropic hormone in plasma, 24-hour urinary free cortisol and urinary catecholamine were high. Computed tomography scan of the abdomen in all cases revealed a mass in the left adrenal gland. Left sided adrenalectomy was performed under treatment with a-blocker doxazosin and b-blocker atenolol. Histological examination revealed in 3 cases – pheocromocytoma and in 1 case corticomedullary mixed tumor of the adrenal gland. Additional immunostaining (IHCof these tumors showed positive immunostaining for chromogranin and ACTH. The IHC search for somatostatin receptors of subtype 2 and 5 (SSTR2, SSTR5 was performed in 3 cases and showed predominately expression SSTR2. The case index of Ki-67 ranged, from 0,5 to 4%. Biochemical signs of hypercortisolism rapidly began to disappear after surgery. Follow up of the patients during the next 2 years on average was with disease remission.

ATR-101, a selective ACAT1 inhibitor, decreases ACTH-stimulated cortisol concentrations in dogs with naturally occurring Cushing's syndrome.

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Langlois, Daniel K; Fritz, Michele C; Schall, William D; Bari Olivier, N; Smedley, Rebecca C; Pearson, Paul G; Bailie, Marc B; Hunt, Stephen W

2018-05-02

Cushing's syndrome in humans shares many similarities with its counterpart in dogs in terms of etiology (pituitary versus adrenal causes), clinical signs, and pathophysiologic sequelae. In both species, treatment of pituitary- and adrenal-dependent disease is met with limitations. ATR-101, a selective inhibitor of ACAT1 (acyl coenzyme A:cholesterol acyltransferase 1), is a novel small molecule therapeutic currently in clinical development for the treatment of adrenocortical carcinoma, congenital adrenal hyperplasia, and Cushing's syndrome in humans. Previous studies in healthy dogs have shown that ATR-101 treatment led to rapid, dose-dependent decreases in adrenocorticotropic hormone (ACTH) stimulated cortisol levels. The purpose of this clinical study was to investigate the effects of ATR-101 in dogs with Cushing's syndrome. ATR-101 pharmacokinetics and activity were assessed in 10 dogs with naturally-occurring Cushing's syndrome, including 7 dogs with pituitary-dependent disease and 3 dogs with adrenal-dependent disease. ATR-101 was administered at 3 mg/kg PO once daily for one week, followed by 30 mg/kg PO once daily for one (n = 4) or three (n = 6) weeks. Clinical, biochemical, adrenal hormonal, and pharmacokinetic data were obtained weekly for study duration. ATR-101 exposure increased with increasing dose. ACTH-stimulated cortisol concentrations, the primary endpoint for the study, were significantly decreased with responders (9 of 10 dogs) experiencing a mean ± standard deviation reduction in cortisol levels of 50 ± 17% at study completion. Decreases in pre-ACTH-stimulated cortisol concentrations were observed in some dogs although overall changes in pre-ACTH cortisol concentrations were not significant. The compound was well-tolerated and no serious drug-related adverse effects were reported. This study highlights the potential utility of naturally occurring canine Cushing's syndrome as a model for human disease and provides proof of

Basal and Adrenocorticotropic Hormone Stimulated Plasma Cortisol Levels Among Egyptian Autistic Children: Relation to Disease Severity

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Hewedi Doaa H

2010-10-01

Full Text Available Abstract Background Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism. Aim To assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH levels in autistic children and their relationship to disease characteristics. Methods Fifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated and ACTH. In addition, electroencephalography (EEG and intelligence quotient (IQ assessment were done for all autistic children. Results Sixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032 and stimulated cortisol (p = 0.04 and higher ACTH (p = 0.01 than controls. Childhood Autism Rating Scale (CARS score correlated positively with ACTH (r = 0.71, p = 0.02 and negatively with each of basal (r = -0.64, p = 0.04 and stimulated cortisol (r = -0.88, p Conclusions The observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism.

Residual adrenal function in autoimmune Addison's disease: improvement after tetracosactide (ACTH1-24) treatment.

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Gan, Earn H; MacArthur, Katie; Mitchell, Anna L; Hughes, Beverly A; Perros, Petros; Ball, Stephen G; James, R Andrew; Quinton, Richard; Chen, Shu; Furmaniak, Jadwiga; Arlt, Wiebke; Pearce, Simon H S

2014-01-01

Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility. We aimed to determine whether tetracosactide (synthetic ACTH1-24) could revive adrenal steroidogenic function in autoimmune Addison's disease. Thirteen patients (aged 16-65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility. The intervention included a 20-week study of regular sc tetracosactide (ACTH1-24) therapy. Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study. Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants throughout the study. However, two women achieved peak serum cortisol concentrations greater than 400 nmol/L after 10 and 29 weeks of tetracosactide therapy, respectively, allowing withdrawal of corticosteroid replacement. Concurrently, urine glucocorticoid and mineralocorticoid metabolite excretion increased from subnormal to above the median of healthy controls. One of these responders remains well with improving peak serum cortisol (672 nmol/L) 28 months after stopping all treatments. The other responder showed a gradual reduction in serum cortisol and aldosterone over time, and steroid therapy was recommenced after a 28-week period without glucocorticoid replacement. This is the first study to demonstrate that established autoimmune Addison's disease is amenable to a regenerative medicine therapy approach.

Aberrant expression of glucagon receptors in adrenal glands of a patient with Cushing's syndrome and ACTH-independent macronodular adrenal hyperplasia

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Valeria de Miguel

2010-06-01

Full Text Available Adrenocorticotropin (ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH is a rare cause of Cushing´s syndrome, characterized by bilateral adrenal lesions and excess cortisol production despite ACTH suppression. Cortisol synthesis is produced in response to abnormal activation of G-protein- coupled receptors, such as gastric inhibitory peptide, vasopressin, beta adrenergic agonists, LH/hCG and serotonin receptors. The aim of this study was to analyze the expression of glucagon receptors in adrenal glands from an AIMAH patient. A patient with ACTH-independent Cushing´s syndrome and bilateral macronodular adrenal hyperplasia was screened for altered activation of adrenal receptors by physiological (mixed meal and pharmacological (gonadotrophin releasing hormone, ACTH and glucagon tests. The results showed abnormally high levels of serum cortisol after stimulation with glucagon. Hypercortisolism was successfully managed with ketoconazole treatment. Interestingly, a 4-month treatment with a somatostatin analogue (octreotide was also able to reduce cortisol secretion. Finally, Cushing's syndrome was cured after bilateral adrenalectomy. Abnormal mRNA expression for glucagon receptor in the patient´s adrenal glands was observed by Real-Time PCR procedure. These results strongly suggest that the mechanism of AIMAH causing Cushing´s syndrome in this case involves the illicit activation of adrenal glucagon receptors. This is the first case reported of AIMAH associated with ectopic glucagon receptors.

Progression from isolated growth hormone deficiency to combined pituitary hormone deficiency.

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Cerbone, Manuela; Dattani, Mehul T

2017-12-01

Growth hormone deficiency (GHD) can present at any time of life from the neonatal period to adulthood, as a result of congenital or acquired insults. It can present as an isolated problem (IGHD) or in combination with other pituitary hormone deficiencies (CPHD). Pituitary deficits can evolve at any time from GHD diagnosis. The number, severity and timing of occurrence of additional endocrinopathies are highly variable. The risk of progression from IGHD to CPHD in children varies depending on the etiology (idiopathic vs organic). The highest risk is displayed by children with abnormalities in the Hypothalamo-Pituitary (H-P) region. Heterogeneous data have been reported on the type and timing of onset of additional pituitary hormone deficits, with TSH deficiency being most frequent and Diabetes Insipidus the least frequent additional deficit in the majority, but not all, of the studies. ACTH deficiency may gradually evolve at any time during follow-up in children or adults with childhood onset IGHD, particularly (but not only) in presence of H-P abnormalities and/or TSH deficiency. Hence there is a need in these patients for lifelong monitoring for ACTH deficiency. GH treatment unmasks central hypothyroidism mainly in patients with organic GHD, but all patients starting GH should have their thyroid function monitored closely. Main risk factors for development of CPHD include organic etiology, H-P abnormalities (in particular pituitary stalk abnormalities, empty sella and ectopic posterior pituitary), midline brain (corpus callosum) and optic nerves abnormalities, genetic defects and longer duration of follow-up. The current available evidence supports longstanding recommendations for the need, in all patients diagnosed with IGHD, of a careful and indefinite follow-up for additional pituitary hormone deficiencies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic ethanol consumption decreases adrenal responsiveness to adrenocorticotropin (ACTH) stimulation

International Nuclear Information System (INIS)

Nolan, C.J.; Bestervelt, L.L.; Cai, Y.; Maimansomsuk, P.; Coleman, L.; Piper, W.N.

1991-01-01

Increased alcohol consumption by adolescents and teenagers has heightened awareness of potential endocrine and developmental alterations. The current study was designed to determine whether chronic ethanol intake alters pituitary and adrenal function in the developing rat. One month old male Sprague Dawley rats were administered 6% ethanol in drinking water. After one month of treatment animals were sacrificed and blood, pituitary and adrenal glands collected. Plasma was assayed for ACTH and corticosterone (CS) by radioimmunossay (RIA). Five anterior pituitary glands per group were challenged with 100 μM corticotropin releasing factor (CRF) for 90 min at 37C under 95% air / 5% CO 2 . Media were analyzed for either ACTH (pituitary) or CS (adrenal) by RIA. Plasma ACTH and CS were unaffected by ethanol consumption. Pituitary response to CRF was not altered by ethanol. The lack of difference in ACTH release was not due to differences in pituitary content of ACTH. However, chronic ethanol consumption did decrease adrenal responsiveness to ACTH stimulation. In vitro corticosterone production was 1.21 ± 0.14 μg/adrenal in controls and 0.70 ± 0.06 μg/adrenal in ethanol consuming rats

Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic hormone in critical illness: a prospective cohort study.

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de Jong, Margriet F C; Molenaar, Nienke; Beishuizen, Albertus; Groeneveld, A B Johan

2015-01-06

Adrenal dysfunction may represent critical illness-related corticosteroid insufficiency (CIRCI), as evidenced by a diminished cortisol response to exogenous adrenocorticotropic hormone (ACTH), but this concept and its clinical significance remain highly controversial. We studied the adrenal response to exogenous ACTH as a function of the endogenous cortisol-to-ACTH ratio, a measure of adrenal sensitivity, and of clinical variables, during critical illness and recovery from the acute phase. We prospectively included 59 consecutive septic and nonseptic patients in the intensive care unit with treatment-insensitive hypotension in whom CIRCI was suspected; patients having received etomidate and prolonged corticosteroids were excluded. An ACTH test (250 μg) was performed, followed by a second test after ≥7 days in acute-phase survivors. Serum total and free cortisol, ACTH, and clinical variables were assessed. Patients were divided according to responses (delta, Δ) of cortisol to ACTH at the first and second tests. Patients with low (endogenous ACTH predicts a low increase of cortisol to exogenous ACTH, suggesting adrenal dysfunction, irrespective of the stage of disease. The data further suggest a role of disease severity and culture-positive sepsis.

Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease.

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Hong, A Ram; Kim, Jung Hee; Hong, Eun Shil; Kim, I Kyeong; Park, Kyeong Seon; Ahn, Chang Ho; Kim, Sang Wan; Shin, Chan Soo; Kim, Seong Yeon

2015-09-01

Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level. We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all Pdisease, especially when the plasma ACTH level alone is not conclusive.

Severe Cushing’s syndrome due to small cell prostate carcinoma: a case and review of literature

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M S Elston

2017-07-01

Full Text Available Cushing’s syndrome (CS due to ectopic adrenocorticotrophic hormone (ACTH is associated with a variety of tumours most of which arise in the thorax or abdomen. Prostate carcinoma is a rare but important cause of rapidly progressive CS. To report a case of severe CS due to ACTH production from prostate neuroendocrine carcinoma and summarise previous published cases. A 71-year-old male presented with profound hypokalaemia, oedema and new onset hypertension. The patient reported two weeks of weight gain, muscle weakness, labile mood and insomnia. CS due to ectopic ACTH production was confirmed with failure to suppress cortisol levels following low- and high-dose dexamethasone suppression tests in the presence of a markedly elevated ACTH and a normal pituitary MRI. Computed tomography demonstrated an enlarged prostate with features of malignancy, confirmed by MRI. Subsequent prostatic biopsy confirmed neuroendocrine carcinoma of small cell type and conventional adenocarcinoma of the prostate. Adrenal steroidogenesis blockade was commenced using ketoconazole and metyrapone. Complete biochemical control of CS and evidence of disease regression on imaging occurred after four cycles of chemotherapy with carboplatin and etoposide. By the sixth cycle, the patient demonstrated radiological progression followed by recurrence of CS and died nine months after initial presentation. Prostate neuroendocrine carcinoma is a rare cause of CS that can be rapidly fatal, and early aggressive treatment of the CS is important. In CS where the cause of EAS is unable to be identified, a pelvic source should be considered and imaging of the pelvis carefully reviewed.

CARDIAC STRUCTURAL AND FUNCTIONAL ABNORMALITIES IN FEMALES WITH UNTREATED HYPOPITUITARISM DUE TO SHEEHAN SYNDROME: RESPONSE TO HORMONE REPLACEMENT THERAPY.

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Laway, Bashir Ahmad; Ramzan, Mahroosa; Allai, Mohd Sultan; Wani, Arshad Iqbal; Misgar, Raiz Ahmad

2016-09-01

Data on cardiac abnormalities in females with untreated hypopituitarism are limited. We investigated echocardiographic abnormalities in females with untreated hypopituitarism and their response to treatment. Twenty-three females with treatment-naïve hypopituitarism and 30 matched healthy controls were evaluated for cardiac structure and function. Echocardiographic evaluation was done at presentation and after achieving a euthyroid and eucortisol state. Fourteen (61%) patients had mitral regurgitation, and 11 (48%) had pericardial effusion as against none among controls. Indices of left ventricular (LV) size like LV end diastolic dimension (LVEDD; 44.5 ± 3.5 mm in cases vs. 47.6 ± 3.8 mm in controls, P = .004), and LV diastolic volume (LVEDV; 91.8 ± 18.0 mL versus 106.5 ± 20.4 mL, P = .009) were significantly lower in the SS group compared with controls. LV mass (LVM) was 70.8 ± 19.2 g in cases and 108.0 ± 33.2 g in controls (P = .02). Similarly, indices of LV systolic function like stroke volume (SV; 59.1 ± 12.0 mL in cases and 74.4 ± 15.8 mL in controls; P = .000), ejection fraction (EF; 64.3 ± 6.2 % in cases against 69.9 ± 9.2 % in controls; P = .03), and fractional shortening (FS; 34.9 ± 4.7% versus 40.1 ± 4.4%, P = .000) were significantly decreased in patients compared with controls. Cardiac abnormalities normalized with restoration of a euthyroid and eucortisol state. Pericardial effusion, mitral regurgitation, and diminished LVM are common in females with untreated hypopituitarism. ACTH = adrenocorticotrophic hormone BMI = body mass index DT = deceleration time EDV = end-diastolic volume EF = ejection fraction FS = fractional shortening GH = growth hormone IGF-1 = insulin growth factor-1 ITT = insulin tolerance test IVSd = interventricular septal diameter LH = luteinizing hormone LV = left ventricular LVEDD = LV end diastolic dimension LVEDV = LV end diastolic volume LVM = LV mass MRI = magnetic resonance imaging MVP = mitral value prolapse PPH

Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome.

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Kato, Akihisa; Hayashi, Kazuki; Naitoh, Itaru; Seno, Kyoji; Okada, Yukiko; Ban, Tesshin; Kondo, Hiromu; Nishi, Yuji; Umemura, Shuichiro; Hori, Yasuki; Natsume, Makoto; Joh, Takashi

2016-07-01

Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin.

Adrenal activity and metabolic risk during randomized escitalopram or placebo treatment in PCOS

DEFF Research Database (Denmark)

Glintborg, Dorte; Altinok, Magda Lambaa; Ravn, Pernille

2018-01-01

BACKGROUND/AIMS: Polycystic ovary syndrome (PCOS) is associated with insulin resistance, adrenal hyperactivity and decreased mental health. We aimed to investigate the changes in adrenal activity, metabolic status and mental health in PCOS during treatment with escitalopram or placebo. METHODS......: Forty-two overweight premenopausal women with PCOS and no clinical depression were randomized to 12-week SSRI (20 mg escitalopram/day, n = 21) or placebo (n = 21). Patients underwent clinical examination, fasting blood samples, adrenocorticotroph hormone (ACTH) test, 3-h oral glucose tolerance test...... (OGTT) and filled in questionnaires regarding mental health and health-related quality of life (HRQoL): WHO Well-Being Index (WHO-5), Major Depression Inventory (MDI), Short Form 36 (SF-36) and PCOS questionnaire. RESULTS: Included women were aged 31 (6) years (mean (s.d.)) and had body mass index (BMI...

CT findings in patients with infantile epilepsy on ACTH therapy

International Nuclear Information System (INIS)

Watanabe, Kazunari; Hara, Kimiko; Hakamada, Akira; Miyazaki, Shuji.

1981-01-01

A case of infantile spasms in which subdural hematoma developed after ACTH-Z therapy was reported. The results of CT evaluated before and after the therapy in 17 cases of infantile epilepsy including infantile spasms. Cerebral atrophy due to ACTH-Z therapy was remarkable, especially in the infants under one year old. We should vary careful in employing ACTH-Z therapy for infants of this age. (Ueda, J.)

Therapeutic benefits of ACTH and levetiracetam in STXBP1 encephalopathy with a de novo mutation: A case report and literature review.

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Liu, Shunli; Wang, Liyuan; Cai, Xiao Tang; Zhou, Hui; Yu, Dan; Wang, Zhiling

2018-05-01

The case report aims to discuss the clinical symptoms and treatment of encephalopathy caused by a novel syntaxin- binding protein 1 (STXBP1) genetic mutation. The patient, a girl, was born at 38+4 weeks of gestation. She had frequent spasm attacks accompanied by obvious psychomotor development retardation since the neonatal period. Genetic screening identified a novel STXBP1 genetic mutation. Early-onset epileptic encephalopathy with STXBP1 mutation. We adjusted the antiepileptic strategy to oral levetiracetam and topiramate, and intravenous administration of adrenocorticotropic hormone(ACTH) for 2 weeks. Subsequently, prednisone was continued, and gradually reduced and withdrawn over 3 months. The treatment was effective with complete control of the epileptic seizures and improvements in the electroencephalogram readings. However, the effects on psychomotor ability were slow and limited. A literature review of STXBP1 mutation cases in which ACTH was administered showed that complete seizure control is observed in 60% of cases, 20% are partially affected, and the remaining 20% show no effect. ACTH and levetiracetam had good therapeutic effects in epilepsy control in this case of de novo STXBP1 mutation. ACTH is an effective drug for early-onset epileptic encephalopathy caused by STXBP1 mutation. However, controlling epilepsy using this therapy does not alter the psychomotor development retardation caused by the STXBP1 mutation.

Effect of adrenal hormones on thyroid secretion and thyroid hormones on adrenal secretion in the sheep.

Science.gov (United States)

Falconer, I R; Jacks, F

1975-01-01

1. Previous work has shown that after stressful stimuli, sheep initially secrete increased amounts of thyroid hormone, at a time when adrenal secretion is also elevated. 2. This study was designed to evaluate (a) any short-term activation or inhibition of thyroid secretion by exogenous cortisol or ACTH administered in quantities comparable to those secreted after stress in sheep and (b) any short-term effect that exogenous thyroxine or triiodothyronine may have on the concentration of plasma cortisol in the sheep. 3. Thyroid activity was measured by determination of plasma protein bound 125I (PB125I) and total 125I in thyroid vein and mixed venous (jugular) blood. Plasma cortisol and thyroxine concentrations were measured by a competitive protein-binding assay at intervals for up to 5 hr after commencement of the experiment. 4. No evidence of an activation of thyroid secretion was found during cortisol or ACTH infusion, as monitored by thyroid vein PB125I. Similarly there was no evidence of any inhibition of thyroid function, as measured by continued secretion of thyroid hormones into thyroid vein blood. 5. No effect on plasma cortisol concentration due to thyroid hormone treatment was observed. 6. It was concluded that (a) elevated circulating corticosteroids in physiological concentrations have no short-term effects on thyroid activity in the sheep and (b) the short-term alterations in thyroid and adrenal cortical secretion observed during stress in the sheep could not be attributed to direct interaction of elevated thyroid hormone concentrations with adrenal cortical secretion. PMID:170400

Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland.

Science.gov (United States)

Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

2016-04-25

Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors.

Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids.

Science.gov (United States)

Yarnell, Kelly; Purcell, Rebecca S; Walker, Susan L

2016-04-25

Adrenal activity can be assessed in the equine species by analysis of feces for corticosterone metabolites. During a potentially aversive situation, corticotrophin releasing hormone (CRH) is released from the hypothalamus in the brain. This stimulates the release of adrenocorticotrophic hormone (ACTH) from the pituitary gland, which in turn stimulates release of glucocorticoids from the adrenal gland. In horses the glucocorticoid corticosterone is responsible for several adaptations needed to support equine flight behaviour and subsequent removal from the aversive situation. Corticosterone metabolites can be detected in the feces of horses and assessment offers a non-invasive option to evaluate long term patterns of adrenal activity. Fecal assessment offers advantages over other techniques that monitor adrenal activity including blood plasma and saliva analysis. The non-invasive nature of the method avoids sampling stress which can confound results. It also allows the opportunity for repeated sampling over time and is ideal for studies in free ranging horses. This protocol describes the enzyme linked immunoassay (EIA) used to assess feces for corticosterone, in addition to the associated biochemical validation.

ACTH radioimmunocytochemistry (RICH) on rat anterior pituitary cells

International Nuclear Information System (INIS)

Rappay, G.; Karteszi, M.; Makara, G.B.

1979-01-01

Radioimmunocytochemistry (RICH) was applied to detect corticotrophs in adult rat pituitaries and 8-day-old anterior pituitary monolayers by incubating sections and cultures with 125 I-ACTH-anti ACTH immune complexes. After incubations autoradiography was made. In comparison, 'conventional' immunostaining was carried out on adjacent sections and parallel cultures. It has been established that RICH is suitable for detection of corticotrophs. (orig.) [de

Marked cortisol production by intracrine ACTH in GIP-treated cultured adrenal cells in which the GIP receptor was exogenously introduced.

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Hiroko Fujii

Full Text Available The ectopic expression of the glucose-dependent insulinotropic polypeptide receptor (GIPR in the human adrenal gland causes significant hypercortisolemia after ingestion of each meal and leads to Cushing's syndrome, implying that human GIPR activation is capable of robustly activating adrenal glucocorticoid secretion. In this study, we transiently transfected the human GIPR expression vector into cultured human adrenocortical carcinoma cells (H295R and treated them with GIP to examine the direct link between GIPR activation and steroidogenesis. Using quantitative RT-PCR assay, we examined gene expression of steroidogenic related proteins, and carried out immunofluorescence analysis to prove that forced GIPR overexpression directly promotes production of steroidogenic enzymes CYP17A1 and CYP21A2 at the single cell level. Immunofluorescence showed that the transfection efficiency of the GIPR gene in H295R cells was approximately 5%, and GIP stimulation enhanced CYP21A2 and CYP17A1 expression in GIPR-introduced H295R cells (H295R-GIPR. Interestingly, these steroidogenic enzymes were also expressed in the GIPR (- cells adjacent to the GIPR (+ cells. The mRNA levels of a cholesterol transport protein required for all steroidogenesis, StAR, and steroidogenic enzymes, HSD3β2, CYP11A1, CYP21A2, and CYP17A1 increased 1.2-2.1-fold in GIP-stimulated H295R-GIPR cells. These changes were reflected in the culture medium in which 1.5-fold increase in the cortisol concentration was confirmed. Furthermore, the levels of adenocorticotropic hormone (ACTH receptor and ACTH precursor proopiomelanocortin (POMC mRNA were upregulated 2- and 1.5-fold, respectively. Immunofluorescence showed that ACTH expression was detected in GIP-stimulated H295R-GIPR cells. An ACTH-receptor antagonist significantly inhibited steroidogenic gene expression and cortisol production. Immunostaining for both CYP17A1 and CYP21A2 was attenuated in cells treated with ACTH receptor antagonists

ACTH stimulation test in the captive cheetah (Acinonyx jubatus

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L.S. Koster

2007-06-01

Full Text Available Serum cortisol response was assessed in 8 captive cheetahs, of varying ages, after the intravenous administration of 500 µg of tetracosactide (Synacthen Depot(R, Novartis, Kempton Park while maintained under general anaesthesia. In addition, 8 cheetahs were anaesthetised and given an equal volume of saline in order to establish baseline cortisol concentrations at similar stages of anaesthesia. A significant difference in the median cortisol concentration measured over time was found following ACTH administration in the ACTH group (P < 0.001. There was no difference between the median cortisol concentrations in the ACTH group at time-points 120, 150 and 180 min after ACTH stimulation (P = 0.867. Thus it appears appropriate to collect serum 120 to 180 min after tetracosactide administration to assess maximal stimulation of the adrenal in the cheetah. No statistically significant rise was seen in the anaesthetised control group following the injection of saline (P = 0.238.

Contagem de células somáticas e produção leiteira em cabras Saanen estressadas via aplicação de ACTH Somatic cell count and milk production of Saanen goats stressed via application of ACTH

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Ana Paula Rodrigues Gaiato

2012-05-01

Full Text Available Avaliou-se neste estudo o efeito do estresse, via administração de ACTH (hormônio adrenocorticotrófico, sobre a quantidade e qualidade do leite produzido e a indicação de estresse pela alteração no nível de cortisol. Assim, 12 cabras lactantes foram distribuídas em dois grupos: seis animais receberam aplicação de 0,06 UI de ACTH/kg de PV (desafiadas e seis receberam solução placebo (controle, todas via intravenosa. O desafio ocorreu ao longo da lactação, com aplicação do protocolo aos 30, 60, 120 e 180 dias do início da lactação, avaliando-se em cada data os níveis de cortisol 30 minutos antes, no ato da aplicação, 60, 120 e 300 minutos depois. A produção leiteira foi mensurada diariamente durante 270 dias e, a cada 20 dias, o leite foi colhido para contagem de células somáticas (CCS pelo método direto. Os teores de cortisol mensurados em -30 e 0 minuto antes da aplicação de ACTH foram baixos e semelhantes entre os grupos. Entretanto, a partir de 60 minutos, constatou-se efeito da aplicação de ACTH, com teor de cortisol de 61,37±6,65 versus 5,47±1,21 ng/mL e de 51,17±10,21 versus 4,67±1,21 ng/mL aos 120 minutos. Aos 300 minutos, o cortisol retornou ao nível basal. Não houve diferença na produção de leite, no teor de proteína e de gordura do leite, cujos valores nos grupos ACTH e Placebo foram 1,37±0,59 e 1,38±0,63 kg de leite, respectivamente. A contagem de células somáticas não foi influenciada pelo estresse e apresentou valores situados na faixa indicada para animais sadios. Constatou-se estresse pontual em decorrência da aplicação de ACTH, porém sem alterações de natureza quantitativa e qualitativa do leite produzido, e isso indica que atividades de manejo que estressam os animais pontualmente não trazem prejuízos ao sistema produtivo.The objective of this study was to analyze the stress effect, via administration of ACTH (adrenocorticotropic hormone, on quantity and quality of milk

Leucine-enkephalin-like immunoreactivity is localized in luteinizing hormone-producing cells in the axolotl (Ambystoma mexicanum) pituitary.

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Suzuki, Hirohumi; Yamamoto, Toshiharu

2014-02-01

In this study, we used immunohistochemical techniques to determine the cell type of leucine-enkephalin (Leu-ENK)-immunoreactive cells in the axolotl (Ambystoma mexicanum) pituitary. Immunoreactive cells were scattered throughout the pars distalis except for the dorso-caudal portion. These cells were immuno-positive for luteinizing hormone (LH), but they were immuno-negative for adrenocorticotrophic, growth, and thyroid-stimulating hormones, as well as prolactin. Immunoelectron microscopy demonstrated that Leu-ENK-like substance and LH co-localized within the same secretory granules. Leu-ENK secreted from gonadotrophs may participate in LH secretion in an autocrine fashion, and/or may participate in the release of sex steroids together with LH. Copyright © 2013 Elsevier Ltd. All rights reserved.

Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial.

Science.gov (United States)

Bomback, Andrew S; Canetta, Pietro A; Beck, Laurence H; Ayalon, Rivka; Radhakrishnan, Jai; Appel, Gerald B

2012-01-01

Adrenocorticotropic hormone (ACTH) has shown promising results in glomerular diseases resistant to conventional therapies, but the reported data have solely been from retrospective, observational studies. In this prospective, open-label study (NCT01129284), 15 subjects with resistant glomerular diseases were treated with ACTH gel (80 units subcutaneously twice weekly) for 6 months. Resistant membranous nephropathy (MN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS) were defined as failure to achieve sustained remission of proteinuria off immunosuppressive therapy with at least 2 treatment regimens; resistant IgA nephropathy was defined as >1 g/g urine protein:creatinine ratio despite maximally tolerated RAAS blockade. Remission was defined as stable or improved renal function with ≥50% reduction in proteinuria to 50% reductions in proteinuria while on ACTH, with proteinuria consistently <1 g/g by 6 months. Three of 15 subjects reported significant steroid-like adverse effects with ACTH, including weight gain and hyperglycemia, prompting early termination of therapy without any clinical response. ACTH gel is a promising treatment for resistant glomerular diseases and should be studied further in controlled trials against currently available therapies for resistant disease. Copyright © 2012 S. Karger AG, Basel.

Linkage of congenital isolated adrenocorticotropic hormone deficiency to the corticotropin releasing hormone locus using simple sequence repeat polymorphisms

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Kyllo, J.H.; Collins, M.M.; Vetter, K.L. [Univ. of Iowa College of Medicine, Iowa City, IA (United States)] [and others

1996-03-29

Genetic screening techniques using simple sequence repeat polymorphisms were applied to investigate the molecular nature of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare cause of hypocortisolism shared by a brother and sister with two unaffected sibs and unaffected parents is inherited as an autosomal recessive single gene mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol sufficiency were investigated for a causal role in this disorder. Southern blotting showed no detectable mutations of the gene encoding pro-opiomelanocortin (POMC), the ACTH precursor. Other candidate genes subsequently considered were those encoding neuroendocrine convertase-1, and neuroendocrine convertase-2 (NEC-1, NEC-2), and corticotropin releasing hormone (CRH). Tests for linkage were performed using polymorphic di- and tetranucleotide simple sequence repeat markers flanking the reported map locations for POMC, NEC-1, NEC-2, and CRH. The chromosomal haplotypes determined by the markers flanking the loci for POMC, NEC-1, and NEC-2 were not compatible with linkage. However, 22 individual markers defining the chromosomal haplotypes flanking CRH were compatible with linkage of the disorder to the immediate area of this gene of chromosome 8. Based on these data, we hypothesize that the ACTH deficiency in this family is due to an abnormality of CRH gene structure or expression. These results illustrate the useful application of high density genetic maps constructed with simple sequence repeat markers for inclusion/exclusion studies of candidate genes in even very small nuclear families segregating for unusual phenotypes. 25 refs., 5 figs., 2 tabs.

Monitoring performance, pituitary-adrenal hormones and mood profiles: how to diagnose non-functional over-reaching in male elite junior soccer players.

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Schmikli, Sándor L; de Vries, Wouter R; Brink, Michel S; Backx, Frank Jg

2012-11-01

To verify if in male elite junior soccer players a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of non-functional over-reaching (NFOR). A prospective case-control study using a monthly performance monitor with a standardised field test to detect the performance changes. Players with a performance decrease lasting at least 1 month were compared with control players without a performance decrease on mood scores and pre-exercise and postexercise levels of stress hormones. Sporting field and sports medical laboratory. Ninety-four young elite soccer players were monitored during the 2006-2008 seasons. Twenty-one players were invited to the laboratory, seven of whom showed a significant performance decrease. Performance change over time, scores on the profile of mood states and premaximal and postmaximal exercise serum levels of adrenocorticotropic hormone (ACTH), growth hormone (GH) and cortisol. Players with a performance decrease showed psychological and hormonal changes typical of the non-functional state of over-reaching. Scores were higher on depression and anger, whereas the resting GH levels and ACTH levels after maximal exercise were reduced. ACTH and GH were capable of classifying all but one player correctly as either NFOR or control. Performance-related criteria in field tests are capable of identifying players with worsened mood and adaptations of the endocrine system that fit the definition of NFOR. Performance, mood and hormone levels may therefore be considered as valid instruments to diagnose NFOR in young elite soccer players.

Stimulation of corticosterone secretion in vitro by brief ACTH exposure

International Nuclear Information System (INIS)

Keith, L.D.; Tam, B.; Greer, M.A.

1986-01-01

The authors examined the relationship between ACTH concentration and exposure duration on stimulation of corticosterone (B) secretion in vitro using perifused enzymatically dispersed rat adrenocortical cells. A modular perifusion apparatus was used that permitted evaluation of 20-24 cell chambers per experimental session. In expt 1,20-1000 pg/ml concentrations of synthetic ACTH-(1-24) were presented to cells for 1 min. In expt 2, 100 pg ACTH-(1-24) was presented to adrenal cells in five dose-duration regimens ranging from 5 pg/min for 20 min to 100 pg/min for 1 min. Perifusal rate was 1 ml/min in all sessions. B was determined by radioimmunoassay. In expt 1 (constant-duration paradigm), 1-min presentation of ACTH-(1-24) produced log-linear dose-response effects across these concentrations. In expt 2 (constant-mass paradigm), identical masses administered in different dose-duration regimens had different steroidogenic efficacies: low-dose long-duration regimens provoked greater total release than high-dose short-duration regimens. Overall, every dose-duration regimen was associated with stimulation of B secretion. These results indicate that 1) very brief exposure to physiological concentrations of ACTH-(1-24) is a significant stimulus for corticosteroid secretion; 2) variations in the dose-duration regimen over the physiological range modifies both the maximum rate of secretion and the duration of secretion, but not the response latency; and 3) ACTH-(1-24) presentation mass is not the sole determinant of B secretion

Relative contributions of pituitary-adrenal hormones to the ontogeny of behavioral inhibition in the rat.

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Takahashi, L K; Kim, H

1995-04-01

Recent investigations revealed that adrenalectomized (ADX) rat pups exhibit deficits in behavioral inhibition. Furthermore, administration of exogenous corticosterone (CORT) restores behavioral inhibition in ADX pups. Although these studies suggest that CORT has an important role in the development of behavioral inhibition, the relative behavioral effects of elevated pituitary hormone secretion induced by ADX are not known. Therefore, experiments were conducted to assess the potential behavioral effects of elevated adrenocorticotropin (ACTH) secretion induced by ADX and to further evaluate the contribution of endogenous CORT to the development of behavioral inhibition. In Experiment 1., we verified that 10-day-old ADX rats exhibit high levels of plasma ACTH throughout the preweaning period associated with the development of behavioral inhibition. In Experiment 2, 10-day-old pups were hypophysectomized (HYPOX) and ADX and were compared behaviorally to sham-operated controls on day 14. When tested in the presence of an anesthetized unfamiliar adult male rat, HYPOX + ADX pups exhibited low levels of freezing accompanied by ultrasonic vocalizations. These pups also had reduced concentrations of plasma ACTH and CORT. In Experiment 3, 10-day-old pups were HYPOX and tested for behavioral inhibition on day 14. In comparison to sham-operated controls, HYPOX rats exhibited significantly lower levels of freezing and had reduced plasma concentrations of ACTH and CORT. Results demonstrate clearly that deficits in freezing occur even in the presence of low plasma ACTH concentrations. Therefore, elevated secretion of pituitary hormones is not a major factor that contributes to the ADX-induced deficits in behavioral inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum corticosterone response to adrenocorticotropic hormone stimulation in Florida sandhill cranes.

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Ludders, J W; Langenberg, J A; Czekala, N M; Erb, H N; McCormick, H

1998-10-01

Florida sandhill cranes (Grus canadensis pratensis) were conditioned to confinement in an enclosure for 7 days, 6 hr a day. On day 8, cranes were catheterized and then confined in an enclosure. Venous blood (2 ml) was collected through the catheter and an attached IV line immediately before (-60 min) and 60 min after (0 min) confinement. Using a randomization table and a restricted cross-over experimental design, cranes were injected intravenously with either saline (control) or adrenocorticotropic hormone (ACTH; cosyntropin, Cortrosyn; 0.25 mg). At 30, 60, 120, 180, 240 and 300 min after injection, blood samples were collected and assayed for corticosterone. The cranes receiving ACTH increased their serum corticosterone concentrations as much as fivefold above baseline concentrations. Serum corticosterone concentrations remained significantly elevated for approximately 60 min after ACTH stimulation. Physical restraint and catheterization caused an increase in serum corticosterone almost comparable to that induced by ACTH stimulation. In cranes injected with saline, serum corticosterone decreased within 1 hr after physical restraint and catheterization, and remained at lower levels throughout the remaining 5 hr of confinement.

Adrenocorticotropic Hormone-Independent Cushing Syndrome with Bilateral Cortisol-Secreting Adenomas

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Eu Jeong Ku

2013-06-01

Full Text Available A 48-year-old woman was incidentally found to have bilateral adrenal masses, 2.8 cm in diameter on the right, and 2.3 cm and 1.7 cm in diameter on the left, by abdominal computed tomography. The patient had a medical history of hypertension, which was not being controlled by carvedilol, at a dose of 25 mg daily. She presented with signs and symptoms that suggested Cushing Syndrome. We diagnosed adrenocorticotropic hormone (ACTH-independent Cushing Syndrome based on the results of basal and dynamic hormone tests. Adrenal vein sampling (AVS was performed to localize a functioning adrenal cortical mass. AVS results were consistent with hypersecretion of cortisol from both adrenal glands, with a cortisol lateralization ratio of 1.1. Upon bilateral laparoscopic adrenalectomy, bilateral ACTH-independent adrenal adenomas were found. The patient's signs and symptoms of Cushing Syndrome improved after surgery just as the blood pressure was normalized. After surgery, the patient was started on glucocorticoid and mineralocorticoid replacement therapy.

Changes of serum contents of cortisol and ACTH in patients after operation

International Nuclear Information System (INIS)

Zhu Lianghong; Zhang Xinlu; Chen Guanghua

2007-01-01

Objective: To study the changes of serum contents of cortisol and ACTH after operation. Methods: Serum cortisol and ACTH levels were measured with RIA both before and ld, 3d post-operatively in 30 patients after Grade III operation and 15 patients after Grade IV operation. Results: On the first post-operative day, the serum cortisol and ACTH levels in both groups of patients were significantly higher than their respective pre-operative levels. Levels in Grade IV group were significantly higher than those in Grade III group. On the third post-operative day, the serum cortisol levels dropped markedly and were lower than their respective pre-operative levels. However, the serum ACTH levels continued to rise in both groups and were significantly higher than the respective levels pre-operatively as well as those on dl. The ACTH levels in the two groups were not significantly different on d3. Conclusion: Serum cortisol and ACTH levels increased in the early post-operative phase and the degree of increase of cortisol was correlated with the magnitude of the operation. (authors)

How do the many etiologies of West syndrome lead to excitability and seizures? The corticotropin releasing hormone excess hypothesis.

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Brunson, K L; Eghbal-Ahmadi, M; Baram, T Z

2001-11-01

West syndrome (WS) is associated with diverse etiological factors. This fact has suggested that there must be a 'final common pathway' for these etiologies, which operates on the immature brain to result in WS only at the maturational state present during infancy. Any theory for the pathogenesis of WS has to account for the unique features of this disorder. For example, how can a single entity have so many etiologies? Why does WS arise only in infancy, even when a known insult had occurred prenatally, and why does it disappear? Why is WS associated with lasting cognitive dysfunction? And, importantly, why do these seizures--unlike most others--respond to treatment by a hormone, ACTH? The established hormonal role of ACTH in human physiology is to function in the neuroendocrine cascade of the responses to all stressful stimuli, including insults to the brain. As part of this function, ACTH is known to suppress the production of corticotropin releasing hormone (CRH), a peptide that is produced in response to diverse insults and stressors.The many etiologies of WS all lead to activation of the stress response, including increased production and secretion of the stress-neurohormone CRH. CRH has been shown, in infant animal models, to cause severe seizures and death of neurons in areas involved with learning and memory. These effects of CRH are restricted to the infancy period because the receptors for CRH, which mediate its action on neurons, are most abundant during this developmental period. ACTH administration is known to inhibit production and release of CRH via a negative feedback mechanism. Therefore, the efficacy of ACTH for WS may depend on its ability to decrease the levels of the seizure-promoting stress-neurohormone CRH.This CRH-excess theory for the pathophysiology of WS is consistent not only with the profile of ACTH effects, but also with the many different 'causes' of WS, with the abnormal ACTH levels in the cerebrospinal fluid of affected infants and

Importance of radioimmunological determinations of hormones of pituitary gland in praxi usage

International Nuclear Information System (INIS)

Rohde, W.; Knappe, G.

1977-01-01

A short introduction into the radioimmunoassay technique as a modern method for hormone determination is given. Some general problems related to the use of the radioimmunoassay technique are discussed. The clinical application of this technique to the determination of hormones of the anterior pituitary such as HGH, PRL, ACTH, MSH, TSH, LH and FSH in combination with dynamic tests are reviewed and illustrated by own results for the determination of HGH, LH and FSH. Analytical problems of the special hormones are mentioned only. (author)

Using microarrays to identify positional candidate genes for QTL: the case study of ACTH response in pigs

DEFF Research Database (Denmark)

Jouffe, Vincent; Rowe, Suzanne; Liaubet, Laurence

2009-01-01

this with information on published QTL. The starting point is a set of 237 differentially expressed cDNA clones in adrenal tissue from two pig breeds, before and after treatment with adrenocorticotropic hormone (ACTH) Results: Different approaches to localize the differentially expressed (DE) genes to the pig genome....... Different approaches to localize the differentially expressed (DE) genes to the pig genome showed different levels of success and a clear lack of concordance for some genes between the various approaches. For a focused analysis on 12 genes, overlapping QTL from the public domain were presented. Also...

Pituitary-adrenal hormones and testosterone across the menstrual cycle in women with premenstrual syndrome and controls.

Science.gov (United States)

Bloch, M; Schmidt, P J; Su, T P; Tobin, M B; Rubinow, D R

1998-06-15

Premenstrual syndrome (PMS) is a cyclic mood disorder, widely believed, yet not conclusively shown, to be of endocrine etiology. This study examines basal levels of several hormones reported, albeit inconsistently, to differ in women with PMS compared with controls. Subjects (10 PMS patients and 10 controls) had their blood drawn for one full menstrual cycle. Subjects' mood and behavioral symptoms were assessed by daily self-ratings and objective ratings. Plasma was assayed for total and free testosterone (T), beta-endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and cortisol. No differences were observed between the PMS and control groups for beta-EP, ACTH, or cortisol. PMS subjects had significantly lower total and free T plasma levels with a blunting of the normal periovulatory peak, a finding that may be epiphenomenal to age. This study does not confirm previous reports of abnormalities in plasma levels of either ACTH or beta-EP in women with PMS; it also fails to replicate a previous observation of high free T levels in women with PMS. These results are not supportive of a primary endocrine abnormality in PMS patients.

In etanercept-treated psoriatic arthritis patients clinical improvement correlated with an increase of serum cortisol relative to other adrenal hormones.

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Atzeni, F; Sarzi-Puttini, P; DePortu, S; Cutolo, M; Carrabba, M; Straub, R H

2008-01-01

In patients with rheumatoid arthritis (RA), long-term therapy with anti-tumor necrosis factor (TNF) antibodies sensitizes the pituitary gland and improves adrenal androgen secretion in prednisolone-naïve patients. However, whether this is similar in psoriatic arthritis (PsA) is not known. The aim of this study was to assess the effect of 12 weeks of etanercept treatment upon the function of the HPA axis in patients with PsA. Eleven prednisolone-naïve patients (mean age 47.3+/-8.9 years) with PsA were included. We measured serum levels of adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17OHP), cortisol, and androstenedione (ASD), at baseline and at 4 and 12 weeks after initiation of anti-TNF therapy (etanercept, 50 mg every week as a single dose by sc. injection). Clinical improvement was assessed using the Disease Activity Score-28 (DAS-28). Mean levels of serum ACTH, serum cortisol, serum 17OHP and serum ASD did not markedly change during 12 weeks of etanercept treatment. Similarly, the ratio of serum cortisol divided by serum ACTH did not change during 12 weeks of anti-TNF treatment. However, an increase of serum cortisol relative to serum 17OHP or ASD was related to clinical improvement. This indicates that improvement was linked to higher serum cortisol levels relative to others adrenal hormones. This is the first study to demonstrate baseline serum levels and the course of HPA axis-related hormones in patients with PsA. An increase of serum cortisol relative to others adrenocortical hormones (i.e., androstenedione and ACTH) was accompanied by clinical improvement.

Behavioral, neuroendocrine and neurochemical effects of the imidazoline I2 receptor selective ligand BU224 in naive rats and rats exposed to the stress of the forced swim test.

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Finn, David P; Martí, Octavi; Harbuz, Michael S; Vallès, Astrid; Belda, Xavier; Márquez, Cristina; Jessop, David S; Lalies, Margaret D; Armario, Antonio; Nutt, David J; Hudson, Alan L

2003-05-01

There is evidence for alterations in imidazoline(2) (I(2)) receptor density in depressed patients. Selective I(2) receptor ligands modulate central monoamine levels and activate the hypothalamo-pituitary-adrenal (HPA) axis and may have potential as antidepressants. To study the behavioral effects of the selective I(2) receptor ligand BU224 in the rat forced swim test (FST) and its effects on the HPA axis and central monoaminergic responses. Rats received saline or BU224 (10 mg/kg IP) 24, 18 and 1 h prior to 15 min exposure to the FST. Saline- and BU224-treated non-stressed groups were included. Time spent immobile, struggling and swimming calmly was measured. Plasma adrenocorticotrophic hormone (ACTH) and corticosterone levels 90 min post-BU224 were measured in addition to tissue levels of monoamines and metabolites in the frontal cortex, hippocampus and hypothalamus. Administration of BU224 significantly reduced immobility and increased mild swimming without affecting struggling. Exposure to the FST significantly increased plasma ACTH and corticosterone levels. BU224 administration also increased ACTH and potentiated the ACTH response to FST with no effect on corticosterone. BU224 administration significantly increased frontal cortex 5-hydroxytryptamine (5-HT) levels and decreased 5-HT turnover in the frontal cortex and hypothalamus of rats exposed to FST. In non-stressed rats, BU224 decreased 5-HT turnover in the hippocampus and hypothalamus and decreased norepinephrine turnover in the frontal cortex. The selective I(2) receptor ligand BU224 reduces immobility of rats in the FST, indicative of antidepressant-like activity. This effect is accompanied by alterations in HPA axis and central monoaminergic activity.

Adrenal activity and metabolic risk during randomized escitalopram or placebo treatment in PCOS.

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Glintborg, Dorte; Altinok, Magda Lambaa; Ravn, Pernille; Stage, Kurt Bjerregaard; Højlund, Kurt; Andersen, Marianne

2018-03-01

Polycystic ovary syndrome (PCOS) is associated with insulin resistance, adrenal hyperactivity and decreased mental health. We aimed to investigate the changes in adrenal activity, metabolic status and mental health in PCOS during treatment with escitalopram or placebo. Forty-two overweight premenopausal women with PCOS and no clinical depression were randomized to 12-week SSRI (20 mg escitalopram/day, n  = 21) or placebo ( n  = 21). Patients underwent clinical examination, fasting blood samples, adrenocorticotroph hormone (ACTH) test, 3-h oral glucose tolerance test (OGTT) and filled in questionnaires regarding mental health and health-related quality of life (HRQoL): WHO Well-Being Index (WHO-5), Major Depression Inventory (MDI), Short Form 36 (SF-36) and PCOS questionnaire. Included women were aged 31 (6) years (mean (s.d.)) and had body mass index (BMI) 35.8 (6.5) kg/m 2 and waist 102 (12) cm. Escitalopram was associated with increased waist (median (quartiles) change 1 (0; 3) cm), P  = 0.005 vs change during placebo and increased cortisol levels (cortisol 0, cortisol 60, peak cortisol and area under the curve for cortisol during ACTH test), all P   PCOS and no clinical depression, whereas metabolic risk markers, mental health and HRQol were unchanged. © 2018 The authors.

Ground transport stress affects bacteria in the rumen of beef cattle: A real-time PCR analysis.

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Deng, Lixin; He, Cong; Zhou, Yanwei; Xu, Lifan; Xiong, Huijun

2017-05-01

Transport stress syndrome often appears in beef cattle during ground transportation, leading to changes in their capacity to digest food due to changes in rumen microbiota. The present study aimed to analyze bacteria before and after cattle transport. Eight Xianan beef cattle were transported over 1000 km. Rumen fluid and blood were sampled before and after transport. Real-time PCR was used to quantify rumen bacteria. Cortisol and adrenocorticotrophic hormone (ACTH) were measured. Cortisol and ACTH were increased on day 1 after transportation and decreased by day 3. Cellulolytic bacteria (Fibrobacter succinogenes and Ruminococcus flavefaciens), Ruminococcus amylophilus and Prevotella albensis were increased at 6 h and declined by 15 days after transport. There was a significant reduction in Succinivibrio dextrinosolvens, Prevotella bryantii, Prevotella ruminicola and Anaerovibrio lipolytica after transport. Rumen concentration of acetic acid increased after transport, while rumen pH and concentrations of propionic and butyric acids were decreased. Body weight decreased by 3 days and increased by 15 days after transportation. Using real-time PCR analysis, we detected changes in bacteria in the rumen of beef cattle after transport, which might affect the growth of cattle after transport. © 2016 Japanese Society of Animal Science.

Hormones, Nicotine and Cocaine: Clinical Studies

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Mello, Nancy K.

2009-01-01

Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels, and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (two min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine’s sustained positive effects (hormones on nicotine dependence and cocaine abuse, and implications for treatment of these addictive disorders is discussed. PMID:19835877

Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS.

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Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R; Changelian, Armen; Laws, Edward R; Santagata, Sandro; Agar, Nathalie Y R; Van Berkel, Gary J

2015-08-01

Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections, using a fully automated droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS system for spatially resolved sampling, HPLC separation, and mass spectrometric detection. Excellent correlation was found between the protein distribution data obtained with this method and data obtained with matrix-assisted laser desorption/ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland. AVP was most abundant in the posterior pituitary gland region (neurohypophysis), and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH-secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH-secreting adenomas and in normal anterior adenohypophysis compared with non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis, as expected. This work reveals that a fully automated droplet-based liquid-microjunction surface-sampling system coupled to HPLC-ESI-MS-MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, including AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity, and specificity of this method support the potential of this basic technology, with further advancement, for assisting surgical decision-making. Graphical Abstract Mass spectrometry based profiling of hormones in human pituitary gland and tumor thin tissue sections.

Somatotype and stress hormone levels in young soccer players.

Science.gov (United States)

Handziska, E; Handziski, Z; Gjorgoski, I; Dalip, M

2015-11-01

The relationship between somatotype and cortisol and adrenocorticotropic (ACTH) hormone concentrations at rest or after exercise in adolescent soccer players at different time points throughout a soccer season is not understood. Therefore, the aim of this study was to examine the relationship between somatotype and cortisol and ACTH concentrations at rest and after exercise in adolescent soccer players at different time points during a soccer season. During the first 4 months of the soccer season, 47 soccer players (between 15-17 years of age) were tested at three different time points including at baseline, after 6 weeks, and at the end of 4 months. Testing included anaerobic threshold (AnT, km/h) and maximal speed of running (Max, km/h) were measured with Conconi protocol on treadmill. Before and after a maximal exercise Test, plasma levels of cortisol (ug/dL) and ACTH (pg/ml) were assessed by chemiluminometry enzyme amplificated method. Heath-Carter anthropometric somatotype model was used to determine 13 elements of somatotype. Descriptive statistics and multiple regression were used for statistical analysis (Psoccer training process could indicate a stagnation of training process, accordingly with insignificant changes of AnT. The significant correlations of some somatotypes with stress hormonal responses could only suggest that the somatotype characteristics of young soccer players could be of interest in process of selection and planning of soccer training process with an essential need for more studies.

Screening for hypopituitarism in 509 patients with traumatic brain injury or subarachnoid hemorrhage.

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Kopczak, Anna; Kilimann, Ingo; von Rosen, Friedrich; Krewer, Carmen; Schneider, Harald Jörn; Stalla, Günter Karl; Schneider, Manfred

2014-01-01

We performed a screening on patients with traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH) to determine the prevalence of post-traumatic hypopituitarism in neurorehabilitation in a cross-sectional, observational single-center study. In addition, the therapeutic consequences of our screening were analyzed retrospectively. From February 2006 to August 2009, patients between 18 and 65 years (n=509) with the diagnosis of TBI (n=340) or SAH (n=169) were screened within two weeks of admittance to neurorehabilitation as clinical routine. Blood was drawn to determine fasting cortisol, free thyroxine (fT4), prolactin, testosterone or estradiol, and insulin-like growth factor I (IGF-I). Patients with abnormalities in the screening or clinical signs of hypopituitarism received further stimulation tests: growth hormone releasing hormone -L-arginine-test and adrenocorticotrophic hormone (ACTH)-test (n=36); ACTH-test alone (n=26); or insulin tolerance test (n=56). In our screening of 509 patients, 28.5% showed lowered values in at least one hormone of the hypothalamus-pituitary axis and 4.5% in two or more axes. The most common disturbance was a decrease of testosterone in 40.7% of all men (in the following 13/131 men were given substitution therapy). Low fT4 was detected in 5.9% (n=3 were given substitution therapy). Low IGF-I was detected in 5.8%, low cortisol in 1.4%, and low prolactin in 0.2%; none were given substitution therapy. Further stimulation tests revealed growth hormone deficiency in 20.7% (n=19/92) and hypocortisolism in 23.7% (n=28/118). Laboratory values possibly indicating hypopituitarism (33%) were common but did not always implicate post-traumatic hypopituitarism. Laboratory values possibly indicating hypopituitarism were common in our screening but most patients were clinically not diagnosed as pituitary insufficient and did not receive hormone replacement therapy. A routine screening of all patients in neurorehabilitation without considering

Hormone levels in radiotherapy treatment related fatigue

International Nuclear Information System (INIS)

Biswal, B.M.; Mallik, G.S.

2003-01-01

Radiotherapy is known to cause debilitating treatment related fatigue. Fatigue in general is a conglomeration of psychological, physical, hematological and unknown factors influencing the internal milieu of the cancer patient. Radiotherapy can add stress at the cellular and somatic level to aggravate further fatigue in cancer patients undergoing radiotherapy. Stress related hormones might be mediating in the development of fatigue. This is an ongoing prospective study to evaluate if the hormonal profile related to stress is influenced by radiotherapy treatment related fatigue. The study was conducted from September 2002 onwards in the division of Radiotherapy and Oncology of our Medical School. Previously untreated patients with histopathology proof of malignancy requiring external beam radiotherapy were considered for this study. Selection criteria were applied to exclude other causes of fatigue. Initial fatigue score was obtained using Pipers Fatigue Score questionnaire containing 23 questions, subsequently final fatigue score was obtained at the end of radiotherapy. Blood samples were obtained to estimate the levels of ACTH, TSH, HGH, and cortisol on the final assessment. The hormone levels were compared with resultant post radiotherapy fatigue score. At the time of reporting 50 patients were evaluable for the study. The total significant fatigue score was observed among 12 (24%) patients. The individual debilitating fatigue score were behavioral severity 14 (28%), affective meaning 14(28%), Sensory 13 (26%) and cognitive mood 10 (20%) respectively. From the analysis of hormonal profile, growth hormone level > 1 ng/mL and TSH <0.03 appears to be associated with high fatigue score (though statistically not significant); whereas there was no correlation with ACTH and serum cortisol level. In our prospective study severe radiotherapy treatment related fatigue was found among our patient population. Low levels of TSH and high levels of GH appear to be associated

Comparative Evaluation of Pain, Stress, Neuropeptide Y, ACTH, and Cortisol Levels Between a Conventional Postoperative Care Protocol and a Fast-Track Recovery Program in Patients Undergoing Major Abdominal Surgery.

Science.gov (United States)

Kapritsou, Maria; Papathanassoglou, Elizabeth D; Bozas, Evangelos; Korkolis, Dimitrios P; Konstantinou, Evangelos A; Kaklamanos, Ioannis; Giannakopoulou, Margarita

2017-03-01

Fast-track (FT) postoperative protocol in oncological patients after major abdominal surgery reduces complications and length of postoperative stay compared to the conventional (CON) protocol. However, stress and pain responses have not been compared between the two protocols. To compare stress, pain, and related neuropeptidic responses (adrenocorticotropic hormone [ACTH], cortisol, and neuropeptide Y [NPY]) between FT and CON protocols. A clinical trial with repeated measurements was conducted (May 2012 to May 2014) with a sample of 63 hepatectomized or pancreatectomized patients randomized into two groups: FT ( n = 29) or CON ( n = 34). Demographic and clinical data were collected, and pain (Visual Analog Scale [VAS] and Behavioral Pain Scale [BPS]) and stress responses (3 self-report questions) assessed. NPY, ACTH, and cortisol plasma levels were measured at T1 = day of admission, T2 = day of surgery, and T3 = prior to discharge. ACTH T1 and ACTH T2 levels were positively correlated with self-reported stress levels (ρ = .43 and ρ = .45, respectively, p .05). Neuropeptidic levels were higher in the FT group. Future research should evaluate this association further, as these biomarkers might serve as objective indicators of postoperative pain and stress.

The dynamics of post-operative plasma ACTH values following transsphenoidal surgery for Cushing's disease.

Science.gov (United States)

Srinivasan, Lakshmi; Laws, Edward R; Dodd, Robert L; Monita, Monique M; Tannenbaum, Christyn E; Kirkeby, Kjersti M; Chu, Olivia S; Harsh, Griffith R; Katznelson, Laurence

2011-12-01

Rapid assessment of adrenal function is critical following transsphenoidal surgery (TSS) for Cushing's disease (CD) in order to determine surgical efficacy. We hypothesize that there may be a role for ACTH measurement as a rapid indicator of adrenal function. Following surgery for CD, glucocorticoids were withheld and paired plasma ACTH and serum cortisol levels were measured every 6 h. Post-operative hypocortisolemia was defined as serum cortisol surgeries: nine subjects attained hypocortisolemia. Plasma ACTH levels decreased more in subjects with hypocortisolemia (0.9 pg/ml/hr, P = 0.0028) versus those with persistent disease (0 0.2 pg/ml/hr, P = 0.26) within the first 48 h after surgery. In contrast to subjects with persistent disease, all subjects with hypocortisolemia achieved a plasma ACTH <20 pg/ml by 19 h (range 1-19 h). Four of the nine subjects with hypocortisolemia achieved plasma ACTH <20 pg/ml by 13 h and the remaining five subjects by 19 h. Hypocortisolemia occurred between 3-36 h following achievement of a plasma ACTH <20 pg/ml. In CD, a reduction in postoperative plasma ACTH levels differentiates subjects with surgical remission versus subjects with persistent disease. The utility of plasma ACTH measurements in the postoperative management of CD remains to be determined.

Clinical features and management of ectopic ACTH syndrome at a single institute in Japan

International Nuclear Information System (INIS)

Doi, Masaru; Sugiyama, Toru; Izumiyama, Hajime; Yoshimoto, Takanobu; Hirata, Yukio

2010-01-01

Ectopic ACTH syndrome (EAS) is a diagnostic challenge because it is often indistinguishable from Cushing's disease. We describe our series of EAS patients referred to us during 1992-2009. Among 16 cases (9 females/7 males), with mean age of 58.4±19.0 yr, the ectopic source was identified in ten (proven EAS), whereas unidentified in six (occult/unknown EAS). Their salient clinical manifestations included Cushingoid feature (88%), skin pigmentation (88%), profound hypokalemia (88%), hypertension (75%), diabetes/impaired glucose tolerance (75%), hyperlipidemia (69%), and severe infection (44%). Dynamic endocrine tests revealed markedly elevated plasma ACTH levels (211±116 pg/mL) and cortisol levels (60.9±30.1 μg/dL) which showed resistance to overnight high-dose (8 mg) dexamethasone suppression test in 15 (94%) and unresponsiveness to corticotropin releasing hormone (CRH) stimulation in 12 (75%). No ACTH gradient during inferior petrosal sampling was noted in 13 of 15 (87%). Imaging tests by CT/MRI identified the tumors in 8 of 16 (50%), in 4 of 11 (36%) and 4 of 6 (66.7%) octreotide-responders by somatostatin receptor scintigraphy, but in only one of 9 (11.1%) by [ 18 F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan. Six cases deceased, including small cell carcinoma (2) and adenocarcinoma (1) of lung, neuroendocrine carcinoma of pancreas (1) and stomach (1), and olfactory neuroblastoma (1), whereas 4 cases survived after removal of the tumors, including bronchial carcinoid tumor (3) and thymic hyperplasia (1). Six occult/unknown EAS patients survived for 67.5 months after medical treatment with metyrapone to control hypercortisolism. Thus, various endocrine tests combined with imaging studies are required to correctly localize the tumors. Control of hypercortisolemia by metyrapone, even if tumor is unrecognized, is critical for better prognosis, and the long-term follow-up by repeated endocrine and imaging tests is mandatory. (author)

Hypothalamic-pituitary-adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones.

Science.gov (United States)

Stephens, Mary Ann C; Mahon, Pamela B; McCaul, Mary E; Wand, Gary S

2016-04-01

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to the

Blunted cortisol response after administration of corticotropin releasing hormone in endotoxemic dogs

NARCIS (Netherlands)

Moeniralam, H. S.; Endert, E.; van Lanschot, J. J.; Sauerwein, H. P.; Romijn, J. A.

1997-01-01

To evaluate the effects of a standard inflammatory challenge on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis, we studied the effects of low-dose endotoxin (1.0 microgram/kg) on plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations in a saline-controlled study in five

Muscarinic supersensibility of anterior pituitary ACTH and beta-endorphin release in major depressive illness

International Nuclear Information System (INIS)

Risch, S.C.; Gillin, J.C.; Janowsky, D.S.

1986-01-01

Since numerious physiological systems display muscarinic receptor supersensitivity in major depressive illnesses, the authors have hypothesize that anterior pituitary release of ACTH and beta-Endorphin immunoreactivity may also be muscarinically supersensitive in depression. The studies were conducted under FDA-approved IND and with local human subjects committee approval. Plasma ACTH concentrations were determined as follows: samples were assayed in duplicate using equilibrium radioimmunoassay utilizing a rabbit anti-porcine ACTH antibody. Significance ofchanges in plasma cortisol, ACTH and beta-endorphin immunoreactivity after physostigmine and saline were determined by repeated measures analysis of variance. In all subject groups, physostigmine (relative to placebo) caused significant increases in plasma concentrations of cortisol, ACTH, and beta-endorphin immonoreactivity

The Value of Perioperative Levels of ACTH, DHEA, and DHEA-S and Tumor Size in Predicting Recurrence of Cushing Disease.

Science.gov (United States)

El Asmar, Nadine; Rajpal, Aman; Selman, Warren R; Arafah, Baha M

2018-02-01

Despite the development of hypocortisolemia after corticotroph surgical adenomectomy, 15% to 20% patients have recurrence of Cushing disease (CD). In this study, we investigated the effect of tumor size and the value of perioperative assessment of corticotropin (ACTH) and adrenal steroid levels in predicting recurrence. Perioperatively, no glucocorticoids were administered until the serum cortisol was ≤3 μg/dL. Blood samples were obtained before and repeatedly after adenomectomy in 79 patients with CD. Of these, 66 had a nadir serum cortisol of ≤3.0 μg/dL and clinical and biochemical remissions. During a median follow-up of 131 months, 11 of 66 had disease recurrence (REC), whereas 55 of 66 did not (NO-REC). Preoperative hormone levels in the REC and NO-REC groups were similar. After adenomectomy, a brief and similar increase in ACTH, cortisol, and dehydroepiandrosterone (DHEA) levels was observed in both groups followed by gradual decline in those levels. Although REC and NO-REC patients had similar cortisol levels (3.4 ± 1.7 μg/dL vs 2.9 ± 2.2 μg/dL) at the 36th postoperative hour, their respective ACTH (33 ± 7.1 ng/L vs 12.1 ± 5.4 ng/L; P 20 in all REC patients and disease recurrence, particularly in those with profound hypocortisolemia. Copyright © 2017 Endocrine Society

ACTH-producing pheochromocytoma: clinical considerations and concise review of the literature

NARCIS (Netherlands)

Nijhoff, M. F.; Dekkers, O. M.; Vleming, L. J.; Smit, J. W. A.; Romijn, J. A.; Pereira, A. M.

2009-01-01

We present a patient with a rare cause of ectopic ACTH-dependent Cushing's syndrome, caused by a pheochromocytoma. The case provides clues for a detailed discussion on the pitfalls and diagnostic difficulties in establishing the correct underlying cause of ACTH-dependent Cushing's syndrome. It

Hypocortisolemic clamp unmasks jointly feedforward- and feedback-dependent control of overnight ACTH secretion.

Science.gov (United States)

Iranmanesh, Ali; Veldhuis, Johannes D

2008-11-01

ACTH secretion is under hypothalamic stimulatory (feedforward) and adrenal inhibitory (feedback) control. Assessment of overnight ACTH secretion during a hypocortisolemic clamp will permit the estimation of changing feedforward and feedback. Seven healthy men. An oral dose of placebo (PLAC), metyrapone (METY, 3 g), or ketoconazole (KTCZ, 1.2 g) was given at midnight (MN) to block glucocorticoid synthesis. Plasma ACTH was sampled every 10 min (MN to 0800 h). Variable-waveform deconvolution analysis of ACTH secretion and approximate entropy (ApEn) analysis of pattern regularity. Compared with PLAC, administration of METY and KTCZ reduced morning cortisol concentrations by >or=77 and 54% respectively (Pfeedforward coordination. The combined data predict overnight amplification and coordination of hypothalamic feedforward drive onto ACTH release. Therefore, disruption of either mechanism might contribute to clinical pathophysiology, such as late-day elevations of cortisol output in fasting, alcoholism, depression, or aging.

Status of calcium regulating hormonal systems in delayed period in persons exposed to occupational exposure of low doses of ionizing radiations

International Nuclear Information System (INIS)

Dospolova, Zh.G.; Abylaev, Zh.A.

1997-01-01

Purpose of study is consideration of endocrine system participation in development of calcium exchange disorders in persons exposed to action of low dose radiation . By radio- immune method in blood serum of 150 liquidators of Chernobyl accident consequences the concentration the following hormones were determined: parathormone, T 3 , T 4 , TSH, cortisol, ACTH, testosteron, insulin. Content of these hormones have been studied in according to following radiation factors: value of absorbed doses of external irradiation, degree of radioactive contamination of zone and exposition duration. It was determined, that basically dishormone disorders development have been concerned with parathormone, cortisol, hormones of thyroid axis, and in some cases to ACTH and insulin. Liquidators' frequencies of normal and changed concentration of calcium regulating hormones are sited in tabular form. It was established, that examined persons in result hormone disorders have of decrease functions of pituitary glands (76.78 %), pancreas (55 %), thyroid gland (24.31 %) and sex glands (19.23 %) and simultaneously cases of increase functions of parathyroid gland (58.2 %), adrenal glands (52.32 %) and adeno-pituitary glands (17.39). It is concluded, that inter hormonal correlation disorders are accompanying with morphologic and functional futures of secretory activity changes

Prolonged whole body immersion in cold water: hormonal and metabolic changes.

Science.gov (United States)

Smith, D J; Deuster, P A; Ryan, C J; Doubt, T J

1990-03-01

To characterize metabolic and hormonal responses during prolonged whole body immersion, 16 divers wearing dry suits completed four immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 meters of sea water. One immersion began in the AM (1000 h) and one began in the PM (2200 h) to evaluate diurnal variations. Venous blood samples were obtained before and after completion of each immersion. Cortisol and ACTH levels demonstrated diurnal variation, with larger increases occurring after PM immersions. A greater than three-fold postimmersion increase occurred in norepinephrine (NE). There were significant increases in triiodothyronine (T3) uptake and epinephrine, but no change in T3, thyroxine, thyrotrophic hormone, and dopamine. Postimmersion free fatty acid levels increased 409% from preimmersion levels; glucose levels declined, and lactate increased significantly. Only changes in NE correlated significantly with changes in rectal temperature. In summary, when subjects are immersed in cold water for prolonged periods, with a slow rate of body cooling afforded by thermal protection and intermittent exercise, hormonal and metabolic changes occur that are similar in direction and magnitude to short-duration unprotected exposures. Except for cortisol and ACTH, none of the other measured variables exhibited diurnal alterations.

Severe Cushing's syndrome and bilateral pulmonary nodules: beyond ectopic ACTH.

Science.gov (United States)

Tavares Bello, Carlos; van der Poest Clement, Emma; Feelders, Richard

2017-01-01

Cushing's syndrome is a rare disease that results from prolonged exposure to supraphysiological levels of glucocorticoids. Severe and rapidly progressive cases are often, but not exclusively, attributable to ectopic ACTH secretion. Extreme hypercortisolism usually has florid metabolic consequences and is associated with an increased infectious and thrombotic risk. The authors report on a case of a 51-year-old male that presented with severe Cushing's syndrome secondary to an ACTH-secreting pituitary macroadenoma, whose diagnostic workup was affected by concurrent subclinical multifocal pulmonary infectious nodules. The case is noteworthy for the atypically severe presentation of Cushing's disease, and it should remind the clinician of the possible infectious and thrombotic complications associated with Cushing's syndrome. Severe Cushing's syndrome is not always caused by ectopic ACTH secretion.Hypercortisolism is a state of immunosuppression, being associated with an increased risk for opportunistic infections.Infectious pulmonary infiltrates may lead to imaging diagnostic dilemmas when investigating a suspected ectopic ACTH secretion.Cushing's syndrome carries an increased thromboembolic risk that may even persist after successful surgical management.Antibiotic and venous thromboembolism prophylaxis should be considered in every patient with severe Cushing's syndrome.

Pubertal-related changes in hypothalamic-pituitary-adrenal axis reactivity and cytokine secretion in response to an immunological stressor.

Science.gov (United States)

Goble, K H; Bain, Z A; Padow, V A; Lui, P; Klein, Z A; Romeo, R D

2011-02-01

Pubertal development is marked by profound changes in stress reactivity. For example, following a brief stressor, such as foot shock, ether inhalation or restraint, prepubertal rats display a prolonged adrenocorticotrophic hormone (ACTH) and corticosterone response that takes twice as long to return to baseline compared to adults. Pubertal-related differences in the recovery of the hormonal stress response following a more protracted systemic stressor, such as an immunological challenge, have not yet been investigated. Moreover, it is unclear whether an immunological stressor leads to a differential cytokine response in animals before and after pubertal maturation. To examine these issues, we used a single injection of lipopolysaccharide (LPS; 0.1 mg/kg) to induce a hormonal stress and innate immune response and measured plasma ACTH, corticosterone, and the pro-inflammatory cytokines interleukin (IL)-1β and IL-6 in prepubertal and adult male rats 0, 2, 4, 6, 8, or 24 h after LPS exposure. In a follow-up experiment, we assessed neural activation, as indexed by FOS immunohistochemistry, in the paraventricular nucleus of the hypothalamus (PVN) in prepubertal and adult males 0, 4, 8, or 24 h after a 0.1 mg/kg injection of LPS. By contrast to the prolonged response observed in prepubertal animals following a variety of acute stressors, we found that corticosterone and IL-6 responses induced by LPS recover toward baseline faster in prepubertal compared to adult rats. Along with these different peripheral responses, we also found that LPS-induced neural activation in the PVN of prepubertal animals showed a faster return to baseline compared to adults. Together, these data indicate that prepubertal and adult animals react in distinct ways, both peripherally and centrally, to an immunological stressor. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

Effect of MSH/ACTH peptides on fast axonal transport in intact and regenerating sciatic nerves

International Nuclear Information System (INIS)

Crescitelli, L.A.

1985-01-01

Fast axonal transport was examined in intact rats treated with ACTH 4-10 or ACTH 4-9 (ORG 2766), hypophysectomized rats, adrenalectomized rats, and in ACTH 4-10 treated rats with crushed regenerating sciatic nerves by injecting 3 H-leucine into the ventral horn region of the spinal cord. The distance traveled by the transported activity along the sciatic nerve and the rate of fast axonal transport were not significantly altered as a result of treatment with ACTH 4-10, ACTH 4-9 (ORG 2766), hypophysectomy, or adrenalectomy. Treatment with ACTH 4-9 (ORG 2766) at concentrations of 1 μg/Kg /day and 10 μg/Kg/day caused significant reductions (62% and 64% respectively) in the crest height of the fast axonal transport curve as compared to 0.9% saline treated control animals. No significant differences were found in comparing the distance, rate, slope, or crest height of ACTH 4-10 treated animals with crushed regenerating (7 or 14d) sciatic nerves to control animals. In the group of animals in days, the amount of radiolabeled activity was significantly increased in the ACTH 4-10 treated animals as compared to control animals. The results indicate that during regeneration the peptide acts to prolong the initially high levels of synthetic activity which occur in regenerating axons

Radioisotope studies of steroid hormone levels of plasma in indigenous subjects living at high altitude and submitted to a low calorie diet

International Nuclear Information System (INIS)

Ramirez, I.

1975-08-01

Radioimmunological techniques were applied to the evaluation of TSH and ACTH in the four groups of Ecuadorian subjects under investigation at Tocachi, Malchingui, Quito and Portoviejo, the first three populations living at a high altitude and the fourth at sea-level. This evaluation was of interest since previous studies had indicated that there were thyroid and adrenal hormone deficiency levels in individuals from Tocachi and Malchingui or, in other words, in populations from a high-altitude region, and also endemic goitre and caloric-protein malnutrition. Furthermore, the Tocachi group was composed of subjects suffering from chronic ''stress''. Parallel to the analysis of TSH and pituitary ACTH levels, the circadian rhythm in the production of these hormones in these subjects was studied. The basal values of TSH and ACHT for the studied groups were found to lie within the normal range. 131 I-TSH and 125 I-ACTH were used. As far as the nycthemeral TSH rhythm is concerned, the values tended to be lowest for the high-altitude populations, while for the groups living at sea-level, where there is also circadian variation, the higher values are found in the morning. Similarly, the circadian rhythm for ACTH was established, with a predominance of diurnal values at Tocachi, Malchingui and Portoviejo

Reactive thymic hyperplasia following treatment of ACTH-producing tumors

International Nuclear Information System (INIS)

Schmidt, S.; Klose, K.J.; Iwinska-Zelder, J.; Frank, M.; Ehlenz, K.; Kisker, O.

1997-01-01

Surgical or conservative treatment of ACTH-producing tumors results in acute drop of the previously excessively high cortisol levels. The following associated pathophysiological changes also occur in the organism's recovery from stress, such as trauma, operation or chemotherapy of tumors. Both cases result in a regeneration of the immune system, which might even be exalted. The corresponding radiographic feature is the 'rebound' enlargement of the thymus occuring about six months after remission of hypercortisolism. Histological examination reveals benign thymus hyperplasia. Especially in cases of still unkown primary tumor the apperance of this anterior mediastinal mass can lead to misdiagnosis. We present the cases of two patients with diffuse thymic hyperplasia following surgical and medical correction of hypercortisolism. One patient suffered from classic Cushing's disease responding to transsphenoidal resection of an ACTH-secreting pituitary microadenoma. Six monsths later CT of the chest incidentally demonstrated an anterior mediastinal mass known as thymic hyperplasia. The second patient presented with an ectopic, still unknown source of ACTH-production. (orig./AJ) [de

[Influence, in normal subjects, of an isocaloric hyperprotein diet on cortisol, ACTH, GH and PRL response to lysine-8-vasopressin].

Science.gov (United States)

Giovannini, C; Sellini, M; Manzo, G; Barletta, C; Scavo, D

1981-12-30

The Lysin-8-Vasopressin test has been experimented in ten healthy subjects during normocaloric balanced diet and after hyperproteic-normocaloric diet. The levels of ACTH, Cortisol and GH are significantly more elevated after hyperproteic-normocaloric diet than in basal conditions. The levels of Prolactin do not show any remarkable change. These results can indicate the increased reactivity of the diencephalon-hypophysis-adrenal axis and of the hormones connected with the mechanisms of homeostasis and stress, probably correlated to more disposable proteic material and to the metabolic effects which follow.

Lycopene and beta-carotene induce growth inhibition and proapoptotic effects on ACTH-secreting pituitary adenoma cells.

Directory of Open Access Journals (Sweden)

Natália F Haddad

Full Text Available Pituitary adenomas comprise approximately 10-15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27(kip1 in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2 and increased expression of p27(kip1 in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27(kip1; and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing's disease.

Short circuit: Disaggregation of adrenocorticotropic hormone and cortisol levels in HIV-positive, methamphetamine-using men who have sex with men.

Science.gov (United States)

Carrico, Adam W; Rodriguez, Violeta J; Jones, Deborah L; Kumar, Mahendra

2018-01-01

This study examined if methamphetamine use alone (METH + HIV-) and methamphetamine use in combination with HIV (METH + HIV+) were associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation as well as insulin resistance relative to a nonmethamphetamine-using, HIV-negative comparison group (METH-HIV-). Using an intact groups design, serum levels of HPA axis hormones in 46 METH + HIV- and 127 METH + HIV+ men who have sex with men (MSM) were compared to 136 METH-HIV- men. There were no group differences in prevailing adrenocorticotropic hormone (ACTH) or cortisol levels, but the association between ACTH and cortisol was moderated by METH + HIV+ group (β = -0.19, p < .05). Compared to METH-HIV- men, METH + HIV+ MSM displayed 10% higher log 10 cortisol levels per standard deviation lower ACTH. Both groups of methamphetamine-using MSM had lower insulin resistance and greater syndemic burden (i.e., sleep disturbance, severe depression, childhood trauma, and polysubstance use disorder) compared to METH-HIV- men. However, the disaggregated functional relationship between ACTH and cortisol in METH + HIV+ MSM was independent of these factors. Further research is needed to characterize the bio-behavioral pathways that explain dysregulated HPA axis functioning in HIV-positive, methamphetamine-using MSM. Copyright © 2017 John Wiley & Sons, Ltd.

[The adaptation reactions in hormonal systems to the internal use of mineral waters].

Science.gov (United States)

Polushina, N D

1991-01-01

A single intake of mineral water Essentuki 17 by male Wistar rats (n-130, b. w. 180-250 g) leads to stress reactions. It is evident from elevated levels of ACTH, hydrocortisone, leuenkephaline, glucagon and gastrin. Course intake of the water brings about a rise in most of the hormones levels studied. However, single doses of Essentuki 17 inhibit production of hormones in the adrenals, hypophysis, hypothalamus, the system of endogenic opiates. The enhancement of relevant levels are noted in the gastroenteropancreatic system.

Influence of ascorbic acid on in vivo amidation of alpha-melanocyte stimulating hormone in guinea pig pituitary

DEFF Research Database (Denmark)

Fenger, M; Hilsted, L

1988-01-01

The effect of ascorbic acid depletion on the amidation of alphamelanocyte stimulating hormone (alpha MSH) was studied in vivo in guinea pig pituitary. After four weeks, the concentration of ascorbic acid was 1.20 +/- 0.11 mumol/g tissue (mean +/- SD) in the pituitary and 0.34 +/- 0.07 mumol......-39) immunoreactivity was observed in the depleted guinea pigs. Gel chromatography and reversed-phase high-performance luquid chromatography showed that the alpha MSH and ACTH (1-14) immunoreactivity was of low molecular weight and partly mono- or diacetylated. Depletion of ascorbic acid had no influence on the degree...... of acetylation of alpha MSH and ACTH (1-14). It is concluded that depletion of ascorbic acid reduces the in vivo amidation of ACTH (1-14) in the guinea pig pituitary....

Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout

International Nuclear Information System (INIS)

Sandhu, Navdeep; Vijayan, Mathilakath M.

2011-01-01

Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium targets genes encoding proteins critical for corticosteroid biosynthesis, including melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc), in rainbow trout (Oncorhynchus mykiss). To test this, head kidney slices (containing the interrenal tissues) were incubated in vitro with cadmium chloride (0, 10, 100 and 1000 nM) for 4 h either in the presence or absence of ACTH (0.5 IU/mL). In the unstimulated head kidney slices, cadmium exposure did not affect basal cortisol secretion and the mRNA levels of MC2R and P450scc, while StAR gene expression was significantly reduced. Cadmium exposure significantly suppressed ACTH-stimulated cortisol production in a dose-related fashion. This cadmium-mediated suppression in corticosteroidogenesis corresponded with a significant reduction in MC2R, StAR and P450scc mRNA levels in trout head kidney slices. The inhibition of ACTH-stimulated cortisol production and suppression of genes involved in corticosteroidogenesis by cadmium were completely abolished in the presence of 8-Bromo-cAMP (a cAMP analog). Overall, cadmium disrupts the expression of genes critical for corticosteroid biosynthesis in rainbow trout head kidney slices. However, the rescue of cortisol production as well as StAR and P450scc gene expressions by cAMP analog suggests that cadmium impact occurs upstream of cAMP production. We propose that MC2R signaling, the primary step in ACTH-induced cortocosteroidogenesis, is a key target for cadmium-mediated disruption of

Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout

Energy Technology Data Exchange (ETDEWEB)

Sandhu, Navdeep [Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada); Vijayan, Mathilakath M., E-mail: mvijayan@uwaterloo.ca [Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada)

2011-05-15

Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium targets genes encoding proteins critical for corticosteroid biosynthesis, including melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc), in rainbow trout (Oncorhynchus mykiss). To test this, head kidney slices (containing the interrenal tissues) were incubated in vitro with cadmium chloride (0, 10, 100 and 1000 nM) for 4 h either in the presence or absence of ACTH (0.5 IU/mL). In the unstimulated head kidney slices, cadmium exposure did not affect basal cortisol secretion and the mRNA levels of MC2R and P450scc, while StAR gene expression was significantly reduced. Cadmium exposure significantly suppressed ACTH-stimulated cortisol production in a dose-related fashion. This cadmium-mediated suppression in corticosteroidogenesis corresponded with a significant reduction in MC2R, StAR and P450scc mRNA levels in trout head kidney slices. The inhibition of ACTH-stimulated cortisol production and suppression of genes involved in corticosteroidogenesis by cadmium were completely abolished in the presence of 8-Bromo-cAMP (a cAMP analog). Overall, cadmium disrupts the expression of genes critical for corticosteroid biosynthesis in rainbow trout head kidney slices. However, the rescue of cortisol production as well as StAR and P450scc gene expressions by cAMP analog suggests that cadmium impact occurs upstream of cAMP production. We propose that MC2R signaling, the primary step in ACTH-induced cortocosteroidogenesis, is a key target for cadmium-mediated disruption of

Effects of Electromagnetic Radiation Exposure on Stress-Related Behaviors and Stress Hormones in Male Wistar Rats

Science.gov (United States)

Mahdavi, Seyed Mohammad; Sahraei, Hedayat; Yaghmaei, Parichehreh; Tavakoli, Hassan

2014-01-01

Studies have demonstrated that electromagnetic waves, as the one of the most important physical factors, may alter cognitive and non-cognitive behaviors, depending on the frequency and energy. Moreover, non-ionizing radiation of low energy waves e.g. very low frequency waves could alter this phenomenon via alterations in neurotransmitters and neurohormones. In this study, short, medium, and long-term exposure to the extremely low frequency electromagnetic field (ELF-EMF) (1 and 5 Hz radiation) on behavioral, hormonal, and metabolic changes in male Wistar rats (250 g) were studied. In addition, changes in plasma concentrations for two main stress hormones, noradrenaline and adrenocorticotropic hormone (ACTH) were evaluated. ELF-EMF exposure did not alter body weight, and food and water intake. Plasma glucose level was increased and decreased in the groups which exposed to the 5 and 1Hz wave, respectively. Plasma ACTH concentration increased in both using frequencies, whereas nor-adrenaline concentration showed overall reduction. At last, numbers of rearing, sniffing, locomotor activity was increased in group receiving 5 Hz wave over the time. In conclusions, these data showed that the effects of 1 and 5 Hz on the hormonal, metabolic and stress-like behaviors may be different. Moreover, the influence of waves on stress system is depending on time of exposure. PMID:25489427

Effects of electromagnetic radiation exposure on stress-related behaviors and stress hormones in male wistar rats.

Science.gov (United States)

Mahdavi, Seyed Mohammad; Sahraei, Hedayat; Yaghmaei, Parichehreh; Tavakoli, Hassan

2014-11-01

Studies have demonstrated that electromagnetic waves, as the one of the most important physical factors, may alter cognitive and non-cognitive behaviors, depending on the frequency and energy. Moreover, non-ionizing radiation of low energy waves e.g. very low frequency waves could alter this phenomenon via alterations in neurotransmitters and neurohormones. In this study, short, medium, and long-term exposure to the extremely low frequency electromagnetic field (ELF-EMF) (1 and 5 Hz radiation) on behavioral, hormonal, and metabolic changes in male Wistar rats (250 g) were studied. In addition, changes in plasma concentrations for two main stress hormones, noradrenaline and adrenocorticotropic hormone (ACTH) were evaluated. ELF-EMF exposure did not alter body weight, and food and water intake. Plasma glucose level was increased and decreased in the groups which exposed to the 5 and 1Hz wave, respectively. Plasma ACTH concentration increased in both using frequencies, whereas nor-adrenaline concentration showed overall reduction. At last, numbers of rearing, sniffing, locomotor activity was increased in group receiving 5 Hz wave over the time. In conclusions, these data showed that the effects of 1 and 5 Hz on the hormonal, metabolic and stress-like behaviors may be different. Moreover, the influence of waves on stress system is depending on time of exposure.

Syndrome of achalasia, ACTH insensitivity and alacrima

Energy Technology Data Exchange (ETDEWEB)

Ambrosino, M.M.; Genieser, N.B.; Becker, M.H.; Bangaru, B.S.; Sklar, C.

1986-05-01

An unusual multisystem disorder characterized by the triad of selective ACTH insensitivity, achalasia and alacrima has recently been described. The following case fulfills the criteria for this syndrome which has not been previously reported in the radiographic literature.

ACTH stimulation test in the captive cheetah (Acinonyx jubatus).

Science.gov (United States)

Köster, L S; Schoeman, J P; Meltzer, D G A

2007-09-01

Serum cortisol response was assessed in 8 captive cheetahs, of varying ages, after the intravenous administration of 500 microg of tetracosactide (Synacthen Depot, Novartis, Kempton Park) while maintained under general anaesthesia. In addition, 8 cheetahs were anaesthetised and given an equal volume of saline in order to establish baseline cortisol concentrations at similar stages of anaesthesia. A significant difference in the median cortisol concentration measured over time was found following ACTH administration in the ACTH group (P cheetah. No statistically significant rise was seen in the anaesthetised control group following the injection of saline (P = 0.238).

Adrenal gland hypofunction in active polymyalgia rheumatica. effect of glucocorticoid treatment on adrenal hormones and interleukin 6.

Science.gov (United States)

Cutolo, Maurizio; Straub, Rainer H; Foppiani, Luca; Prete, Camilla; Pulsatelli, Lia; Sulli, Alberto; Boiardi, Luigi; Macchioni, Pierluigi; Giusti, Massimo; Pizzorni, Carmen; Seriolo, Bruno; Salvarani, Carlo

2002-04-01

To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in patients with recent onset polymyalgia rheumatica (PMR) not previously treated with glucocorticoids; and to detect possible correlations between adrenal hormone levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and during 12 months of glucocorticoid treatment. Forty-one PMR patients of both sexes with recent onset disease and healthy sex and age matched controls were enrolled into a longitudinal study. Patients were monitored for serum cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione (ASD), and clinical and laboratory measures of disease activity such as C-reactive protein and IL-6 concentrations at baseline and after 1, 3, 6, 9 and 12 months of glucocorticoid treatment. To assess dynamic HPA axis function, serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were evaluated in another 8 patients with recent onset PMR not treated with glucocorticoid in comparison to controls after challenge with ovine corticotropin releasing hormone (oCRH) test. In addition, serum cortisol and 17-hydroxyprogesterone (17-OHP) levels were evaluated after stimulation with low dose (1 microg) intravenous ACTH. Serum cortisol and ASD levels of all PMR patients at baseline did not differ from controls. During followup, cortisol levels dipped at one and 3 months. Serum DHEAS levels in all patients were significantly lower than in controls at baseline. In female PMR patients a significant correlation was found at baseline between cortisol levels and duration of disease. Serum concentrations of IL-6 at baseline were significantly higher in PMR patients than in controls. During 12 months of glucocorticoid treatment IL-6 levels dropped significantly at one month; thereafter they remained stable and did not increase again despite tapering of the glucocorticoid dose. After oCRH stimulation, a similar cortisol response was found in patients and controls. After ACTH

Aberrant expression of glucagon receptors in adrenal glands of a patient with Cushing's syndrome and ACTH-independent macronodular adrenal hyperplasia Expresion aberrante de receptores de glucagón en tejido adrenal de un paciente con síndrome de Cushing e hiperplasia adrenal macronodular indedependiente de ACTH

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Valeria de Miguel

2010-06-01

Full Text Available Adrenocorticotropin (ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH is a rare cause of Cushing´s syndrome, characterized by bilateral adrenal lesions and excess cortisol production despite ACTH suppression. Cortisol synthesis is produced in response to abnormal activation of G-protein- coupled receptors, such as gastric inhibitory peptide, vasopressin, beta adrenergic agonists, LH/hCG and serotonin receptors. The aim of this study was to analyze the expression of glucagon receptors in adrenal glands from an AIMAH patient. A patient with ACTH-independent Cushing´s syndrome and bilateral macronodular adrenal hyperplasia was screened for altered activation of adrenal receptors by physiological (mixed meal and pharmacological (gonadotrophin releasing hormone, ACTH and glucagon tests. The results showed abnormally high levels of serum cortisol after stimulation with glucagon. Hypercortisolism was successfully managed with ketoconazole treatment. Interestingly, a 4-month treatment with a somatostatin analogue (octreotide was also able to reduce cortisol secretion. Finally, Cushing's syndrome was cured after bilateral adrenalectomy. Abnormal mRNA expression for glucagon receptor in the patient´s adrenal glands was observed by Real-Time PCR procedure. These results strongly suggest that the mechanism of AIMAH causing Cushing´s syndrome in this case involves the illicit activation of adrenal glucagon receptors. This is the first case reported of AIMAH associated with ectopic glucagon receptors.La hiperplasia adrenal macronodular bilateral independiente de ACTH (HAMIA es una causa infrecuente de Síndrome de Cushing, caracterizada por lesiones adrenales bilaterales, hipercortisolismo y ACTH plasmática suprimida. La síntesis de cortisol estaría regulada a través de ligandos de receptores asociados a proteína G que se expresan en forma aberrante en la corteza de las glándulas adrenales. El objetivo de este trabajo es analizar

Imaging in covert ectopic ACTH secretion: a CT pictorial review

Energy Technology Data Exchange (ETDEWEB)

Sookur, Paul A.; Sahdev, Anju; Rockall, Andrea G.; Reznek, Rodney H. [St Bartholomew' s Hospital, Department of Academic Radiology, Dominion House, London (United Kingdom); Isidori, Andrea M. [Sapienza University of Rome, Department of Medical Pathophysiology, Rome (Italy); Monson, John P.; Grossman, Ashley B. [St Bartholomew' s Hospital, Department of Endocrinology, London (United Kingdom)

2009-05-15

The syndrome of ectopic adrenocorticotrophin secretion (EAS) is rare and is due to excess adrenocorticotrophin (ACTH) production from a nonpituitary tumour. These tumours can be covert, where the tumours are not readily apparent, and very small making them challenging to image. It is clinically and biochemically difficult to distinguish between covert EAS and Cushing's disease. The first-line investigation in locating the source of ACTH production is computed tomography (CT). The aim of this pictorial review is to illustrate the likely covert sites and related imaging findings. We review the CT appearances of tumours resulting in covert EAS and the associated literature. The most common tumours were bronchial carcinoid tumours, which appear as small, well-defined, round or ovoid pulmonary lesions. Rarer causes included thymic carcinoids, gastrointestinal carcinoids and pancreatic neuroendocrine tumours. Awareness of the imaging characteristics will aid identification of the source of ACTH production and allow potentially curative surgical resection. (orig.)

Effect of noise pollution on testicular tissue and hormonal assessment in rat.

Science.gov (United States)

Farzadinia, P; Bigdeli, M; Akbarzadeh, S; Mohammadi, M; Daneshi, A; Bargahi, A

2016-11-01

Many studies have focused on the effect of noise stress on the health. So far, few studies have been conducted on the effect of noise on reproductive system. The aim of study was to investigate the effect of noise pollution on morphometric parameters of testicular tissue and hormonal assessment (ACTH, cortisol and testosterone). In this study, 40 male rats were exposed to control, 95, 105 and 115 dB noise intensity for sixty days. At the end of study, blood sampling was performed and ACTH, cortisol and testosterone concentrations were assessed. The results showed that noise stress decreased testosterone levels in the 115 dB-treated group, while it increased the ACTH and cortisol levels. Histological sections of testis showed that the mean diameter of the seminiferous tubules and thickness of the germinal epithelium reduced compared to the control group. Also the ratio of the interstitial tissue area to the total testicular tissue area was increased significantly. Our study shows that noise stress may have negative influences on male fertility. © 2016 Blackwell Verlag GmbH.

Association of PCB, PBDE and PCDD/F body burdens with hormone levels for children in an e-waste dismantling area of Zhejiang Province, China

Energy Technology Data Exchange (ETDEWEB)

Xu, Peiwei, E-mail: pwxu@cdc.zj.cn; Lou, Xiaoming; Ding, Gangqiang; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Han, Guangen; Wang, Xiaofeng, E-mail: zjcdcwxf@gmail.com

2014-11-15

Increased electronic waste (e-waste) has raised public concerns regarding exposure to numerous toxic contaminants, particularly polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). In China, the body burdens of PCBs, PBDEs and PCDD/Fs are associated with thyroid hormones in populations from e-waste dismantling sites; however, it is unclear whether this association occurs in children. In this study, we determined the serum levels of PCBs, PBDEs and PCDD/Fs and the endocrine hormones including free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), total thyroxine (TT4), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), cortisol and growth hormone (GH) in 21 children from an e-waste dismantling area and 24 children from a control area. The results showed that the mean levels of ∑ PCBs and ∑ PBDEs in the exposure group were significantly higher than in the control group (40.56 and 32.09 ng g{sup −1} lipid vs. 20.69 and 8.43 ng g{sup −1} lipid, respectively, p < 0.01 for each), and the mean level of ∑ PCDD/Fs in the exposure group was higher than in the control group, but the difference was not significant (206.17 vs. 160.27 pg g{sup −1} lipid, p > 0.05). For the endocrine hormones, we did not find significant differences between the exposed and control groups, although the mean levels of FT3, TT3, TT4, ACTH, cortisol and GH were higher, whereas the mean levels of FT4 and TSH were lower in the exposed group. The mean level of ∑ PBDEs was positively correlated with the mean levels of ∑ PCBs (r = 0.60, p < 0.05) and ∑ PCDD/Fs (r = 0.61, p < 0.05). Furthermore, the mean level of ∑ PBDEs was positively correlated with ACTH (r = 0.61, p < 0.05). In conclusion, our data suggested that exposure to e-waste dismantling environment increased the body burdens of PCBs and PBDEs in local children and that these contaminants

Association of PCB, PBDE and PCDD/F body burdens with hormone levels for children in an e-waste dismantling area of Zhejiang Province, China

International Nuclear Information System (INIS)

Xu, Peiwei; Lou, Xiaoming; Ding, Gangqiang; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Han, Guangen; Wang, Xiaofeng

2014-01-01

Increased electronic waste (e-waste) has raised public concerns regarding exposure to numerous toxic contaminants, particularly polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). In China, the body burdens of PCBs, PBDEs and PCDD/Fs are associated with thyroid hormones in populations from e-waste dismantling sites; however, it is unclear whether this association occurs in children. In this study, we determined the serum levels of PCBs, PBDEs and PCDD/Fs and the endocrine hormones including free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), total thyroxine (TT4), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), cortisol and growth hormone (GH) in 21 children from an e-waste dismantling area and 24 children from a control area. The results showed that the mean levels of ∑ PCBs and ∑ PBDEs in the exposure group were significantly higher than in the control group (40.56 and 32.09 ng g −1 lipid vs. 20.69 and 8.43 ng g −1 lipid, respectively, p < 0.01 for each), and the mean level of ∑ PCDD/Fs in the exposure group was higher than in the control group, but the difference was not significant (206.17 vs. 160.27 pg g −1 lipid, p > 0.05). For the endocrine hormones, we did not find significant differences between the exposed and control groups, although the mean levels of FT3, TT3, TT4, ACTH, cortisol and GH were higher, whereas the mean levels of FT4 and TSH were lower in the exposed group. The mean level of ∑ PBDEs was positively correlated with the mean levels of ∑ PCBs (r = 0.60, p < 0.05) and ∑ PCDD/Fs (r = 0.61, p < 0.05). Furthermore, the mean level of ∑ PBDEs was positively correlated with ACTH (r = 0.61, p < 0.05). In conclusion, our data suggested that exposure to e-waste dismantling environment increased the body burdens of PCBs and PBDEs in local children and that these contaminants released from the e

Changes in mean plasma ACTH reflect changes in amplitude and frequency of secretory pulses

International Nuclear Information System (INIS)

Carnes, M.; Lent, S.J.; Erisman, S.; Feyzi, J.

1988-01-01

ACTH is secreted in an episodic manner from the anterior pituitary. Unanesthetized rats with indwelling jugular and femoral venous cannulae were continuously bled and simultaneously infused with isotonic fluid by peristaltic pump. Two-minute blood samples were collected for up to five hours in 8 male rats. ACTH was measured by radioimmunoassay. The resulting time series were analyzed for significant secretory pulses with the PULSAR program. Elevations or declines in mean plasma ACTH levels were associated with significant changes in amplitude and frequency of secretory pulses

Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

Science.gov (United States)

Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

2015-07-01

Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

Cortisol secretion after adrenocorticotrophin (ACTH and Dexamethasone tests in healthy female and male dogs

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Castillo Victor

2009-08-01

Full Text Available Abstract Background For the conclusive diagnosis of Cushing's Syndrome, a stimulating ACTH test or a low suppressive Dexamethasone test is used. Reports in other species than the dog indicate that plasma cortisol concentration after ACTH administration is affected by gender. We investigated the effect of gender on the cortisol response to ACTH and Dexamethasone tests in dogs. Methods Seven healthy adult Cocker Spaniels (4 females and 3 males were assigned to a two by two factorial design: 4 dogs (2 females and 2 males received IV Dexamethasone 0.01 mg/kg, while the other 3 dogs received an IV saline solution (control group. Two weeks later the treatments were reversed. After one month, ACTH was given IV (250 μg/animal to 4 dogs (2 female and 2 males while the rest was treated with saline solution (control group. Cortisol concentrations were determined by a direct solid-phase radioimmunoassay and cholesterol and triglycerides by commercial kits. Results and Discussion No effect of treatment was observed in metabolite concentrations, but females presented higher cholesterol concentrations. ACTH-treated dogs showed an increase in cortisol levels in the first hour after sampling until 3 hours post injection. Cortisol concentrations in Dexamethasone-treated dogs decreased one hour post injection and remained low for 3 hours, thereafter cortisol concentrations increased. The increase in cortisol levels from one to two hours post ACTH injection was significantly higher in females than males. In Dexamethasone-treated males cortisol levels decreased one hour post injection up to 3 hours; in females the decrease was more pronounced and prolonged, up to 5 hours post injection. Conclusion We have demonstrated that cortisol response to ACTH and Dexamethasone treatment in dogs differs according to sex.

Inhibitory effects of a selective Jak2 inhibitor on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT20 cells

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Asari Y

2017-09-01

Full Text Available Yuko Asari, Kazunori Kageyama, Yuki Nakada, Mizuki Tasso, Shinobu Takayasu, Kanako Niioka, Noriko Ishigame, Makoto Daimon Department of Endocrinology and Metabolism, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan Purpose: The primary cause of Cushing’s disease is adrenocorticotropic hormone (ACTH-producing pituitary adenomas. EGFR signaling induces POMC mRNA-transcript levels and ACTH secretion from corticotroph tumors. The Jak–STAT pathway is located downstream of EGFR signaling; therefore, a Jak2 inhibitor could be an effective therapy for EGFR-related tumors. In this study, we determined the effect of a potent and selective Jak2 inhibitor, SD1029, on ACTH production and proliferation in mouse AtT20 corticotroph tumor cells.Materials and methods: AtT20 pituitary corticotroph tumor cells were cultured after transfection with PTTG1- or GADD45β-specific siRNA. Expression levels of mouse POMC, PTTG1, and GADD45β mRNAs were evaluated using quantitative real-time polymerase chain reaction. ACTH levels were measured using ACTH ELISA. Western blot analysis was performed to examine protein expression of phosphorylated STAT3/STAT3. Viable cells and DNA fragmentation were measured using a cell-proliferation assay and cell-death detection ELISA, respectively. Cellular DNA content was analyzed using fluorescence-activated cell sorting.Results: SD1029 decreased POMC and PTTG1 mRNA and ACTH levels, while increasing GADD45β levels. The drug also decreased AtT20-cell proliferation and induced apoptosis, but did not alter cell-cycle progression. SD1029 also inhibited STAT3 phosphorylation. PTTG1 knockdown inhibited POMC mRNA levels and cell proliferation. However, combined treatment with PTTG1 knockdown and SD1029 had no additive effect on POMC mRNA levels or cell proliferation. GADD45β knockdown inhibited the SD1029-induced decrease in POMC mRNA levels and also partially inhibited the decrease in cell proliferation.Conclusion: Both

Molecular transduction mechanisms in ACTH-induced grooming

NARCIS (Netherlands)

Gispen, W.H.; Colbern, D.; Spruijt, B.M.

1988-01-01

Intraventricular administration of ACTH1-24 induces excessive grooming in the rat. Ethogram analysis shows that the peptide does not alter grooming behavior seen in a novel box, but that it prolongs the duration of the grooming bout. Extensive structure-activity studies have been performed which

Blood-ACTH, cortisole and aldosterone levels following complex radiation treatment for cancer of the uterine cervix

International Nuclear Information System (INIS)

Modnikov, O.P.

1984-01-01

Blood-ACTH, cortisole and aldosterone levels in patients with cancer of the uterine cervix were measured radioimmunologically prior to complex radiotherapy, following a half-dose exposure of tumor focus and immediately on completion of the treatment course. Patients showed a rise in cortisole and aldosterone levels and a slight increase in ACTH. Radiation therapy inhibited production of cortisole and aldosterone matched by a rise in ACTH output

Thyroid-stimulating hormone pituitary adenomas.

Science.gov (United States)

Clarke, Michelle J; Erickson, Dana; Castro, M Regina; Atkinson, John L D

2008-07-01

Thyroid-stimulating hormone (TSH)-secreting pituitary adenomas are rare, representing secreting or clinically silent TSH-immunostaining pituitary tumors among all pituitary adenomas followed at their institution between 1987 and 2003. Patient records, including clinical, imaging, and pathological and surgical characteristics were reviewed. Twenty-one patients (6 women and 15 men; mean age 46 years, range 26-73 years) were identified. Of these, 10 patients had a history of clinical hyperthyroidism, of whom 7 had undergone ablative thyroid procedures (thyroid surgery/(131)I ablation) prior to the diagnosis of pituitary adenoma. Ten patients had elevated TSH preoperatively. Seven patients presented with headache, and 8 presented with visual field defects. All patients underwent imaging, of which 19 were available for imaging review. Sixteen patients had macroadenomas. Of the 21 patients, 18 underwent transsphenoidal surgery at the authors' institution, 2 patients underwent transsphenoidal surgery at another facility, and 1 was treated medically. Patients with TSH-secreting tumors were defined as in remission after surgery if they had no residual adenoma on imaging and had biochemical evidence of hypo-or euthyroidism. Patients with TSH-immunostaining tumors were considered in remission if they had no residual tumor. Of these 18 patients, 9 (50%) were in remission following surgery. Seven patients had residual tumor; 2 of these patients underwent further transsphenoidal resection, 1 underwent a craniotomy, and 4 underwent postoperative radiation therapy (2 conventional radiation therapy, 1 Gamma Knife surgery, and 1 had both types of radiation treatment). Two patients had persistently elevated TSH levels despite the lack of evidence of residual tumor. On pathological analysis and immunostaining of the surgical specimen, 17 patients had samples that stained positively for TSH, 8 for alpha-subunit, 10 for growth hormone, 7 for prolactin, 2 for adrenocorticotrophic hormone

Stress Hormones and their Regulation in a Captive Dolphin Population

Science.gov (United States)

2015-09-30

out-of- water stress protocol. The observed response to the stress protocol was similar to that of ACTH administrations (see Parent Project for...CD, Booth R, Wasser S, Cotte L, Jensen E, Crocker D, Houser D (2013). The progestin megestrol acetate suppresses the HPA axis in bottlenose dolphin...Kellar, N.M., Cockrem, J., Romano, T., Booth, R.K. and Wasser , S.K. (2015) Natural variation in stress hormones, comparisons across matrices, and

Effects of ACTH4–10 on self-stimulation behavior in the rat

NARCIS (Netherlands)

Nyakas, C.; Bohus, B.; Wied, D. de

The threshold current evoking self-stimulation or multiples of this current was used to investigate the effect of ACTH4–10 on response performance for brain stimulation reward in the medial septum (MS) and the medial forebrain bundle (MFB). ACTH4–10 in a dose of 50 μg administered SC enhanced

Lycopene and Beta-Carotene Induce Growth Inhibition and Proapoptotic Effects on ACTH-Secreting Pituitary Adenoma Cells

Science.gov (United States)

Leite de Oliveira, Felipe; Soares, Nathália; de Mattos, Rômulo Medina; Hecht, Fábio; Dezonne, Rômulo Sperduto; Vairo, Leandro; Goldenberg, Regina Coeli dos Santos; Gomes, Flávia Carvalho Alcântara; de Carvalho, Denise Pires; Gadelha, Mônica R.; Nasciutti, Luiz Eurico; Miranda-Alves, Leandro

2013-01-01

Pituitary adenomas comprise approximately 10–15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27kip1 in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2) and increased expression of p27kip1 in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27kip1; and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing’s disease. PMID:23667519

Diagnostic value of ACTH stimulation test in determining the subtypes of primary aldosteronism.

Science.gov (United States)

Jiang, Yiran; Zhang, Cui; Wang, Weiqing; Su, Tingwei; Zhou, Weiwei; Jiang, Lei; Zhu, Wei; Xie, Jing; Ning, Guang

2015-05-01

Adrenal venous sampling is recommended as the golden standard for subtyping primary aldosteronism (PA). However, it is invasive and inconvenient, and seeking a better way to make differential diagnosis of PA is necessary. The objective of the study was to evaluate the diagnostic value of ACTH stimulation test under 1 mg dexamethasone suppression test (DST) in determining the subtypes of PA. Ninety-five patients with PA confirmed by saline infusion test were included in this study. According to adrenal venous sampling and histopathology, 39 patients were diagnosed as bilateral adrenal hyperplasia (BAH), 37 as aldosterone-producing adenoma (APA), and 19 as unilateral adrenal hyperplasia (UAH). An ACTH stimulation test under 1 mg DST was performed in all patients. Plasma aldosterone and cortisol levels were measured every 30 minutes until 120 minutes after the iv injection of 50 IU ACTH. During the ACTH stimulation test, aldosterone levels in APA and UAH were similar (P > .05) but higher than those in BAH (P APA and UAH) were significantly higher than bilateral PA (BAH) (P guide further treatment in PA patients.

Beta-endorphin and ACTH in plasma during attacks of common and classic migraine

DEFF Research Database (Denmark)

Bach, F W; Jensen, K; Blegvad, N

1985-01-01

Plasma levels of beta-endorphin and ACTH were measured during and outside migraine attacks in 17 patients with common migraine and 11 patients with classic migraine. Specific radioimmunoassays for beta-endorphin and ACTH were used. The beta-endorphin assay did not cross-react with beta......-lipotropin. In common migraine, median plasma beta-endorphin was 3.3 pmol/l (95% confidence limits: 2.5-4.0 pmol/l) during attacks and 2.9 (2.4-3.2) pmol/l in the headache-free period. In classic migraine, plasma beta-endorphin was 3.2 (1.4-4.3) pmol/l during attacks and 2.4 (1.1-3.6) pmol/l outside attacks. ACTH...

Changes of blood levels of several hormones, catecholamines, prostaglandins, electrolytes and cAMP in man during emotional stress.

Science.gov (United States)

Tigranian, R A; Orloff, L L; Kalita, N F; Davydova, N A; Pavlova, E A

1980-01-01

The levels of several hormones (ACTH, GH, TSH, FSH, LH, parathyroid hormone--PTH, insulin, thyroxine--T4, triiodothyronine--T3, cortisol, testosterone, aldosterone, renin), catecholamines (epinephrine, norepinephrine, dopamin), prostaglandins (F1 alpha, F2 alpha, A + E), electrolytes (Na, K, Ca, Mg), cAMP and glucose in blood were measured before and immediately after the examination in 15 male students aged 28 to 35 years. Simultaneously the blood pressure was measured and hemodynamic measures were registered with the aid of echocardiography. A remarkable increase of catecholamines, ACTH, renin, T3, PTH, cAMP, PG F1 alpha, PG F2 alpha and Ca was found before the examination together with the increase of blood pressure. After the examination the levels of catecholamines, renin, aldosterone, T3, PTH, GH, FSH, LH, testosterone, PG A + E, glucose and Ca were found to be increased, while these of insulin, Na, PG F1 alpha, PG F2 alpha were decreased. The decrease of blood pressure was also found.

Effects of Carbaryl and Deltamethrin Pesticides on Some Pituitary Hormones of Male Albino Rats

International Nuclear Information System (INIS)

Abdel-Kader, S.M.; Ezz El-Arab, A.; Aly, M.A.S.

2005-01-01

This investigation aims to study the effects of oral administrations of 1/10 LD 5 0 of both carbaryl and deltamethrin pesticides on some pituitary hormones of male rats namely; adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), growth hormone (GH), beta-endorphin (b-end) and prolactin hormone (prol). At different time intervals of 1,3,7 and 10 days, blood samples were collected and sera were separated and analyzed for hormonal assessment using RIA technique. The data clarified that daily oral administrations of 1/10 LD 5 0 of both carbaryl (28.6 mg/kg body weight) and deltamethrin (12.8 mg/kg body weight) to male albino rats resulted in gradual and significant decreases in serum ACTH recording 70.60% and 71.75% as compared to control on the 1 0 ''th day of carbaryl and deltamethrin treatments, respectively. Similarly, serum TSH and GH levels were significantly decreased one day after treatment showing their maximum decreases on the 1 0t h day recording 30.09% and 40.25% for TSH and 43.84% and 41.47% for GH after treatment with carbaryl and deltamethrin, respectively. Moreover, serum b-endorphin level showed maximum and significant decreases of 29.47% and 33.28% on day 10 of treatment with carbaryl and deltamethrin, respectively. On the other hand, serum prolactin level was significantly increased one day after treatment showing its maximum increase at the end of the experimental period recording 92.06% and 84.52% for carbaryl and deltamethrin, respectively. From the present data, it could be suggested that the pituitary gland is a major target for the two pesticides carbaryl and deltamethrin which have the potential to influence the modulation of endocrine system via the hypothalamus pituitary axis

Bilateral symmetrical adrenal hypermetabolism on FDG PET/CT due to Cushing syndrome in well differentiated neuroendocrine carcinoma.

Science.gov (United States)

Aktas, G E; Soyluoglu Demir, S; Sarikaya, A

2016-01-01

The (18)F-FDG PET/CT scan has been suggested for whole-body imaging to identify ectopic adrenocorticotrophic hormone secreting tumours, but there are some challenges involved. The case of a patient is presented, who was admitted with the pre-diagnosis of ectopic ACTH syndrome. On the CT, a nodular lesion was detected in the medial segment of the right lung. The FDG uptake of the lesion seemed to be increased visually, but was not pathological quantitatively (SUVmax: 1.8) on the PET/CT. There was also diffuse increased uptake (SUVmax: 14.2) in the enlarged adrenal glands. The lesion was reported as a possible malignant lesion with low FDG affinity, such as a low grade neuroendocrine tumour, while the diffuse enlarged adrenal glands with high uptake were interpreted as diffusely hyperplasic, due to Cushing's syndrome. The patient was treated with a surgical wedge resection. The histopathological diagnosis confirmed that the tumour was a grade 1 well-differentiated neuroendocrine carcinoma. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Transcription controls growth, cell kinetics and cholesterol supply to sustain ACTH responses

Directory of Open Access Journals (Sweden)

Robert I Menzies

2017-09-01

Full Text Available Chronic ACTH exposure is associated with adrenal hypertrophy and steroidogenesis. The underlying molecular processes in mice have been analysed by microarray, histological and immunohistochemical techniques. Synacthen infused for 2 weeks markedly increased adrenal mass and plasma corticosterone levels. Microarray analysis found greater than 2-fold changes in expression of 928 genes (P 4-fold and cross-sectional area of fasciculata cells was 2-fold greater. In contrast, genes associated with apoptosis (eg Casp12, Clu, were downregulated and apoptotic cells (Tunel staining were fewer (P < 0.001 and more widely distributed throughout the cortex. In summary, long-term steroidogenesis with ACTH excess is sustained by genes controlling cholesterol supply and adrenal mass. ACTH effects on adrenal morphology and genes controlling cell hypertrophy, proliferation and apoptosis suggest the involvement of different cell types and separate molecular pathways.

Transcription controls growth, cell kinetics and cholesterol supply to sustain ACTH responses.

Science.gov (United States)

Menzies, Robert I; Zhao, Xin; Mullins, Linda J; Mullins, John J; Cairns, Carolynn; Wrobel, Nicola; Dunbar, Donald R; Bailey, Matthew A; Kenyon, Christopher J

2017-10-01

Chronic ACTH exposure is associated with adrenal hypertrophy and steroidogenesis. The underlying molecular processes in mice have been analysed by microarray, histological and immunohistochemical techniques. Synacthen infused for 2 weeks markedly increased adrenal mass and plasma corticosterone levels. Microarray analysis found greater than 2-fold changes in expression of 928 genes ( P  4-fold and cross-sectional area of fasciculata cells was 2-fold greater. In contrast, genes associated with apoptosis (eg Casp12, Clu, ) were downregulated and apoptotic cells (Tunel staining) were fewer ( P  < 0.001) and more widely distributed throughout the cortex. In summary, long-term steroidogenesis with ACTH excess is sustained by genes controlling cholesterol supply and adrenal mass. ACTH effects on adrenal morphology and genes controlling cell hypertrophy, proliferation and apoptosis suggest the involvement of different cell types and separate molecular pathways. © 2017 The authors.

Post-inflammatory fatigue in sarcoidosis: personality profiles, psychological symptoms and stress hormones.

Science.gov (United States)

Korenromp, Ingrid H E; Grutters, Jan C; van den Bosch, Jules M M; Heijnen, Cobi J

2012-02-01

Chronic fatigue following inflammatory diseases has been well documented. However, little is known about possible risk factors of chronic post-inflammatory fatigue. The aim of this study was to investigate whether chronic post-inflammatory fatigue after clinical remission of the disease sarcoidosis is associated with specific dimensions of personality, psychological symptoms and baseline levels of stress hormones. Thirty-seven non-fatigued and 33 fatigued patients in clinical remission of sarcoidosis were evaluated with the Temperament and Character Inventory-short form (TCI); the Symptom CheckList-90 (SCL), and the Checklist Individual Strength (CIS). Baseline levels of ACTH and cortisol were measured in plasma. Principal component analysis with orthogonal rotation (varimax) was conducted on all personality, psychological and stress hormone data in order to obtain a smaller set of components. Logistic regression was performed to associate these components with chronic post-inflammatory fatigue. Principal component analyses identified 5 components, of which two components were significantly associated with chronic post-inflammatory fatigue. The first component comprised the personality trait Harm Avoidance and all SCL-subscales except Sleep. The second component consisted of baseline levels ACTH and cortisol, and showed an inverse association with chronic post-inflammatory fatigue. The 3 other components, consisting of respectively SCL-Sleep, TCI-Novelty Seeking-Reward Dependence-Self Transcendence, and TCI-Persistence, were not significantly associated with chronic fatigue. Chronic post-inflammatory fatigue after clinical remission of sarcoidosis is associated with a triad of risk factors: a specific personality profile with profound neurotic characteristics in combination with high levels of psychological distress, and decreased baseline ACTH/cortisol levels. Copyright © 2011 Elsevier Inc. All rights reserved.

Gradual Loss of ACTH Due to a Novel Mutation in LHX4: Comprehensive Mutation Screening in Japanese Patients with Congenital Hypopituitarism

Science.gov (United States)

Takagi, Masaki; Ishii, Tomohiro; Inokuchi, Mikako; Amano, Naoko; Narumi, Satoshi; Asakura, Yumi; Muroya, Koji; Hasegawa, Yukihiro; Adachi, Masanori; Hasegawa, Tomonobu

2012-01-01

Mutations in transcription factors genes, which are well regulated spatially and temporally in the pituitary gland, result in congenital hypopituitarism (CH) in humans. The prevalence of CH attributable to transcription factor mutations appears to be rare and varies among populations. This study aimed to define the prevalence of CH in terms of nine CH-associated genes among Japanese patients. We enrolled 91 Japanese CH patients for DNA sequencing of POU1F1, PROP1, HESX1, LHX3, LHX4, SOX2, SOX3, OTX2, and GLI2. Additionally, gene copy numbers for POU1F1, PROP1, HESX1, LHX3, and LHX4 were examined by multiplex ligation-dependent probe amplification. The gene regulatory properties of mutant LHX4 proteins were characterized in vitro. We identified two novel heterozygous LHX4 mutations, namely c.249-1G>A, p.V75I, and one common POU1F1 mutation, p.R271W. The patient harboring the c.249-1G>A mutation exhibited isolated growth hormone deficiency at diagnosis and a gradual loss of ACTH, whereas the patient with the p.V75I mutation exhibited multiple pituitary hormone deficiency. In vitro experiments showed that both LHX4 mutations were associated with an impairment of the transactivation capacities of POU1F1 andαGSU, without any dominant-negative effects. The total mutation prevalence in Japanese CH patients was 3.3%. This study is the first to describe, a gradual loss of ACTH in a patient carrying an LHX4 mutation. Careful monitoring of hypothalamic–pituitary -adrenal function is recommended for CH patients with LHX4 mutations. PMID:23029363

The effect of ACTH analogues on motor behavior and visual evoked responses in rats

NARCIS (Netherlands)

Wolthuis, O.L.; Wied, D. de

1976-01-01

Averaged visual evoked responses (VER) in cortical area 17 were recorded one hour after the administration of 7-l-phe ACTH(4-10) or 7-d-phe ACTH(4-10) to artificially ventilated rats, paralysed with gallamine. In addition, the effects of these peptides on spontaneous motor behavior were analyzed.

Plurihormonal cells of normal anterior pituitary: Facts and conclusions.

Science.gov (United States)

Mitrofanova, Lubov B; Konovalov, Petr V; Krylova, Julia S; Polyakova, Victoria O; Kvetnoy, Igor M

2017-04-25

plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment.

Hypothalamo-pituitary hormone insufficiency associated with cleft lip and palate.

Science.gov (United States)

Roitman, A; Laron, Z

1978-01-01

Two male patients with congenital cleft lip and palate first seen at ages 10.2 and 21.5 years presented with typical signs of hypothalamic-interior pituitary hormone deficiencies. They were found to lack GH, LH, and FSH and to be partially deficient in TSH and ACTH. Several congenital defects may explain this rare syndrome affecting midline structures in the proximity of the maldeveloped palate, including Rathke's pouch, which migrates distally to develop into the anterior pituitary. PMID:747400

Adrenal activity and metabolic risk during randomized escitalopram or placebo treatment in PCOS

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Dorte Glintborg

2018-03-01

Full Text Available Background/aims: Polycystic ovary syndrome (PCOS is associated with insulin resistance, adrenal hyperactivity and decreased mental health. We aimed to investigate the changes in adrenal activity, metabolic status and mental health in PCOS during treatment with escitalopram or placebo. Methods: Forty-two overweight premenopausal women with PCOS and no clinical depression were randomized to 12-week SSRI (20 mg escitalopram/day, n = 21 or placebo (n = 21. Patients underwent clinical examination, fasting blood samples, adrenocorticotroph hormone (ACTH test, 3-h oral glucose tolerance test (OGTT and filled in questionnaires regarding mental health and health-related quality of life (HRQoL: WHO Well-Being Index (WHO-5, Major Depression Inventory (MDI, Short Form 36 (SF-36 and PCOS questionnaire. Results: Included women were aged 31 (6 years (mean (s.d. and had body mass index (BMI 35.8 (6.5 kg/m2 and waist 102 (12 cm. Escitalopram was associated with increased waist (median (quartiles change 1 (0; 3 cm, P = 0.005 vs change during placebo and increased cortisol levels (cortisol 0, cortisol 60, peak cortisol and area under the curve for cortisol during ACTH test, all P < 0.05 vs changes during placebo. Escitalopram had no significant effect on measures of insulin sensitivity, insulin secretion, fasting lipids, mental health or HRQoL. Conclusion: Waist circumference and cortisol levels increased during treatment with escitalopram in women with PCOS and no clinical depression, whereas metabolic risk markers, mental health and HRQol were unchanged.

Alpha 2-adrenoceptor blockade, pituitary-adrenal hormones, and agonistic interactions in rats.

Science.gov (United States)

Haller, J; Barna, I; Kovács, J L

1994-08-01

The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. Alpha 2 adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an alpha 2 adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different alpha 2 adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the alpha 2 adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.

Beta-endorphin and ACTH in plasma during attacks of common and classic migraine

DEFF Research Database (Denmark)

Bach, F W; Jensen, K; Blegvad, N

1985-01-01

Plasma levels of beta-endorphin and ACTH were measured during and outside migraine attacks in 17 patients with common migraine and 11 patients with classic migraine. Specific radioimmunoassays for beta-endorphin and ACTH were used. The beta-endorphin assay did not cross-react with beta-lipotropin...... migraine. Accordingly, we could not add evidence to the theory of a dysfunction of the endogenous opioid system in migraine....

Chronic inhibition of nitric oxide synthase augments the ACTH response to exercise.

Science.gov (United States)

Jankord, Ryan; McAllister, Richard M; Ganjam, Venkataseshu K; Laughlin, M Harold

2009-03-01

Exercise can activate the hypothalamo-pituitary-adrenocortical (HPA) axis, and regular exercise training can impact how the HPA axis responds to stress. The mechanism by which acute exercise induces HPA activity is unclear. Therefore, the purpose of this study was to test the hypothesis that nitric oxide modulates the neuroendocrine component of the HPA axis during exercise. Female Yucatan miniature swine were treated with N-nitro-l-arginine methyl ester (l-NAME) to test the effect of chronic nitric oxide synthase (NOS) inhibition on the ACTH response to exercise. In addition, we tested the effect of NOS inhibition on blood flow to tissues of the HPA axis and report the effects of handling and treadmill exercise on the plasma concentrations of ACTH and cortisol. Chronic NOS inhibition decreased plasma NO(x) levels by 44%, increased mean arterial blood pressure by 46%, and increased expression of neuronal NOS in carotid arteries. Vascular conductance was decreased in the frontal cortex, the hypothalamus, and the adrenal gland. Chronic NOS inhibition exaggerated the ACTH response to exercise. In contrast, chronic NOS inhibition decreased the ACTH response to restraint, suggesting that the role of NO in modulating HPA activity is stressor dependent. These results demonstrate that NOS activity modulates the response of the neuroendocrine component of the HPA axis during exercise stress.

Tratamento das formas severas de miastenia pelo ACTH por via intravenosa

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José Lamartine de Assis

1960-12-01

Full Text Available O autor inicia o trabalho referindo as bases bioquímicas, fisiopatológicas e anátomo-patológicas do tratamento da miastenia pelo ACTH. Na miastenia grave há diminuição da síntese da acetilcolina no organismo, atuando o ACTH no sentido de aumentar esta síntese seja diretamente, por ativação da colinacetilase, seja indiretamente, mediante a redução da massa dos tecidos linfóides, em particular do timo, responsáveis pela elaboração de substâncias que diminuem a síntese da acetilcolina. O autor empregou o ACTH "Armour" e a Cortrofina "Organon", nas doses de 2,5 a 25 mg, sempre pela via intravenosa, diluídos em 250 a 1.000 ml de soluto glicosado a 5%, administrado gota a gôta, na velocidade média de 20 gôtas por minuto, durante 8 horas. Como medicação associada foi administrada a Prostigmina a todos os pacientes, substituída, depois, em alguns casos, pelo Mestinon ou pela Mytelaze. Como adjuvantes foram empregados o cloreto de potássio (2 a 8 g por dia e o sulfato de efedrina (25 mg 3 vêzes ao dia. Os pacientes foram mantidos em regime hiperprotéico e acloretado, sendo tomados todos os cuidados inerentes ao uso do ACTH. Foram estudados 10 pacientes portadores de miastenia com sintomatologia acentuada (8 casos e média (2 casos. Todos os doentes vinham sendo tratados com drogas anticolinesterásicas em doses adequadas (Prostigmina, Mestinon, Mytelaze e a sua sintomatologia respondia cada vez menos a esta terapêutica. Em alguns casos haviam sido tentados outros tratamentos (timectomia, denervação do seio carotídeo, irradiação da região tímica sem resultado. É de notar que as remissões espontâneas neste grupo de enfermos foram excepcionais e de curta duração. A evolução foi acompanhada do ponto de vista clínico, com a sintomatologia classificada como muito acentuada, acentuada, média e leve. Em todos os casos houve remissão completa ou quase completa da sintomatologia após dosagens variáveis de ACTH; no

Role of hormonal factor in development of primary and secondary tumorous process in the brain

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O. I. Kit

2016-01-01

.The present study was aimed at comparing the level of certain some hormones in tissue of glioblastomes, metastases of breast cancer into the brain and meningiomas, as well as the respective peritumoral zones.Materials and methods. Examined were samples of tissue obtained from a total of 56 patients admitted for operative treatment to our Department. Of these, 24 glioblastomas, 19 breast cancer metastases to the brain, 13 meningiomes without peritumoral edema. The histological control was carried out in all cases. The patients’ age varied form 35 to 72 years. During operative interventions we carried out removed neoplasms of the brain followed by biochemical study of the samples of tumor tissue and immediately adjoining to the tumorous foci tissue (perifocal zone. In 10 % of cytozolic fractions of tissue prepared on the potassium-phosphate buffer of pH 7.4 containing 0.15 of Tween-20 and 1 % of bovine serum albumin by means of immunoenzymatic assay (IEA using standard test systems we determined the level of steroid hormones – cortisole, testosterone, progesterone, estradiole, estriole, prolactine (IEA, HEMA, Russia estrone (IEA, DBC, Canada as well as sex-steroid-binding globulin (IEA, Alcor-Bio, Russia and hormones of adrenohypophysis – adrenocorticotropine (ACTH and somatotropic hormone (STH.Results. The obtained findings showed that the most hormonally saturated were metastases of breast cancer. In them along with elevated levels of cortisole, prolactine ACTH and STH concentrations whose concentrations increased virtually in any proliferative process we determined growth of saturation of tissues with estrone and free testosterone on the background of decrease level of active metabolite of estrogens – estriole. Besides, disorders of the steroid metabolism also touched the perifocal zone. Presence of glioblastoma turned out characteristic of identity of tumorous tissue and the perifocal zone by the level of cortizole, which is not found observed if tumors of other

ACTH-secreting bronchial carcinoid: a diagnostic and therapeutic challenge.

LENUS (Irish Health Repository)

McDermott, J H

2008-09-01

We describe a case of Cushing\\'s syndrome due to ectopic ACTH secretion, where the only potential source on conventional imaging was a tiny benign-appearing lung nodule, which failed to take up radiolabelled octreotide.

Influence of different anesthesia methods on stress reaction and hemodynamics for elderly orthopedics patients during operations

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Lin Li

2017-07-01

Full Text Available Objective: To study the influence of general anesthesia, epidural anesthesia and combined spinal and epidural anesthesia method on stress reaction and hemodynamics for elderly orthopedics patients during operations. Methods: A total of 90 cases of elder patients who received orthopedic operations were randomly divided to group A, B and C, with 30 cases per group. Three groups of patients were separately given by general anesthesia, epidural anesthesia and combined spinal and epidural anesthesia for operations; The variations of adrenocorticotrophic hormone (ACTH, Cortisol (Cor, β-endorphin (β-EP, Angiotensin- Ⅱ(Ang-Ⅱ, heart rate (HR and blood pressure (SBP, DBP on patients in three groups before anesthesia (T0, during skin incision (T1, after skin incision (T2 and extubation after operation (T3 were compared and analyzed. Results: During T1, T2, ACTH, Cor, β-EP and Ang-Ⅱlevels in 3 groups of patients were significantly higher than those during T0; SBP and DBP were significantly lower than that during T0; HR during T2 was significantly lower than that during T0; During T3, every index in 3 groups were recovered to levels close to that during T0; During T1, T2, ACTH, Cor, β-EP, Ang-Ⅱ levels in group B and C were significantly lower than that in group A. And levels in C was lower than that in B; SBP and DBP in group B and C were significantly higher than A. No HR statistical significance appeared between each group. Conclusions: During clinical anesthesia, we should choose suitable anesthesia method combined with actual situations of patients. Combined spinal and epidural anesthesia had a slight influence on hemodynamics of elder orthopedics patients during operation, and it could effectively alleviate stress reaction during operation.

Plurihormonal cells of normal anterior pituitary: Facts and conclusions

Science.gov (United States)

Mitrofanova, Lubov B.; Konovalov, Petr V.; Krylova, Julia S.; Polyakova, Victoria O.; Kvetnoy, Igor M.

2017-01-01

Introduction plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. Objective To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. Materials and methods We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. Results We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). Conclusion Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment. PMID:28418929

Retrospective analysis of clinical efficacy of protocol-based management of postdural puncture headache in patients undergoing cesarean section under spinal anesthesia

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Zainab Salim Said Al Amri

2017-01-01

Full Text Available Despite advances in needle size and design, postdural puncture headache (PDPH still remains a significant cause of morbidity in parturients receiving spinal anesthesia. Several treatment options have been suggested to treat PDPH ranging from bed rest, rehydration, and analgesics to epidural blood patch. At our institution, we adhere to a strict protocol for managing PDPH wherein adrenocorticotrophic hormone (ACTH is one of the treatment steps in cases of unrelieved PDPH. We carried out a 1-year retrospective analysis to note the efficacy of ACTH in managing PDPH in patients undergoing spinal anesthesia for cesarean section. All patients with PDPH were followed up for at least 2 months after being discharged from the hospital to note recurrence, if any. Data revealed that a total of 614 patients received spinal anesthesia during this period using a 25- or 26-G Quincke needle with the patient in the sitting position using a midline approach. Totally 31 patients developed PDPH and all patients reported their headache spontaneously. As per protocol, if the PDPH did not resolve or lessen in intensity with bed rest and simple analgesics (paracetamol, diclofenac or tramadol alone, or in combination over the first 24 h, two injections of ACTH (1.5 μg/kg in 500 ml saline intravenous over 30 min were administered 12 h apart. No further injections of ACTH were administered. If any treatment modality demonstrated relief or attenuation in PDPH, the patient was observed for the next 2 days. If there was no further improvement, next step of the protocol using epidural blood patch was adopted. Of these 614 patients, 31 developed PDPH giving an incidence of 5.04%. The first line of conservative treatment with bed rests and simple analgesics was successful in relieving or alleviating PDPH in 20 patients (64.5% within 24 h. About 11 patients (35.5% went on to receive ACTH as the second conservative line of management. In 10 of these 11 patients (90.9%, PDPH

In vivo fate of a behaviorally potent ACTH 4-9 analog; evidence for its specific uptake in the brain septal area

International Nuclear Information System (INIS)

Verhoef, J.

1977-01-01

The effects of ACTH-like neuropeptides on conditioned avoidance behavior and their tentative central sites of action are reviewed. The in vivo fate of the [ 3 H]-ACTH 4-9 analog after various routes of peripheral administration in mice and rats are described, in particular, the uptake of intact peptide in the brain is emphasized, since ACTH-like neuropeptides elicit their behavioral activities by directly affecting the central nervous system. Subsequently, the metabolic profiles of the ACTH 4-9 analog in plasma and brain tissue are reported. The distribution of the [ 3 H]-ACTH 4-9 analog throughout the rat brain is studied after intraventricular injection to allow detection in small brain areas and nuclei and to limit (peripheral) proteolysis. Finally, the effects of increased and decreased circulating levels of both ACTH-like peptides and structurally non-related but behaviorally active neuropeptides on the central distribution profile of intraventricularly injected [ 3 H]-ACTH 4-9 analog are reviewed

Radioisotope studies of steroid hormone levels of plasma in indigenous subjects living at high altitude and submitted to a low calorie diet. Final report for the period of 1 April 1971--30 June 1975

Energy Technology Data Exchange (ETDEWEB)

Ramirez, I

1975-08-01

Radioimmunological techniques were applied to the evaluation of TSH and ACTH in the four groups of Ecuadorian subjects under investigation at Tocachi, Malchingui, Quito and Portoviejo, the first three populations living at a high altitude and the fourth at sea-level. This evaluation was of interest since previous studies had indicated that there were thyroid and adrenal hormone deficiency levels in individuals from Tocachi and Malchingui or, in other words, in populations from a high-altitude region, and also endemic goitre and caloric-protein malnutrition. Furthermore, the Tocachi group was composed of subjects suffering from chronic ''stress''. Parallel to the analysis of TSH and pituitary ACTH levels, the circadian rhythm in the production of these hormones in these subjects was studied. The basal values of TSH and ACHT for the studied groups were found to lie within the normal range. /sup 131/I-TSH and /sup 125/I-ACTH were used. As far as the nycthemeral TSH rhythm is concerned, the values tended to be lowest for the high-altitude populations, while for the groups living at sea-level, where there is also circadian variation, the higher values are found in the morning. Similarly, the circadian rhythm for ACTH was established, with a predominance of diurnal values at Tocachi, Malchingui and Portoviejo.

A rare case of an ACTH/CRH co-secreting midgut neuroendocrine tumor mimicking Cushing’s disease

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Regina Streuli

2017-06-01

Full Text Available Ectopic ACTH/CRH co-secreting tumors are a very rare cause of Cushing’s syndrome and only a few cases have been reported in the literature. Differentiating between Cushing’s disease and ectopic Cushing’s syndrome may be particularly difficult if predominant ectopic CRH secretion leads to pituitary corticotroph hyperplasia that may mimic Cushing’s disease during dynamic testing with both dexamethasone and CRH as well as bilateral inferior petrosal sinus sampling (BIPSS. We present the case of a 24-year-old man diagnosed with ACTH-dependent Cushing’s syndrome caused by an ACTH/CRH co-secreting midgut NET. Both high-dose dexamethasone testing and BIPSS suggested Cushing’s disease. However, the clinical presentation with a rather rapid onset of cushingoid features, hyperpigmentation and hypokalemia led to the consideration of ectopic ACTH/CRH-secretion and prompted a further workup. Computed tomography (CT of the abdomen revealed a cecal mass which was identified as a predominantly CRH-secreting neuroendocrine tumor. To the best of our knowledge, this is the first reported case of an ACTH/CRH co-secreting tumor of the cecum presenting with biochemical features suggestive of Cushing’s disease.

In vitro gamma irradiation of some purified polypeptide hormones and their biological and radioimmunological activity

International Nuclear Information System (INIS)

Hromadova, M.; Macho, L.; Strbak, V.; Vigas, M.; Mikulaj, L.

1979-01-01

Some polypeptide hormones (adrenocorticotropin - ACTH, human and bovine growth hormone - GH, human menopausal gonadotropin - HMG, human luteinizing hormone - LH, and bovine thyrotropin - TSH) were irradiated either with 2.5 or 12.5 Mrad (1.1 Mrad/h) or both and their biological activity or immunoreactivity was tested within few days or 3 to 5 months after irradiation. Biological activity of irradiated ACTH (estimation of corticosterone released into medium by incubated adrenals - Saffran and Schally 1955) was not decreased in both time intervals tested. Ten days after irradiation of bovine GH no changes in biological activity (tibia test - Wilhelmi 1973) were found. No decrease of biological activity of irradiated HMG (augmentation of ovarian and uterine weight - Butt 1973) was found 4 months after irradiation and, finaly, no decrease of bovine TSH activity (radioiodine release from prelabelled thyroid in mice - McKenzie 1958) was found 2 to 30 days after irradiation with 2.5 Mrad, while a decrease was observed after 12.5 Mrad. Three to five months after irradiation, however, there was a decrease of biological activity after both doses. The immunological reactivity of irradiated HMG and LH did not differ from that of nonirradiated samples. The same was found with human GH after 2.5 Mrad, while a decrease of reactivity after 12.5 Mrad was detected. It was concluded that, in most of cases, the sterilizing dose of gamma radiation (2.5 Mrad) did not affect the biological activity of polypeptide hormones and that their sensitivity to irradiation appears to differ. (author)

[Uncommon neonatal case of hypoglycemia: ACTH resistance syndrome].

Science.gov (United States)

Delmas, O; Marrec, C; Caietta, E; Simonin, G; Morel, Y; Girard, N; Roucher, F; Sarles, J; Chabrol, B; Reynaud, R

2014-12-01

Monitoring of blood glucose is usually reported to reduce the risk of hypoglycemia in term newborns with high risk factors and for prematurity in neonatal intensive care unit patients. Differential diagnosis has rarely been discussed. In the eutrophic term newborn, hypoglycemia remains rare and an etiological diagnosis must be made. Intensive management of neonatal hypoglycemia is required to prevent neurodevelopmental defects. Without evident cause or if hypoglycemia persists, a systematic review of possible causes should be made. We report isolated glucocorticoid deficiency diagnosed in an infant at 10 months of age. This boy had neonatal hypoglycemia and mild jaundice that had not been investigated. During his first 9 months of life, he presented frequent infections. At 10 months of age, febrile seizures occurred associated with shock, hypoglycemia, hyponatremia, mild hyperpigmentation, and coma. He was diagnosed with hypocortisolemia and elevated ACTH levels. Brain injury was revealed by MRI after resuscitation, with hypoxic-ischemic and hypoglycemic encephalopathy. The molecular studies demonstrated the presence of p.Asp107Asn and previously unreported frameshift p.Pro281GlnfsX9 MC2R gene mutations. A substitutive hormone therapy was provided and during a follow-up of 12 months no adrenal crisis was noted. We report an unusual case of familial glucocorticoid deficiency with severe neurological injury. This case demonstrates the importance of an appropriate etiological diagnosis in neonatal hypoglycemia. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The effects of ACTH- and vasopressin-analogues on CO2-induced retrograde amnesia in rats

NARCIS (Netherlands)

Rigter, H.; Riezen, H. van; Wied, D. de

Amnesia for a one-trial step-through passive avoidance response was induced in rats by application of CO2 until respiratory arrest occurred. The ACTH-analogue ACTH4–10 alleviated the amnesia when administered 1 hr prior to the retrieval test but not when given 1 hr prior to the acquisition trial.

[Study on the reproducibility of ACTH concentrations in plasma of horses with and without equine Cushing syndrome].

Science.gov (United States)

Gehlen, Heidrun; Bradaric, Zrinkja

2013-01-01

The evaluation of plasma ACTH and the dexamethasone suppression test are considered the methods of choice to evaluate the course of therapy of pituitary pars intermedia dysfunction (PPID). Sampling protocols as well as vacutainers for analysis differ between the laboratories. To evaluate the reproducability of plasma ACTH measurement between four different laboratories (A, B, C, D) in Germany as well as within the laboratories themselves, ten horses with previously diagnosed PPID and four healthy horses were sampled and analyzed. Each laboratory received two differently labeled samples of each horse which had been drawn at the same time (blinded samples). Sampling was performed in the morning at the same time. The sampling vacutainers (with and without addition of coagulation and proteinase inhibitors) and postage of the samples was performed according to laboratory standards. In one laboratory the influence of the time of centrifugation (immediately after taking blood versus after one hour) was determined. The samples were processed and analyzed according to laboratory protocols. Determination of ACTH levels was performed using chemiluminescence immunoassay. In total 132 blood samples were analyzed. The results of doubled blood samples of the same horse showed a standard deviation ranging from +/- 6 to +/- 27 pg/ml within the laboratories (Ø 19,29 pg/ml). The standard deviation of the repeatability of the variation coefficient was 13,48%. Blood samples of the same horse resulted in ACTH levels of 121 pg/ml in the first probe and in < 5 pg/ml in the second probe. Standard deviation of measured ACTH values between the laboratories was +/- 26,4 pg/ml (Ø 27,44 pg/ml). The standard deviation of the reproducibility of the variation coefficient was 18,36%. In a 20 year old gelding the lowest ACTH value was 60.9 pg/ml whereas the highest measured value was 108 pg/ml. Immediate centrifugation of blood samples resulted in significantly higher ACTH values at an average of

Resposta do ACTH plasmático ao estímulo com CRH ou CRH + desmopressina em pacientes com síndrome de Cushing ACTH- dependente submetidos a cateterismo bilateral simultâneo dos seios petrosos inferiores Response of plasmatic ACTH to CRH or combined CRH/desmopressin stimulation in patients with ACTHdependent Cushing's syndrome submitted to simultaneous bilateral petrosal sinuses sampling

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Daniella Maria Carneiro do Rêgo

2007-12-01

Full Text Available OBJETIVO: Comparar a resposta do ACTH plasmático após estímulo com CRH ou CRH + desmopressina em pacientes com síndrome de Cushing ACTH-dependente que realizaram cateterismo bilateral simultâneo dos seios petrosos inferiores. MATERIAIS E MÉTODOS: O procedimento foi realizado em 21 pacientes - 14 mulheres e 7 homens - com síndrome de Cushing ACTH-dependente no período de janeiro de 1998 a dezembro de 2003. Após a cateterização de ambos os seios petrosos, amostras de sangue para ACTH foram colhidas, simultaneamente, nos seios petrosos e veia periférica, tanto no estado basal como após três e cinco minutos da administração de CRH humano (100 mg (6 pacientes ou CRH + desmopressina (100 mg + 10 mg (15 pacientes. RESULTADOS: Aos três minutos, houve aumento percentual do ACTH tanto no grupo CRH (257,77 ± 240,36 no seio petroso direito e 718,78 ± 1.358,82 no seio petroso esquerdo [média ± desvio-padrão] como no grupo CRH + desmopressina (1.263,35 ± 1.842,91 no seio petroso direito [p = 0,06] e 583,93 ± 1.020,03 no seio petroso esquerdo [p = 0,83]. Aos cinco minutos houve declínio percentual do ACTH no grupo do CRH (181,07 ± 217,39 no seio petroso direito e 188,25 ± 270,15 no seio petroso esquerdo e aumento progressivo no grupo do CRH + desmopressina (1.365,29 ± 1.832,31 no seio petroso direito [p = 0,03] e 866,43 ± 1.431,72 no seio petroso esquerdo [p = 0,11]. Nos três pacientes com secreção ectópica não houve gradiente. CONCLUSÃO: A estimulação combinada CRH + desmopressina induziu maior produção de ACTH em adenomas corticotróficos em comparação ao CRH, o que pode melhorar a sensibilidade diagnóstica deste procedimento.OBJECTIVE: To compare the responses of plasmatic ACTH to CRH or combined CRH/desmopressin stimulation in patients with ACTH-dependent Cushing's syndrome submitted to simultaneous, bilateral inferior petrosal sinuses sampling. MATERIALS AND METHODS: The procedure was performed in 21 patients - 14

Autosomal Dominant Growth Hormone Deficiency (Type II).

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Alatzoglou, Kyriaki S; Kular, Dalvir; Dattani, Mehul T

2015-06-01

Isolated growth hormone deficiency (IGHD) is the commonest pituitary hormone deficiency resulting from congenital or acquired causes, although for most patients its etiology remains unknown. Among the known factors, heterozygous mutations in the growth hormone gene (GH1) lead to the autosomal dominant form of GHD, also known as type II GHD. In many cohorts this is the commonest form of congenital isolated GHD and is mainly caused by mutations that affect the correct splicing of GH-1. These mutations cause skipping of the third exon and lead to the production of a 17.5-kDa GH isoform that exerts a dominant negative effect on the secretion of the wild type GH. The identification of these mutations has clinical implications for the management of patients, as there is a well-documented correlation between the severity of the phenotype and the increased expression of the 17.5-kDa isoform. Patients with type II GHD have a variable height deficit and severity of GHD and may develop additional pituitary hormone defiencies over time, including ACTH, TSH and gonadotropin deficiencies. Therefore, their lifelong follow-up is recommended. Detailed studies on the effect of heterozygous GH1 mutations on the trafficking, secretion and action of growth hormone can elucidate their mechanism on a cellular level and may influence future treatment options for GHD type II.

ACTH-Secreting tumor of cecum. Case report

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N S Kuznetsov

2013-06-01

Full Text Available Ectopic hormonesecreting of cecum are rare. We report the case of a 52yearold woman with a typical clin ical picture of Cushing disease. Diagnostic tests confirmed ACTH dependent Cushing’s syndrome, which is caused by neuroendocrine tumor of the cecum. Due to the rarity of the disease, we believe it appropriate to share our experience of this group of patients.

[The effect of a single inhalation of mineral water on the blood hormonal status in healthy volunteers].

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Khinchagov, B P; Polushina, N D; Frolkov, V K

1998-01-01

Concentrations of ACTH, TTH, STH, LH, PSH, hydrocortisone, insulin, glucagone, triiodthyronine, thyroxine, aldosterone, glucose and unesterified fatty acids (NEFA) were measured in the blood of 23 healthy male volunteers aged 18 to 35 years 15, 30 and 60 min after a single nose inhalation and oral intake of mineral water Essentuki No. 17. Inhalation of Essentuki No. 17 stimulated secretion of the hormones and some parameters of metabolic reactions: the levels of glucose, NEFA, hydrocortisone, aldosterone, TTH, PSH and LH rose while those of insulin and growth hormone decreased. Oral intake of this water brought about the same changes in the hormone status except blood insulin the levels of which went up.

Ectopic adrenocorticotropic hormone syndrome in a case of duodenal neuroendocrine tumor presenting with liver metastasis

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J Khare

2018-01-01

Full Text Available Ectopic adrenocorticotropic hormone (ACTH syndrome is an uncommon disorder and comprises about 15% of all patients with Cushing's syndrome (CS. Duodenal carcinoids are rare, indolent tumors usually associated with a benign progression. We hereby report a rare case of CS resulting from ectopic ACTH secretion from a duodenal neuroendocrine tumor (NET presenting with liver metastasis. A 37-year-old female presented with abdominal discomfort and dyspepsia of 1-month duration. Ultrasound abdomen suggested a well-defined hypoechoic lesion in the left lobe of the liver, suggestive of neoplasia. On clinical examination, she had Cushingoid features and persistent hypokalemia. Midnight ACTH and cortisol levels were grossly elevated at 1027 pg/ml (n < 46 pg/ml and 87.56 μg/dl (n < 7.5 μg/ml, respectively. Both overnight and high-dose dexamethasone suppression test confirmed nonsuppressed cortisol levels - 86.04 and 84.42 μg/dl (n < 1.8 μg/ml, respectively. Magnetic resonance imaging brain showed a structurally normal pituitary gland. Computed tomography scan of the abdomen revealed hepatic lesion with bilateral adrenal enlargement. A diagnosis of ectopic ACTH-dependent CS was made. Intraoperatively, a duodenal lesion of 0.5 cm × 0.5 cm was identified alongside an 8 cm × 6 cm exophytic lesion in segment IV of the liver. Frozen section of the duodenal lesion was positive for NET. She underwent a Whipple's surgery, cholecystectomy, and left hepatic lobectomy. Postoperatively, she showed clinical and biochemical remission. Herewith, we report the third case of duodenal carcinoid tumor presenting as ectopic ACTH syndrome and the first with liver metastasis.

The function of the adrenal cortex in patients with paracoccidioidomycosis: a study by radioimmunoassay of plasma ACTH

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Tendrich, M.; Vaisman, M.; Pedrosa, P.N.; Guimaraes, M.M.; Cordeiro, J.G.H.

1987-01-01

Fifteen patients with paracoccidioidomycosis were studied: ten with the chronic disseminated form (adult types), 4 with the acute or subacute disseminated form (juvenile type) and 1 with the progressive pulmonary form. Ten patients reported no previous treatment and 5 had relapse of the disease. In all cases P. brasiliensis was demonstrated in specimens obtained from the lesions by direct microscopy (KOH), histopathology and/or culture. The adrenocortical function was evaluated by means of basal plasma determination of ACTH and cortisol, and 24 hour urine determination of 17 hydroxisteroids (17 OHCS); after stimulation by ACTH determinations were repeated. Patients were classified in 3 groups: 1) plasma ACTH 58 pg/ml. According to the correlation between ACTH and cortisol level after simulation test 8 patients were classified in group 1, 2 of them with cortisol response lower than twice the basal levels; four patients were classified in group 3. All them had ACTH levels definitely above the normal, 2 of them had no cortisol response after stimulation in addition to signs and symptoms of Addison's disease, thus fulfilling the criteria of primary adrenal insufficiency. The correlation between ACTH and 17 OHCS after stimulation test demonstrated that in 7 out of 8 patientes from group 1 response was lower than twice the basal and that in 3 out of 4 patientes from group 3 proven primary adrenal insufficiency was present. (The other patient showed a 17 OHCS response three times higher than the basal levels). (author) [pt

Effects of Qiangji Jianli Yin on the hypothalamus CRH contents and plasma ACTH, cortisol levels in rat models of kidney-yang deficiency syndrome

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Zhao Hui; Chen Zhixi; Chen Jinyan; Li Zhiqiang; He Zanhou

2007-01-01

Objective: To investigate the effects of qiangji jianli yin on hypothalamus CRH contents and plasma ACTH, Cortisol levels in rat models with kidney-yang deficiency syndrome. Methods: Rat models of kidney-yang deficiency syndrome were prepared with intramuscular injuection of hydroeortisone and divided into 5 groups: (1) no further treatment, n=13 (2) treated with high dosage d qiangji jiandi yin, n=12 (3) treated with medium dosage of qiangji jianli yin, n=12 (4) treated with low dosage of qiangji jianli yin n=12, (5) treated with yougui wan, n=12. Ten rats injuected with intramuscular distilled water only served as controls. The animals were sacrificied 14 days later and the hypothalamus CRH contents as well as plasma AOM and cortisol levels were measured with RIA. The thymus gland weight index and the adrenal gland index were calculated. Results: (1) The hypothalamus CRH contents and plasma ACTH, cortisol levels were significantly lower (P<0.01) in the rat models of kidney-yang deficiency syndrome without any treatment thas those in controls rats; the thymus and adrenal gland weight index were significantly decreased too (P <0.01). The CRH conteats and ACTH, cortisol levels in all the three group of rat model treated with different dosage of qiangji jianli yin were significantly higher than those in the models without any treatment (P<0.05-0.01). Conclusion: In rat models of kidney-yang deficiency syndrome, dysfunction of the hypothalamus-pituitary-adrenal axis (HPAA) led to decreased secretion of related hormones. The HPAA function might be partially restored with administation of qiangji jianli yin. (authors)

Change and significance of serum inflammatory factors, NSE, S100 protein and stress hormone levels in patients with craniocerebral injury

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Rui-Feng Liu

2017-09-01

Full Text Available Objective: To investigate the change and significance of serum inflammatory factors, neuron specific enolase (NSE, S100 protein and stress hormone levels in patients with brain diseases. Methods: A total of 115 patients with craniocerebral injury were selected as the observation group, according to the Glasgow Coma Scale (GCS, they were divided into light-sized group (n=38, middle-sized group (n=40 and severe-sized group (n=37, at the same time the other 120 healthy subjects were selected as the control group. The levels of serum inflammatory cytokines [tumor necrosis factor alpha (TNF-α and procalcitonin (PCT], neuron specific enolase (NSE, S100 protein and the stress hormone cortisol [(COR, adrenocorticotropic hormone (ACTH, β-endorphin (β-EP] of both groups were compared. Results: The levels of TNF-α, PCT, NSE, S100, COR, ACTH and β-EP in the observation group were (145.73±19.24 ng/L, (2.41±0.64 ng/mL, (38.11±12.28 ng/mL, (0.87±0.32 μg/L, (818.87±121.14 nmol/L, (107.38±13.94 ng/L, (126.74±39.04 ng/mL, which were significantly higher than control group, the difference was statistically significant; Comparison of indexes among the observation group, NF-α, PCT, NSE, S100, COR, ACTH and β-EP levels in the middle-sized group and severe-sized group were significantly higher than those in the light-sized group, and the levels in the severe-sized group were significantly higher than those of the middle-sized group, the difference was statistically significant. Conclusion: The levels of Serum inflammatory factors, NSE, S100 protein and stress hormone were significantly increased in patients with craniocerebral injury, the level was related to the degree of traumatic brain injury, which could be used as an important indicator to assess the severity of the disease.

Stress and immunological response of heifers divergently ranked for residual feed intake following an adrenocorticotropic hormone challenge.

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Kelly, A K; Lawrence, P; Earley, B; Kenny, D A; McGee, M

2017-01-01

When an animal is exposed to a stressor, metabolic rate, energy consumption and utilisation increase primarily through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Changes to partitioning of energy by an animal are likely to influence the efficiency with which it is utilised. Therefore, this study aimed to determine the physiological stress response to an exogenous adrenocorticotropic hormone (ACTH) challenge in beef heifers divergently ranked on phenotypic residual feed intake (RFI). Data were collected on 34 Simmental weaning beef heifers the progeny of a well characterized and divergently bred RFI suckler beef herd. Residual feed intake was determined on each animal during the post-weaning stage over a 91-day feed intake measurement period during which they were individually offered adlibitum grass silage and 2 kg of concentrate per head once daily. The 12 highest [0.34 kg DM/d] and 12 lowest [-0.48 kg DM/d] ranking animals on RFI were selected for use in this study. For the physiological stress challenge heifers (mean age 605 ± 13 d; mean BW 518 ± 31.4 kg) were fitted aseptically with indwelling jugular catheters to facilitate intensive blood collection. The response of the adrenal cortex to a standardised dose of ACTH (1.98 IU/kg metabolic BW 0.75 ) was examined. Serial blood samples were analysed for plasma cortisol, ACTH and haematology variables. Heifers differing in RFI did not differ ( P  = 0.59) in ACTH concentrations. Concentration of ACTH peaked ( P  response than Low RFI from 40 min to 150 min relative to ACTH administration. Cortisol response was positively associated with RFI status ( r  = 0.32; P  responsiveness of the HPA axis is likely to contribute to appreciable variation in the efficiency feed utilisation of cattle.

The inhibitory effect of ACTH 1–10 on extinction of a conditioned avoidance response: Its independence of thyroid function

NARCIS (Netherlands)

Wied, D. de; Pirie, Gail

The effect of the ACTH analogue ACTH 1–10 was studied on the rate of extinction of a pole jumping avoidance response in thyroidectomized rats with or without replacement therapy with 1-thyroxin. ACTH 1–10 appeared to delay the rate of extinction of the CAR in thyroidectomized rats in a similar way

High-end normal adrenocorticotropic hormone and cortisol levels are associated with specific cardiovascular risk factors in pediatric obesity: a cross-sectional study.

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Prodam, Flavia; Ricotti, Roberta; Agarla, Valentina; Parlamento, Silvia; Genoni, Giulia; Balossini, Caterina; Walker, Gillian Elisabeth; Aimaretti, Gianluca; Bona, Gianni; Bellone, Simonetta

2013-02-20

The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been reported to be involved in obesity-associated metabolic disturbances in adults and in selected populations of adolescents. The aim of this study was to investigate the association between morning adrenocorticotropic hormone (ACTH) and cortisol levels and cardiovascular risk factors in overweight or obese Caucasian children and adolescents. This cross-sectional study of 450 obese children and adolescents (aged 4 to 18 years) was performed in a tertiary referral center. ACTH, cortisol, cardiovascular risk factors (fasting and post-challenge glucose, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, and hypertension) and insulin resistance were evaluated. All analyses were corrected for confounding factors (sex, age, puberty, body mass index), and odds ratios were determined. ACTH and cortisol levels were positively associated with systolic and diastolic blood pressure, triglycerides, fasting glucose and insulin resistance. Cortisol, but not ACTH, was also positively associated with LDL-cholesterol. When adjusted for confounding factors, an association between ACTH and 2 h post-oral glucose tolerance test glucose was revealed. After stratification according to cardiovascular risk factors and adjustment for possible confounding factors, ACTH levels were significantly higher in subjects with triglycerides ≥90th percentile (P cortisol levels were found in subjects with blood pressure ≥95th percentile and LDL-cholesterol ≥90th percentile. Overall, the highest tertiles of ACTH (>5.92 pmol/l) and cortisol (>383.5 nmol/l) although within the normal range were associated with increases in cardiovascular risk factors in this population. In obese children and adolescents, high morning ACTH and cortisol levels are associated with cardiovascular risk factors. High ACTH levels are associated with high triglyceride levels and hyperglycemia

Experience with 99mTc-tektrotyd in the diagnosis of ectopic localization of acth-secreting tumors in patients with cushings syndrome

International Nuclear Information System (INIS)

Novikova, T.G.; Makeev, S.S.; Koval', S.S.; Guk, N.A.

2015-01-01

The differential diagnosis of Cushings disease is often carried out with Cushings syndrome, caused by the presence of tumors producing bioactive ACTH or ACTH-like substance. The aim of the study was to determine the effectiveness of the use of scintigraphy with 99m Tc-Tektrotyd in the diagnosis of ectopic localization of ACTH-secreting tumors in patients with Cushings syndrome. The survey of 25 patients with elevated levels of ACTH in the peripheral blood, allowed in 10 (40 %) patients identify foci of increased uptake radiopharmaceutical analog of somatostatin. It was found that the scintigraphy 99m Tc-Tektrotyd is sensitive and specific method in determining the foci of ectopic ACTH production. The use of scintigraphy with 99m Tc-Tektrotyd may be a good alternative to studies with octreotide labeled with 1U In or 123 I in the diagnosis of ectopic ACTH syndrome due to lower radiation dose to the patient, the higher picture quality and greater availability of this radiopharmaceutical

Effects of itopride hydrochloride on plasma gut-regulatory peptide and stress-related hormone levels in healthy human subjects.

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Katagiri, Fumihiko; Shiga, Toru; Inoue, Shin; Sato, Yuhki; Itoh, Hiroki; Takeyama, Masaharu

2006-01-01

Itopride hydrochloride (itopride), a gastrokinetic drug, has recently been evaluated for its clinical usefulness in functional dyspepsia. We investigated effects of itopride on human plasma gastrin-, somatostatin-, motilin-, and cholecystokinin (CCK)-like immunoreactive substances (IS); adrenocorticotropic hormone (ACTH)-immunoreactive substances (IS), and cortisol under stress conditions in healthy subjects. A single administration of itopride caused significant increases in plasma somatostatin- and motilin-IS levels compared to placebo. Itopride significantly decreased plasma CCK-IS, and suppressed the ACTH-IS level compared to placebo. We hypothesize that itopride may have an accelerating gastric emptying effect, and a modulatory effect on the hypothalamo-pituitary-adrenal axis and autonomic nervous functions. These effects might be beneficial in stress-related diseases, suggesting that itopride has clinicopharmacological activities.

ACTH-induced caveolin-1 tyrosine phosphorylation is related to podosome assembly in Y1 adrenal cells

International Nuclear Information System (INIS)

Colonna, Cecilia; Podesta, Ernesto J.

2005-01-01

Y1 adrenocortical cells respond to ACTH with a characteristic rounding-up that facilitates cAMP signaling, critical for transport of cholesterol to the mitochondria and increase in steroid secretion. We here demonstrate that caveolin-1 participates in coupling activation of protein kinase A (PKA) to the control of cell shape. ACTH/8-Br-cAMP induced reorganization of caveolin-1-positive structures in correlation with the cellular rounding-up. Concomitant with this change, there was an increase in the phosphorylation of caveolin-1 (Tyr-14) localized at focal adhesions (FA) with reorganization of FA to rounded, ringlike structures. Colocalization with phalloidin showed that phosphocaveolin is present at the edge of actin filaments and that after ACTH stimulation F-actin dots at the cell periphery become surrounded by phosphocaveolin-1. These observations along with electron microscopy studies revealed these structures as podosomes. Podosome assembly was dependent on both PKA and tyrosine kinase activities because their formation was impaired after treatment with specific inhibitors [myristoylated PKI (mPKI) or PP2, respectively] previous to ACTH/8-Br-cAMP stimulation. These results show for the first time that ACTH induces caveolin-1 phosphorylation and podosome assembly in Y1 cells and support the view that the morphological and functional responses to PKA activation in steroidogenic cells are related to cytoskeleton dynamics

Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane.

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Malik, Sundeep; Dolan, Terrance M; Maben, Zachary J; Hinkle, Patricia M

2015-11-13

The melanocortin-2 (MC2) receptor is a G protein-coupled receptor that mediates responses to ACTH. The MC2 receptor acts in concert with the MC2 receptor accessory protein (MRAP) that is absolutely required for ACTH binding and signaling. MRAP has a single transmembrane domain and forms a highly unusual antiparallel homodimer that is stably associated with MC2 receptors at the plasma membrane. Despite the physiological importance of the interaction between the MC2 receptor and MRAP, there is little understanding of how the accessory protein works. The dual topology of MRAP has made it impossible to determine whether highly conserved and necessary regions of MRAP are required on the intracellular or extracellular face of the plasma membrane. The strategy used here was to fix the orientation of two antiparallel MRAP molecules and then introduce inactivating mutations on one side of the membrane or the other. This was achieved by engineering proteins containing tandem copies of MRAP fused to the amino terminus of the MC2 receptor. The data firmly establish that only the extracellular amino terminus (Nout) copy of MRAP, oriented with critical segments on the extracellular side of the membrane, is essential. The transmembrane domain of MRAP is also required in only the Nout orientation. Finally, activity of MRAP-MRAP-MC2-receptor fusion proteins with inactivating mutations in either MRAP or the receptor was rescued by co-expression of free wild-type MRAP or free wild-type receptor. These results show that the basic MRAP-MRAP-receptor signaling unit forms higher order complexes and that these multimers signal. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Tipepidine, a non-narcotic antitussive, exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone-treated rats.

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Kawaura, Kazuaki; Ogata, Yukino; Honda, Sokichi; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

2016-04-01

We investigated whether tipepidine exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone (ACTH)-treated rats, which is known as a treatment-resistant depression model, and we studied the pharmacological mechanisms of the effects of tipepidine. Male Wistar rats (5-7 weeks old) were used in this study. Tipepidine (20 and 40 mg/kg, i.p.) decreased the immobility time in the forced swimming test in ACTH-treated rats. The anti-immobility effect of tipepidine was blocked by a catecholamine-depleting agent, alpha-methyl-p-tyrosine (300 mg/kg, s.c.), but not by a serotonin-depleting agent, p-chlorophenylalanine. The anti-immobility effect of tipepidine was also blocked by a dopamine D1 receptor antagonist, SCH23390 (0.02 mg/kg, s.c.) and an adrenaline α2 receptor antagonist, yohimbine (2 mg/kg, i.p.). In microdialysis technique, tipepidine (40 mg/kg, i.p.) increased the extracellular dopamine level of the nucleus accumbens (NAc) in ACTH-treated rats. These results suggest that tipepidine exerts an antidepressant-like effect in the forced swimming test in ACTH-treated rats, and that the effect of tipepidine is mediated by the stimulation of dopamine D1 receptors and adrenaline α2 receptors. The results also suggest that an increase in the extracellular dopamine level in the NAc may be involved in the antidepressant-like effect of tipepidine in ACTH-treated rats. Copyright © 2016. Published by Elsevier B.V.

Infundibular neurons of the human hypothalamus simultaneously reactive with antisera against endorphins, ACTH, MSH and beta-LPH.

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Bugnon, C; Bloch, B; Lenys, D; Fellmann, D

1979-06-27

In man, discrete neurons of the infundibular (arcuate) nucleus contain compounds that can be stained with anti-endorphin (alpha and beta), anti-ACTH, anti-MSH (alpha and beta) and anti-beta-LPH immune sera (I.S.). In the fetus, certain neurons stain with anti-beta-endorphin or anti((17--39)ACTH starting from the 11th week of fetal life. At the ultrastructural level, these neurons contain elementary granules that are immunoreactive with anti-beta-endorphin. In the adult, neurons immunoreactive with anti-beta-endorphin are found in the infundibular nucleus. Their axonal fibers terminate around blood vessels in the neurovascular zone and in the pituitary stalk, or establish contacts with non-immunoreactive perikarya of the infundibular nucleus. These neurons can be stained with anti(17--39)ACTH and anti-beta-endorphin I.S. The most reactive are also stained moderately with anti-alpha-MSH, anti-beta-MSH, anti-beta-LPH, anti-alpha-endorphin, or anti(1--24)ACTH I.S. These results indicate that, in man, compound(s) identical with or immunologically related to endorphins, beta-LPH, ACTH and MSH are secreted by certain hypothalamic neurons. These agents probably originate from a common precursor molecula similar to the so-called pro-opiocortin.

Effects of ACTH on RNA synthesis and migration in the adrenal cortex cells of the young rat, as shown by radioautography

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Magalhaes, M.C.; Vitor, A.B.; Magalhaes, M.M.

1986-01-01

The effect of ACTH on the RNA synthesis in adrenal zona fasciculata cells of the young rat were studied by light and electron microscope radioautography. Two units of ACTH were administered sc to animals and immediately followed by an iv injection of (/sup 3/)uridine. ACTH-injected and control rats, which received the isotope alone, were sacrificed at various time intervals. Labelling over extranucleolar areas was higher in the ACTH-treated animals at 20 min, then becoming lower than in the controls at 60 min and 24 h. Nucleolar radioactivity, however, was consistently decreased by ACTH at all experimental times. Apart from these changes in the rate of synthesis, the over-all curves of labelling were similar to those in the control animals with a striking peak at 1 h. The short-term increase in extranucleolar RNA synthesis observed after ACTH injection was considered to be consistent with the hypothesis that an enhanced extranucleolar synthesis of mRNA takes place early in stimulated animals and is associated with the synthesis of steroidogenic proteins. On the other hand, the relatively decreased uridine uptake of the label by the nucleolus in ACTH-treated animals, suggests an inhibition of nucleolar transcription with diminished pre-rRNA formation in treated animals.

Effects of ACTH on RNA synthesis and migration in the adrenal cortex cells of the young rat, as shown by radioautography

International Nuclear Information System (INIS)

Magalhaes, M.C.; Vitor, A.B.; Magalhaes, M.M.

1986-01-01

The effect of ACTH on the RNA synthesis in adrenal zona fasciculata cells of the young rat were studied by light and electron microscope radioautography. Two units of ACTH were administered sc to animals and immediately followed by an iv injection of [ 3 ]uridine. ACTH-injected and control rats, which received the isotope alone, were sacrificed at various time intervals. Labelling over extranucleolar areas was higher in the ACTH-treated animals at 20 min, then becoming lower than in the controls at 60 min and 24 h. Nucleolar radioactivity, however, was consistently decreased by ACTH at all experimental times. Apart from these changes in the rate of synthesis, the over-all curves of labelling were similar to those in the control animals with a striking peak at 1 h. The short-term increase in extranucleolar RNA synthesis observed after ACTH injection was considered to be consistent with the hypothesis that an enhanced extranucleolar synthesis of mRNA takes place early in stimulated animals and is associated with the synthesis of steroidogenic proteins. On the other hand, the relatively decreased uridine uptake of the label by the nucleolus in ACTH-treated animals, suggests an inhibition of nucleolar transcription with diminished pre-rRNA formation in treated animals. (author)

T cell lymphoblastic lymphoma/leukemia within an adrenocorticotropic hormone and thyroid stimulating hormone positive pituitary adenoma: A cytohistological correlation emphasizing importance of intra-operative squash smear.

Science.gov (United States)

Gupta, Rakesh K; Saran, Ravindra K; Srivastava, Arvind K; Jagetia, Anita; Garg, Lalit; Sharma, Mehar C

2017-08-01

We present a rare case of primary pituitary T cell lymphoma/leukemia (T-LBL) in association with adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH) expressing pituitary adenoma in a 55-year-old woman highlighting the importance of intra-operative squash smears examination. The patient presented with complaints of headache, diminution of vision and recent onset altered sensorium. MRI revealed a mass lesion in the sellar-suprasellar region with non-visualization of pituitary gland separately, extending to involve adjacent structures diagnosed as invasive pituitary macroadenoma. Intra-operative tissue was sent for squash smear examination. The cytology showed a tumor comprising of sheets of immature lymphoid cells intermixed with clusters of pituitary acinar cells with many mitoses and tingible body macrophages. A diagnosis of presence of immature lymphoid cells within the pituitary was offered and differentials of infiltration by lymphoma cells from systemic disease versus primary central nervous lymphoma-like lymphoma arising in the pituitary adenoma were considered. Later paraffin section examination and immunohistochemistry corroborated with the squash findings and a final diagnosis of primary pituitary T cell lymphoma/leukemia in association with ACTH and TSH expressing pituitary adenoma was made. To date, only six cases of primary pituitary T cell lymphomas, including three T-LBL cases, have been reported. This is the seventh case and first one additionally describing cytohistological correlation and importance of intra-operative cytology. © 2017 Japanese Society of Neuropathology.

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

International Nuclear Information System (INIS)

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

Cushing's disease and craniopharyngioma.

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Ackland, F M; Stanhope, R; Preece, M A

1987-01-01

A 14-year old girl presented with growth failure and Cushing's disease. Histological examination confirmed a craniopharyngioma but failed to show that the tumour secreted adrenocorticotrophic hormone. We suggest that her Cushing's disease was caused by hypothalamic dysfunction associated with increased corticotrophin-releasing hormone secretion, secondary to the craniopharyngioma. Images Figure PMID:2823728

Value of the radioimmunological ACTH-determination in plasma for the diagnosis and therapy control of Addison's disease

International Nuclear Information System (INIS)

Wagner, H.; Degenhardt, G.; Wenning, N.

1974-01-01

The findings obtained before suggest that plasma ACTH determination is another valuable parameter supplementing the determination of plasma corticoids in the diagnosis of Addison's disease. In the assessment of the success of the treatment, plasma ACTH measurement is superior to the determination of plasma corticoids. (orig./AK) [de

Hormone and enzyme determination as influenced by corticoids and tocolytics in the final stage of pregnancy

International Nuclear Information System (INIS)

Kaminsky, G.; Kayser, I.B.

1981-01-01

In order to prevent membrane syndrome, the synthetic corticoids betamethasone, dexamethasone and 16-methylene prednisolone combined with tokolytic substances. The hormones ACTH, cortisol, oestriol, and the enzyme renine have been investigated by RIA in order to find out whether the various corticoids cause different changes in the endocrinous parameters of mother and foetus. A suppression of the four measured parameters was found in the presence of corticoids. (orig./MG) [de

Proteomic analysis of adrenocorticotropic hormone treatment of an infantile spasm model induced by N-methyl-D-aspartic acid and prenatal stress.

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Jing Wang

Full Text Available Infantile spasms is an age-specific epileptic syndrome associated with poor developmental outcomes and poor response to nearly all traditional antiepileptic drugs except adrenocorticotropic hormone (ACTH. We investigated the protective mechanism of ACTH against brain damage. An infantile spasm rat model induced by N-methyl-D-aspartate (NMDA in neonate rats was used. Pregnant rats were randomly divided into the stress-exposed and the non-stress exposed groups, and their offspring were randomly divided into ACTH-treated spasm model, untreated spasm model, and control groups. A proteomics-based approach was used to detect the proteome differences between ACTH-treated and untreated groups. Gel image analysis was followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric protein identification and bioinformatics analysis. Prenatal stress exposure resulted in more severe seizures, and ACTH treatment reduced and delayed the onset of seizures. The most significantly up-regulated proteins included isoform 1 of tubulin β-5 chain, cofilin-1 (CFL1, synaptosomal-associated protein 25, malate dehydrogenase, N(G,N(G-dimethylarginine dimethylaminohydrolase 1, annexin A3 (ANXA3, and rho GDP-dissociation inhibitor 1 (ARHGDIA. In contrast, tubulin α-1A chain was down-regulated. Three of the identified proteins, ARHGDIA, ANXA3, and CFL1, were validated using western blot analysis. ARHGDIA expression was assayed in the brain samples of five infantile spasm patients. These proteins are involved in the cytoskeleton, synapses, energy metabolism, vascular regulation, signal transduction, and acetylation. The mechanism underlying the effects of ACTH involves the molecular events affected by these proteins, and protein acetylation is the mechanism of action of the drug treatment.

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.

Ectopic corticotropin-releasing hormone (CRH syndrome from metastatic small cell carcinoma: a case report and review of the literature

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Shahani Sadeka

2010-08-01

Full Text Available Abstract Background Cushing's Syndrome (CS which is caused by isolated Corticotropin-releasing hormone (CRH production, rather than adrenocorticotropin (ACTH production, is extremely rare. Methods We describe the clinical presentation, course, laboratory values and pathologic findings of a patient with isolated ectopic CRH causing CS. We review the literature of the types of tumors associated with this unusual syndrome and the behavior of these tumors by endocrine testing. Results A 56 year old woman presented with clinical and laboratory features consistent with ACTH-dependent CS. Pituitary imaging was normal and cortisol did not suppress with a high dose dexamethasone test, consistent with a diagnosis of ectopic ACTH. CT imaging did not reveal any discrete lung lesions but there were mediastinal and abdominal lymphadenopathy and multiple liver lesions suspicious for metastatic disease. Laboratory testing was positive for elevated serum carcinoembryonic antigen and the neuroendocrine marker chromogranin A. Serum markers of carcinoid, medullary thyroid carcinoma, and pheochromocytoma were in the normal range. Because the primary tumor could not be identified by imaging, biopsy of the presumed metastatic liver lesions was performed. Immunohistochemistry was consistent with a neuroendocrine tumor, specifically small cell carcinoma. Immunostaining for ACTH was negative but was strongly positive for CRH and laboratory testing revealed a plasma CRH of 10 pg/ml (normal 0 to 10 pg/ml which should have been suppressed in the presence of high cortisol. Conclusions This case illustrates the importance of considering the ectopic production of CRH in the differential diagnosis for presentations of ACTH-dependent Cushing's Syndrome.

The hormonal and radiological evaluation of adrenal glands, and the determination of the usefulness of low dose ACTH test in patients with renal amyloidosis.

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Gündüz, Z; Keleştimur, F; Durak, A C; Utaş, C; Büyükberber, M; Düşünsel, R; Kurtoğlu, S; Poyrazoglu, M H

2001-03-01

Amyloidosis is a multisystem disease which may cause organ loss. Renal involvement is the most common clinical problem in amyloidosis, however involvement of endocrin organs is possible. In this study to assess adrenocortical function and to evaluate the usefulness of low dose ACTH test in patients with renal amyloidosis, we determined cortisol, 17-hydroxyprogesteron (17-OHP) and 11-deoxycortisol (11-DOC) responses to both 1 microg and 250 microg Synacthen. We also determined the size of adrenal glands radiologically by using computerized tomography. Twenty one patients with renal amyloidosis and 16 healthy subjects for hormonal evaluation, and 20 patients with renal amyloidosis and 22 healthy subjects for radiologic evaluation were included in the study. In four patients (19%) peak serum cortisol levels following stimulation with the low dose of Synacthen were less than 20 microg/dL (550 nmol/L). Two of them had also subnormal cortisol response to the 250 microg Synacthen stimulation test. Basal and stimulated levels of 11-DOC were lower than those of control values (p=0.000 and p<0.01 respectively). The mean 11-DOC responses to stimulation with 1 microg Synacthen were also significantly lower than the values obtained after the simulation with 250 microg Synacthen (p<0.01 and p=0.000). Cortisol responses to the stimulation with 250 microg Synacthen were also lower than the control responses (p<0.05). 17-OHP responses were similar to the control values in both tests. In the radiological evaluation the mean maximum width of right adrenal glands and the mean anterior and maximum width of left adrenal glands were significantly greater in the patient group (p<0.01). In conclusion, adrenal involvement and adrenal insufficiency is common in amyloidosis. Low 11-DOC levels in amyloidosis is a new finding and further detailed studies is required to explain its cause.

Latest diagnostic approaches to determine the cause of ACTH ...

African Journals Online (AJOL)

A case of a 50-year-old woman who was referred for the evaluation of possible ACTH-dependent Cushing's syndrome (CS) is described. The localisation of ... and facial plethora. On bone mineral density assessment she had ..... the source of EC, PET/CT using 68 Ga-DOTA-labelled octreotide analogues had the best ...

Effect of salinity changes on olfactory memory-related genes and hormones in adult chum salmon Oncorhynchus keta.

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Kim, Na Na; Choi, Young Jae; Lim, Sang-Gu; Jeong, Minhwan; Jin, Deuk-Hee; Choi, Cheol Young

2015-09-01

Studies of memory formation have recently concentrated on the possible role of N-methyl-d-aspartate receptors (NRs). We examined changes in the expression of three NRs (NR1, NR2B, and NR2C), olfactory receptor (OR), and adrenocorticotropic hormone (ACTH) in chum salmon Oncorhynchus keta using quantitative polymerase chain reaction (QPCR) during salinity change (seawater→50% seawater→freshwater). NRs were significantly detected in the diencephalon and telencephalon and OR was significantly detected in the olfactory epithelium. The expression of NRs, OR, and ACTH increased after the transition to freshwater. We also determined that treatment with MK-801, an antagonist of NRs, decreased NRs in telencephalon cells. In addition, a reduction in salinity was associated with increased levels of dopamine, ACTH, and cortisol (in vivo). Reductions in salinity evidently caused NRs and OR to increase the expression of cortisol and dopamine. We concluded that memory capacity and olfactory imprinting of salmon is related to the salinity of the environment during the migration to spawning sites. Furthermore, salinity affects the memory/imprinting and olfactory abilities, and cortisol and dopamine is also related with olfactory-related memories during migration. Copyright © 2015 Elsevier Inc. All rights reserved.

A novel mutation of the adrenocorticotropin receptor (ACTH-R) gene in a family with the syndrome of isolated glucocorticoid deficiency, but no ACTH-R abnormalities in two families with the triple A syndrome

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Tsigos, C.; Arai, K.; Latronico, A.C. [National Inst. of Child Health and Human Development, Bethesda, MD (United States)]|[Temple Univ. School of Medicine, Philadelphia, PA (United States)]|[Children`s Hospital of New Jersey, Newark, NJ (United States)] [and others

1995-07-01

Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by primary adrenocortical insufficiency, usually without mineralocorticoid deficiency. Occasionally, the disorder is associated with alacrima and achalasia of the esophagus (triple A syndrome), suggesting potential heterogeneity in its etiology. Mutations in the ACTH receptor gene have been reported in several families with IGD. We have amplified and directly sequenced the entire intronless ACTH receptor gene in 1 other family with IGD and 2 famlies with triple A syndrome. The proband with IGD was a homozygote for an A {r_arrow}G substitution, changing tyrosine 254 to cysteine in the third extracellular loop of the receptor protein, probably interfering with ligand binding. Both of her parents were heterozygotes for this mutation, which was not detected in 100 normal alleles. No mutations were identified in the entire coding area of the ACTH receptor in the 2 families with triple A syndrome, supporting the idea of a developmental or postreceptor defect in this syndrome. 19 refs., 1 fig.

New PCOS-like phenotype in older infertile women of likely autoimmune adrenal etiology with high AMH but low androgens.

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Gleicher, Norbert; Kushnir, Vitaly A; Darmon, Sarah K; Wang, Qi; Zhang, Lin; Albertini, David F; Barad, David H

2017-03-01

How anti-Müllerian hormone (AMH) and testosterone (T) interrelate in infertile women is currently largely unknown. We, therefore, in a retrospective cohort study investigated how infertile women with high-AMH (AMH ≥75th quantile; n=144) and with normal-AMH (25th-75th quantile; n=313), stratified for low-T (total testosterone ≤19.0ng/dL), normal-T (19.0-29.0ng/dL) and high-T (>29.0ng/dL) phenotypically behaved. Patient age, follicle stimulating hormone (FSH), dehyroepiandrosterone (DHEA), DHEA sulphate (DHEAS), cortisol (C), adrenocorticotrophic hormone (ACTH), IVF outcomes, as well as inflammatory and immune panels were then compared between groups, with AMH and T as variables. We identified a previously unknown infertile PCOS-like phenotype, characterized by high-AMH but, atypically, low-T, with predisposition toward autoimmunity. It presents with incompatible high-AMH and low-T (lean PCOS-like patients, presenting delayed for tertiary fertility services. Since also characterized by low DHEAS, low-T is likely of adrenal origina, and consequence of autoimmune adrenal insufficiency since also accompanied by low-C and evidence of autoimmunity. DHEA supplementation in such patients equalizes low- to normal-T and normalizes IVF cycle outcomes. Once recognized, this high-AMH/low-T phenotype is surprisingly common in tertiary fertility centers but, currently, goes unrecognized. Its likely adrenal autoimmune etiology offers interesting new directions for investigations of adrenals control over ovarian function via adrenal androgen production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Computed tomographic study of hormone-secreting microadenomas

International Nuclear Information System (INIS)

Hemminghytt, S.; Kalkhoff, R.K.; Daniels, D.L.; Williams, A.L.; Grogan, J.P.; Haughton, V.M.

1983-01-01

A review was made of the computed tomographic (CT) studies of 33 patients with hormone-secreting microadenomas that had been verified by transsphenoidal surgery and endocrinologic evaluation. In previous studies in small series of patients, the CT appearance of pituitary microadenomas has been reported as hypodense, isodense, and hyperdense. In this study, CT showed a region of diminished enhancement and ususally an enlarged pituitary gland in cases of prolactin-secreting adenomas. HGH- or ACTH-secreting adenomas were less consistently hypodense. It is concluded that hypodensity and enlargement in the pituitary gland are the most useful criteria for identification of microadenomas. Some technical factors that may affect the CT appearance of microadenomas and lead to conflicting reports are discussed

ACTH (Adrenocorticotropic Hormone) Test

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... Reviews Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition]. Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory ... Medical Encyclopedia [On-line information]. Available online at http:// ...

Myxedema coma in a patient with subclinical hypothyroidism.

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Mallipedhi, Akhila; Vali, Hamza; Okosieme, Onyebuchi

2011-01-01

Myxedema coma is the extreme manifestation of hypothyroidism, typically seen in patients with severe biochemical hypothyroidism. Its occurrence in association with subclinical hypothyroidism is extremely unusual. We describe a patient with subclinical hypothyroidism who developed clinical manifestations of myxedema coma. A 47-year-old woman presented to our endocrine clinic with complaints of fatigue and biochemical findings of subclinical hypothyroidism. She was started on treatment with thyroxine (T4) but remained unwell and was later admitted to hospital with hormone profile showing persisting subclinical hypothyroidism (elevated thyrotropin and normal free T4 [FT4] and free triiodothyronine [FT3]): FT4 10.7 pmol/L (reference range 10.3-24.5), FT3 2.7 pmol/L (reference range 2.67-7.03), and thyrotropin 6.09 mU/L (reference range 0.4-4.0). She subsequently developed hypothermia (temperature 33.2°C), circulatory collapse, and coma. Biochemical profile showed hyponatremia, elevated creatinine phosphokinase, metabolic acidosis, and renal failure. An echocardiogram revealed a moderate-sized pericardial effusion. We diagnosed myxedema coma and started treatment with intravenous T3. She responded dramatically with improvement in level of consciousness and normalization of metabolic parameters. We found no explanation other than hypothyroidism to account for the presentation. Adrenocorticotrophic hormone (ACTH) stimulation tests excluded adrenal insufficiency, and serum gonadotrophins were within the normal reference range. FT4 estimation by equilibrium dialysis excluded analytical interference, and molecular analysis for the thyroid hormone receptor β gene associated with thyroid hormone resistance was negative. To the best of our knowledge this is the first report of myxedema coma in a patient with subclinical hypothyroidism. The reason for normal thyroid hormone levels is unclear but may reflect deviation from a higher pre-morbid set-point. The case

Effects of β-Hydroxy-β-methylbutyrate-free Acid Supplementation on Strength, Power and Hormonal Adaptations Following Resistance Training

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Abbas Asadi

2017-12-01

Full Text Available Background: β-Hydroxy-β-methylbutyrate-free acid (HMB-FA has been ingested prior to exercise to reduce muscle damage, however the effects of HMB-FA supplementation on hormonal, strength and power adaptation are unclear. Methods: Sixteen healthy men were matched and randomized into two groups and performed six-week resistance training while supplementing with either HMB-FA or placebo (3 g per day. The subjects were evaluated for 1 repetition maximum (1RM bench press and leg press and vertical jump (VJ prior to and after training intervention. In addition, blood samples were obtained before and after resistance training to evaluate resting growth hormone (GH, insulin like growth factor 1 (IGF-1, testosterone (TEST, cortisol (CORT, and adrenocorticotropic hormone (ACTH responses. The HMB-FA supplementation group showed greater gains compared with the placebo group in peak power (effect size ES = 0.26 vs. 0.01 and 1RM leg press (ES = 1.52 vs. 0.96. In addition, the HMB-FA supplementation group indicated greater decrements in ACTH and CORT responses to training in comparison to the placebo group (p < 0.05. Likewise, in GH (ES = 1.41 vs. 0.12 and IGF-1 (ES = 0.83 vs. 0.41, the HMB-FA indicated greater training effects when compared with the placebo group. Conclusions: These findings provide further support for the potential anabolic benefits associated with HMB-FA supplementation.

Diagnosis application of ACTH radioimmunoassay in diseases of hypothalamus, hypophysis and adrenal axis

International Nuclear Information System (INIS)

Moreira, A.C.; Foss, M.C.; Iazigi, N.

1988-01-01

The diagnostic value of 900-1,100 am plasma ACTH radioimmunoassay were studied in 10 patients with Cushing's disease before and after treatment, three patients with Cushing's syndrome with adrenal tumours, one Nelson's syndrome patient; 13 patients with Addison's disease and 12 patients with hypo-pituitarism. Twenty-seven normal subjects were controls. The measurement of basal plasma ACTH gave good differentiation between: a. pituitary Cushing's disease from adrenal tumors; b. Addison's disease from hypo-pituitarism. However this assay has a limited value for the differentiation between Cushing's disease from normal subjects and it is often unhelpful in the differential diagnosis of hypo-pituitarism from normal subjects. (author)

Pivagabine decreases stress-related hormone secretion in women with hypothalamic amenorrhea.

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Genazzani, A D; Stomati, M; Bersi, C; Luisi, S; Fedalti, M; Santuz, M; Esposito, G; Petraglia, F; Genazzani, A R

2000-09-01

Stress-induced neuroendocrine activities influence the regulation of endocrine glands and axes. Weight loss-related hypothalamic amenorrhea is a typical stress-induced physiopathological condition. It is characterized by increased adrenal cortex activation and by reduced GH, LH, FSH and gonadal steroid hormone levels. The aim of the present study was to investigate the effects of pivagabine, a neurotropic drug (1800 mg/day for 7 days) or placebo administration on ACTH, cortisol, GH, LH, FSH and PRL plasma levels in patients with hypothalamic amenorrhea related to weight loss. Hormonal parameters and the pulsatile release of cortisol (6-hour pulsatility, sampling every 10 minutes) were evaluated before and after 7 days of treatment. Pivagabine administration significantly reduced mean plasma ACTH (from 21.7+/-1.7 to 15.4+/-1.2 pg/ml, p<0.05) and cortisol levels (from 12.2+/-0.7 to 9.7+/-0.7 ng/ml, p<0.05) and increased GH levels (from 1.4+/-0.5 to 3.0+/-0.9 ng/ml, p<0.05). A significant reduction of cortisol pulse amplitude was observed (p<0.01) while no change in pulse frequency occurred. No changes were observed in placebo-treated subjects. LH, FSH and PRL levels were not modified by placebo or pivagabine administration. In conclusion, in patients with hypothalamic amenorrhea related to weight loss pivagabine induced a significant decrease of cortisol secretion and an increase of GH release by pivagabine administration, suggesting that this drug exerts a specific neuroendocrine modulatory role.

Radioimmunoassay of plasma 18-hydroxy-11-deoxycorticosterone and its response to ACTH

International Nuclear Information System (INIS)

May, C.N.; Lewis, P.S.; Horth, C.E.

1979-01-01

A radioimmunoassay for 18-OH-DOC in plasma was developed using an antiserum raised against the γ-lactone derivative. The steroids with the greatest degree of cross reaction were 18-OH-corticosterone-γ-lactone and aldosterone-γ-lactone which showed cross-reactivities of 1.96% and 0.47% respectively. These and other interfering steroids were eliminated by chromatography of the extracts on columns of Sephadex LH-20. The lowest limit of detection of 18-OH-DOC in 1 ml of plasma corresponded to 33 pmol -1 . The intra-assay precision was 9.7, 4.8 and 2.6% at 102.0, 316.1 and 1144.0 pmol l -1 respectively and the interassay precision was 15.3 and 5.4% at 71.3 and 404.7 pmol l -1 respectively. The concentration of 18-OH-DOC in ten normal subjects was 172.1 +- 39.1 pmol l -1 at 09.00 h, 100.9 +- 16.9 pmol l -1 at 12.00 h and 95.8 +-33.3 pmol l -1 at 16.30 h. Plasma 18-OH-DOC and cortisol levels were measured after various intravenous doses of ACTH in three patients with essential hypertension. Lower doses of ACTH caused considerably greater increases in 18-OH-DOC. These results confirm the ACTH dependency of 18-OH-DOC secretion. (author)

Hostile behavior during marital conflict alters pituitary and adrenal hormones.

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Malarkey, W B; Kiecolt-Glaser, J K; Pearl, D; Glaser, R

1994-01-01

We evaluated hormonal changes and problem-solving behaviors in 90 newlywed couples who were admitted to a hospital research unit for 24 hours. The subjects were selected on the basis of stringent mental and physical health criteria, and admissions were scheduled during the follicular phase of the woman's menstrual cycle. For frequent, unobtrusive endocrine sampling during the interaction tasks, a long polyethylene tube was attached to a heparin well, allowing nurses to draw blood samples at set intervals, out of subjects' sight. Five blood samples were obtained before, during, and after a 30-minute structured problem-solving or conflict task. The conflict session was recorded on videotapes that were later scored for problem-solving behaviors using the Marital Interaction Coding System (MICS). Marital conflict and MICS-coded hostile or negative behavior during conflict was closely linked to changes in serum hormonal levels across five of the six hormones we studied, in spite of the high marital satisfaction of our newlywed couples and the healthy lifestyles demanded by our exclusion criteria. Hostile behavior was associated with decreased levels of prolactin (PRL) and increases in epinephrine (EPI), norepinephrine (NEPI), ACTH, and growth hormone (GH), but not cortisol. These data suggest that the endocrine system may be an important mediator between personal relationships and health.

Effect of different types of stress on adrenal gland parameters and adrenal hormones in the blood serum of male Wistar rats

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Adžić M.

2009-01-01

Full Text Available In the present study, we examined gross changes in the mass of whole adrenal glands and that of the adrenal cortex and medulla in mature male Wistar rats subjected to three different stress types: acute, chronic, and combined, i.e., chronic followed by acute stress. These parameters were correlated with adrenal activity as judged from serum levels of corticosterone and catecholamine, respectively, as well as with serum levels of ACTH and glucose. Under all three conditions, we observed bilaterally asymmetric and stress-type-independent hypertrophy of whole adrenals, as well as adrenal cortices and medullas. Under acute and combined stress, adrenal hypertrophy was followed by increase of adrenal hormones in the blood serum. However, under chronic stress, both cortical and medullar activities as judged from low or unaltered levels of the respective hormones and glucose were compromised and disconnected from the input signal of ACTH. Since all of the studied adrenal activities could be restored by subsequent acute stress, it is concluded that chronic isolation can be viewed as partly maladaptive stress with characteristics resembling stress resistance rather than the stress exhaustion stage of the general adaptation syndrome.

Plasma. beta. -endorphin and stress hormone levels during adaptation and stress

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Lishmanov, Yu.B.; Trifonova, Zh.V.; Tsibin, A.N.; Maslova, L.V.; Dement' eva, L.A.

1987-09-01

This paper describes a comparative study of ..beta..-endorphin and stress hormone levels in the blood plasma of rats during stress and adaptation. Immunoreactive ..beta..-endorphin in the blood plasma was assayed by means of a kit after preliminary isolation of the ..beta..-endorphin fraction by affinity chromatography on sepharose; ACTH was assayed with a kit and cortisol, insulin, thyroxine and tri-iodothyronine by means of kits from Izotop. Determination of plasma levels of ..beta..-endorphin and other opioids could evidently be an important method of assessing the state of resistance of the organism to stress.

Hormones in the immune system and their possible role. A critical review.

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Csaba, György

2014-09-01

Immune cells synthesize, store and secrete hormones, which are identical with the hormones of the endocrine glands. These are: the POMC hormones (ACTH, endorphin), the thyroid system hormones (TRH, TSH, T3), growth hormone (GH), prolactin, melatonin, histamine, serotonin, catecholamines, GnRH, LHRH, hCG, renin, VIP, ANG II. This means that the immune cells contain all of the hormones, which were searched at all and they also have receptors for these hormones. From this point of view the immune cells are similar to the unicells (Tetrahymena), so it can be supposed that these cells retained the properties characteristic at a low level of phylogeny while other cells during the evolution accumulated to form endocrine glands. In contrast to the glandular endocrine cells, immune cells are polyproducers and polyreceivers. As they are mobile cells, they are able to transport the stored hormone to different places (packed transport) or attracted by local factors, accumulate in the neighborhood of the target, synthesizing and secreting hormones locally. This is taking place, e.g. in the case of endorphin, where the accumulating immune cells calms pain caused by the inflammation. The targeted packed transport is more economical than the hormone-pouring to the blood circulation of glandular endocrines and the targeting also cares the other receptor-bearing cells timely not needed the effect. Mostly the immune-effects of immune-cell derived hormones were studied (except endorphin), however, it is not exactly cleared, while the system could have scarcely studied important roles in other cases. The evolutionary aspects and the known as well, as possible roles of immune-endocrine system and their hormones are listed and discussed.

Changes of serum endocrine hormone levels in patients with cancerrelated fatigue and their correlation with anti-tumor immune response and tumor load

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Lu Yang

2017-08-01

Full Text Available Objective: To study the changes of serum endocrine hormone levels in patients with cancerrelated fatigue (CRF and their correlation with anti-tumor immune response and tumor load. Methods: A total of 137 patients who were diagnosed with primary lung cancer in West China Hospital, Sichuan University between June 2014 and November 2016 were selected and then divided into CRF group and control group according to their self-reported symptoms, serum was collected to determine the levels of endocrine hormones and tumor markers, and peripheral blood was collected to detect the levels of immune cells. Results: Serum ACTH and TSH levels of CRF group were significantly higher than those of control group while Cor, FT3 and FT4 levels were significantly lower than those of control group; peripheral blood CD11b+ CD15 - CD33+ CD14+ M-MDSC, CD11b+ CD15-CD33+ CD14- G-MDSC, CD4+ CD25+ CD127lowTreg and CD19+ CD5+ CD1d+ Breg levels as well as serum CEA, Cyfra21-1, SCC-Ag, HE4, GDF- 15 and PCNA levels of CRF group were significantly higher than those of control group, positively correlated with serum ACTH and TSH levels, and negatively correlated with Cor, FT3 and FT4 levels. Conclusion: The changes of thyroid hormone and adrenal cortical hormone levels in patients with cancer-related fatigue are closely related to the inhibited antitumor immune response and increased tumor load.

Using microarrays to identify positional candidate genes for QTL: the case study of ACTH response in pigs.

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Jouffe, Vincent; Rowe, Suzanne; Liaubet, Laurence; Buitenhuis, Bart; Hornshøj, Henrik; SanCristobal, Magali; Mormède, Pierre; de Koning, D J

2009-07-16

Microarray studies can supplement QTL studies by suggesting potential candidate genes in the QTL regions, which by themselves are too large to provide a limited selection of candidate genes. Here we provide a case study where we explore ways to integrate QTL data and microarray data for the pig, which has only a partial genome sequence. We outline various procedures to localize differentially expressed genes on the pig genome and link this with information on published QTL. The starting point is a set of 237 differentially expressed cDNA clones in adrenal tissue from two pig breeds, before and after treatment with adrenocorticotropic hormone (ACTH). Different approaches to localize the differentially expressed (DE) genes to the pig genome showed different levels of success and a clear lack of concordance for some genes between the various approaches. For a focused analysis on 12 genes, overlapping QTL from the public domain were presented. Also, differentially expressed genes underlying QTL for ACTH response were described. Using the latest version of the draft sequence, the differentially expressed genes were mapped to the pig genome. This enabled co-location of DE genes and previously studied QTL regions, but the draft genome sequence is still incomplete and will contain many errors. A further step to explore links between DE genes and QTL at the pathway level was largely unsuccessful due to the lack of annotation of the pig genome. This could be improved by further comparative mapping analyses but this would be time consuming. This paper provides a case study for the integration of QTL data and microarray data for a species with limited genome sequence information and annotation. The results illustrate the challenges that must be addressed but also provide a roadmap for future work that is applicable to other non-model species.

Prolactin as a Marker of Successful Catheterization during IPSS in Patients with ACTH-Dependent Cushing's Syndrome

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Sharma, S. T.; Raff, H.

2011-01-01

Context: Anomalous venous drainage can lead to false-negative inferior petrosal sinus sampling (IPSS) results. Baseline inferior petrosal sinus to peripheral (IPS/P) prolactin ratio higher than 1.8 ipsilateral to the highest ACTH ratio has been proposed to verify successful catheterization. Prolactin-normalized ACTH IPS/P ratios may differentiate Cushing's disease (CD) from ectopic ACTH syndrome (EAS). Objective: Our objective was to examine the utility of prolactin measurement during IPSS. Design, Setting, and Participants: We conducted a retrospective analysis of prolactin levels in basal and CRH-stimulated IPSS samples in ACTH-dependent Cushing's syndrome (2007–2010). Results: Twenty-five of 29 patients had a pathologically proven diagnosis (17 CD and eight EAS). IPSS results were partitioned into true positive for CD (n = 16), true negative (n = 7), false negative (n = 1), and false positive (n = 1). Prolactin IPS/P ratio suggested successful IPSS in eight of 11 with abnormal venograms. Baseline prolactin IPS/P ratio was helpful in two patients with abnormal venograms and false-negative (catheterization unsuccessful) or true-negative (catheterization successful) IPSS results; the normalized ratio correctly diagnosed their disease. Normalized ACTH IPS/P ratio was at least 1.3 in all with CD, but prolactin IPS/P ratios were misleadingly low in two. One patient with cyclic EAS had a false-positive IPSS when eucortisolemic (baseline prolactin IPS/P = 1.7; normalized ratio = 5.6). All other EAS patients had normalized ratios no higher than 0.7. Conclusion: Prolactin measurement and evaluation of the venogram can improve diagnostic accuracy when IPSS results suggest EAS but is not necessary with positive IPSS results. Confirmation of hypercortisolemia remains a prerequisite for IPSS. A normalized ratio of 0.7–1.3 was not diagnostic. PMID:22031511

Forced swimming-induced oxytocin release into blood and brain: Effects of adrenalectomy and corticosterone treatment.

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Torner, Luz; Plotsky, Paul M; Neumann, Inga D; de Jong, Trynke R

2017-03-01

The oxytocin (OXT) system is functionally linked to the HPA axis in a reciprocal and complex manner. Certain stressors are known to cause the simultaneous release of OXT and adrenocorticotrophic hormone (ACTH) followed by corticosterone (CORT). Furthermore, brain OXT attenuates ACTH and CORT responses. Although there are some indications of CORT influencing OXT neurotransmission, specific effects of CORT on neurohypophyseal or intra-hypothalamic release of OXT have not been studied in detail. In the present set of experiments, adult male rats were adrenalectomized (ADX) or sham-operated and fitted with a jugular vein catheter and/or microdialysis probe targeting the hypothalamic paraventricular nucleus (PVN). Blood samples and dialysates were collected before and after forced swimming (FS) and analyzed for CORT, ACTH and AVP concentrations (in plasma) and OXT concentrations (in plasma and dialysates). Experimental treatments included acute infusion of CORT (70 or 175μg/kg i.v.) 5min prior to FS, or subcutaneous placement of 40% CORT pellets resulting in stable CORT levels in the normal basal range. Although ADX did not alter basal OXT concentrations either in plasma or in microdialysates from the PVN, it did cause an exaggerated peripheral secretion of OXT and a blunted intra-PVN release of OXT in response to FS. CORT pellets did not influence either of these ADX-induced effects, while acute infusion of 175μg/kg CORT rescued the stress-induced rise in OXT release within the PVN and modestly increased peripheral OXT secretion. In conclusion, these results indicate that CORT regulates both peripheral and intracerebral OXT release, but in an independent manner. Whereas the peripheral secretion of OXT occurs simultaneously to HPA axis activation in response to FS and is modestly influenced by CORT, HPA axis activation and circulating CORT strongly contribute to the stress-induced stimulation of OXT release within the PVN. Copyright © 2016 Elsevier Ltd. All rights

Therapeutic Effects of Pre-Gelatinized Maca (Lepidium Peruvianum Chacon) used as a Non-Hormonal Alternative to HRT in Perimenopausal Women - Clinical Pilot Study.

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Meissner, H O; Reich-Bilinska, H; Mscisz, A; Kedzia, B

2006-06-01

Roots of cruciferous plant Lepidium peruvianum Chacon cultivated in high plateaus of Andes and known under its common name Maca, have been traditionally-used as an energizing vegetable with therapeutic properties for both men and women. Maca has been recognized by natives of Peru as herbal remedy helping to treat conditions affecting menopausal women. The effects of Pre-Gelatinized Organic Maca (Maca-GO) on quantitative physiological responses and alleviation of symptoms contributing to menopausal discomfort in perimenopausal women was examined. IN THIS, FOUR MONTHS, DOUBLE BLIND, CROSSOVER, RANDOMIZED PILOT TRIAL, MONTHLY MEASUREMENTS OF THE FOLLOWING BLOOD SERUM CONSTITUENTS WERE TAKEN: Estrogen (E2), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and Progesterone (PGS), Cortisol (CT), Adrenocorticotropic Hormone (ACTH), Thyroid Hormones (TSH, T3, T4), minerals (Ca, K, Fe) and lipid profile (Triglicerides, Total Cholesterol, LDL, HDL). In monthly interviews conducted by gynecologist, body weight and blood pressure were registered and Menopausal Index according to Kupperman's was determined. Toxicity of Maca -GO determined on rats showed its safe use at the level of 7.5mg/kg body weight. A group of 20 women (aged 41-50 years), who fulfilled criteria of being in perimenopausal stage (E2 above 40pg/ml and FSH below 30IU/ml), were randomly allocated to two even groups, one receiving for two months Maca-GO and the other Placebo capsules followed by a crossover with treatment change for another two months period. All participants signed informed consent to participate. Two 500mg hard capsules with Maca-GO or Placebo were self-administered by participants twice daily with meals (total 2g/day). Two months administration of Maca-GO significantly alleviated symptoms of discomfort observed in majority of women involved in the study (74%-87%) as assessed by Kupperman's Menopausal index. This was associated with significant increase in E2 and FSH, Progesterone

ACTH- and cortisol-associated neutrophil modulation in coronary artery disease patients undergoing stent implantation.

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Margit Keresztes

Full Text Available Psychosocial stress and activation of neutrophil granulocytes are increasingly recognized as major risk factors of coronary artery disease (CAD, but the possible relationship of these two factors in CAD patients is largely unexplored. Activation of neutrophils was reported to be associated with stenting; however, the issue of neutrophil state in connection with percutaneous coronary intervention (PCI is incompletely understood from the aspect of stress and its hypothalamic-pituitary-adrenal axis (HPA background. Thus, we aimed to study cortisol- and ACTH-associated changes in granulocyte activation in patients undergoing PCI.Blood samples of 21 stable angina pectoris (SAP and 20 acute coronary syndrome (ACS patients were collected directly before (pre-PCI, after (post-PCI and on the following day of PCI (1d-PCI. Granulocyte surface L-selectin, CD15 and (neutrophil-specific lactoferrin were analysed by flow cytometry. Plasma cortisol, ACTH, and lactoferrin, IL-6 were also assayed. In both groups, pre- and post-PCI ratios of lactoferrin-bearing neutrophils were relatively high, these percentages decreased substantially next day; similarly, 1d-PCI plasma lactoferrin was about half of the post-PCI value (all p≤0.0001. Post-PCI ACTH was reduced markedly next day, especially in ACS group (SAP: p<0.01, ACS: p≤0.0001. In ACS, elevated pre-PCI cortisol decreased considerably a day after stenting (p<0.01; in pre-PCI samples, cortisol correlated with plasma lactoferrin (r∼0.5, p<0.05. In 1d-PCI samples of both groups, ACTH showed negative associations with the ratio of lactoferrin-bearing neutrophils (SAP: r = -0.601, p<0.005; ACS: r = -0.541, p<0.05 and with plasma lactoferrin (SAP: r = -0.435, p<0.05; ACS: r = -0.609, p<0.005.Pre- and post-PCI states were associated with increased percentage of activated/degranulated neutrophils indicated by elevated lactoferrin parameters, the 1d-PCI declines of which were associated with plasma

Differential diagnosis of adrenocorticotropic hormone-independent Cushing syndrome: role of adrenal venous sampling.

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Martins, Raquel G; Agrawal, Reshma; Berney, Daniel M; Reznek, Rodney; Matson, Matthew; Grossman, Ashley B; Druce, Maralyn R

2012-01-01

To outline the potential role for adrenal venous sampling in the diagnosis and management of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS). We present a case description and discuss the management of a 59-year-old woman with an 8-year history of weight gain, centripetal obesity, a round plethoric face, skin thinning, easy bruising, hirsutism, and progressive muscle weakness. The patient reported a prior personal history of asthma, type 2 diabetes mellitus, hypertension, dyslipidemia, and bilateral leg ulcers, but she denied having any personal or family history of endocrinopathy and was not taking any corticosteroid medication. Elevated midnight serum cortisol, failure to suppress cortisol levels with a low-dose dexamethasone suppression test, and undetectable plasma ACTH all indicated ACTH-independent CS. Additional investigations including dynamic tests and adrenal imaging were supported by adrenal venous sampling in order to make a diagnosis and formulate a management plan. She was ultimately noted to have bilateral functioning adrenal nodules (adenoma and adenolipoma) and underwent successful bilateral laparoscopic adrenalectomy, with postoperative glucocorticoid and mineralocorticoid replacement. Adrenal venous sampling may be an important step in the differential diagnosis of CS and localization of the source of cortisol excess. It may distinguish pheochromocytoma or benign nonfunctioning adrenal nodules from cortisol-secreting adenomas and may avoid unnecessary bilateral adrenalectomy. It can also ensure that the correct operation is completed, if required, and thus avoid the increased morbidity and mortality associated with repeated surgical interventions.

Study of hormonal status of surgical patients with endometrial carcinoma

International Nuclear Information System (INIS)

Musina, R.Kh.; Kiseleva, N.S.; Modnikov, O.P.

1987-01-01

A radioimmunoassay was conducted in the pituitary-ovary and pituitary-adrenals systems in 37 cases of endometrial carcinoma treatment and 1, 3, 5 and 14 days after extirpation of the uterus and appendages. The levels of follicle - stimulating (FSH) and luteinizing (LH) hormones of the pituitary, prolactin, ACTH, estradiol, progesterone, testosterone, cortisol and aldosterone were studied. Such disturbances as decreased production of FSH, LH, progesterone and testosterone were observed before operation. Surgery was followed by a considerable rise in prolactin production and basal levels of FSH and LH, a decrease in estradiol, progesterone and testosterone concentrations and was accompanied by a sizeable release of cortisol and aldosterone

Loss of ACTH expression in cultured human corticotroph macroadenoma cells is consistent with loss of the POMC gene signal sequence.

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Rees, D A; Hepburn, P J; McNicol, A M; Francis, K; Jasani, B; Lewis, M D; Farrell, W E; Lewis, B M; Scanlon, M F; Ham, J

2002-03-28

The proopiomelanocortin (POMC) gene is highly expressed in the pituitary gland where the resulting mRNA of 1200 base pairs (bp) gives rise to a full-length protein sequence. In peripheral tissues however both shorter and longer POMC variants have been described, these include for example placental tissue which contain 800 (truncated at the 5' end) and 1500 as well as the 1200 bp transcripts. The importance of the 800 bp transcript is unclear as the lack of a signal sequence renders the molecule to be non-functional. This transcript has not been previously demonstrated in the pituitary gland. In this report we show evidence of a 5' truncated POMC gene in human pituitary corticotroph macroadenoma cells (JE) maintained in primary culture for >1 year. The original tumour tissue and the derived cells during early passage (up to passage 4-5) immunostained for ACTH and in situ hybridisation confirmed the presence of the POMC gene in the cultured cells. These cells also secreted 15-40 pg/10(5) cells/24 h ACTH. In addition, as expected RT-PCR demonstrated the presence of all three POMC gene exons and is thus indicative of a full-length POMC gene. In late culture passages (passages 8-15) JE cells ceased to express ACTH and cell growth became very slow due presumably to cells reaching their Hayflick limit. ACTH immunostaining in these cells was undetectable and ACTH secretion was also at the detection limits of the assay and no greater than 10 pg/10(5) cells/24 h. ACTH precursor molecules were also undetectable. RT-PCR for the POMC gene in these late passage cells showed that only exon 3 was detectable, in contrast to early passage cells where all three exons were present. In summary we isolated in culture, human pituitary cells that possessed initially all three exons of the POMC gene and immunostained for ACTH. On further passaging these cells showed a loss of exons 1 and 2 in the POMC gene and a loss of ACTH immunostaining and secretion. We would like to suggest that the

Addison's disease and ACTH-producing pituitary microadenoma

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S.S. Ortega

2015-10-01

Full Text Available A 28-year-old man diagnosed with primary adrenal insufficiency (Addison's disease in 2002. Following diagnosis, replacement therapy with hydrocortisone and fludrocortisone was indicated. Hydrocortisone replacement therapy was unsuccessful, and increased ACTH levels as high as 996 pg/dl were observed on outpatient follow-up. A pituitary MRI revealed a pituitary microadenoma. These findings raised three possibilities: (1 treatment is insufficient; (2 there is no relationship between Addison's disease and pituitary microadenoma; and (3 the microadenoma is similar to Nelson's syndrome. This latter is the most satisfactory explanation of this patient's clinical picture.

[Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome].

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Zhang, Weiwei; Yu, Yerong; Tan, Huiwen; Wang, Chun; Li, Jianwei; An, Zhenmei; Liu, Yuping

2016-03-22

To investigate the value of desmopressin (DDAVP) stimulation test and high dose dexamethasone suppression test (HDDST) in establishing the cause of ACTH dependent Cushing's syndrome. The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to September 30, 2015 was analyzed. The sensitivity and specificity of DDAVP stimulation test, HDDST, and the diagnostic accordance rate when the two tests were combined, were evaluated based on the diagnostic gold standard. A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included. The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10, respectively. The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test. When the two tests had consistent results, the diagnostic accordance rate was 100%. DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease and ectopic ACTH syndrome. The accuracy of diagnosis can be further improved by combining the two tests.

Effects of simultaneous combined exposure to CDMA and WCDMA electromagnetic fields on serum hormone levels in rats

International Nuclear Information System (INIS)

Jin, Yeung Bae; Choi, Hyung-Do; Kim, Byung Chan; Pack, Jeong-Ki; Kim, Nam; Lee, Yun-Sil

2013-01-01

Despite more than a decade of research on the endocrine system, there have been no published studies about the effects of concurrent exposure of radiofrequency electromagnetic fields (RF-EMF) on this system. The present study investigated the several parameters of the endocrine system including melatonin, thyroid stimulating hormone, stress hormone and sex hormone after code division multiple access (CDMA, 849 MHz) and wideband code division multiple access (WCDMA, 1.95 GHz) signals for simultaneous exposure in rats. Sprague-Dawley rats were exposed to RF-EMF signals for 45 min/day, 5 days/week for up to 8 weeks. The whole-body average specific absorption rate (SAR) of CDMA or WCDMA was 2.0 W/kg (total 4.0 W/kg). At 4 and 8 weeks after the experiment began, each experimental group's 40 rats (male 20, female 20) were autopsied. Exposure for 8 weeks to simultaneous CDMA and WCDMA RF did not affect serum levels in rats of melatonin, thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxin (T4), adrenocorticotropic hormone (ACTH) and sex hormones (testosterone and estrogen) as assessed by the ELISA method

Burnout and Hypocortisolism - A Matter of Severity? A Study on ACTH and Cortisol Responses to Acute Psychosocial Stress.

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Lennartsson, Anna-Karin; Sjörs, Anna; Währborg, Peter; Ljung, Thomas; Jonsdottir, Ingibjörg H

2015-01-01

Common consequences of long-term psychosocial stress are fatigue and burnout. It has been suggested that burnout could be associated with hypocortisolism, thus, inability to produce sufficient amounts of cortisol. This study aimed to investigate whether patients with clinical burnout exhibit aberrant ACTH and cortisol responses under acute psychosocial stress compared with healthy individuals. Nineteen patients (9 men and 10 women) and 37 healthy subjects (20 men and 17 women), underwent the Trier Social Stress Test. Blood samples and saliva samples were collected before, after, and during the stress test for measurements of plasma ACTH, serum cortisol, and salivary cortisol. Several statistical analyses were conducted to compare the responses between patients and controls. In addition, in order to investigate the possibility that burnout patients with more severe symptoms would respond differently, sub-groups of patients reporting higher and lower burnout scores were compared. In both patients and healthy controls, we observed elevated levels of ACTH and cortisol after exposure to the stressor. There were no differences in responses of ACTH, serum cortisol, or salivary cortisol between patients and controls. Patients reporting higher burnout scores had lower salivary cortisol responses than controls, indicating that patients with more severe burnout symptoms may be suffering from hypocortisolism. In addition, patients with more severe burnout symptoms tended to have smaller ACTH responses than the other patients. However, there was no corresponding difference in serum cortisol. This study indicates that hypocortisolism is not present in a clinical burnout patient group as a whole but may be present in the patients with more severe burnout symptoms.

The effect of acute heat exposure on rat pituitary corticotroph activation: the role of vasopressin.

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Nebojsa Jasnic

2010-04-01

Full Text Available The increased ambient temperature affects the function of hypothalamic-pituitary-adrenal (HPA axis. Since thecorrelation among vasopressin (VP, adrenocorticotropic hormone (ACTH and corticosterone (CORT responses to variousstressors have been long recognized, the aim of this study was to reveal the aforementioned hormones production andmorphology of the pituitary gland after exposure to acute heat. Rats were exposed to high ambient temperature (38°C for20 or 60 minutes. The circulating hormones were determined by an ELISA test or chemiluminescence's method. The resultsobtained show the elevation in ACTH and CORT secretion depending on the duration of heat exposure. The VP concentrationincreased only after prolonged exposure to heat (60 min. The pituitary morphology was examined by routine and fluorescentimmunohistochemistry as well as electron microscopy. Observed changes in the anterior and posterior pituitarywell corresponded to circulating hormones, regarding the volume density of ACTH-immunopositive cells, percentage ofACTH immunopositive area v. total area and number of VP-immunopositive containing varicose fibers per total area. Acuteheat exposure also induced changes in shapes of ACTH-immunopositive cells. Cells appeared stellate with numerous slendercytoplasmic processes and degranulated, which is the most obvious after 20 min. In addition, immunopositivity ofendothelial and anterior pituitary cells for VP suggests its influence on ACTH secretion.

Can psychological well-being scales and hormone levels be used to predict acute performance of anaerobic training tasks in elite female volleyball players?

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Mielgo-Ayuso, Juan; Zourdos, Michael C; Clemente-Suárez, Vicente J; Calleja-González, Julio; Shipherd, Amber M

2017-10-15

The purpose of this study was to examine relationships between pre-training psychological well-being assessment scales (General Health Questionnaire-28-GHQ-28, Competitive State Anxiety Inventory-2-CSAI-2, Sport Competition Anxiety Test-SCAT, State-Trait Anxiety Inventory-S-STAI-S, Oviedo Sleep Questionnaire-OSQ and Psychological Characteristics Related to Sport Performance-PCSP), and pre-training stress hormone concentrations (cortisol-C, total testosterone-TT, free testosterone-FT, adrenocorticotropic hormone-ACTH and testosterone/cortisol-T/C ratios), on acute neuromuscular performance (ANP) in female volleyballers. Forty elite female volleyballers (27±4yrs.; 178.3±8.5cm; 67.9±7.2kg) participated. Bivariate correlations were performed between psychological assessments and hormone levels with ANP. All psychological scales presented at least one significant (pvolleyballers than pre-training stress hormone concentrations. Copyright © 2017 Elsevier Inc. All rights reserved.

Terapêutica hormonal na coréia de Sydenham

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José Geraldo Albernaz

1957-09-01

Full Text Available Cinco casos de coréia de Sydenham foram submetidos à terapêutica hormonal com Cortisona, Prednisona e Prednisolona; o fenobarbital e a clorpromazina foram utilizados como medicação sintomática e a Penicilina-Benzatina como profilática. Depois de analisadas as referências bibliográficas, comparados os resultados de ν;rios autores, e ajuizados os resultados obtidos em nossos casos, acreditamos poder concluir que: 1 a terapêutica hormonal da coréia de Sydenham, com o uso de ACTH, Cortisona, Prednisona ou Pred-nisclona apresenta resultados satisfatórios; 2 a Prednisona e a Prednisolona são os hormônios mais úteis no tratamento da coréia de Sydenham, sendo possível que sua associação aos salicilatos permita obter resultados ainda melhores; 3 o tratamento deve prolongar-se até o completo desaparecimento dos sintomas, as doses variando de acôrdo com a gravidade e a evolução da moléstia; 4 a terapêutica hormonal deve ser usada sem prejuízo de medicação sintomática (sedativa e profilática (antibiótica.

Successful long-term control of Cushing’s disease after partial resection of gigantic ACTH-secreting pituitary adenoma

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Vatroslav Čerina

2016-03-01

Full Text Available Only 4-9% of patients with Cushing’s disease (CD harbor pituitary macroadenomas. Clinical and biochemical features of macrocorticotropinomas are poorly understood. Some evidence exist that these tumors presents clinical features more similar to a non-functioning adenomas, being though defined silent corticotropinomas, rather than to ACTH-secreting adenomas. In this paper, we report a case of a 60-year old woman with a history of obesity, arterial hypertension and diabetes mellitus who presented with overt central hypothyroidism. Magnetic resonance imaging disclosed giant pituitary adenoma measuring 50 mm. Endocrinological evaluation confirmed CD: ACTH 50.3 pmol/L, urinary free-cortisol of 739 nmol/24h and cortisol of 639 nmol/L after 1 mg dexamethasone suppression test. Tumor mass was reduced by 50% using purely endoscopic transsphenoidal approach. Thirty-eight months after the partial resection, the patient had well controlled CD: ACTH 20.2 pmol/L, urinary free-cortisol of 238 nmol/24h, cortisol of 105 nmol/L after 1 mg dexamethasone suppression test. To the best of our knowledge, this is the largest ACTH-secreting adenoma ever reported. Our case suggests that tumor size does not necessarily correlate with aggressiveness of CD in patients with macrocorticotropinomas and that long-term control of CD may be achieved albeit incomplete surgical removal. Further studies are needed in order to determine the best treatment option for patients with macrocorticotropinomas.

Sensitivity of anterior pituitary hormones to graded levels of psychological stress.

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Armario, A; Lopez-Calderón, A; Jolin, T; Castellanos, J M

1986-08-04

The effect of graded levels of stressor intensity on anterior pituitary hormones was studied in adult male rats. Corticosterone, considered as a reflection of ACTH release, and prolactin responses showed a good correlation with the intensity of the stressors. On the contrary, neither LH, GH nor TSH release showed a parallelism with the intensity of the stressors in spite of the fact that they clearly responded to all the stimuli. It appears that the hormones of the anterior pituitary might be divided into two groups: those whose response is sensitive to the levels of emotional arousal elicited by stress, and those displaying a clear but stereotyped response during stress. However, other alternative explanations might exist to justify the present results. The neural mechanisms underlying the two types of response are at present unknown. These data indicate that only the pituitary-adrenal axis and prolactin have some potential utilities as quantitative indices of emotional arousal elicited by currently applied stressors in the rat.

Cardiovascular and hormonal responses of conscious pigs during physical restraint

International Nuclear Information System (INIS)

Wade, C.E.; Bossone, C.A.; Hannon, J.P.; Hunt, M.M.; Rodkey, W.G.

1986-01-01

We investigated the effect of physical restraint on cardiovascular function and plasma hormone levels in 20 to 25 kg conscious Duroc pigs. Pigs were placed in a Pavlov sling or remained in a portable holding cage. Blood pressure and heart rate were monitored and blood samples taken at 0, 2.5, 5, 10, 30, 60, 120 and 240 min. Placement into the sling increased heart rate from 106 ''+ or -'' 3 to 151 ''+ or -'' 13 beats/min and mean arterial pressure rose from 95 ''+ or -'' 2 to 115 ''+ or -'' 2 mm Hg. Both heart rate and blood pressure returned to basal values within 10 min. Hematocrit was increased from 26 ''+ or -'' 1 to 32 ''+ or -'' 1%. Heart rate, blood pressure and hematocrit were not changed in caged animals. Plasma norepinephrine increased from 179 ''+ or -'' 32 to 461 ''+ or -'' 52 pg/ml returning to basal values within 10 min. Epinephrine showed a similar trend rising from 69 ''+ or -'' 10 to 337 ''+ or -'' 53 pg/ml. Plasma renin activity increased after 5 min in the sling and remained increased from a basal level of 1.0 ''+ or -'' 0.2 to 2.8 ''+ or -'' 0.5 ng AI/ml/hr at four hr. Plasma cortisol (4.5 ''+ or -'' 0.6 to 8.2 ''+ or -'' 1.5 microg/dl), ACTH (45 ''+ or -'' 9 to 169 ''+ or -'' pg/ml) and aldosterone (3.5 ''+ or -'' 0.4 to 11.2 ''+ or -'' 1.1 ng/dl) rose over the four hr period. Pigs in cages showed no change in plasma hormones. Placement of an untrained pig into a sling raises heart rate, blood pressure and hematocrit and produces increases in plasma concentrations of epinephrine, ACTH, cortisol and aldosterone

Profound amplification of secretory-burst mass and anomalous regularity of ACTH secretory process in patients with Nelson's syndrome compared with Cushing's disease

NARCIS (Netherlands)

van Aken, Maarten O.; Pereira, Alberto M.; van den Berg, Gerrit; Romijn, Johannes A.; Veldhuis, Johannes D.; Roelfsema, Ferdinand

2004-01-01

As described originally, Nelson's syndrome is characterized by grossly elevated ACTH concentrations, a sellar mass and skin hyperpigmentation emerging in the course of Cushing's disease after bilateral adrenalectomy. No detailed studies have defined whether the mechanisms directing ACTH secretion

A NEW CLINICAL PREDICTION CRITERION ACCURATELY DETERMINES A SUBSET OF PATIENTS WITH BILATERAL PRIMARY ALDOSTERONISM BEFORE ADRENAL VENOUS SAMPLING.

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Kocjan, Tomaz; Janez, Andrej; Stankovic, Milenko; Vidmar, Gaj; Jensterle, Mojca

2016-05-01

Adrenal venous sampling (AVS) is the only available method to distinguish bilateral from unilateral primary aldosteronism (PA). AVS has several drawbacks, so it is reasonable to avoid this procedure when the results would not affect clinical management. Our objective was to identify a clinical criterion that can reliably predict nonlateralized AVS as a surrogate for bilateral PA that is not treated surgically. A retrospective diagnostic cross-sectional study conducted at Slovenian national endocrine referral center included 69 consecutive patients (mean age 56 ± 8 years, 21 females) with PA who underwent AVS. PA was confirmed with the saline infusion test (SIT). AVS was performed sequentially during continuous adrenocorticotrophic hormone (ACTH) infusion. The main outcome measures were variables associated with nonlateralized AVS to derive a clinical prediction rule. Sixty-seven (97%) patients had a successful AVS and were included in the statistical analysis. A total of 39 (58%) patients had nonlateralized AVS. The combined criterion of serum potassium ≥3.5 mmol/L, post-SIT aldosterone AVS. The best overall classification accuracy (50/67 = 75%) was achieved using the post-SIT aldosterone level AVS. Our clinical prediction criterion appears to accurately determine a subset of patients with bilateral PA who could avoid unnecessary AVS and immediately commence with medical treatment.

Peculiarities of hormonal status of patients with exogenous constitutional obesity before and after nalorphine administration

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Spesivtseva, V.G.; Berestov, L.A.; Shiyan, I.V.; Kokhanenko, Eh.M. (Pervyj Moskovskij Meditsinskij Inst. (USSR))

1984-11-01

By means of radioimmunoassay the peculiarities of hormonal status of 24 patients with exogenous constitutional obesity before and after nalorphine intravenous administration are studied. Nalorphine is found to stimulate the ACTH and hydrocortisone synthesis, to suppress the b-endorphine and synthesisprolactin to stimulate the STH secretion. A repeated nalorphine administration revealed latent peculiarities of the endocrine system connected with the pathogenesis of obesity. It is shown that the use of nalorphine is not followed by side-effects neither at a single administration nor in case of a three-days treatment.

Cytokine modulation by stress hormones and antagonist specific hormonal inhibition in rainbow trout (Oncorhynchus mykiss) and gilthead sea bream (Sparus aurata) head kidney primary cell culture.

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Khansari, Ali Reza; Parra, David; Reyes-López, Felipe E; Tort, Lluís

2017-09-01

A tight interaction between endocrine and immune systems takes place mainly due to the key role of head kidney in both hormone and cytokine secretion, particularly under stress situations in which the physiological response promotes the synthesis and release of stress hormones which may lead into immunomodulation as side effect. Although such interaction has been previously investigated, this study evaluated for the first time the effect of stress-associated hormones together with their receptor antagonists on the expression of cytokine genes in head kidney primary cell culture (HKPCC) of the freshwater rainbow trout (Oncorhynchus mykiss) and the seawater gilthead sea bream (Sparus aurata). The results showed a striking difference when comparing the response obtained in trout and seabream. Cortisol and adrenocorticotropic hormone (ACTH) decreased the expression of immune-related genes in sea bream but not in rainbow trout and this cortisol effect was reverted by the antagonist mifepristone but not spironolactone. On the other hand, while adrenaline reduced the expression of pro-inflammatory cytokines (IL-1β, IL-6) in rainbow trout, the opposite effect was observed in sea bream showing an increased expression (IL-1β, IL-6). Interestingly, this effect was reverted by antagonist propranolol but not phentolamine. Overall, our results confirm the regional interaction between endocrine and cytokine messengers and a clear difference in the sensitivity to the hormonal stimuli between the two species. Copyright © 2017 Elsevier Inc. All rights reserved.

VENOUS SAMPLING FOR CUSHING DISEASE: COMPARISON OF INTERNAL JUGULAR VEIN AND INFERIOR PETROSAL SINUS SAMPLING.

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Radvany, Martin G; Quinones-Hinojosa, Alfredo; Gallia, Gary L; Wand, Gary S; Salvatori, Roberto

2016-09-01

Because magnetic resonance imaging (MRI) fails to detect many adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, inferior petrosal sinus sampling (IPSS) is considered the gold standard to differentiate Cushing disease (CD) from ectopic ACTH secretion syndrome (EAS). Some authors have suggested internal jugular vein sampling (IJVS) as an alternative to IPSS. We simultaneously compared IJVS to IPSS in 30 consecutive patients referred for ACTH-dependent Cushing syndrome and equivocal MRI exams. Five sites were simultaneously sampled in each patient (right and left IPS, right and left IJV, and femoral vein) before and after the administration of corticotrophin-releasing hormone or desmopressin. The test was considered consistent with CD when the IPS to peripheral ratio was >2 at baseline or >3 after stimulus and the IJV to peripheral ratio was >1.7 at baseline or >2 after stimulus. In 27 of 30 patients, IPSS results were consistent with a central source of ACTH. Two of the other 3 patients had EAS (one lung carcinoid and one occult), and 1 patient had pathology-proven CD. The sensitivity of IPSS was 96.4%. Only 64.2% of these patients had results meeting criteria for a central source of ACTH by IJVS criteria. Twenty patients with centralizing IPPS have undergone pituitary surgery. Of these, the central origin of excessive ACTH was confirmed with certainty in 16 patients. Among these 16 patients, the IPSS sensitivity was 93.8%, whereas 5 patients had false-negative IJVS (68.7% sensitivity). These results do not support the routine use of IJVS in establishing if the pituitary is the source of excessive ACTH. ACTH = adrenocorticotropic hormone CD = Cushing disease CRH = corticotrophin-releasing hormone CS = Cushing syndrome DDAVP = desmopressin EAS = ectopic ACTH secretion IJVS = internal jugular vein sampling IPSS = inferior petrosal sinus sampling JVS = jugular venous sampling MRI = magnetic resonance imaging.

The impact of acute stress on hormones and cytokines, and how their recovery is affected by music-evoked positive mood.

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Koelsch, Stefan; Boehlig, Albrecht; Hohenadel, Maximilian; Nitsche, Ines; Bauer, Katrin; Sack, Ulrich

2016-03-29

Stress and recovery from stress significantly affect interactions between the central nervous system, endocrine pathways, and the immune system. However, the influence of acute stress on circulating immune-endocrine mediators in humans is not well known. Using a double-blind, randomized study design, we administered a CO2 stress test to n = 143 participants to identify the effects of acute stress, and recovery from stress, on serum levels of several mediators with immune function (IL-6, TNF-α, leptin, and somatostatin), as well as on noradrenaline, and two hypothalamic-pituitary-adrenal axis hormones (ACTH and cortisol). Moreover, during a 1 h-recovery period, we repeatedly measured these serum parameters, and administered an auditory mood-induction protocol with positive music and a neutral control stimulus. The acute stress elicited increases in noradrenaline, ACTH, cortisol, IL-6, and leptin levels. Noradrenaline and ACTH exhibited the fastest and strongest stress responses, followed by cortisol, IL-6 and leptin. The music intervention was associated with more positive mood, and stronger cortisol responses to the acute stressor in the music group. Our data show that acute (CO2) stress affects endocrine, immune and metabolic functions in humans, and they show that mood plays a causal role in the modulation of responses to acute stress.

The effect of acute heat exposure on rat pituitary corticotroph activation: the role of vasopressin.

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Sinisa Djurasevic

2011-04-01

Full Text Available The increased ambient temperature affects the function of hypothalamic-pituitary-adrenal (HPA axis. Since the correlation among vasopressin (VP, adrenocorticotropic hormone (ACTH and corticosterone (CORT responses to various stressors have been long recognized, the aim of this study was to reveal the aforementioned hormones production and morphology of the pituitary gland after exposure to acute heat. Rats were exposed to high ambient temperature (38 °C for 20 or 60 minutes. The circulating hormones were determined by an ELISA test or chemiluminescence's method. The results obtained show the elevation in ACTH and CORT secretion depending on the duration of heat exposure. The VP concentration increased only after prolonged exposure to heat (60 min. The pituitary morphology was examined by routine and fluorescent immunohistochemistry as well as electron microscopy. Observed changes in the anterior and posterior pituitary well corresponded to circulating hormones, regarding the volume density of ACTH-immunopositive cells, percentage of ACTH immunopositive area v. total area and number of VP-immunopositive containing varicose fibers per total area. Acute heat exposure also induced changes in shapes of ACTH-immunopositive cells. Cells appeared stellate with numerous slender cytoplasmic processes and degranulated, which is the most obvious after 20 min. In addition, immunopositivity of endothelial and anterior pituitary cells for VP suggests its influence on ACTH secretion.

Early-onset severe obesity with ACTH deficiency and red hair in a boy: the POMC deficiency.

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Ozen, S; Aldemir, O

2012-01-01

The patient is a 2.8 years old male who is extremely obese and severe hyperphagic from birth. He had seizures attacks and apnea from the second week of his life. He has red hair and serum cortisol and ACTH levels are very low. We examined our patient as a hypocortisolism due to ACTH deficiency and central hypothyrodism. After the corticosteroid replacement therapy hair color changed to brown. We performed molecular genetic analysis at the Institue for Experimental Pediatric Endocrinology laboratory in Berlin, Germany by Krude H. and found compound heterozygous mutations. As a result the case is diagnosed as POMC deficiency.

Level of cortisol and reactivity of adrenal cortex to exogenous ACTH at neonatal period in calves

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Friedrich, M.

1992-01-01

The studies were carried out on calves from 1st to 21st day of life. Cortisol level and reactivity of adrenal cortex to exogenous ACTH were analysed. The highest level of cortisol in blood was observed in first days of life in the calves. Then the level became considerably decreased. In the experimental group two subgroups differing in cortisol level were distinguished. High or low level occurred on the first day and the difference kept over two weeks of their life. Adrenal cortex just on the day of birth showed full functional maturity of molecular receptors binding ACTH. (author). 15 refs

Changes of Pituitary Hormones after Injection of Naloxone in the Hypotensive Phase of Korean Hemorrhagic Fever

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Lim, Sang Moo; Cho, Bo Youn; Lee, Hong Gyu; Lee, Jung Sang; Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Byung Tae [Hallym Medical College, Seoul (Korea, Republic of)

1986-09-15

The opiate antagonist, naloxone, was injected for the reversal of hypotension due to Korean hemorrhagic fever, and the authors observed changes in pituitary hormones. In the hypotensive phase of the Korean hemorrhagic fever, the beta-endorphin was high, and normalized gradually in the diuretic and convalescent period. The naloxone raised the pulse rate and the blood pressure within 30 minutes without change in the central venous pressure. Around 30 minuted after the injection of the naloxone, the beta-endorphin, ACTH and cortisol rose. The prolactin fell down 60 minutes after the naloxone injection.

Burnout and hypocortisolism – a matter of severity? A study on ACTH and cortisol responses to acute psychosocial stress

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Anna-Karin eLennartsson

2015-02-01

Full Text Available Background: Common consequences of long-term psychosocial stress are fatigue and burnout. It has been suggested that burnout could be associated with hypocortisolism, thus, inability to produce sufficient amounts of cortisol. This study aimed to investigate whether patients with clinical burnout exhibit aberrant ACTH and cortisol responses under acute psychosocial stress compared with healthy individuals. Methods: Nineteen patients (9 men and 10 women and 37 healthy subjects (20 men and 17 women, underwent the Trier Social Stress Test. Blood samples and saliva samples were collected before, after and during the stress test for measurements of plasma ACTH, serum cortisol and salivary cortisol. Several statistical analyses were conducted to compare the responses between patients and controls. In addition, in order to investigate the possibility that burnout patients with more severe symptoms would respond differently, sub-groups of patients reporting higher and lower burnout scores were compared. Results: In both patients and healthy controls, we observed elevated levels of ACTH and cortisol after exposure to the stressor. There were no differences in responses of ACTH, serum cortisol or salivary cortisol between patients and controls. Patients reporting higher burnout scores had lower salivary cortisol responses than controls, indicating that patients with more severe burnout symptoms may be suffering from hypocortisolism. In addition patients with more severe burnout symptoms tended to have smaller ACTH responses than the other patients. There was no corresponding difference in serum cortisol however. Conclusion: This study indicates that hypocortisolism is not present in a clinical burnout patient group as a whole but may be present in the patients with more severe burnout symptoms.

The role of inferior petrosal sinus sampling in ACTH-dependent Cushing's syndrome: review and joint opinion statement by members of the Italian Society for Endocrinology, Italian Society for Neurosurgery, and Italian Society for Neuroradiology.

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Pecori Giraldi, Francesca; Cavallo, Luigi Maria; Tortora, Fabio; Pivonello, Rosario; Colao, Annamaria; Cappabianca, Paolo; Mantero, Franco

2015-02-01

In the management of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, inferior petrosal sinus sampling (IPSS) provides information for the endocrinologist, the neurosurgeon, and the neuroradiologist. To the endocrinologist who performs the etiological diagnosis, results of IPSS confirm or exclude the diagnosis of Cushing's disease with 80%-100% sensitivity and over 95% specificity. Baseline central-peripheral gradients have suboptimal accuracy, and stimulation with corticotropin-releasing hormone (CRH), possibly desmopressin, has to be performed. The rationale for the use of IPSS in this context depends on other diagnostic means, taking availability of CRH and reliability of dynamic testing and pituitary imaging into account. As regards the other specialists, the neuroradiologist may collate results of IPSS with findings at imaging, while IPSS may prove useful to the neurosurgeon to chart a surgical course. The present review illustrates the current standpoint of these 3 specialists on the role of IPSS.

Evaluation of aldosterone-and cortisol levels in blood plasma in normal conditions of ingestion of sodium and potassium, after saline-increase and depletion, in regard to position, and after stimulation with ACTH and angiotensin II

International Nuclear Information System (INIS)

Okada, H.

1979-01-01

Methods for the determination of plasma aldosterone and cortisol, by radioimmunoassay, were performed utilizing highly specific antisera. With this methodology it was possible to evaluate cortisol and aldosterone secretion, in six normal subjects, submitted to a basal rice diet on standing and recumbent positions, the effects of exogenous cortrosyn (β1-24 ACTH) and angiotensin II and the same manoevres with progressively increased Na + content of the diet. Aldosterone basal levels decreased with the increase of Na + content in the diet. However, there were no significant differences between the relative increments observed on the recumbent position, at the three levels of sodium intake. The relative increase of plasma aldosterone after ACTH was similar for each basal level of aldosterone induced by different sodium intakes. The responsiveness of aldosterone secretion to cortrosyn and standing position was similar, with no relation to the sodium intake. The infusion of angiotensin II induced an increase in plasma aldosterone, and the relative increment in the levels of the hormone were higher with high sodium than on the rice diet. The average basal cortisol value at the different levels of sodium intake was significantly different being greater on the basal, rice diet, and there was a decrease in cortisol level after recumbency, with the theree diets. The injection of ACTH induced similar cortisol secretion with no relation to the sodium intake. The infusion of non-hypertensive doses of angiotensin II resulted in an anomalous fall in cortisol level, probably because of 'shunt' of substrates to biosynthesis with the added effect of cortisol diurnal rhythmycity. (Author) [pt

Effect of flurbiprofen axetil pretreatment on the pain degree as well as stress hormone and mediator secretion after abdominal surgery

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Ying Chen

2017-07-01

Full Text Available Objective: To study the effect of flurbiprofen axetil pretreatment on the pain degree as well as stress hormone and mediator secretion after abdominal surgery. Methods: Patients undergoing abdominal surgery in our hospital between May 2015 and March 2017 were selected and randomly divided into two groups, intervention group received flurbiprofen axetil pretreatment combined with routine intravenous anesthesia, and the control group only accepted conventional intravenous anesthesia. The levels of pain neurotransmitters and cytokines, stress hormones and mediators in serum were detected before operation as well as 12 h and 24 h after operation. Results: 12 h and 24 h after operation, serum NPY, SP, Glu, TNF-α, IL-2, IL-6, IL- 10, ACTH, Cor, Ins, NE and E levels of both groups of patients were significantly higher than those before operation while SOD, GHS-Px and HO-1 levels were significantly lower than those before operation, and serum NPY, SP, Glu, TNF-α, IL-2, IL-6, IL-10, ACTH, Cor, Ins, NE and E levels of intervention group 12 h and 24 h after operation were significantly lower than those of control group while SOD, GHS-Px and HO-1 levels were significantly higher than those of control group. Conclusion: Flurbiprofen axetil pretreatment can reduce the pain degree and stress response after abdominal surgery.

A rare cause of Cushing's syndrome

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Folkestad, Lars; Andersen, Marianne Skovsager; Nielsen, Anne Lerberg

2014-01-01

Excess glucocorticoid levels cause Cushing's syndrome (CS) and may be due to pituitary, adrenal or ectopic tumours. Adrenocorticotropic hormone (ACTH) levels are useful in identifying adrenal tumours. In rare cases, ACTH-producing phaeochromocytomas are the cause of CS. We present two cases of ACTH...

Human recombinant factor VIIa may improve heat intolerance in mice by attenuating hypothalamic neuronal apoptosis and damage.

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Hsu, Chuan-Chih; Chen, Sheng-Hsien; Lin, Cheng-Hsien; Yung, Ming-Chi

2014-10-01

Intolerance to heat exposure is believed to be associated with hypothalamo-pituitary-adrenocortical (HPA) axis impairment [reflected by decreases in blood concentrations of both adrenocorticotrophic-hormone (ACTH) and corticosterone]. The purpose of this study was to determine the effect of human recombinant factor VIIa (rfVIIa) on heat intolerance, HPA axis impairment, and hypothalamic inflammation, ischemic and oxidative damage, and apoptosis in mice under heat stress. Immediately after heat stress (41.2 °C for 1 h), mice were treated with vehicle (1 mL/kg of body weight) or rfVIIa (65-270 µg/kg of body weight) and then returned to room temperature (26 °C). Mice still alive on day 4 of heat exposure were considered survivors. Cellular ischemia markers (e.g., glutamate, lactate-to-pyruvate ratio), oxidative damage markers (e.g., nitric oxide metabolite, hydroxyl radials), and pro-inflammatory cytokines (e.g., interleukin-6, interleukin-1β, tumor necrosis factor-α) in hypothalamus were determined. In addition, blood concentrations of both ACTH and corticosterone were measured. Hypothalamic cell damage was assessed by determing the neuronal damage scores, whereas the hypothalamic cell apoptosis was determined by assessing the numbers of cells stained with terminal deoxynucleotidyl transferase-mediated αUTP nick-end labeling, caspase-3-positive cells, and platelet endothelial cell adhesion molecula-1-positive cells in hypothalamus. Compared with vehicle-treated heated mice, rfVIIa-treated heated mice had significantly higher fractional survival (8/10 vs 1/10), lesser thermoregulatory deficit (34.1 vs 24.8 °C), lesser extents of ischemic, oxidative, and inflammatory markers in hypothalamus, lesser neuronal damage scores and apoptosis in hypothalamus, and lesser HPA axis impairment. Human recombinant factor VIIa appears to exert a protective effect against heatstroke by attenuating hypothalamic cell apoptosis (due to ischemic, inflammatory, and oxidative damage

Immunoglobulin changes in boars exposed to administration of levamisole and exogenous adrenocorticotropic hormone

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Bilandžić Nina

2012-01-01

Full Text Available The objective of this paper was to determine the effect of levamisole (LEV on immunoglobulin concentration in the serum of boars exposed to 3-day stress induced by exogenous ACTH. Boars were assigned to 4 groups (n=7. The first group received LEV for 3 days (2.5 mg/kg BW, the second group received ACTH (10 μg/kg BW for 3 days and the third group received LEV for 3 consecutive days and ACTH for the following 3 days (2.5 mg/kg BW; ACTH 10 μg/kg BW. The control group received saline solution during the 6 days. Concentrations of cortisol, total protein, globulin, albumin and immunoglobulin (IgG, IgA and IgM were determined during treatments and on the 16th day post-administration. Cortisol concentration was increased in both ACTH treated groups during all three days of administration and the day after the last ACTH treatment (p<0.05. ACTH increased total protein levels during the stress period and over the next 16 days (p<0.05. However, in the LEV+ACTH group total protein levels were elevated only on day 1 and 2 of ACTH injection (p<0.05 and after the end of treatment on day 11 and 22 (p<0.05. LEV stimulated the increase of protein concentrations compared to control values after LEV treatment, on days 5, 14, 18 and 22 (p<0.05. Serum albumins were not affected by LEV or ACTH treatment. Globulin concentrations were increased throughout and on the 16th day after administration of ACTH in the ACTH and LEV+ACTH groups (p<0.05. Globulin concentrations did not differ between LEV and control groups of boars. ACTH treatment elevated serum IgG concentration during the stress period (p<0.05 and over the next 16 days (p<0.05. However, in the LEV+ACTH group of boars, IgG levels were elevated on days 1 and 3 after ACTH injection (p<0.05 and days 1 and 5 in the post-treatment period (p<0.05. LEV had no impact on IgG levels compared to the control boars. However, increased IgA concentrations in boars treated with LEV were determined on day 2 (p<0.05 and day 11 (p

[Clinical study on the postburn change in the hypothalamus-pituitary-adrenal hormones in severely burned patients].

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Li, Hong-mian; Liang, Zi-qian; Luo, Zuo-jie

2003-06-01

To investigate the postburn dynamic changes in the hypothalamus-pituitary-adrenal hormones in severely burned patients. Fifty burn patients were enrolled in the study. The plasma contents of total GC (cortisol), ACTH and aldosterone (ALDO) and urinary contents of 17-OHO and 17-KS were determined with radio-immunological assay (RIA) method after burn injury to compare with the normal values which were well established clinically. The postburn plasma and urinary contents of the above indices were increased evidently with two peak values in shock and infectious stages, whilst the majority of he indices were lower than the normal values after 6 postburn weeks (PBWs). The values of these hormones were the lowest in dying patients. On the other hand, the values approached normal levels in those patients whose burn wounds were healing. Increases of the plasma and urinary levels of hypothalamus-pituitary -adrenal hormones in severely burned patients were constantly seen. Burn shock and infection seemed to be the two major factors in inducing postburn stress reaction in burn victims. Abrupt decrease of the hormone levels in plasma and or urine indicated adrenal failure predicting a poor prognosis of the burn patients.

CCR4 agonists CCL22 and CCL17 are elevated in pediatric OMS sera: rapid and selective down-regulation of CCL22 by ACTH or corticosteroids.

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Pranzatelli, Michael R; Tate, Elizabeth D; McGee, Nathan R; Colliver, Jerry A; Ransohoff, Richard M

2013-05-01

To study the role of Th2-attracting chemokines in opsoclonus-myoclonus syndrome (OMS), a serious neurological paraneoplastic disorder in need of better immunological understanding and therapy. The CCR4 agonists CCL22 and CCL17 were measured in serum by ELISA in children with OMS (238 and 260, respectively), pediatric controls (115 and 143), and other inflammatory neurological disorders (33 and 24). Both CCL22 (+55 %) and CCL17 (+121 %) were significantly elevated in untreated OMS compared to controls and inter-correlated (p OMS also were higher than in OIND (21 %, 41 %). The concentration of CCL22 in ACTH and steroids groups (not IVIg) was 51 % lower than in controls, but only a smaller effect of ACTH on CCL17 was found. Prospective longitudinal studies revealed a precipitous 81 % drop in CCL22 even by the first week of high-dose ACTH therapy, staying below control mean for at least 12 weeks, and a 34 % reduction after 8 months of combined treatment. Response to ACTH was dose-related (r = -0.50, p OMS. Marked and rapid reduction in CCL22, not CCL17, with either ACTH or steroid therapy suggests differential regulation and cellular sources of CCR4 ligands, and CCL22 as a potential candidate biomarker for ACTH or corticosteroid effect.

Outcome of synthetic adrenocorticotropin hormone treatment in children with infantile spasm

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I Gusti Ngurah Made Suwarba

2011-04-01

Full Text Available Background Infantile spasms (IS is an age-spedfic epilepsy syndrome characterized by flexor, extensor, and mixed flexor-extensor spasms which often occur in clusters during the first 2 years of life. IS is often difficult to manage 'With the usual anti-epilepsy drugs (AEDs. Therapy with adrenocorticotropin honnone (ACTH has been used since 1958. In Indonesia, ACTH usage is still rare. Objective This study aims to examine the effectiveness of ACTH as an anti-epileptic drug in managing IS. Methods This was descriptive retrospective cohort study. Subjects were IS patients who visited the neurology outpatient clinic in Sanglah Hospital, Bali, from January 2007 until June 2010. Each subject received AED(s plus either ACTH or methylprednisolone for 46 weeks. Results There were 19 IS patients over the four year duration of this study. They were mostly boys (11, aged 2 weeks to 17 months, with a mean age at treatment of 9 months. Eighteen patients received poly therapy, while one patient received only phenobarbital as monotherapy. Most patients who received ACTH (13/16 had a seizure-free period, while the 3 that did not receive ACTH continued having seizures. Patients who received ACTH showed a good response (seizure-free after 5-13 days therapy and their EEG pattern showed disappearance of burst suppression Mthin 1-2 weeks. ACTH side effects included weight gain and cushingoid appearance. One patient died from pneumonia. Conclusions Diagnosis of IS should be considered in patients pre-senting Mth spasms at less than 6 months old. IS treatment should begin as soon as possible. IS patients responded well to a short course of ACTH therapy.

Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies

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Baker, Peter R.; Nanduri, Priyaanka; Gottlieb, Peter A.; Yu, Liping; Klingensmith, Georgeanna J.; Eisenbarth, George S.; Barker, Jennifer M.

2016-01-01

Summary Context Autoantibodies to 21-hydroxylase (21OH-AA) precede onset of autoimmune Addison's disease (AD). Progression to AD can take months to years, and early detection of metabolic decompensation may prevent morbidity and mortality. Objective To define optimal methods of predicting progression to overt AD (defined by subnormal peak cortisol response to Cosyntropin) in 21OH-AA+ individuals. Design, Setting and Participants Individuals were screened for 21OH-AA at the Barbara Davis Center from 1993 to 2011. Subjects positive for 21OH-AA (n = 87) were tested, and the majority prospectively followed for the development of Addison's disease, including seven diagnosed with AD upon 21OH-AA discovery (discovered), seven who progressed to AD (progressors) and 73 nonprogressors. Main Outcome Measured Plasma renin activity (PRA), ACTH, baseline cortisol, peak cortisol and 21OH-AA were measured at various time points relative to diagnosis of AD or last AD-free follow-up. Results Compared with nonprogressors, in the time period 2 months–2 years prior to the onset of AD, progressors were significantly more likely to have elevated ACTH (11–22 pm, P < 1E-4), with no significant differences in mean PRA (P = 0·07) or baseline cortisol (P = 0·08), and significant but less distinct differences seen with 21OH-AA levels (P < 1E-4) and poststimulation cortisol levels (P = 6E-3). Conclusion Moderately elevated ACTH is a more useful early indicator of impending AD than 21OH-AA, PRA or peak cortisol, in the 2 months–2 years preceding the onset of AD. PMID:22066755

What can we know from pituitary-adrenal hormones about the nature and consequences of exposure to emotional stressors?

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Armario, Antonio; Daviu, Núria; Muñoz-Abellán, Cristina; Rabasa, Cristina; Fuentes, Silvia; Belda, Xavier; Gagliano, Humberto; Nadal, Roser

2012-07-01

Exposure to stress induces profound physiological and behavioral changes in the organisms and some of these changes may be important regarding stress-induced pathologies and animal models of psychiatric diseases. Consequences of stress are dependent on the duration of exposure to stressors (acute, chronic), but also of certain characteristics such as intensity, controllability, and predictability. If some biological variables were able to reflect these characteristics, they could be used to predict negative consequences of stress. Among the myriad of physiological changes caused by stress, only a restricted number of variables appears to reflect the intensity of the situation, mainly plasma levels of ACTH and adrenaline. Peripheral hypothalamic-pituitary-adrenal (HPA) hormones (ACTH and corticosterone) are also able to reflect fear conditioning. In contrast, the activation of the HPA axis is not consistently related to anxiety as evaluated by classical tests such as the elevated plus-maze. Similarly, there is no consistent evidence about the sensitivity of the HPA axis to psychological variables such as controllability and predictability, despite the fact that: (a) lack of control over aversive stimuli can induce behavioral alterations not seen in animals which exert control, and (b) animals showed clear preference for predictable versus unpredictable stressful situations. New studies are needed to re-evaluate the relationship between the HPA axis and psychological stress characteristics using ACTH instead of corticosterone and taking advantages of our current knowledge about the regulation of this important stress system.

Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.

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Mehta, M K; Garde, S V; Sheth, A R

1995-01-01

To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. These regulatory peptides may be involved in the pathophysiology of the testes.

Bilateral catheterization of the inferior petrosal sinuses in 23 cases of ACTh-dependent hypercoarisolism

International Nuclear Information System (INIS)

Castro, E.; Nombela, L.; Brasa, J.

1996-01-01

Our purpose is to assess the results of catheterization of the inferior petrosal sinuses, a measure that is included in the diagnostic protocol for ACTH-dependent hypercortisolism. We analyzed retrospectively the data obtained for 23 patients (20 women and 3 men) subjected to this procedure. The test was complete (catheterization both inferior petrosal sinuses) in 21 patients (91%). The sensitivity in differentiating between Cushing's disease (n=21) and ectopic ACTH syndrome (n=21) was 95.2% after administration of CRH, with a specificity of 100%, and the positive predictive value for the intra pituitary localization of the micro adenoma (confirmed by histological study in 19 cases) was 61%. Catheterization of the inferior petrosal sinuses shows an elevated sensitivity and specificity in the diagnosis of Cushing's disease, although the positive predictive value for determining the intrapituitary localization of the adenoma is low. (Author) 12 refs

Effects of anabolic hormones on structural, metabolic and functional aspects of skeletal muscle

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Flávio de Oliveira Pires

2009-06-01

Full Text Available This study reviewed information regarding the effects of anabolic hormones on strength gain and muscle hypertrophy, emphasizing the physiological mechanisms that may increase muscle strength. Structural, metabolic and functional aspects were analyzed and special attention was paid to the dose-response relationship. The Pubmed database was searched and studies were selected according to relevance and date of publication (last 15 years. The administration of high testosterone doses (~600 mg/week potentiates the effects of strength training, increasing lean body mass, muscle fiber type IIA and IIB cross-sectional area, and the number of myonuclei. There is no evidence of conversion between MHC isoforms. The interaction between testosterone administration and strength training seems to modify some metabolic pathways, increasing protein synthesis, glycogen and ATP-CP muscle stores and improving fat mobilization. Changes in 17-estradiol concentration or in the ACTH-cortisol and insulin-glucagon ratios seem to be associated with these metabolic alterations. Regarding performance, testosterone administration may improve muscle strength by 5-20% depending on the dose used. On the other hand, the effects of growth hormone on the structural and functional aspects of skeletal muscle are not evident, with this hormone more affecting metabolic aspects. However, strictly controlled human studies are necessary to establish the extent of the effects of anabolic hormones on structural, metabolic and functional aspects.

Longitudinal changes in pituitary-adrenal hormones in South African women with burnout.

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Moch, Shirra L; Panz, Vanessa R; Joffe, Barry I; Havlik, Ivan; Moch, Jonathan D

2003-08-01

The authors' goal was to document baseline pituitary-adrenal hormonal and related metabolic variables in 16 female patients with burnout. Then, following stress management intervention, to compare the changes with an equal number of untreated control subjects. At monthly intervals for 4 mo, 24-h urine samples were obtained for determination of free cortisol excretion. In addition, fasting blood samples were analyzed for levels of cortisol, dehydroepiandrosterone sulfate (DHEAS), ACTH, aldosterone, and catecholamines. Other biochemical measurements included growth hormone, prolactin, insulin, glucose, and lipid components. The Maslach Burnout Inventory, General Health Questionnaire- 28, and Zung depression rating scale were completed on each consecutive visit. The most striking finding was the reduction of urine free-cortisol excretion in the patients compared with controls. Initial urinary free cortisol was significantly lower in the patients (mean +/- SEM = 47.2 +/- 11.0 vs 79.0 +/- 6.8 nmol/L, p = 0.02) and remained significantly reduced at 4 mo (mean +/- SEM = 44.0 +/- 6.1 vs 91.1 +/- 8.8 nmol/L, p = 0.0001). There were no significant changes in the other hormonal and biochemical data. We conclude that there is functional hypocortisolism in burnout, which is not immediately restored on stress management intervention despite clinical and psychological improvement.

Biomarcadores de estresse em ratos exercitados por natação em intensidades igual e superior à máxima fase estável de lactato Biomarkers of stress in rats exercised in swimming at intensities equal and superior to the maximal estable lactate phase

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Ricardo Vinicius Ledesma Contarteze

2007-06-01

Full Text Available INTRODUÇÃO: O estresse alcançado durante exercício agudo/crônico é relevante, pois altos índices de estresse podem prejudicar o bem-estar dos animais. As concentrações dos hormônios adrenocorticotrófico (ACTH e corticosterona, bem como as concentrações de ácido ascórbico e colesterol das glândulas adrenais são importantes biomarcadores de estresse. OBJETIVO: Analisar a sensibilidade de diferentes biomarcadores de estresse em ratos durante exercício agudo de natação em diferentes intensidades. MÉTODO: Ratos (18 adaptados à natação foram submetidos a três testes de 25 minutos suportando cargas 5,0; 5,5 e 6,0% do peso corporal (PC, para obtenção da máxima fase estável de lactato (MFEL. Em seguida, os animais foram divididos em dois grupos: M (n = 9, sacrificado após 25 minutos de exercício na intensidade de MFEL e S (n = 9, sacrificado após exercício exaustivo, em intensidade 25% superior a MFEL. Para comparações, um grupo controle C (n = 10 foi sacrificado em repouso. RESULTADOS: As concentrações séricas de ACTH e corticosterona foram superiores após exercício em ambas as intensidades comparadas com o grupo controle (P INTRODUCTION: The level of stress during acute/chronic exercise is important, since higher levels of stress may impair animal welfare. The adrenocorticotrophic (ACTH and corticosterone hormone concentrations, as well as cholesterol and ascorbic acid concentrations in adrenal gland, are considered an important stress biomarker. PURPOSE: To analyze the sensitivity of the different biomarkers during acute swimming exercise in different intensities performed by rats. METHODS: Male Wistar adult rats (n = 18 previously adapted to swimming were submitted to three 25 min. swimming tests with loads of 5.0; 5.5 and 6.0% of their body weight (BW, for maximum lactate steady state (MLSS determination. After MLSS attainment, the animals were divided into two groups: M (n = 9 sacrificed shortly after a 25

Association of HPA axis hormones with copeptin after psychological stress differs by sex.

Science.gov (United States)

Spanakis, Elias K; Wand, Gary S; Ji, Nan; Golden, Sherita Hill

2016-01-01

Copeptin levels are elevated in severe medical conditions, an effect that is attributed to elevated arginine vasopressin (AVP) levels in response to physiological stress, resulting in activation of hypothalamus-pituitary-adrenal (HPA) axis. In the current study, we wanted to determine if copeptin is responsive to psychological stress, correlates with cortisol and adrenocorticotropin hormone (ACTH), and if associations differed by sex. In a cross-sectional study that included 100 healthy men (41%) and women (59%) (aged 18-30 years; mean 24.6 ± 3 years), who underwent the Trier Social Stress Test (TSST), we examined the association between percent change (peak-baseline/baseline) in copeptin levels and percent change in log ACTH and cortisol. Three baselines samples were drawn followed by blood sampling at 20, 35, 50, 65 and 85 min after TSST. There was a significant positive association between the percent change in copeptin and the percent change in log-transformed salivary cortisol (β-coefficient=0.95; p=0.02). The association between percent change in copeptin and log-transformed serum cortisol was not statistically significant in the overall population. There was a trend for a non-significant association between percent change in copeptin and percent change in log-transformed ACTH (β-coefficient=1.14; p=0.06). In males, there was a significant positive association between the percent change in copeptin levels and log-transformed salivary (β-coefficient=1.33, p=0.016) and serum cortisol (β-coefficient=0.69, p=0.01), whereas in women there was no statistically significant association. We found a significant positive association between percent change in copeptin and percent change in salivary and serum cortisol among males only. Copyright © 2015 Elsevier Ltd. All rights reserved.

Variations in adrenal hormones in law enforcement servicemen during a mission to local armed conflict

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Roman Victorovich Koubassov

2014-09-01

Full Text Available In a previous study, we reported changes in the adrenocorticotropic hormone (ACTH and cortisol secretion in blood samples from law enforcement personnel during the mission to local armed conflict region. In the present study, we demonstrate those changes collectively with additional data on changes in the adrenaline and noradrenaline in the urine samples of the same individuals. The study was conducted on 48 male officers who were deployed to an army conflict teritory for a duration of 4 months.At the onset of the mission, there was a modestincreasein all hormones corresponding to the general adaptation syndrome theory. As the mission started, significant increases were observed in the mean levels of the hormonal parameters in both serum and urine at different time points as compared to those before the mission. At first week of deployment, a sharp increase in the secretory activity of medulla and cortical adrenal gland was found and at the termination of the mission a dysfunction of hypophysis-adrenal gland regulation system was identified. These findings might lead to disturbances in interhormonal relationships and causedecreased stress tolerance in the relevant individals.

Hyperthyroidism due to thyroid-stimulating hormone secretion after surgery for Cushing's syndrome: a novel cause of the syndrome of inappropriate secretion of thyroid-stimulating hormone.

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Tamada, Daisuke; Onodera, Toshiharu; Kitamura, Tetsuhiro; Yamamoto, Yuichi; Hayashi, Yoshitaka; Murata, Yoshiharu; Otsuki, Michio; Shimomura, Iichiro

2013-07-01

Hyperthyroidism with the syndrome of inappropriate secretion of TSH (SITSH) occurred by a decrease in hydrocortisone dose after surgery for Cushing's syndrome. This is a novel cause of SITSH. The aim of this study was to describe and discuss 2 cases of SITSH patients that were found after surgery for Cushing's syndrome. We also checked whether SITSH occurred in 7 consecutive patients with Cushing's syndrome after surgery. A 45-year-old Japanese woman with ACTH-independent Cushing's syndrome and a 37-year-old Japanese man with ACTH-dependent Cushing's syndrome presented SITSH caused by insufficient replacement of hydrocortisone for postoperative adrenal insufficiency. When the dose of hydrocortisone was reduced to less than 20 mg/d within 18 days after surgery, SITSH occurred in both cases. We examined whether the change of the hydrocortisone dose induced the secretion of TSH. Free T₃ and TSH were normalized by the hydrocortisone dose increase of 30 mg/d, and these were elevated by the dose decrease of 10 mg/d. We also checked TSH and thyroid hormone levels of the 7 consecutive patients with Cushing's syndrome after surgery. Six (66.6 %) of 9 patients showed SITSH. This is the first report that insufficient replacement of hydrocortisone after surgery for Cushing's syndrome caused SITSH. Hyperthyroidism by SITSH as well as adrenal insufficiency can contribute to withdrawal symptoms of hydrocortisone replacement. We need to consider the possibility of SITSH for the pathological evaluation of withdrawal syndrome of hydrocortisone replacement.

La melatonina reduce la respuesta de cortisol al ACTH en humanos

OpenAIRE

Campino,Carmen; Valenzuela,Francisco; Arteaga,Eugenio; Torres-Farfán,Claudia; Trucco,Cristián; Velasco,Alfredo; Guzmán,Sergio; Serón-Ferré,María

2008-01-01

Background: Melatonin receptors are widely distributed in human tissues but they have not been reported in human adrenal gland. Aim: To assess if the human adrenal gland expresses melatonin receptors and if melatonin affeets cortisol response to ACTH in dexamethasone suppressed volunteers. Material and methods: Adrenal glands were obtained from 4 patients undergoing unilateral nephrectomy-adrenalectomy for renal cáncer. Expression of mRNA MT1 and MT2 melatonin receptors was measured by Revers...

Lepidium meyenii (Maca) enhances the serum levels of luteinising hormone in female rats.

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Uchiyama, Fumiaki; Jikyo, Tamaki; Takeda, Ryosuke; Ogata, Misato

2014-02-03

Lepidium meyenii (Maca) is traditionally employed in the Andean region for its supposed fertility benefits. This study investigated the effect of Maca on the serum pituitary hormone levels during the pro-oestrus phase. Maca powder was made from the tubers of Lepidium meyenii Walp collected, dried, and reduced to powder at the plantation in Junín Plateau and was purchased from Yamano del Perú SAC. The Maca powder was identified by chemical profiling and taxonomic methods. Two groups of female Sprague-Dawley rats were provided feed with normal feed containing 5%, 25%, or 50% Maca powder ad libitum for 7 weeks. At 1800h of the proestrus stage, the rats were euthanised, and blood samples were collected for serum isolation. The serum pituitary hormone levels were measured using enzyme-linked immunosorbent assays (ELISAs). No significant differences in feed intake or growth rate were observed among the rats. During the pro-oestrus stage, a 4.5-fold increase (PMaca powder compared with the control rats. No significant differences were observed in the levels of the other pituitary hormones, including growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), and thyroid-stimulating hormone (TSH). A dose-dependent increase of LH serum levels was observed within the range of 3-30g Maca/kg. Furthermore, the enhancement of the LH serum levels was specific to the pro-oestrus LH surge. The present study demonstrates that Maca uniquely enhances the LH serum levels of pituitary hormones in female rats during the pro-oestrus LH surge and acts in a pharmacological, dose-dependent manner. These findings support the traditional use of Maca to enhance fertility and suggest a potential molecular mechanism responsible for its effects. © 2013 Elsevier Ireland Ltd. All rights reserved.

Relationship of long-term macronutrients intake on anabolic-catabolic hormones in female elite volleyball players.

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Mielgo Ayuso, Juan; Zourdos, Michael C; Urdampilleta, Aritz; Calleja González, Julio; Seco, Jesús; Córdova, Alfredo

2017-10-24

Specific macronutrient distribution and training can alter acute and chronic hormone behavior and, subsequently, sport performance. The main aim was to examine relationships between dietary intake and anabolic/catabolic hormone response in elite female volleyball players during a 29-week season. Twenty-two elite female volleyballers (26.4 ± 5.6 years; 178 ± 9 cm; 67.1 ± 7.5 kg) had dietary intake (seven-day dietary recall and food frequency questionnaire), blood concentration of anabolic/catabolic hormones concentration, physical performance, and body composition assessed at four time points: a) T1: baseline/pre-testing; b) T2: eleven weeks after T1; c) T3: ten weeks after T2; and d) T4: eight weeks after T3. Hormones evaluated were: total testosterone (TT), free testosterone (FT) adrenocorticotropic hormone (ACTH), and cortisol (C), along with hormone ratios. Positive correlations were observed between carbohydrate/protein ratio with ΔFT (r = 0.955; p 0.05) in body mass or body mass index at any time point, and the sum of six skinfolds improved (p < 0.05) from T1 (86.5 ± 6.9 mm) to T4 (75.2 ± 5.6 mm) as did muscle mass (T1: 28.9 ± 0.7 kg vsT4: 30.1 ± 0.8 kg). Vertical jump, spike-jump and speed improved (p < 0.05) from T1 to T4. A high carbohydrate/protein ratio was associated with positive changes in anabolism, while high protein and low carbohydrates (CHO) were associated with an attenuated anabolic response.

A rare cause of respiratory distress and edema in neonate: Panhypopituitarism.

Science.gov (United States)

Dursun, Fatma; Kirmizibekmez, Heves; Metin, Fazilet

2017-01-01

Clinical presentation of hypopituitarism may be variable in the neonate. Symptoms are generally nonspecific, ranging from absent to severe, and even life-threatening, due to adrenocorticotrophic hormone deficiency. Presently described is a case of unexplained respiratory distress and edema in a neonate. Initial screening revealed panhypopituitarism. Respiratory distress improved after replacement treatment with hydrocortisone and thyroxine.

Radioimmunoassay of plasma corticotrophin

International Nuclear Information System (INIS)

Hummer, L.

1977-01-01

An assay has been established, based on antibodies against the N-terminal part of the ACTH molecule with a high affinity, a detection limit of 2 pg ACTH when assaying 200 ul unextracted plasma, and implying a total incubation time of three days. The antibody has been obtained by immunizing guinea-pigs with synthetic human 1-24 ACTH coupled to bovine serum albumin. The selected antibody has an equilibrium constant of 4 x 10 11 litres/mole in a final dilution of 1/320.000. The antiserum reacts with synthetic human 1-39 ACTH as well as with synthetic human 1-24 ACTH, and the hormonally inactive synthetic human 11-24 ACTH fragment as well as alpha- and beta-melanocyte-stimulating hormones do not cross-react in the assay. The interassay coefficient of variation of replicate estimates was 11-13%. The reproducibility of the standard curve have been evaluated by calculating the amount of ACTH corresponding to 5% of the (B/T)o value, 1.2+-0.4 pg ACTH/tube+-SD and 50% of (B/T)o value, 15.7+-2.6 pg ACTH/tube+-SD. Validation of the assay has been obtained by assaying samples from patients with verified adrenal disorders, and the accuracy is supported by ACTH determinations in test, where metyrapon had been administered intravenously. A stimulation of ACTH production by insulin-induced hypoglycaemia has been found as well. Special attention is always paid as to the conditions for the blood sampling. A reference interval of 10-76 ng/l has been found (115 normal subjects). (orig.) [de

Mapping the human corticotropin releasing hormone binding protein gene (CRHBP) to the long arm of chromosome 5 (5q11.2-q13.3)

Energy Technology Data Exchange (ETDEWEB)

Vamvakopoulos, N.C. [Univ. of Thessaly School of Medicine, Larisa (Greece); Sioutopoulou, T.O. [Univ. of Athens Medical School (Greece); Durkin, S.A. [American Type Culture Collection, Rockville, MD (United States)

1995-01-01

Unexpected stimulation or stress activates the heat shock protein (hsp) system at the cellular level and the hypothalamic-pituitary-adrenal (HPA) axis at the level of the whole organism. At the molecular level, these two systems communicate through the functional interaction between hsp90 and glucocorticoid receptor (GR). The corticotropin releasing hormone (CRH) system regulates the mammalian stress response by coordinating the activity of the HPA axis. It consists of the 41-amino-acid-long principal hypothalamic secretagogue for pituitary adrenocorticotropic hormone (ACTH), CRH, its receptor (CRHR), and its binding protein (CRHBP). Because of its central role in the coordination of stress response and whole body homeostasis, the CRH system has been implicated in the pathogenesis of neuroendocrine and psychiatric disease. 19 refs., 1 fig.

Beta-endorphin in the plasma: Radioimmunological determination and findings in patients showing disorders at the level of the hypothalamus-pituitary-adrenal axis

International Nuclear Information System (INIS)

Hoerl, A.

1985-01-01

Beta-endorphin and adrenocorticotropic hormone (ACTH) were determined simultaneously in the plasma using a radioimmunological procedure. It was found that in patients showing imbalances within the hypothalamus-pituitary-adrenal system (Addison's disease, Cushing's Syndrome, Nelson's Syndrome) as well as elevated levels of beta-endorphin the values of ACHT invariably were also increased. The behaviour of the plasma levels of beta-endorphin and ACTH before, during and subsequent to hypophyseal surgery gives evidence to prove the close link between the two hormones. Tests performed to examine the function of the corticotropin releasing factor (CRF) both in healthy volunteers and patients suffering from endocrinological disorders likewise pointed to a parallel behaviour pattern of the two hormones in their responding or failure to respond to stimulation. The fact that a significant correlation was established between all measured values of beta-endorphin and ACTH is further evidence in confirmation of a parallel release of these two hormones in man. (TRV) [de

Hypopituitarism

Science.gov (United States)

... is affected by this hormone. Tests may include: Brain CT scan Pituitary MRI ACTH Cortisol Estradiol (estrogen) Follicle-stimulating hormone (FSH) Insulin-like growth factor 1 (IGF-1) Luteinizing hormone ( ...

Change of blood glucose level and its possible mechanism in patients with cerebral stroke

International Nuclear Information System (INIS)

Chen Weizhen; Zhang Yong; Zhang Zikang; Mo Congjian

2003-01-01

To study the mechanism of the change of blood glucose levels in patients with cerebral stroke, the levels of blood glucose, cortisol, glucogen, insulin, growth hormone, triiodothyronine (T 3 ), thyroxine (T 4 ) and adrenocorticotropic hormone (ACTH) were dynamically measured in 90 patients with cerebral stroke. The circumstances of brain middle line movement, lateral ventricle oppression and entrance brain ventricle of burst hematoma of the patients were examines by CT scan. The total incidence of hyperglycemia in the patients was 42.22%. The blood glucose level was positively related to the cortisol and glucogen levels, and negatively related to the T 3 level. The changed level of blood glucose and its related hormones both returned to normal range in 10 days. Both the ACTH level and the rate of cerebral pathological change in hyperglycemia group were significantly higher than that in normoglycemia and control groups. The rate of cerebral pathological change in elevated ACTH level group was higher than that in normal ACTH level group. The mechanism of hyperglycemia in the patients with cerebral stroke might be related to the stimulation of the hypothalamus, which may induce the discharge of ACTH and glucagon releasing factor, and to that the level of cortisol and glucagon increased, the level of T 3 decreased

Adrenocorticotropin, beta-endorphin, and beta-lipotropin in normal thyroid and lung: possible implications for ectopic hormone secretion.

Science.gov (United States)

Clements, J A; Funder, J W; Tracy, K; Morgan, F J; Campbell, D J; Lewis, P; Hearn, M T

1982-12-01

The expression of the proopiomelanocortin (POMC) gene by normal lung and thyroid was examined by measurement of the content of ACTH, beta-lipotropin (beta LPH), and beta-endorphin (beta EP) in porcine lung and thyroid tissue. Acid extracts of normal porcine lung and thyroid tissue each contained appreciable amounts of immunoreactive (ir) ACTH, ir-beta LPH, and ir-beta EP. The content of ir-beta LPH in both tissues exceeded by severalfold, on a molar basis, the content of ir-ACTH and ir-beta EP, suggesting that the common precursor POMC was processed predominantly to peptides other than ir-ACTH and ir-beta EP. A porcine thyroid extract (Calcitare, porcine calcitonin, Armour) showed equivalent levels of beta EP-like immunoreactivity and bioactivity, measured by opiate radioreceptor assay; in contrast, ACTH-like bioactivity, measured by rat zona fasciculata steroidogenesis, was only 4% of ACTH-like immunoreactivity. On reversed phase high performance liquid chromatography, Calcitare showed multiple peaks of ACTH-like immunoreactivity, one of which coeluted with porcine ACTH-(1-39), and two much smaller peaks of beta EP-like immunoreactivity, of which the smaller coeluted with porcine beta EP. These data suggest that both lung and thyroid gland synthesize POMC, which in normal tissue is usually predominantly processed to species other than ACTH and beta EP. Ectopic secretion of ACTH and beta EP by lung and thyroid neoplasms may thus represent the loss of a system(s) normally responsible for processing the precursor beyond ACTH and beta EP.

Effects of anabolic hormones on structural, metabolic and functional aspects of skeletal muscle

Directory of Open Access Journals (Sweden)

Flávio de Oliveira Pires

2009-01-01

Full Text Available http://dx.doi.org/10.5007/1980-0037.2009v11n3p350   This study reviewed information regarding the effects of anabolic hormones on strength gain and muscle hypertrophy, emphasizing the physiological mechanisms that may increase muscle strength. Structural, metabolic and functional aspects were analyzed and special attention was paid to the dose-response relationship. The Pubmed database was searched and studies were selected according to relevance and date of publication (last 15 years. The administration of high testosterone doses (~600 mg/week potentiates the effects of strength training, increasing lean body mass, muscle fiber type IIA and IIB cross-sectional area, and the number of myonuclei. There is no evidence of conversion between MHC isoforms. The interaction between testosterone administration and strength training seems to modify some metabolic pathways, increasing protein synthesis, glycogen and ATP-CP muscle stores and improving fat mobilization. Changes in 17-estradiol concentration or in the ACTH-cortisol and insulin-glucagon ratios seem to be associated with these metabolic alterations. Regarding performance, testosterone administration may improve muscle strength by 5-20% depending on the dose used. On the other hand, the effects of growth hormone on the structural and functional aspects of skeletal muscle are not evident, with this hormone more affecting metabolic aspects. However, strictly controlled human studies are necessary to establish the extent of the effects of anabolic hormones on structural, metabolic and functional aspects.

Pro-opiomelanocortin-derived peptides in the pig pituitary: alpha- and gamma 1-melanocyte-stimulating hormones and their glycine-extended forms

DEFF Research Database (Denmark)

Fenger, M

1988-01-01

Pro-opiomelanocortin (POMC)-related peptides in extracts of anterior and neurointermediate pituitary lobes from pigs were characterized by gel chromatography, reversed-phase chromatography and radioimmunoassays. The peptide content was ca. 3-fold greater in the anterior lobe compared...... to the neurointermediate lobe (19.8 nmol POMC/anterior lobe vs 7.0 nmol/neurointermediate lobe). In the neurointermediate lobe 93% of POMC was processed to alpha-melanocyte-stimulating hormone (alpha-MSH) and analogs exclusively of low molecular weight. Most of the remaining adrenocorticotropic hormone (ACTH...... as alpha-MSH and analogs (94%). However, more than 95% of these peptides were of high molecular weight. In the anterior lobe 2.3% of N-POMC was processed and 94% was amidated gamma-MSH of only high molecular weight. These results show that gamma-MSH and alpha-MSH are amidated to the same extent...

The diversity of abnormal hormone receptors in adrenal Cushing's syndrome allows novel pharmacological therapies

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Lacroix A.

2000-01-01

Full Text Available Recent studies from several groups have indicated that abnormal or ectopic expression and function of adrenal receptors for various hormones may regulate cortisol production in ACTH-independent hypercortisolism. Gastric inhibitory polypeptide (GIP-dependent Cushing's syndrome has been described in patients with either unilateral adenoma or bilateral macronodular adrenal hyperplasia; this syndrome results from the large adrenal overexpression of the GIP receptor without any activating mutation. We have conducted a systematic in vivo evaluation of patients with adrenal Cushing's syndrome in order to identify the presence of abnormal hormone receptors. In macronodular adrenal hyperplasia, we have identified, in addition to GIP-dependent Cushing's syndrome, other patients in whom cortisol production was regulated abnormally by vasopressin, ß-adrenergic receptor agonists, hCG/LH, or serotonin 5HT-4 receptor agonists. In patients with unilateral adrenal adenoma, the abnormal expression or function of GIP or vasopressin receptor has been found, but the presence of ectopic or abnormal hormone receptors appears to be less prevalent than in macronodular adrenal hyperplasia. The identification of the presence of an abnormal adrenal receptor offers the possibility of a new pharmacological approach to control hypercortisolism by suppressing the endogenous ligands or by using specific antagonists for the abnormal receptors.

Hypothermic and antipyretic effects of ACTH (1-24) and alpha-melanotropin in guinea-pigs

Science.gov (United States)

Kandasamy, S. B.; Williams, B. A.

1984-01-01

Intracerebroventricular administration of adrenocorticotropin (ACTH 1-24) and alpha-melanotropin (alpha-MSH), peptides which occur naturally in brain induced dose-related hypothermia in guinea-pigs at room temperature (21 C) and also produced greater hypothermia at low (10 C) ambient temperature. However, when the experiments were repeated in a warm (30 C) environment, no effect on body temperature was observed. These results indicate that the peptides did not reduce the central set-point of temperature control. The hypothermia induced by ACTH and alpha-MSH was not mediated via histamine H1- or H2-receptors and serotonin since the H1-receptor antagonist, mepyramine, the H2-receptor antagonist, cimetidine, and the serotonin antagonist, methysergide, had no antagonistic effects. The peptides were antipyretic since they reduced pyrogen-induced-fever and hyperthermia due to prostaglandin E2, norepinephrine and dibutyryl cAMP, at a dose which did not affect normal body temperature. The powerful central effects of these peptides on normal body temperature, fever and hyperthermia, together with their presence of the brain regions important to temperature control, suggest that they participate in thermoregulation.

A role for 11C-methionine PET imaging in ACTH-dependent Cushing's syndrome.

Science.gov (United States)

Koulouri, Olympia; Steuwe, Andrea; Gillett, Daniel; Hoole, Andrew C; Powlson, Andrew S; Donnelly, Neil A; Burnet, Neil G; Antoun, Nagui M; Cheow, Heok; Mannion, Richard J; Pickard, John D; Gurnell, Mark

2015-10-01

We report our experience of functional imaging with (11)C-methionine positron emission tomography-computed tomography (PET-CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushing's syndrome. Twenty patients with i) de novo Cushing's disease (CD, n=10), ii) residual or recurrent hypercortisolism following first pituitary surgery (±radiotherapy; n=8) or iii) ectopic Cushing's syndrome (n=2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients with de novo CD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI. All patients underwent (11)C-methionine PET-CT. For pituitary imaging, co-registration of PET-CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of (11)C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging. In seven of ten patients with de novo CD, asymmetric (11)C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal (11)C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushing's syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome, (11)C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region. (11)C-methionine PET-CT can aid the detection of

Determination of the source of androgen excess in functionally atypical polycystic ovary syndrome by a short dexamethasone androgen-suppression test and a low-dose ACTH test.

Science.gov (United States)

Rosenfield, Robert L; Mortensen, Monica; Wroblewski, Kristen; Littlejohn, Elizabeth; Ehrmann, David A

2011-11-01

Polycystic ovary syndrome (PCOS) patients typically have 17-hydroxyprogesterone (17OHP) hyperresponsiveness to GnRH agonist (GnRHa) (PCOS-T). The objective of this study was to determine the source of androgen excess in the one-third of PCOS patients who atypically lack this type of ovarian dysfunction (PCOS-A). Aged-matched PCOS-T (n= 40), PCOS-A (n= 20) and controls (n= 39) were studied prospectively in a General Clinical Research Center. Short (4 h) and long (4-7 day) dexamethasone androgen-suppression tests (SDAST and LDAST, respectively) were compared in subsets of subjects. Responses to SDAST and low-dose adrenocorticotropic hormone (ACTH) were then evaluated in all. Testosterone post-SDAST correlated significantly with testosterone post-LDAST and 17OHP post-GnRHa (r = 0.671-0.672), indicating that all detect related aspects of ovarian dysfunction. An elevated dehydroepiandrosterone peak in response to ACTH, which defined functional adrenal hyperandrogenism, was similarly prevalent in PCOS-T (27.5%) and PCOS-A (30%) and correlated significantly with baseline dehydroepiandrosterone sulfate (DHEAS) (r = 0.708). Functional ovarian hyperandrogenism was detected by subnormal testosterone suppression by SDAST in most (92.5%) PCOS-T, but significantly fewer PCOS-A (60%, PPCOS-A, but present in 30% of PCOS-T (P PCOS-A cases with normal testosterone suppression in response to SDAST (5/8) lacked evidence of adrenal hyperandrogenism and were obese. Functional ovarian hyperandrogenism was not demonstrable by SDAST in 40% of PCOS-A. Most of these cases had no evidence of adrenal hyperandrogenism. Obesity may account for most hyperandrogenemic anovulation that lacks a glandular source of excess androgen, and the SDAST seems useful in making this distinction.

A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing's syndrome.

Science.gov (United States)

Reincke, Martin; Ritzel, Katrin; Oßwald, Andrea; Berr, Christina; Stalla, Günter; Hallfeldt, Klaus; Reisch, Nicole; Schopohl, Jochen; Beuschlein, Felix

2015-10-01

Our aim was to review short- and long-term outcomes of patients treated with bilateral adrenalectomy (BADx) in ACTH-dependent Cushing's syndrome. We reviewed the literature and analysed our experience with 53 patients treated with BADx since 1990 in our institution. BADx is considered if ACTH-dependent Cushing's syndrome is refractory to other treatment modalities. In Cushing's disease (CD), BADx is mainly used as an ultima ratio after transsphenoidal surgery and medical therapies have failed. In these cases, the time span between the first diagnosis of CD and treatment with BADx is relatively long (median 44 months). In ectopic Cushing's syndrome, the time from diagnosis to BADx is shorter (median 2 months), and BADx is often performed as an emergency procedure because of life-threatening complications of severe hypercortisolism. In both situations, BADx is relatively safe (median surgical morbidity 15%; median surgical mortality 3%) and provides excellent control of hypercortisolism; Cushing's-associated signs and symptoms are rapidly corrected, and co-morbidities are stabilised. In CD, the quality of life following BADx is rapidly improving, and long-term mortality is low. Specific long-term complications include the development of adrenal crisis and Nelson's syndrome. In ectopic Cushing's syndrome, long-term mortality is high but is mostly dependent on the prognosis of the underlying malignant neuroendocrine tumour. BADx is a relatively safe and highly effective treatment, and it provides adequate control of long-term co-morbidities associated with hypercortisolism. © 2015 European Society of Endocrinology.

Difficulties in the diagnosis of ACTH-dependent Cushings syndrome in a patient after left adrenalectomy and treated with glucocorticoids

International Nuclear Information System (INIS)

Brzezinska, B.; Junik, R.; Kaminska, A.; Zielinski, G.

2009-01-01

Cushings syndrome (CS), that is a consequence of chronic excess of corticosteroides, is most frequently of iatrogenic origin. Corticotropin secreting pituitary adenomas are responsible for most cases of endogenous Cushings syndrome. Difficulties in the diagnosis and treatment of ACTH-dependent Cushings syndrome concern with localization of the source of pathological ACTH secretion, particularly when magnetic resonance imaging is unable to identify the pituitary microadenoma. In this paper we present the case of a patient with symptoms of Cushings syndrome and describe problems with localization of the source of hypercortisolemia. The diagnostic process was additionally complicated by the treatment with corticosteroids, occasionally applied due to concomitant diseases. This delayed the right diagnosis and treatment. (authors)

Disease: H01011 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available ated adrenocorticotropic hormone deficiency (IAD) is a rare disease characterized by low plasma ACTH and cortisol...se TBX19 [HSA:9095] [KO:K10184] ... Low plasma ACTH [CPD:C02017] and cortisol [CPD:C00735] levels ... ICD-10: E

Crossing the other side of the algorithm: a challenging case of adrenal Cushing's syndrome.

Science.gov (United States)

Antonio, Imelda Digna Soberano; Sandoval, Mark Anthony Santiago; Lantion-Ang, Frances Lina

2011-12-01

The diagnosis of endogenous Cushing's syndrome and its aetiology involved documenting the hypercotisolism and then determining whether that hypercortisolism is adrenocorticotropic hormone-dependent (ACTH-dependent) or not. Hence, following the algorithm, an undetected ACTH level points to an adrenal Cushing's while a detectable or elevated ACTH level points to either a pituitary or ectopic Cushing's syndrome. The authors present a case of florid adrenal Cushing's syndrome initially presenting with a normal ACTH level, which led to the investigation for an ACTH-secreting tumour. Adding to the confusion, a MRI done showed an intrasellar focus. Knowledge of how ACTH-dependent (versus ACTH-independent) Cushing's syndrome manifests clinically, supported by results of repeat laboratory tests, led to the true diagnosis. This case illustrates that a detectable ACTH does not rule out an adrenal Cushing's syndrome nor does a positive pituitary imaging confirm Cushing's disease.

Usefulness of Time-Point Serum Cortisol and ACTH Measurements for the Adjustment of Glucocorticoid Replacement in Adrenal Insufficiency.

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Rousseau, Elise; Joubert, Michael; Trzepla, Géraldine; Parienti, Jean Jacques; Freret, Thomas; Vanthygem, Marie Christine; Desailloud, Rachel; Lefebvre, Hervé; Coquerel, Antoine; Reznik, Yves

2015-01-01

Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over- or under-replacement but have been poorly evaluated. Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m2/d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients' cortisol AUC in the control range. Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients' cortisol AUC to controls showed that 81.5% AI patients receiving 6mg/m2/d were adequately replaced, whereas most patients receiving higher doses were over-replaced. The correlation coefficient between 1000h/1400h cortisol concentrations and 0800-1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h ΔACTH fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis indicated that the 1000h and 1400h cortisol concentrations best predicted over-replacement. Patients receiving a 6mg/m2 hydrocortisone daily dose exhibited the most physiological daytime cortisol profile. Single point plasma cortisol correlated with daytime cortisol AUC in AI patients. Although hydrocortisone dose should be currently determined on clinical grounds, our data suggest that single point plasma cortisol may be an adjunct for further hydrocortisone

Hypothalamic and pituitary clusterin modulates neurohormonal responses to stress.

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Shin, Mi-Seon; Chang, Hyukki; Namkoong, Churl; Kang, Gil Myoung; Kim, Hyun-Kyong; Gil, So Young; Yu, Ji Hee; Park, Kyeong Han; Kim, Min-Seon

2013-01-01

Clusterin is a sulfated glycoprotein abundantly expressed in the pituitary gland and hypothalamus of mammals. However, its physiological role in neuroendocrine function is largely unknown. In the present study, we investigated the effects of intracerebroventricular (ICV) administration of clusterin on plasma pituitary hormone levels in normal rats. Single ICV injection of clusterin provoked neurohormonal changes seen under acute stress condition: increased plasma adrenocorticotropic hormone (ACTH), corticosterone, GH and prolactin levels and decreased LH and FSH levels. Consistently, hypothalamic and pituitary clusterin expression levels were upregulated following a restraint stress, suggesting an involvement of endogenous clusterin in stress-induced neurohormonal changes. In the pituitary intermediate lobe, clusterin was coexpressed with proopiomelanocortin (POMC), a precursor of ACTH. Treatment of clusterin in POMC expressing AtT-20 pituitary cells increased basal and corticotropin-releasing hormone (CRH)-stimulated POMC promoter activities and intracellular cAMP levels. Furthermore, clusterin treatment triggered ACTH secretion from AtT-20 cells in a CRH-dependent manner, indicating that increased clusterin under stressful conditions may augment CRH-stimulated ACTH production and release. In summary, hypothalamic and pituitary clusterin may function as a modulator of neurohormonal responses under stressful conditions. © 2013 S. Karger AG, Basel.

Prevalence of and markers for the attenuated form of congenital adrenal hyperplasia and hyperprolactinemia masquerading as polycystic ovarian disease.

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Benjamin, F; Deutsch, S; Saperstein, H; Seltzer, V L

1986-08-01

To determine the prevalence of the attenuated form of congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPPN) relative to polycystic ovarian disease (PCOD), 100 consecutive women presenting with the classic clinical features of PCOD were evaluated by basal hormonal profiles and subsequent adrenocorticotropic hormone (ACTH) stimulation tests. The study also sought biochemical markers for CAH other than ACTH stimulation. The prevalences were found to be as follows: PCOD, 65%; PCOD with HPPN, 9%; HPPN, 3%, end-organ hypersensitivity (EOH), 4%; homozygotic CAH, 4%; and heterozygotic CAH, 15%. Other than the differential response to ACTH, the only other biochemical markers observed for homozygotic CAH were significantly higher basal levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17-OHP). Luteinizing hormone/follicle-stimulating hormone ratio, androstenedione, and dehydroepiandrosterone sulfate all showed no significant differences between homozygotic CAH, heterozygotic CAH, HPPN, PCOD, and EOH. This study establishes the relative prevalences of the syndromes commonly mimicking PCOD. We also conclude that the observed low incidence of CAH does not justify routine ACTH testing on all patients presenting with features of PCOD--however, our data suggest that patients with basal serum levels of T and 17-OHP greater than 50% above the upper limit of normal should undergo this dynamic test, especially if there are also certain clinical features suggestive of CAH.

In Situ Hybridization Method Reveals (Pro)renin Receptor Expressing Cells in the Pituitary Gland of Rats: Correlation with Anterior Pituitary Hormones.

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Takahashi, Kazuhiro; Yatabe, Megumi; Fujiwara, Ken; Hirose, Takuo; Totsune, Kazuhito; Yashiro, Takashi

2013-02-28

Expression of (pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, was studied in rat pituitary gland. In situ hybridization showed that cells expressing (P)RR mRNA were widely distributed in the anterior lobe and intermediate lobe of the pituitary gland. Double-staining using in situ hybridization for (P)RR mRNA and immunohistochemistry for the pituitary hormones showed that (P)RR mRNA was expressed in most of the GH cells and ACTH cells in the anterior lobe. (P)RR mRNA was also expressed in a few prolactin cells and TSH cells, but not in LH cells. The present study has shown for the first time the distribution of (P)RR mRNA expressing cells in the rat pituitary gland. These findings suggest that (P)RR plays physiological roles in the pituitary gland, such as the modulation of the pituitary hormone secretion.

In Situ Hybridization Method Reveals (Pro)renin Receptor Expressing Cells in the Pituitary Gland of Rats: Correlation with Anterior Pituitary Hormones

International Nuclear Information System (INIS)

Takahashi, Kazuhiro; Yatabe, Megumi; Fujiwara, Ken; Hirose, Takuo; Totsune, Kazuhito; Yashiro, Takashi

2013-01-01

Expression of (pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, was studied in rat pituitary gland. In situ hybridization showed that cells expressing (P)RR mRNA were widely distributed in the anterior lobe and intermediate lobe of the pituitary gland. Double-staining using in situ hybridization for (P)RR mRNA and immunohistochemistry for the pituitary hormones showed that (P)RR mRNA was expressed in most of the GH cells and ACTH cells in the anterior lobe. (P)RR mRNA was also expressed in a few prolactin cells and TSH cells, but not in LH cells. The present study has shown for the first time the distribution of (P)RR mRNA expressing cells in the rat pituitary gland. These findings suggest that (P)RR plays physiological roles in the pituitary gland, such as the modulation of the pituitary hormone secretion

Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture

International Nuclear Information System (INIS)

Cronin, M.J.; Evans, W.S.; Rogol, A.D.; Weiss, A.A.; Thorner, M.O.; Orth, D.N.; Nicholson, W.E.; Yasumoto, T.; Hewlett, E.L.

1986-01-01

Bordetella pertussis synthesis a variety of virulence factors including a calmodulin-dependent adenylate cyclase (AC) toxin. Treatment of anterior pituitary cells with this AC toxin resulted in an increase in cellular cAMP levels that was associated with accelerated exocytosis of growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH). The kinetics of release of these hormones, however, were markedly different; GH and prolactin were rapidly released, while LH and ACTH secretion was more gradually elevated. Neither dopamine agonists nor somatostatin changes the ability of AC toxin to generate cAMP (up to 2 h). Low concentrations of AC toxin amplified the secretory response to hypophysiotrophic hormones. The authors conclude that bacterial AC toxin can rapidly elevate cAMP levels in anterior pituitary cells and that it is the response that explains the subsequent acceleration of hormone release

Drug: D09937 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available cal group: DG01344 ... syntheses Corticotropin (ACTH) [CPD:C02017] MC1R [HSA:4157] [KO:K04199]; MC2R [HSA:4158...e Arg Trp Gly Lys Pro Val Gly Lys Lys Arg Arg-NH2 ... Other ... DG01629 ... Adrenocorticotropic hormone (ACTH) Chemi

Effects of irradiation on the anterior pituitary of young rats

International Nuclear Information System (INIS)

Kiriishi, Reijiro; Tsunoda, Shigeru; Sakaki, Toshisuke; Yoshimura, Hitoshi; Ohishi, Hajime; Okamoto, Shingo; Tsujii, Tadasu

1994-01-01

We examined irradiation-induced damage to the anterior pituitary of young rats, particularly to the folliculo-stellate (F-S) cells. The whole brain of 3-week-old Wistar rats (n=24), was irradiated once with a linear accelerator (Linac). The pituitary gland was removed after sacrifice and fixed in formalin. Pituitary specimens were stained with hematoxylin and eosin (H and E), or immunostained for S-100 protein, growth hormone (GH), and adrenocorticotropic hormone (ACTH) by the ABC technique. Angiogenesis in the chronic stage after irradiation was related to an increase of F-S cells in the subacute stage. The decrease in GH cells and ACTH cells after irradiation was dose-dependent, with more severe irradiation-induced damage being in GH cells than in ACTH cells. (author)

Does the corticoadrenal adenoma with ''pre-Cushing's syndrome'' exist

International Nuclear Information System (INIS)

Charbonnel, B.; Chatal, J.F.; Ozanne, P.

1981-01-01

An adrenal tumor was discovered fortuitously in a patient with no clinical features of Cushing's syndrome. On adrenal imaging, there was good uptake in the nodule but no visualization of the contralateral adrenal. The latter was seen, however, in a second scan performed under ACTH treatment. In the hormone assessment, basal cortisol and 17-hydroxycorticoids were normal and cortisol diurnal variation was near normal, but a dexamethasone suppression test and ACTH responses to metyrapone and insulin hypoglycemia were abnormal. Eight months after excision of a spongiocytic-type adenoma, the remaining adrenal was visible on scintigram and the hormonal tests were normal. This pattern suggests that the clinical Cushing's syndrome was enough to partially suppress ACTH and, consequently, visualization of the contralateral gland

Chronic hypopituitarism is uncommon in survivors of aneurysmal subarachnoid haemorrhage.

Science.gov (United States)

Hannon, M J; Behan, L A; O'Brien, M M; Tormey, W; Javadpour, M; Sherlock, M; Thompson, C J

2015-01-01

The incidence of hypopituitarism after aneurysmal subarachnoid haemorrhage (SAH) is unclear from the conflicting reports in the literature. As routine neuroendocrine screening for hypopituitarism for all patients would be costly and logistically difficult, there is a need for precise data on the frequency of hypopituitarism and on factors which might predict the later development of pituitary dysfunction. We aimed to: (i) Establish the incidence of long-term hypopituitarism in patients with aneurysmal SAH. (ii) Determine whether data from patients' acute admission with SAH could predict the occurrence of long-term hypopituitarism. One hundred patients were studied prospectively from the time of presentation with acute SAH. Plasma cortisol, plasma sodium and a variety of clinical and haemodynamic parameters were sequentially measured for the first 12 days of their acute admission. Forty-one patients then underwent dynamic pituitary testing at median 15 months following SAH (range 7-30 months), with insulin tolerance test (ITT) or, if contraindicated, a glucagon stimulation test (GST) plus short synacthen test (SST). If symptoms of cranial diabetes insipidus (CDI) were present, a water deprivation test was also performed. Forty-one patients attended for follow-up dynamic pituitary testing. Although 14 of 100 had acute glucocorticoid deficiency immediately following SAH, only two of 41 had long-term adrenocorticotrophic hormone (ACTH) deficiency and four of 41 had growth hormone (GH) deficiency. None were hypothyroid or gonadotrophin deficient. None had chronic CDI or hyponatraemia. There was no association between acute glucocorticoid deficiency, acute CDI or acute hyponatraemia and long-term pituitary dysfunction. Both anterior and posterior hypopituitarism are very uncommon following SAH and are not predicted by acute clinical, haemodynamic or endocrinological parameters. Routine neuroendocrine screening is not justified in SAH patients. © 2014 John Wiley & Sons

Impact and Timing of Bilateral Adrenalectomy for Refractory ACTH-Dependent Cushing’s Syndrome

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Morris, Lilah F.; Harris, Rachel S.; Milton, Denái R.; Waguespack, Steven G.; Habra, Mouhammed A.; Jimenez, Camilo; Vassilopoulou-Sellin, Rena; Lee, Jeffrey E.; Perrier, Nancy D.; Grubbs, Elizabeth G.

2014-01-01

Introduction In patients with refractory ACTH-dependent Cushing’s syndrome (CS), we evaluated steroidogenesis inhibition (SI) and bilateral adrenalectomy (BA) to predict which patients might benefit most from each treatment modality. Methods Clinical data from patients treated 1970-2012 were retrospectively reviewed by treatment group (SI or SI+BA). Validated severity scales were used to calculate metabolic (M) score (hypokalemia, hyperglycemia, hypertension, proximal muscle weakness) and adverse events (AE) score (thrombosis, fracture, infection). Results 65 patients (16 pituitary, 49 ectopic) were treated with SI+BA (n=21,32%) or SI alone (n=44,68%). Presenting M scores and source of ACTH excess (ectopic vs. pituitary) were similar. Both groups improved metabolically after treatment. 39% of AEs in the SI+BA group occurred within 12 months of presentation. 24(55%) SI patients died (median survival 24.0 months); steroid excess contributed to 71%. Six SI+BA patients died (29%), including all 3 patients with recurrent CS after BA. Minor perioperative complications occurred in 7 patients (33%). Conclusions Post-treatment M and AE scores improved for all patients and 70% of AEs occurred in SI+BA patients within 12 months of presentation, emphasizing the importance of early surgical intervention. These data argue for the safety and efficacy of early BA in selected patients with uncontrollable CS. PMID:24383115

A Case Report of Adrenocorticotropic Hormone to Treat Recurrent Focal Segmental Glomerular Sclerosis Post-transplantation and Biomarker Monitoring

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Anwar eSiddiq

2015-03-01

Full Text Available Background: Recurrent focal segmental glomerular sclerosis (rFSGS in renal transplant recipients (RTR is difficult to predict and treat. Early rFSGS is likely from circulating factors and preformed antibodies. Methods: We present the case of a 23-year-old white man who presented with rFSGS and acute renal failure requiring dialysis 9-months after a 1-haplotype matched living-related transplant. We retrospectively analyzed serum samples from various clinical stages for rFSGS biomarkers: serum glomerular albumin permeability (Palb, soluble urokinase-type plasminogen activator receptor (suPAR serum level with suPAR-β3 integrin signaling on human podocytes, and angiotensin II type I receptor-antibody (AT1R-Ab titer. Results: All biomarkers were abnormal at 1-year pre-transplant prior to initiation of dialysis and at the time of transplant. After initiation of hemodialysis, β3 integrin activity on human podocytes, in response to patient serum, as well as AT1R-Ab were further elevated. At the time of biopsy-proven recurrence, all biomarkers were abnormally high. One week after therapy with aborted plasmapheresis (secondary to intolerance, and high dose steroids, the Palb and suPAR- β3 integrin activity remained significantly positive. After 12-weeks of treatment with high-dose steroids, rituximab, and galactose, the patient remained hemodialysis-dependent. Three-months after his initial presentation we commenced adrenocorticotropic hormone (ACTH, Acthar® Gel, 80 units subcutaneously twice weekly. Four-weeks later he was able to discontinue dialysis. After 8-months of maintenance ACTH therapy, his serum creatinine stabilized at 1.79 mg/dL with less than 1 gram of proteinuria. Conclusion: ACTH therapy was associated with improvement in renal function within 4 weeks. The use of rFSGS biomarkers may aid in predicting development of rFSGS.

Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH.

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Amanda E Hernan

Full Text Available Children with epilepsy often present with pervasive cognitive and behavioral comorbidities including working memory impairments, attention deficit hyperactivity disorder (ADHD and autism spectrum disorder. These non-seizure characteristics are severely detrimental to overall quality of life. Some of these children, particularly those with epilepsies classified as Landau-Kleffner Syndrome or continuous spike and wave during sleep, have infrequent seizure activity but frequent focal epileptiform activity. This frequent epileptiform activity is thought to be detrimental to cognitive development; however, it is also possible that these IIS events initiate pathophysiological pathways in the developing brain that may be independently associated with cognitive deficits. These hypotheses are difficult to address due to the previous lack of an appropriate animal model. To this end, we have recently developed a rat model to test the role of frequent focal epileptiform activity in the prefrontal cortex. Using microinjections of a GABA(A antagonist (bicuculline methiodine delivered multiple times per day from postnatal day (p 21 to p25, we showed that rat pups experiencing frequent, focal, recurrent epileptiform activity in the form of interictal spikes during neurodevelopment have significant long-term deficits in attention and sociability that persist into adulthood. To determine if treatment with ACTH, a drug widely used to treat early-life seizures, altered outcome we administered ACTH once per day subcutaneously during the time of the induced interictal spike activity. We show a modest amelioration of the attention deficit seen in animals with a history of early life interictal spikes with ACTH, in the absence of alteration of interictal spike activity. These results suggest that pharmacological intervention that is not targeted to the interictal spike activity is worthy of future study as it may be beneficial for preventing or ameliorating adverse

Etiology and clinical profile of patients with Cushing′s syndrome: A single center experience

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Ariacherry C Ammini

2014-01-01

Full Text Available Background: There is little published literature on the profile of patients with Cushing′s syndrome (CS from India. The aim of this study was to compile data of CS patients treated at this hospital. Materials and Methods: Patients referred to the endocrine services of this hospital for diagnosis/treatment of CS from January 1985 to July 2012 were the subjects for this study. All patients had detailed medical history, physical examination and biochemical and hormonal assays (which changed with availability of tests and changing views. Assays for plasma adrenocorticotropic hormone (ACTH (late 90s, salivary cortisol estimation, IJV sampling for ACTH and corticotrophin releasing hormone stimulation tests were added on later. Imaging included computed tomography (CT, magnetic resonance imaging (since the late 80′s and 68 Ga DOTA-TOC/FDG PET-CT (2008. Results: Three hundred sixty-four patients (250 females, 114 males, age 6 months to 65 years, mean 28 years + 12 years were diagnosed to have CS during this period. Two hundred and ninety-three patients (80.5% were ACTH dependent (CD 215, ectopic ACTH syndrome 22, occult ACTH source 56 while 71 (19.5% were ACTH independent (adrenal carcinoma 36, adenoma 30, primary pigmented nodular adrenal disease 4, AIMAH 1. Pituitary macro adenoma was seen in 14% of the CD cases. The most common presenting complaints were hypertension and diabetes mellitus. A total of 63% patients complained of weight gain while 15% had lost weight. Myopathy, infections, skeletal fractures and psychiatric problems were the other common observations in our patients. Conclusion: The clinical spectrum was broad. CD was the most common cause for CS.

HORMONAL PROFILE AND NONSPECIFIC RESISTANCE IN BOAR UNDER PRE-SLAUGHTER STRESS

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S.S. Grabovskyi

2016-03-01

Full Text Available The article is devoted to determination of hormonal profile and nonspecific resistance in boars blood before slaughter after using of biologically active substances — animal origin antistressors andimmunostimulators. The purpose of research — determination of changes of insulin, adrenocorticotropic hormone (ACTH, cortisol content in boars blood before slaughter and their correction of natural origin biologically active substances of spleen extract. Object and research methods. The spleen extract has been additionally entered to the boars feed at 5 days before slaughter as an antistressors and immunostimulators in pre-slaughter period. The experiment was conducted on 15 boars with standard diet. Three groups of boars six months of age (5 boars each were formed for research. The pig’s spleen extract was obtained with ultrasound application (Iresearch group were using as a biologically active substances to the feed boars in pre-slaughter period. The extracts were applied to dry feed by aerosol method (70 % alcohol solution of spleen extract volume of 1.4 ml per kg body weight. The boars of II research group in the same way received to the feed of 70 % ethanol solution in the same volume. The boars of control group received only dry feed economy. Theboars slaughter was held on day 13 hours a.m. Mathematical treatment of the research results worked statistically using the software package Statistica 6.0. Results and discussion. The ACTH and cortisol level in the boars’ blood plasma of experimental and control groups significantly increased after transportation (before the slaughter compared with the indexes before transportation to meat plant. The ACTH concentration in the boars’ blood plasma of І experimental group, which was added to the basic diet spleen extract, was 10 % lower than in the control group boars compared with indicators before and after transportation

Diagnosis and Treatment of Hypopituitarism

Science.gov (United States)

2015-01-01

Hypopituitarism is a chronic endocrine illness that caused by varied etiologies. Clinical manifestations of hypopituitarism are variable, often insidious in onset and dependent on the degree and severity of hormone deficiency. However, it is associated with increased mortality and morbidity. Therefore, early diagnosis and prompt treatment is necessary. Hypopituitarism can be easily diagnosed by measuring basal pituitary and target hormone levels except growth hormone (GH) and adrenocorticotropic hormone (ACTH) deficiency. Dynamic stimulation tests are indicated in equivocal basal hormone levels and GH/ACTH deficiency. Knowledge of the use and limitations of these stimulation tests is mandatory for proper interpretation. It is necessary for physicians to inform their patients that they may require lifetime treatment. Hormone replacement therapy should be individualized according to the specific needs of each patient, taking into account possible interactions. Long-term endocrinological follow-up of hypopituitary patients is important to monitor hormonal replacement regimes and avoid under- or overtreatment. PMID:26790380

Morphological and functional alterations in the adenohypophysis in cases of brain death.

Science.gov (United States)

Ishikawa, Takaki; Michiue, Tomomi; Quan, Li; Zhao, Dong; Komatsu, Ayumi; Bessho, Yasumori; Maeda, Hitoshi

2009-04-01

In order to examine the function of the adenohypophysis during brain death, levels of adrenocorticotropic hormone (ACTH), growth hormone (GH), and thyroid stimulating hormone (TSH) were investigated during forensic autopsy. Cases examined were those of brain death (n=12; within 24h postmortem; time to cardiac death after cerebral death was diagnosed, approximately 4-25 days), including those in which the cause of death was head injury (subdural hematoma or brain contusion, n=10) and asphyxia (strangulation, n=2). The concentrations of ACTH and TSH were measured by enzyme chemiluminescent immunoassay (ECLIA), and that of GH by radioimmunoassay (RIA). The immunoreactivities of ACTH, GH, and TSH in the adenohypophysis were observed and analyzed with electron microscopy. Morphological studies revealed partial necrosis of the central anterior lobe, but preservation of its periphery. Immunohistochemical staining revealed the appearance of peripheral adenohypophysis with each hormone. Ultrastructural findings for the pituitary and hypothalamus indicated swelling of the mitochondria and dilation of both the smooth endoplasmic reticulum and Golgi apparatus. Furthermore, in most cases, concentrations of the anterior pituitary hormones in the serum and cerebrospinal fluid (CSF) were generally within the clinical reference range. These results indicate that the pituitary is partially preserved after brain death.

Menstrual Abnormalities in a Woman with Acth-Dependent Pituitary Macroadenoma Mimicking Polycystic Ovary Syndrome

OpenAIRE

Chun-Cheng Liao; Shih-Yi Lin; Hsin-Wang Lin; Kuang-Hua Chen; Lan-Hua Chang; Shun-Tien Chen; John Wang

2006-01-01

Objective: Here, we present a case of ACTH-dependent pituitary macroadenoma (Cushing's disease) resulting in secondary amenorrhea mimicking polycystic ovary syndrome (PCOS). Case Report: A 20-year-old nulligravid woman had been suffering from oligomenorrhea, amenorrhea, and moderate hirsutism since the age of 18 years. She visited a gynecologic clinic where PCOS was impressed according to the clinical manifestation and ultrasound finding. The patient responded to medication in the 1st year...

Differential Activation in Amygdala and Plasma Noradrenaline during Colorectal Distention by Administration of Corticotropin-Releasing Hormone between Healthy Individuals and Patients with Irritable Bowel Syndrome.

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Yukari Tanaka

Full Text Available Irritable bowel syndrome (IBS often comorbids mood and anxiety disorders. Corticotropin-releasing hormone (CRH is a major mediator of the stress response in the brain-gut axis, but it is not clear how CRH agonists change human brain responses to interoceptive stimuli. We tested the hypothesis that brain activation in response to colorectal distention is enhanced after CRH injection in IBS patients compared to healthy controls. Brain H215O- positron emission tomography (PET was performed in 16 male IBS patients and 16 age-matched male controls during baseline, no distention, mild and intense distention of the colorectum using barostat bag inflation. Either CRH (2 μg/kg or saline (1:1 was then injected intravenously and the same distention protocol was repeated. Plasma adrenocorticotropic hormone (ACTH, serum cortisol and plasma noradrenaline levels were measured at each stimulation. At baseline, CRH without colorectal distention induced more activation in the right amygdala in IBS patients than in controls. During intense distention after CRH injection, controls showed significantly greater activation than IBS patients in the right amygdala. Plasma ACTH and serum cortisol secretion showed a significant interaction between drug (CRH, saline and distention. Plasma noradrenaline at baseline significantly increased after CRH injection compared to before injection in IBS. Further, plasma noradrenaline showed a significant group (IBS, controls by drug by distention interaction. Exogenous CRH differentially sensitizes brain regions of the emotional-arousal circuitry within the visceral pain matrix to colorectal distention and synergetic activation of noradrenergic function in IBS patients and healthy individuals.

Nelson′s syndrome presenting as bilateral oculomotor palsy

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Abhay Gundgurthi

2013-01-01

Full Text Available Nelson′s syndrome refers to a clinical spectrum arising from progressive enlargement of pituitary adenoma and elevated adrenocorticotrophic hormone after total bilateral adrenalectomy for Cushing′s disease comprising of hyperpigmentation, visual field defects which can be life threatening. We report here a 50-year male presenting with rapid onset of Nelson′s syndrome with an unusual finding of bilateral oculomotor palsy mistakenly treated as ocular myasthenia.

Staged Bilateral Laparoscopic Adrenalectomy for Infantile ACTH-independent Cushing's Syndrome (Bilateral Micronodular Non-pigmented Adrenal Hyperplasia): A Case Report.

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Simforoosh, Nasser; Razzaghy Azar, Maryam; Soltani, Mohmmad Hossein; Nourbakhsh, Mona; Shemshaki, Hamidreza

2017-08-29

ACTH-independent Cushing's syndrome is an uncommon disorder in children. While laparoscopic adrenalectomy is well-established in adults, it is rarely used in infants and is associated with some concerns. A seven-month infant was referred to our hospital due to progressive signs and symptoms of Cushing's syndrome. Laboratory data confirmed ACTH-independent hypercortisolism. No history of exogenous corticosteroid contact was observed. The patient underwent left transperitoneal laparoscopic adrenalectomy when she was 7 months old, nevertheless,complete response was not seen. The patient underwent right laparoscopic adrenalectomy (contra-lateral adrenal gland) when she was 20 months old. The signs and symptoms of Cushing's syndrome began to resolve and serum and urine cortisol levels became normal 3 months after the second surgery. laparoscopic adrenalectomy is safe and feasible in infants, and in this case, relieved patient of the symptoms and saved her life.

Ghrelin increases intracellular Ca²⁺ concentration in the various hormone-producing cell types of the rat pituitary gland.

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Yamazaki, Mami; Aizawa, Sayaka; Tanaka, Toru; Sakai, Takafumi; Sakata, Ichiro

2012-09-20

Ghrelin, isolated from the stomach as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), has potent growth hormone release ability in vivo and in vitro. Although GHS-R is abundantly expressed in the pituitary gland, there is no direct evidence of a relationship between hormone-producing cells and functional GHS-R in the pituitary gland. The aim of this study was to determine which anterior pituitary cells respond to ghrelin stimulation in male rats. We performed Fura-2 Ca(2+) imaging analysis using isolated pituitary cells, and performed immunocytochemistry to identify the type of pituitary hormone-producing cells. In Fura-2 Ca(2+) imaging analysis, ghrelin administration increased the intracellular Ca(2+) concentration in approximately 50% of total isolated anterior pituitary cells, and 20% of these cells strongly responded to ghrelin. Immunocytochemical analysis revealed that 82.9 ± 1.3% of cells that responded to ghrelin stimulation were GH-immunopositive. On the other hand, PRL-, LH-, and ACTH-immunopositive cells constituted 2.0 ± 0.3%, 12.6 ± 0.3%, and 2.5 ± 0.8% of ghrelin-responding pituitary cells, respectively. TSH-immunopositive cells did not respond to ghrelin treatment. These results suggest that ghrelin directly acts not only on somatotrophs, but also on mammotrophs, gonadotrophs, and corticotrophs in the rat pituitary gland. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Co-administration of the neurotrophic ACTH(4-9) analogue, ORG 2766, may reduce the cochleotoxic effects of cisplatin

NARCIS (Netherlands)

Gispen, W.H.; Groot, J.C.M.J. de; Hamers, F.P.T.; Smoorenburg, G.F.

1997-01-01

In this study the effect of the neurotrophic ACTH(4-9) analogue, ORG 2766, on cisplatin cochleotoxicity was investigated with both light- and transmission electron microscopy. Guinea pigs were treated with either cisplatin+ORG 2766 (n=11) or cisplatin+physiological saline (n=9). All animals treated

Systemic N-terminal fragments of adrenocorticotropin reduce inflammation- and stress-induced anhedonia in rats.

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Markov, Dmitrii D; Yatsenko, Ksenia A; Inozemtseva, Lyudmila S; Grivennikov, Igor A; Myasoedov, Nikolai F; Dolotov, Oleg V

2017-08-01

Emerging evidence implicates impaired self-regulation of the hypothalamic-pituitary-adrenal (HPA) axis and inflammation as important and closely related components of the pathophysiology of major depression. Antidepressants show anti-inflammatory effects and are suggested to enhance glucocorticoid feedback inhibition of the HPA axis. HPA axis activity is also negatively self-regulated by the adrenocorticotropic hormone (ACTH), a potent anti-inflammatory peptide activating five subtypes of melanocortin receptors (MCRs). There are indications that ACTH-mediated feedback can be activated by noncorticotropic N-terminal ACTH fragments such as a potent anti-inflammatory MC1/3/4/5R agonist α-melanocyte-stimulating hormone (α-MSH), corresponding to ACTH(1-13), and a MC3/5R agonist ACTH(4-10). We investigated whether intraperitoneal administration of rats with these peptides affects anhedonia, which is a core symptom of depression. Inflammation-related anhedonia was induced by a single intraperitoneal administration of a low dose (0.025mg/kg) of lipopolysaccharide (LPS). Stress-related anhedonia was induced by the chronic unpredictable stress (CUS) procedure. The sucrose preference test was used to detect anhedonia. We found that ACTH(4-10) pretreatment decreased LPS-induced increase in serum corticosterone and tumor necrosis factor (TNF)-α, and a MC3/4R antagonist SHU9119 blocked this effect. Both α-MSH and ACTH(4-10) alleviated LPS-induced anhedonia. In the CUS model, these peptides reduced anhedonia and normalized body weight gain. The data indicate that systemic α-MSH and ACTH(4-10) produce an antidepressant-like effect on anhedonia induced by stress or inflammation, the stimuli that trigger the release of ACTH and α-MSH into the bloodstream. The results suggest a counterbalancing role of circulating melanocortins in depression and point to a new approach for antidepressant treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome.

Science.gov (United States)

Calis, M; Gökçe, C; Ates, F; Ulker, S; Izgi, H B; Demir, H; Kirnap, M; Sofuoglu, S; Durak, A C; Tutus, A; Kelestimur, F

2004-01-01

Primary fibromyalgia syndrome (PFS) is characterized by widespread chronic pain that affects the musculoskeletal system, fatigue, anxiety, sleep disturbance, headache and postural hypotension. The pathophysiology of PFS is unknown. The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in PFS. Both hyperactivity and hypoactivity of the HPA axis have been reported in patients with PFS. In this study we assessed the HPA axis by 1 microg ACTH stimulation test and metyrapone test in 22 patients with PFS and in 15 age-, sex-, and body mass index (BMI)- matched controls. Metyrapone (30 mg/kg) was administered orally at 23:00 h and blood was sampled at 08:30 h the following morning for 11-deoxycortisol. ACTH stimulation test was carried out by using 1 microg (iv) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. Peak cortisol level (659.4 +/- 207.2 nmol/l) was lower in the patients with PFS than peak cortisol level (838.7 +/- 129.6 nmol/l) in the control subjects (p < 0.05). Ten patients (45%) with PFS had peak cortisol responses to 1 microg ACTH test lower than the lowest peak cortisol detected in healthy controls. After metyrapone test 11-deoxycortisol level was 123.7 +/- 26 nmol/l in patients with PFS and 184.2 +/- 17.3 nmol/l in the controls (p < 0.05). Ninety five percent of the patients with PFS had lower 11-deoxycortisol level after metyrapone than the lowest 11-deoxycortisol level after metyrapone detected in healthy controls. We also compared the adrenal size of the patients with that of the healthy subjects and we found that the adrenal size between the groups was similar. This study clearly shows that HPA axis is underactivated in PFS, rather than overactivated.

Hypopituitarism.

Science.gov (United States)

Higham, Claire E; Johannsson, Gudmundur; Shalet, Stephen M

2016-11-12

Hypopituitarism refers to deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Hypopituitarism is associated with excess mortality, a key risk factor being cortisol deficiency due to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or insidious, and the most common cause in adulthood is a pituitary adenoma, or treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed based on baseline blood sampling for thyroid stimulating hormone, gonadotropin, and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic hormone deficiency dynamic stimulation tests are usually needed. Repeated pituitary function assessment at regular intervals is needed for diagnosis of the predictable but slowly evolving forms of hypopituitarism. Replacement treatment exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone, and desmopressin. If onset is acute, cortisol deficiency should be replaced first. Modifications in replacement treatment are needed during the transition from paediatric to adult endocrine care, and during pregnancy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stress system changes associated with marijuana dependence may increase craving for alcohol and cocaine

Science.gov (United States)

Fox, Helen C.; Tuit, Keri L.; Sinha, Rajita

2013-01-01

Objective To date, little research exists defining bio-behavioral adaptations associated with both marijuana abuse and risk of craving and relapse to other drugs of abuse during early abstinence. Method Fifty-nine treatment-seeking individuals dependent on alcohol and cocaine were recruited. Thirty of these individuals were also marijuana (MJ) dependent; 29 were not. Twenty-six socially drinking healthy controls were also recruited. All participants were exposed to three 5-min guided imagery conditions (stress, alcohol/cocaine cue and relaxing), presented randomly, one per day across three consecutive days. Measures of craving, anxiety, heart rate, blood pressure, plasma adrenocorticotrophic hormone and cortisol were collected at baseline and subsequent recovery time points. Results The MJ-dependent group showed increased basal anxiety ratings and cardiovascular output alongside enhanced alcohol craving and cocaine craving, and dampened cardiovascular response to stress and cue. They also demonstrated elevated cue-induced anxiety and stress-induced cortisol and adrenocorticotrophic hormone levels, which were not observed in the non-MJ-dependent group or controls. Cue-related alcohol craving and anxiety were both predictive of a shorter number of days to marijuana relapse following discharge from inpatient treatment. Conclusions Findings provide some support for drug cross-sensitization in terms of motivational processes associated with stress-related and cue-related craving and relapse. PMID:23280514

A case of radiation myelopathy responded to ACTH therapy

International Nuclear Information System (INIS)

Matsui, Toshiyuki; Kawanami, Sachiko; Nishimaru, Katsuya

1981-01-01

A patient with nasal reticulum-cell sarcoma received 60 Co irradiation in a total dose of 10,000 rad in 25 fractions and intracarotid arterial transfusion of 5-Fu 4,000 mg. The prognosis was favorable without subjective symptoms for about one year before disturbance in walking and abnormal sensation in legs occurred. Metastasis of tumor was ruled out, and diagnosis of acute radiculoneuritis was made for the reason that the region which exposed to irradiation coincided the level of neurological disturbances which rapidly advanced. This patient received ACTH therapy. Administration of dexamethasone in a dose of 4 mg per day relieved subjective pain and lowered the level of impaired sensation, and arrested progress of motor paralysis. However, the symptoms was exacerbated again after 2 weeks and the decrease of the dose caused an highered the level of impaired and resulted in motor paralysis. Total dose was 171 mg. (Ueda, J.)

Hormonal changes in spontaneous and aglépristone-induced parturition in dogs.

Science.gov (United States)

Baan, M; Taverne, M A M; de Gier, J; Kooistra, H S; Kindahl, H; Dieleman, S J; Okkens, A C

2008-03-01

To increase our understanding of the endocrine changes associated with parturition in dogs, plasma concentrations of progesterone (P4), 15-ketodihydroprostaglandin F(2alpha) (PGFM), estradiol-17-beta (E2beta), cortisol, ACTH, prolactin (PRL), LH, and FSH were measured in six spontaneously whelping bitches and in six bitches in which parturition was induced with the progesterone-receptor blocker aglépristone on day 58 of pregnancy. Expulsion of pups in the induced group took place in the presence of P4 concentrations that were still elevated. PGFM concentrations increased before parturition in both groups, but levels were lower in the induced bitches. PGFM levels reached a maximum in both groups during parturition and quickly decreased in the spontaneously whelping group after parturition, but remained elevated in the induced group. In both groups, cortisol concentrations reached similar maximum levels during the last 30 h before the onset of expulsion. During the 3 days postpartum, cortisol concentrations were higher in the induced group. The highly variable ACTH concentrations did not differ significantly throughout the study within or between groups. In both groups, E2beta concentrations decreased and PRL concentrations increased between the late gestational period and the 30-h period before parturition. Concentrations of both LH (spontaneously whelping group) and FSH (both groups) decreased between late gestation and the postpartum period. The results of this study illustrate the hormonal changes around parturition in the bitch, and reveal that aglépristone-induced parturition is associated with still incomplete luteolysis, an altered PGFM profile, and elevated postpartum cortisol concentrations as compared with spontaneously whelping dogs.

Effects of general anaesthesia on endocrine system of body in paediatric patients during surgical intervention

International Nuclear Information System (INIS)

Mahmood, N.

1990-01-01

A total of 50 children (mean age 7, range 2-12 years), undergoing minor to major surgical operations were evaluated for hormonal changes induced by anaesthesia 15 hormones i.e. GH, ACTH, OH, FISH, TSH, PTH, FT4, T3, prolactin, insulin estradiol, testosterone, aldosterone, progesterone, and cortisol were studies results obtained showed significant increase in the levels of GH, cortisol, aldosterone, prolactin, progesterone, and PTH at the time of induction of anaesthesia. Of these GH, prolactin and aldosterone levels showed further increase during surgery (maintenance of anaesthesia). Values of TSH, LH, FSH, FT4 and testosterone levels remained essentially unaffected at induction of anaesthesia, but showed significant rise during surgery (maintenance of anaesthesia). Serum levels of ACTH, insulin, estradiol, and T3 were basically unaffected by anaesthesia and surgery. Furthermore, increase in cortisol and PTH levels was more prominent in patients anaesthetized with halothane alone. In this group ACTH level recorded a decrease while in thiopentone, halothane+nitrous oxide anaesthesia group ACTH showed a significantly rise. Growth hormone and insulin response was significantly more prominent in patients undergoing major surgery as compared to others. These findings under score the importance of stress response resulting from general anaesthesia and surgical trauma in children, and brings into focus the need of careful pre and post operative monitoring of patients in this age group. (author)

The active sequence in the acth molecule responsible for inhibition of the extinction of conditioned avoidance behaviour in rats

NARCIS (Netherlands)

Greven, H.M.; Wied, D. de

1967-01-01

The effect of structural analogues of the N-terminal decapeptide of ACTH on inhibition of extinction of a conditioned avoidance response in rats has been studied. Studies involving the relation between chain length and behavioural activity revealed that the sequence 4–10 is the shortest peptide

Electromagnetic field effect or simply stress? Effects of UMTS exposure on hippocampal longterm plasticity in the context of procedure related hormone release.

Directory of Open Access Journals (Sweden)

Nora Prochnow

Full Text Available Harmful effects of electromagnetic fields (EMF on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF signals of the Universal Mobile Telecommunications System (UMTS to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH and on hippocampal derived synaptic long-term plasticity (LTP and depression (LTD as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg. The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg cannot be excluded.

Cushing Syndrome: Diagnostic Workup and Imaging Features, With Clinical and Pathologic Correlation.

Science.gov (United States)

Wagner-Bartak, Nicolaus A; Baiomy, Ali; Habra, Mouhammed Amir; Mukhi, Shalini V; Morani, Ajaykumar C; Korivi, Brinda R; Waguespack, Steven G; Elsayes, Khaled M

2017-07-01

Cushing syndrome (CS) is a constellation of clinical signs and symptoms resulting from chronic exposure to excess cortisol, either exogenous or endogenous. Exogenous CS is most commonly caused by administration of glucocorticoids. Endogenous CS is subdivided into two types: adrenocorticotropic hormone (ACTH) dependent and ACTH independent. Cushing disease, which is caused by a pituitary adenoma, is the most common cause of ACTH-dependent CS for which pituitary MRI can be diagnostic, with bilateral inferior petrosal sinus sampling useful in equivocal cases. In ectopic ACTH production, which is usually caused by a tumor in the thorax (e.g., small cell lung carcinoma, bronchial and thymic carcinoids, or medullary thyroid carcinoma) or abdomen (e.g., gastroenteropancreatic neuroendocrine tumors or pheochromocytoma), CT, MRI, and nuclear medicine tests are used for localizing the source of ACTH. In ACTH-independent CS, which is caused by various adrenal abnormalities, adrenal protocol CT or MRI is usually diagnostic.

Copeptin during rest and exercise in major depression

DEFF Research Database (Denmark)

Krogh, Jesper; Gøtze, Jens Peter; Jørgensen, Martin Balslev

2013-01-01

High vasopressin levels and a correlation between vasopressin and cortisol has been observed in patients with depression. The aim was to assess copeptin, the c-terminal of provasopressin, and the association between cortisol, adrenocorticotropic hormone (ACTH) and copeptin in patients with depres...... with depression. Secondly, to examine the copeptin response to acute exercise and aerobic training.......High vasopressin levels and a correlation between vasopressin and cortisol has been observed in patients with depression. The aim was to assess copeptin, the c-terminal of provasopressin, and the association between cortisol, adrenocorticotropic hormone (ACTH) and copeptin in patients...

Quantification of the adrenal cortex hormones with radioimmunoassay

Energy Technology Data Exchange (ETDEWEB)

Badillo A, V.; Carrera D, A. A.; Ibarra M, C. M., E-mail: vbadillocren@hotmail.co [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Calle Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico)

2010-10-15

The pathologies of the adrenal cortex -adrenal insufficiency and Cushing syndrome- have their origin on the deficit or hypersecretion of some of the hormones that are secreted by the adrenal cortex, which is divided in three zones anatomically defined: the external zone, also called the zona glomerulosa, which is the main production site of aldosterone and mineralocorticoids; the internal zone, or zona reticularis, that produces androgens; and the external zone, or zone 1 orticotrop, which is responsible for producing glucocorticoids. In this work, a quantitative analysis of those hormones and their pathologic trigger was made; the quantification was made in the laboratory by means of highly sensitive and specific techniques, in this case, the radioimmunoassay, in which a radioisotope I-125 is used. This technique is based on the biochemical bond-type reaction, because it requires of a substance called the linker, which bonds to another called ligand. This reaction is also known as antigen-antibody (Ag-Ab), where the results of the reaction will depend on the quantity of antigen in the sample and on its affinity for the antibody. In this work, a 56 patients (of which 13 were men and 43 women) study was made. The cortisol, the ACTH, the androsterone and the DHEA values were very elevated in the majority of the cases corresponding to women, predominating cortisol; while in men, a notorious elevation of the 17 {alpha}-OH-PRG and of the DHEA-SO{sub 4} was observed. Based on that, we can conclude that 51 of them did not have mayor complications, because they just went to the laboratory once, while the remaining 5 had a medical monitoring, and they visited the laboratory more than one occasion, tell about a difficulty on their improvement. According to the results, an approximate relation of 8:2 women:men, respectively, becomes clear to the hormonal pathologies of the adrenal cortex. (Author)

Quantification of the adrenal cortex hormones with radioimmunoassay

International Nuclear Information System (INIS)

Badillo A, V.; Carrera D, A. A.; Ibarra M, C. M.

2010-10-01

The pathologies of the adrenal cortex -adrenal insufficiency and Cushing syndrome- have their origin on the deficit or hypersecretion of some of the hormones that are secreted by the adrenal cortex, which is divided in three zones anatomically defined: the external zone, also called the zona glomerulosa, which is the main production site of aldosterone and mineralocorticoids; the internal zone, or zona reticularis, that produces androgens; and the external zone, or zone 1 orticotrop, which is responsible for producing glucocorticoids. In this work, a quantitative analysis of those hormones and their pathologic trigger was made; the quantification was made in the laboratory by means of highly sensitive and specific techniques, in this case, the radioimmunoassay, in which a radioisotope I-125 is used. This technique is based on the biochemical bond-type reaction, because it requires of a substance called the linker, which bonds to another called ligand. This reaction is also known as antigen-antibody (Ag-Ab), where the results of the reaction will depend on the quantity of antigen in the sample and on its affinity for the antibody. In this work, a 56 patients (of which 13 were men and 43 women) study was made. The cortisol, the ACTH, the androsterone and the DHEA values were very elevated in the majority of the cases corresponding to women, predominating cortisol; while in men, a notorious elevation of the 17 α-OH-PRG and of the DHEA-SO 4 was observed. Based on that, we can conclude that 51 of them did not have mayor complications, because they just went to the laboratory once, while the remaining 5 had a medical monitoring, and they visited the laboratory more than one occasion, tell about a difficulty on their improvement. According to the results, an approximate relation of 8:2 women:men, respectively, becomes clear to the hormonal pathologies of the adrenal cortex. (Author)

Gene array and real time PCR analysis of the adrenal sensitivity to adrenocorticotropic hormone in pig

Directory of Open Access Journals (Sweden)

SanCristobal Magali

2008-02-01

Full Text Available Abstract Background Variability in hypothalamic-pituitary-adrenal (HPA axis activity has been shown to be influenced by genetic factors and related to great metabolic differences such as obesity. The aim of this study was to investigate molecular bases of genetic variability of the adrenal sensitivity to ACTH, a major source of variability, in Meishan (MS and Large White (LW pigs, MS being reported to exhibit higher basal cortisol levels, response to ACTH and fatness than LW. A pig cDNA microarray was used to identify changes in gene expression in basal conditions and in response to ACTH stimulation. Results Genotype and/or ACTH affected the expression of 211 genes related to transcription, cell growth/maintenance, signal transduction, cell structure/adhesion/extra cellular matrix and protein kinase/phosphatase activity. No change in the expression of known key regulator proteins of the ACTH signaling pathway or of steroidogenic enzymes was found. However, Mdh2, Sdha, Suclg2, genes involved in the tricarboxylic acid (TCA pathway, were over-expressed in MS pigs. Higher TCA cycle activity in MS than in LW may thus result in higher steroidogenic activity and thus explain the typically higher cortisol levels in MS compared to LW. Moreover, up-regulation of Star and Ldlr genes in MS and/or in response to ACTH suggest that differences in the adrenal function between MS and LW may also involve mechanisms requisite for cholesterol supply to steroidogenesis. Conclusion The present study provides new potential candidate genes to explain genetic variations in the adrenal sensitivity to ACTH and better understand relationship between HPA axis activity and obesity.

Optimising glucocorticoid replacement therapy in severely adrenocorticotropin (ACTH) deficient hypopituitary male patients.

LENUS (Irish Health Repository)

Behan, Lucy-Ann

2011-04-18

Context:  The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15mg to 30mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. Objective:  Primarily to define the hydrocortisone regimen which results in a 24hour cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). Design:  10 male hypopituitary patients with severe ACTH deficiency (basal cortisol <100nM and peak response to stimulation <400nM) were enrolled in a prospective, randomised, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24hour serum cortisol sampling and QoL assessment with the Short Form 36 and the Nottingham Health Profile questionnaires. Free cortisol was calculated using Coolen\\'s equation. All results were compared to those of healthy, matched controls. Results:  CBG was significantly lower across all dose regimens compared to controls (p<0.05). The lower dose regimen C(10mg mane\\/5mg tarde) produced a 24hour free cortisol profile which most closely resembled that of controls. Both regimen A(20mg mane\\/10mg tarde) and B(10mg mane\\/10mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (p<0.001). Conclusions:  The lower dose of HC(10mg\\/5mg) produces a more physiological cortisol profile, without compromising quality of life, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.

Enriched environment influences hormonal status and hippocampal brain derived neurotrophic factor in a sex dependent manner.

Science.gov (United States)

Bakos, J; Hlavacova, N; Rajman, M; Ondicova, K; Koros, C; Kitraki, E; Steinbusch, H W M; Jezova, D

2009-12-01

The present study is aimed at testing the hypothesis that an enriched environment (EE) induces sex-dependent changes in stress hormone release and in markers of increased brain plasticity. The focus was on hypothalamic-pituitary-adrenocortical (HPA) axis activity, plasma levels of stress hormones, gene expression of glutamate receptor subunits and concentrations of brain-derived neurotrophic factor (BDNF) in selected brain regions. Rats exposed to EE were housed in groups of 12 in large cages with various objects, which were frequently changed, for 6 weeks. Control animals were housed four per cage under standard conditions. In females the EE-induced rise in hippocampal BDNF, a neurotrophic factor associated with increased neural plasticity, was more pronounced than in males. Similar sex-specific changes were observed in BDNF concentrations in the hypothalamus. EE also significantly attenuated oxytocin and aldosterone levels only in female but not male rats. Plasma testosterone positively correlated with hippocampal BDNF in female but not male rats housed in EE. In male rats housing in EE led to enhanced levels of testosterone and adrenocorticotropic hormone (ACTH), this was not seen in females. Hippocampal glucocorticoid but not mineralocorticoid receptor levels decreased in rats housed in EE irrespective of sex. Housing conditions failed to modify mRNA levels of glutamate receptor type 1 (Glur1) and metabotropic glutamate receptor subtype 5 (mGlur5) subunits of glutamate receptors in the forebrain. Moreover, a negative association between corticosterone and BDNF was observed in both sexes. The results demonstrate that the association between hormones and changes in brain plasticity is sex related. In particular, testosterone seems to be involved in the regulatory processes related to neuroplasticity in females.

Alpha-amidated peptides derived from pro-opiomelanocortin in normal human pituitary

DEFF Research Database (Denmark)

Fenger, M; Johnsen, A H

1988-01-01

Normal human pituitaries were extracted in boiling water and acetic acid, and the alpha-amidated peptide products of pro-opiomelanocortin (POMC), alpha-melanocyte-stimulating hormone (alpha MSH), gamma-melanocyte-stimulating hormone (gamma 1MSH), and amidated hinge peptide (HP-N), as well...... (ACTH)-(1-39), ACTH-(1-14) and alpha MSH immunoreactivity]. alpha MSH and ACTH-(1-14) were only present in non- or mono-acetylated forms. Only large forms of gamma 1MSH and gamma 2MSH were present in partly glycosylated states. The hinge peptides were amidated to an extent two to three orders...... amidated POMC-related peptides are present in normal human pituitary. It also shows that cleavage in vivo at all dibasic amino acids but one, takes place at the N-terminal POMC region; the exception is at the POMC-(49-50) N-terminal of the gamma MSH sequence. The pattern of peptides produced suggests...

Immunohistochemical distribution of regulatory peptides in the human fetal adenohypophysis

Science.gov (United States)

Reyes, R; Valladares, F; Gutiérrez, R; González, M; Bello, A R

2008-01-01

We have studied here the cellular distribution of several regulatory peptides in hormone-producing cells of the human pituitary during the fetal period. Immunohistochemistry was used to show the expression of several regulatory peptides, namely Angiotensin-II, Neurotensin and Galanin, at successive gestational stages and their co-localization with hormones in the human fetal adenohypophysis. Somatotrophs, gonadotrophs and thyrotrophs were differentiated earliest. At gestational week 9, Angiotensin-II immunoreactivity was co-localized only with growth hormone immunoreactivity in somatotrophs, one of the first hormone-producing cells to differentiate. This co-localization remained until week 37. Neurotensin immunoreactivity was present in gonadotrophs and thyrotrophs in week 23, after FSH and TSH hormone differentiation. Galanin immunoreactivity was present in all hormone-producing cell types except corticotrophs. The different pro-opiomelanocortin-derived peptides were detected at different stages of gestation and adrenocorticotrophic hormone immunoreaction was the last to be detected. Our results show an interesting relationship between regulatory peptides and hormones during human fetal development, which could imply that these peptides play a regulatory role in the development of pituitary function. PMID:18510508

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

Possibility of radioimmunoassay using for the estimation of endocrine status in autoimmune pathology

International Nuclear Information System (INIS)

Piven', N.V.; Mrochek, A.G.

2000-01-01

Usability of radioimmunoassay (RIA) for assessing the functioning and potentialities of different hormonal systems was studied as well as pathogenetic role of revealed violations and interconnection of them and clinical symptomatology and the type of therapy performed in case of pathology (illustrated by the case of rheumatoid arthritis (RA)). RIA method was used to assess the features of function of gonads, adrenal cortex and pituitary body - thyroid system in RA patients (45-60 y.o.) by means of study of the concentration of corresponding hormones and regulatory proteins in combination with pharmacological load of adrenocorticotropic hormone (ACTH) before and after the therapy. Grave violations in endocrine homeostasis were found in the form of androgen-extragen disbalance, adrenal insufficiency and hypothyrosis in combination with hormone level dissociation resulted from pharmacological sample with ACTH. Revealed violations are connected with clinical symptomatology, criticality and lingering of disease [ru

Inferior petrosal sinus sampling in the diagnosis of adrenocorticotropin dependent Cushing syndrome with unknown origin

International Nuclear Information System (INIS)

Shen Xuefeng; Yuan Dequan; Yue Ming; Feng Juanjuan

2011-01-01

Objective: To evaluate the value of inferior petrosal sinus sampling (IPSS) in the diagnosis of adrenocorticotropic hormone (ACTH) dependent Cushing syndrome (CS) with unknown origin. Methods: IPSS was carried out for the diagnosis of 16 cases with ACTH dependent CS who had not been identified after a series of dexamethasone suppression tests and radiological examinations. The ratio of inferior petrosal sinus/peripheral ACTH was assayed. The sensitivity and specificity of diagnosis of the Cushing disease were estimated. Results: The inferior petrosal sinus/peripheral ACTH ratio was over 2.0 in 13 cases. Twelve cases underwent surgery with pathological diagnosis of pituitary ACTH adenoma, 1 patient relieved after γ knife treatment. The ratio was < 2.0 in 3 cases including 2 pulmonary carcinoid and one pituitary ACTH adenoma. The sensitivity and specify of IPSS for the diagnosis of Cushing disease were 13/14 and 2/2 respectively. Conclusion: IPSS was a safe technique with high sensitivity, specify and infrequent complications in the diagnosis of ACTH dependent Cushing disease. It had great clinical value in the differential diagnosis of ACTH dependent Cushing disease with unknown origin. (authors)

The 14th quality control survey for radioisotope in vitro tests in Japan, 1992

Energy Technology Data Exchange (ETDEWEB)

1993-11-01

This report presents the results of the 14th quality control nationwide survey. Of 490 facilities performing RI in vitro tests as of December 1992, 261 (53.3%) participated in the present 1992 survey. Free testosterone and renin were added to the following conventional 37 test items: adrenocorticotropic hormone (ACTH), growth hormone (GH), somatomedin C, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, thyroid stimulating hormone (TSH), triiodothyronine (T[sub 3]), free T[sub 3], thyroxine (T[sub 4]), free T[sub 4], T[sub 3] uptake, thyroglobulin, T[sub 3] binding globulin (TBG), parathyroid hormone (PTH), calcitonin, insulin, C-peptide, glucagon, gastrin, testosterone, estradiol, progesterone, 17[alpha]-hydroxyprogesterone, aldosterone, cortisol, immunoglobulin E (IgE), digoxin, [alpha]-fetoprotein, carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), CA125, CA19-9, CA15-3, prostatic acid phosphatase (PAP), [beta][sub 2]-microglobulin, and ferritin. Measurement data for each kit were analyzed by a mean value of measurements, standard deviation, and coefficient of variation (CV). Both 'within kit variation' between facilities and 'between kit variation' showed a CV of 20% or less for GH, somatomedin C, TSH, T[sub 3], T[sub 4], T[sub 3] uptake, TBG, cortisol, IgE, CA125, PAP, and [beta][sub 2]-microglobulin, revealing satisfactory results. There was a great 'within kit variation' between facilities in ACTH, free T[sub 4], and calcitonin; and there was a great 'between kit variation' in ACTH, LH, free T[sub 4], thyroglobulin, PTH, calcitonin, and [alpha]-fetoprotein. (N.K.).

Hormone action. Part I. Peptide hormones

International Nuclear Information System (INIS)

Birnbaumer, L.; O'Malley, B.W.

1985-01-01

The major sections of this book on the hormonal action of peptide hormones cover receptor assays, identification of receptor proteins, methods for identification of internalized hormones and hormone receptors, preparation of hormonally responsive cells and cell hybrids, purification of membrane receptors and related techniques, assays of hormonal effects and related functions, and antibodies in hormone action

Smoking is associated with increased adrenal responsiveness, decreased prolactin levels and a more adverse lipid profile in 650 white patients with polycystic ovary syndrome

DEFF Research Database (Denmark)

Glintborg, Dorte; Mumm, Hanne; Hougaard, David M.

2011-01-01

We investigated the associations between smoking status and metabolic risk factors and sex hormones in polycystic ovary syndrome (PCOS). The study was designed as a retrospective trans-sectional study including 650 white premenopausal women with the diagnoses hirsutism or PCOS divided according...... to smoking status: non-smokers (NS-PCOS = 390) and smokers (S-PCOS = 260). One hundred and nineteen healthy women were studied as controls (NS-Control = 105, S-Control = 14). Patients and controls underwent clinical evaluation, hormone analyses, transvaginal ultrasound, oral glucose tolerance tests (OGTT......) and adrenocorticotropic hormone (ACTH) tests. S-PCOS has significantly higher fasting lipid profile and 17-hydroxyprogesterone levels (basal and ACTH-stimulated) than NS-PCOS patients, whereas prolactin levels were decreased. No significant differences were found in body composition and measures of insulin resistance...

AN INDIVIDUALIZED APPROACH TO THE EVALUATION OF CUSHING SYNDROME.

Science.gov (United States)

Sharma, Susmeeta T

2017-06-01

Cushing syndrome (CS) is caused by chronic exposure to excess glucocorticoids. Early recognition and treatment of hypercortisolemia can lead to decreased morbidity and mortality. The diagnosis of CS and thereafter, establishing the cause can often be difficult, especially in patients with mild and cyclic hypercortisolism. Surgical excision of the cause of excess glucocorticoids is the optimal treatment for CS. Medical therapy (steroidogenesis inhibitors, medications that decrease adrenocorticotropic hormone [ACTH] levels or glucocorticoid antagonists) and pituitary radiotherapy may be needed as adjunctive treatment modalities in patients with residual, recurrent or metastatic disease, in preparation for surgery, or when surgery is contraindicated. A multidisciplinary team approach, individualized treatment plan and long-term follow-up are important for optimal management of hypercortisolemia and the comorbidities associated with CS. ACTH = adrenocorticotropic hormone; BIPSS = bilateral inferior petrosal sinus sampling; CBG = corticosteroid-binding globulin; CD = Cushing disease; CRH = corticotropin-releasing hormone; CS = Cushing syndrome; Dex = dexamethasone; DST = dexamethasone suppression test; EAS = ectopic ACTH syndrome; FDA = U.S. Food & Drug Administration; HDDST = high-dose DST; IPS/P = inferior petrosal sinus to peripheral; MRI = magnetic resonance imaging; NET = neuroendocrine tumor; PET = positron emission tomography; UFC = urinary free cortisol.

Measures of Autonomic Nervous System

Science.gov (United States)

2011-04-01

from the hypothalamus and binds to receptors on the anterior pituitary lobe. This activates release of adrenocorticotropic hormone (ACTH) from the... anterior pituitary . Cortisol is released when ACTH binds to receptors in the adrenal medulla. In addition to stress or trauma, many studies link...target organ. There are two exceptions in which preganglionic sympathetic nerve fibers directly innervate the target organ: the sweat glands and the

Leydig Cell Tumor Associated with Testicular Adrenal Rest Tumors in a Patient with Congenital Adrenal Hyperplasia due to 11β-Hydroxylase Deficiency

OpenAIRE

Charfi, Nadia; Kamoun, Mahdi; Feki Mnif, Mouna; Mseddi, Neila; Mnif, Fatma; Kallel, Nozha; Ben Naceur, Basma; Rekik, Nabila; Fourati, Hela; Daoud, Emna; Mnif, Zainab; Hadj Sliman, Mourad; Sellami-Boudawara, Tahia; Abid, Mohamed

2012-01-01

Congenital adrenal hyperplasia (CAH) describes a group of inherited autosomal recessive disorders characterized by enzyme defects in the steroidogenic pathways that lead to the biosynthesis of cortisol, aldosterone, and androgens. Chronic excessive adrenocorticotropic hormone (ACTH) stimulation may result in hyperplasia of ACTH-sensitive tissues in adrenal glands and other sites such as the testes, causing testicular masses known as testicular adrenal rest tumors (TARTs). Leydig cell tumors (...

Leptin inhibits and ghrelin augments hypothalamic noradrenaline release after stress.

Science.gov (United States)

Kawakami, Akio; Okada, Nobukazu; Rokkaku, Kumiko; Honda, Kazufumi; Ishibashi, Shun; Onaka, Tatsushi

2008-09-01

Metabolic conditions affect hypothalamo-pituitary-adrenal responses to stressful stimuli. Here we examined effects of food deprivation, leptin and ghrelin upon noradrenaline release in the hypothalamic paraventricular nucleus (PVN) and plasma adrenocorticotropic hormone (ACTH) concentrations after stressful stimuli. Food deprivation augmented both noradrenaline release in the PVN and the increase in plasma ACTH concentration following electrical footshocks (FSs). An intracerebroventricular injection of leptin attenuated the increases in hypothalamic noradrenaline release and plasma ACTH concentrations after FSs, while ghrelin augmented these responses. These data suggest that leptin inhibits and ghrelin facilitates neuroendocrine stress responses via noradrenaline release and indicate that a decrease in leptin and an increase in ghrelin release after food deprivation might contribute to augmentation of stress-induced ACTH release in a fasting state.

ACTH, Lipoproteins and salivary cortisol as adrenal insufficiency markers in patients with septic shock

OpenAIRE

Josiane Festti

2012-01-01

A sepse e o choque séptico são as principais causas de mortalidade em UTI. Muitos pacientes em choque séptico evoluem com insuficiência suprarrenal, um diagnóstico difícil de ser determinado. A realização do teste com ACTH sintético não é indicada rotineiramente, devido aos custos elevados e pouca praticidade. O HDL colesterol é precursor na biossíntese do cortisol e estudos têm mostrado que baixos níveis de HDL colesterol estão associados a aumento de mortalidade na sepse. Este estudo teve c...

Case Study

African Journals Online (AJOL)

IndexCopernicus Portal System

The medium- term evolution was marked by prolonged amenorrhea, fatigue and apathy. In the light of this clinical picture, Sheehan's syndrome was suspected and confirmed by a pituitary and cerebral MRI which showed an empty sella turcica (figure1). Hormone profiles including cortisol, plasma ACTH, thyroid hormones,.

Effect of dopamine, dopamine D-1 and D-2 receptor modulation on ACTH and cortisol levels in normal men and women

DEFF Research Database (Denmark)

Boesgaard, S; Hagen, C; Andersen, A N

1990-01-01

The regulation of the hypothalamic-pituitary-adrenal axis by dopamine is not fully understood. Therefore, we have studied the effect of dopamine, metoclopramide, a D-2 receptor antagonist, and fenoldopam, a specific D-1 receptor agonist, on ACTH and cortisol levels in normal subjects. Normal women...

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

Science.gov (United States)

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.

The Effect of Geographic Location on Circannual Adrenocorticotropic Hormone Plasma Concentrations in Horses in Australia.

Science.gov (United States)

Secombe, C J; Tan, R H H; Perara, D I; Byrne, D P; Watts, S P; Wearn, J G

2017-09-01

Longitudinal evaluation of plasma endogenous ACTH concentration in clinically normal horses has not been investigated in the Southern Hemisphere. To longitudinally determine monthly upper reference limits for plasma ACTH in 2 disparate Australian geographic locations and to examine whether location affected the circannual rhythm of endogenous ACTH in the 2 groups of horses over a 12-month period. Clinically normal horses horses from Perth and ≤67 pg/mL (upper limit of the 90% CI) in horses from Townsville, than at the acrophase, ≤94 pg/mL (upper limit of the 90% CI) in horses from Perth, ≤101 pg/mL (upper limit of the 90% CI) in horses from Townsville. Circannual rhythms of endogenous ACTH concentrations vary between geographic locations, this could be due to changes in photoperiod or other unknown factors, and upper reference limits should be determined for specific locations. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism

Directory of Open Access Journals (Sweden)

Wen-Bo Wang

2016-01-01

Conclusions: The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.

Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

Science.gov (United States)

Genazzani, A D; Bersi, C; Luisi, S; Fruzzetti, F; Malavasi, B; Luisi, M; Petraglia, F; Genazzani, A R

2001-09-01

To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. Controlled clinical study. Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

Infrasellar pituitary gangliocytoma causing Cushing's syndrome.

Science.gov (United States)

Domingue, Marie-Eve; Marbaix, Etienne; Do Rego, Jean-Luc; Col, Vincent; Raftopoulos, Christian; Duprez, Thierry; Vaudry, Hubert; Maiter, Dominique

2015-10-01

Pituitary gangliocytomas are uncommon neuronal tumours that may present with endocrine disorders, the most frequent being acromegaly caused by growth hormone hypersecretion. Cushing's syndrome is very rarely seen with gangliocytomas. We report the unique case of a 62 year-old woman whose clinical picture and endocrine testing clearly demonstrated adrenocorticotropin (ACTH)-dependent Cushing's syndrome. Pituitary magnetic resonance imaging showed a 12-mm homogeneous, infra- and retrosellar mass first diagnosed as pituitary macroadenoma. Transsphenoidal surgery was performed and allowed complete resection of the tumour with sparing of normal anterior pituitary. Very low postoperative serum cortisol and ACTH levels were observed in the early postoperative period and the patient is still in remission 18 months after surgery, thus demonstrating that the resected lesion was entirely responsible for the clinical picture. Histological and immunocytochemical analyses demonstrated a benign tumour composed of mature neuronal cells suggestive of a gangliocytoma, expressing both ACTH and corticotropin-releasing hormone (CRH). The tumour was surrounded by a rim of pituitary tissue containing ACTH-producing endocrine cells. Careful analysis of the resected lesion did not reveal any pituitary microadenoma. We search literature for similar cases and retraced only nine cases of gangliocytomas associated with Cushing's syndrome. In most of them, the tumour was combined with either pituitary corticotroph adenoma or hyperplasia. Our case represents a unique case of an infrasellar pituitary gangliocytoma which was able to cause Cushing's syndrome by both direct ACTH production and CRH-induced stimulation of neighbour normal corticotroph cells.

ADRENOCORTICOTROPIN HORMONE AND CORTISOL DYNAMIC VARIATION IN CASE OF CHILDREN›S NEUROINFECTIONS

Directory of Open Access Journals (Sweden)

T. N. Malyugina

2016-01-01

Full Text Available The  data  presented in the  article  deal  with  research  of hormone changes in hypophysial-paranephric system in the course  of neuroinfections. The  given  work  was  carried  out with  the  purpose of detection of dependence of the  cortisol and adrenocorticotropin hormone level on aetiology, gender, severity and  period  (cycle  of the  disease.A comprehensive clinical  and  laboratorial checkup of 109 children with  different  nosological forms of neuroinfections was carried  out: meningitis: viral, enteroviral, purulent and  cerebromeningitis. Control board group was composed of 10 healthy children of the identical age. All the patients underwent the Adrenocorticotropin Hormone and  Cortisol  blood  serum  level,  IFA technique being  used,  during acuity and  reconvalesence. It has  been  determined that  in  case  of neuroinfections  irrrespective of the ethiology, hypophysis trophic funtction undergoes arrest during the whole disease period. While studying adrenal gland  functioning during the  acuity the  increased cortisol secretion is observed, the degree of which  is authentically  higher  in case  of purulent meningitis and  meningoencephalitis compared to hydromeningitis. On recovery  the cortisol values decrease to healthy children’s level. A reliable dependence of the  ACTH  and  cortisol  level  on the  severity degree in case of purulent meningitis and meningoencephalitis was discovered ( brought to light. It is also satisfactorily brought to light that ACTH and cortisol levels depend on the severity degree in case of purulent meningitis and meningoencephalitis. It is proved that adrenal gland  system function does  not depend on the patients’ gender and  age in case of neuroinfections.

Comparison of the effects of single and daily repeated immobilization stress on resting activity and heterotypic sensitization of the hypothalamic-pituitary-adrenal axis.

Science.gov (United States)

Daviu, Núria; Rabasa, Cristina; Nadal, Roser; Armario, Antonio

2014-03-01

Acute exposure to severe stressors causes marked activation of the hypothalamic-pituitary-adrenal (HPA) axis that is reflected on the day after higher resting levels of HPA hormones and sensitization of the HPA response to novel (heterotypic) stressors. However, whether a single exposure to a severe stressor or daily repeated exposure to the same (homotypic) stressor modifies these responses to the same extent has not been studied. In this experiment, we studied this issue in adult male Sprague-Dawley rats daily exposed for seven days to a severe stressor such as immobilization on boards (IMO). A first exposure to 1 h IMO resulted in a marked activation of the HPA axis as reflected in plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone, and such activation was significantly reduced after the seventh IMO. On the day after the first IMO, higher resting levels of ACTH and corticosterone and sensitization of their responses to a short exposure to an open-field (OF) were observed, together with a marked hypoactivity in this environment. Repeated exposure to IMO partially reduced hypoactivity, the increase in resting levels of HPA hormones and the ACTH responsiveness to the OF on the day after the last exposure to IMO. In contrast, corticosterone response was gradually increased, suggesting partial dissociation from ACTH. These results indicate that daily repeated exposure to the same stressor partially reduced the HPA response to the homotypic stressor as well as the sensitization of HPA axis activity observed the day after chronic stress cessation.

The recovery of the hypothalamo-pituitary-adrenal axis after transsphenoidal operation in three patients with Cushing's disease

International Nuclear Information System (INIS)

Lamberts, S.W.J.; Klijn, J.G.M.; Jong, F.H. de; Birkenhager, J.C.

1981-01-01

The recovery of the hypothalamo-pituitary-adrenal axis after selective transsphenoidal adenomectomy was studied in 3 patients with Cushing's disease by measuring basal plasma ACTH and cortisol concentrations, cortisol secretion rate, the diurnal rhythm of cortisol, and the reaction of cortisol to lysine vasopressin (LVP), of compound S to metyrapone and of cortisol and growth hormone to an insulin-induced hypoglycaemia. The third patient had been treated previously by external pituitary irradiation. In 2 patients basal plasma ACTH levels returned within normal values before plasma cortisol, but no supra-physiological plasma concentrations of ACTH were seen as has been observed after withdrawal of exogenous glucocorticoids. With regard to the different stimulation tests: at first the normal reaction of plasma cortisol to LVP returned after 3 months, at the same time as the restoration of growth hormone secretion in response to hypoglycaemia. A normalization of the reaction to metyrapone was seen thereafter while finally the reaction of cortisol to an insulin-induced hypoglycaemia and the diurnal rhythm of plasma cortisol returned 15 to 18 months after operation in the first patient and after 12 months in the second patient. Selective adenomectomy had also been carried out in the third patient, as evidenced by normal TSH, LH and FSH secretion. Hypocortisolism, and a deficient ACTH and growth hormone secretion in response to the stimuli mentioned, however, did not normalize up till 22 months after operation. The restoration of the hypothalamo-pituitary-adrenal axis after selective pituitary adenomectomy in Cushing's disease was prevented in this patient by prior external pituitary irradiation. (author)

NERVE REGENERATION THROUGH A 2-PLY BIODEGRADABLE NERVE GUIDE IN THE RAT AND THE INFLUENCE OF ACTH4-9 NERVE GROWTH-FACTOR

NARCIS (Netherlands)

ROBINSON, PH; VANDERLEI, B; HOPPEN, HJ; LEENSLAG, JW; PENNINGS, AJ; NIEUWENHUIS, P

1991-01-01

Biodegradable polyurethane-based (PU) nerve guides, instilled with or without ACTH4-9 analog (a melanocortin) were used for bridging an 8 mm gap in the rat sciatic nerve and were evaluated for function and histological appearance after 16 weeks of implantation. Autologous nerve grafts functioned as

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

Directory of Open Access Journals (Sweden)

Renzhi Wang

2016-09-01

Full Text Available Adrenocorticotrophin (ACTH-secreting pituitary adenoma, also known as Cushing disease (CD, is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT. We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1, collagen type I α 1 chain (COL1A1, 5′-nucleotidase ecto (NT5E, HtrA serine peptidase 1 (HTRA1 and angiopoietin 1 (ANGPT1 and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.

Cushing's disease; inferior petrosal sinus venography and samplings

International Nuclear Information System (INIS)

Chung, Tae Sub; Suh, Jung Ho; Kim, Dong Ik; Lee, Hyun Chul; Huh, Kap Bum; Kim, Young Soo; Chung, Sang Sup

1991-01-01

Hypersecretion of ACTH in patients with Cushing's syndrome originates from either a pituitary tumor (Cushing's disease) or an ectopic ACTH-secreting tumor. These 2 entities may be clinically indistinguishable, and additional difficulty arise because pituitary microadenomas may be radiologically occult. Recently, bilateral selective venous sampling from the inferior petrosal sinuses became the procedure of choice for confirming a false negative study of a combined hormonal test and pituitary ACTH hypersecretion. We performed selective venous catheterization and sampling for ACTH. The central location of the lesion was detected in 1 case (intersinus gradient = 1.1 : 1), and the remaining 5 cases revealed lateralization of the lesions (intersinus gradient = 3.7 - 20.1 : 1), which correlated well with transsphenoidal microadenomectomies in all the cases. We concluded that selective venous ACTH sampling from the inferior petroal sinus is a reliable and useful aid in the diagnosis of Cushing's disease when standard clinical and biochemical studies are inconclusive

Stress hormones at rest and following exercise testing predict coronary artery disease severity and outcome.

Science.gov (United States)

Popovic, Dejana; Damjanovic, Svetozar; Djordjevic, Tea; Martic, Dejana; Ignjatovic, Svetlana; Milinkovic, Neda; Banovic, Marko; Lasica, Ratko; Petrovic, Milan; Guazzi, Marco; Arena, Ross

2017-09-01

Despite considerable knowledge regarding the importance of stress in coronary artery disease (CAD) pathogenesis, its underestimation persists in routine clinical practice, in part attributable to lack of a standardized, objective assessment. The current study examined the ability of stress hormones to predict CAD severity and prognosis at basal conditions as well as during and following an exertional stimulus. Forty Caucasian subjects with significant coronary artery lesions (≥50%) were included. Within 2 months of coronary angiography, cardiopulmonary exercise testing (CPET) on a recumbent ergometer was performed in conjunction with stress echocardiography (SE). At rest, peak and after 3 min of recovery following CPET, plasma levels of cortisol, adrenocorticotropic hormone (ACTH) and NT-pro-brain natriuretic peptide (NT-pro-BNP) were measured by immunoassay sandwich technique, radioimmunoassay, and radioimmunometric technique, respectively. Subjects were subsequently followed a mean of 32 ± 10 months. Mean ejection fraction was 56.7 ± 9.6%. Subjects with 1-2 stenotic coronary arteries (SCA) demonstrated a significantly lower plasma cortisol levels during CPET compared to those with 3-SCA (p  .05). Among CPET, SE, and hormonal parameters, cortisol at rest and during CPET recovery demonstrated the best predictive value in distinguishing between 1-, 2-, and 3-SCA [area under ROC curve 0.75 and 0.77 (SE = 0.11, 0.10; p = .043, .04) for rest and recovery, respectively]. ΔCortisol peak/rest predicted cumulative cardiac events (area under ROC curve 0.75, SE = 0.10, p = .049). Cortisol at rest and following an exercise test holds predictive value for CAD severity and prognosis, further demonstrating a link between stress and unwanted cardiac events.

Processing of high-molecular-weight form adrenocorticotropin in human adrenocorticotropin-secreting tumor cell line (DMS-79) after transfection of prohormone convertase 1/3 gene.

Science.gov (United States)

Tateno, T; Kato, M; Tani, Y; Yoshimoto, T; Oki, Y; Hirata, Y

2010-02-01

Ectopic ACTH-producing tumors preferentially secrete biologically inactive ACTH precursors and ACTH-related fragments. DMS-79 is known to secrete unprocessed high-molecular-weight (HMW) form ACTH. To determine whether prohormone convertase (PC) 1/3 is involved in the abnormal processing of proopiomelanocortin (POMC), we studied whether PC1/3 and 2 genes are expressed in DMS-79, and whether overexpression of PC1/3 gene affects POMC processing pattern. Steady-state mRNA levels of PC1/3 and 2 were determined by real-time RT-PCR. Molecular weights of ACTH-related peptides were determined by chromatographical analyses coupled with ACTH and beta-endorphin (beta-END) radioimmunoassays. PC1/3 gene was transfected into DMS-79 by retrovirus transduction using pMX-IP vector encoding PC1/3 cDNA. The steady-state mRNA levels of PC1/3 and 2 in DMS-79 were lower than those in ACTH-secreting and nonfunctioning pituitary tumors. DMS-79 predominantly secreted HMW form with both ACTH and beta-END immunoreactivities by size-exclusion chromatography. After purification by immunoaffinity chromatography with anti-ACTH antibody, the apparent molecular weight of HMW form ACTH was estimated to be 16 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver staining. After retroviral transfection of PC1/3 cDNA into DMS-79 and puromycin selection, PC1/3 stably-expressing cell line (DMS-79T) secreted two immunoreactive ACTH components, a major one coeluting with ACTH(1-39) and a minor one as a HMW form as well as two beta- END immunoreactive components coeluting with beta-lipotropic hormone and beta-END, respectively. Thus, we have established PC1/3 stably-expressing cell line (DMS-79T) capable of proteolytically processing ACTH precursor molecule(s) into mature ACTH and beta-END.

The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis

Science.gov (United States)

Minneci, P. C.; Deans, K. J.; Eichacker, P. Q.; Natanson, C.

2012-01-01

A previous meta-analysis determined that the effects of steroids during sepsis were dose-dependent; since then, additional trials have been published. The current analysis updates our previous analysis examining the effects of steroids during sepsis. A literature search from 2004 to 2008 identified seven randomized controlled trials in adult patients; these were added to 14 previously identified trials. The effects of steroids on mortality were highly variable among the 21 trials (p steroids, steroids increased mortality (n = 8, I2 = 14%, OR of death 1.39 (95% CI 1.04–1.86), p 0.03). In trials published after 1997, which involved longer courses of lower-dose steroids, steroids consistently improved shock reversal (n = 7, I2 = 0%, OR of shock reversal 1.66 [95% CI 1.25–2.20), p effect on mortality (n = 12, I2 = 25%, OR of death 0.64 (95% CI 0.45–0.93), p 0.02). An inverse linear relationship between severity of illness and the effects of steroids on mortality was identified across all trials (p 0.03) and within the subgroup of trials published after 1997 (p 0.03); steroids were harmful in less severely ill patient populations and beneficial in more severely ill patient populations. There was no effect of response to adrenocorticotrophic hormone (ACTH) stimulation testing concerning the effects of steroids and no increase in steroid-associated adverse events. Low-dose steroids appear to improve mortality rates in patients with septic shock who are at high risk of death; however, additional trials in this subpopulation are necessary to definitively determine the role of low-dose steroids during sepsis. PMID:19416302

Spontaneous resolution of avascular necrosis of femoral heads following cure of Cushing’s syndrome

Directory of Open Access Journals (Sweden)

A Pazderska

2016-05-01

Full Text Available Avascular necrosis (AVN is a rare presenting feature of endogenous hypercortisolism. If left untreated, complete collapse of the femoral head may ensue, necessitating hip replacement in up to 70% of patients. The majority of the described patients with AVN due to endogenous hypercortisolaemia required surgical intervention. A 36-year-old female, investigated for right leg pain, reported rapid weight gain, bruising and secondary amenorrhoea. She had abdominal adiposity with violaceous striae, facial plethora and hirsutism, atrophic skin, ecchymosis and proximal myopathy. Investigations confirmed cortisol excess (cortisol following low-dose 48h dexamethasone suppression test 807nmol/L; 24h urinary free cortisol 1443nmol (normal<290nmol. Adrenocorticotrophic hormone (ACTH was <5.0pg/mL. CT demonstrated subtle left adrenal gland hypertrophy. Hypercortisolaemia persisted after left adrenalectomy. Histology revealed primary pigmented micronodular adrenal disease. Post-operatively, right leg pain worsened and left leg pain developed, affecting mobility. MRI showed bilateral femoral head AVN. She underwent right adrenalectomy and steroid replacement was commenced. Four months after surgery, leg pain had resolved and mobility was normal. Repeat MRI showed marked improvement of radiological abnormalities in both femoral heads, consistent with spontaneous healing of AVN. We report a case of Cushing’s syndrome due to primary pigmented nodular adrenocortical disease, presenting with symptomatic AVN of both hips. This was managed conservatively from an orthopaedic perspective. Following cure of hypercortisolaemia, the patient experienced excellent recovery and remains symptom free 4 years after adrenalectomy. This is the first report of a favourable outcome over long-term follow-up of a patient with bilateral AVN of the hip, which reversed with treatment of endogenous hypercortisolaemia.

Transplantation of human dental pulp-derived stem cells protects against heatstroke in mice.

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Tseng, Ling-Shu; Chen, Sheng-Hsien; Lin, Mao-Tsun; Lin, Ying-Chu

2015-01-01

Stem cells from human exfoliated deciduous tooth pulp (SHED) is a promising approach for the treatment of stroke and spinal cord injury. In this study, we investigated the therapeutic effects of SHED for the treatment of multiple organ (including brain, particularly hypothalamus) injury in heatstroke mice. ICR male mice were exposed to whole body heating (WBH; 41.2°C, relative humidity 50-55%, for 1 h) and then returned to normal room temperature (26°C). We observed that intravenous administration of SHED immediately post-WBH exhibited the following therapeutic benefits for recovery after heatstroke: (a) inhibition of WBH-induced neurologic and thermoregulatory deficits; (b) reduction of WBH-induced ischemia, hypoxia, and oxidative damage to the brain (particularly the hypothalamus); (c) attenuation of WBH-induced increased plasma levels of systemic inflammatory response molecules, such as tumor necrosis factor-α and intercellular adhesion molecule-1; (d) improvement of WBH-induced hypothalamo-pituitary-adrenocortical (HPA) axis activity (as reflected by enhanced plasma levels of both adrenocorticotrophic hormone and corticosterone); and (e) attenuation of WBH-induced multiple organ apoptosis as well as lethality. In conclusion, post-WBH treatment with SHED reduced induction of proinflammatory cytokines and oxidative radicals, enhanced plasma induction of both adrenocorticotrophic hormone and corticosterone, and improved lethality in mouse heatstroke. The protective effect of SHED may be related to a decreased inflammatory response, decreased oxidative stress, and an increased HPA axis activity following the WBH injury.

Ghrelin receptor expression and colocalization with anterior pituitary hormones using a GHSR-GFP mouse line.

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Reichenbach, Alex; Steyn, Frederik J; Sleeman, Mark W; Andrews, Zane B

2012-11-01

Ghrelin is the endogenous ligand for the GH secretagogue receptor (GHSR) and robustly stimulates GH release from the anterior pituitary gland. Ghrelin also regulates the secretion of anterior pituitary hormones including TSH, LH, prolactin (PRL), and ACTH. However, the relative contribution of a direct action at the GHSR in the anterior pituitary gland vs. an indirect action at the GHSR in the hypothalamus remains undefined. We used a novel GHSR-enhanced green fluorescent protein (eGFP) reporter mouse to quantify GHSR coexpression with GH, TSH, LH, PRL, and ACTH anterior pituitary cells in males vs. females and in chow-fed or calorie-restricted (CR) mice. GHSR-eGFP-expressing cells were only observed in anterior pituitary. The number of GHSR-eGFP-expressing cells was higher in male compared with females, and CR did not affect the GHSR-eGFP cell number. Double staining revealed 77% of somatotrophs expressed GHSR-eGFP in both males and females. Nineteen percent and 12.6% of corticotrophs, 21% and 9% of lactotrophs, 18% and 19% of gonadotrophs, and 3% and 9% of males and females, respectively, expressed GHSR-eGFP. CR increased the number of TSH cells, but suppressed the number of lactotrophs and gonadotrophs, expressing GHSR-eGFP compared with controls. These studies support a robust stimulatory action of ghrelin via the GHSR on GH secretion and identify a previously unknown sexual dimorphism in the GHSR expression in the anterior pituitary. CR affects GHSR-eGFP expression on lactotrophs, gonadotrophs, and thyrotrophs, which may mediate reproductive function and energy metabolism during periods of negative energy balance. The low to moderate expression of GHSR-eGFP suggests that ghrelin plays a minor direct role on remaining anterior pituitary cells.

Central Adrenal Insufficiency and Diabetes Insipidus Misdiagnosed as Severe Depression

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Naoki Hiroi

2010-01-01

Full Text Available A 68 year-old Japanese man, who had been suffering from immobilization and disuse syndrome, was admitted to our hospital for evaluation of polyuria with polyposia, hyponatremia and low blood pressure. His plasma osmolality was greater than that of his urine. His endocrinological examination revealed low levels of plasma adrenocorticotropic hormone (ACTH and cortisol, and a normal response of ACTH to the corticotrophin-releasing hormone (CRH challenge. Plasma ACTH did not increase with insulin loading. A low plasma vasopressin (AVP level and no response of AVP to a 5% saline administration were observed. We diagnosed central adrenal insufficiency with central diabetes insipidus. Six months after starting administration of hydrocortisone and 1-deamino-8D-arginine vasopressin, his psychological symptoms had improved, and 1.5 years after starting treatment, he was able to walk. In conclusion, it is not particularly rare for adrenal insufficiency to be misdiagnosed as depression. However, a correct early diagnosis is necessary, because, if adrenal insufficiency is not definitively diagnosed, the patient's quality of life diminishes markedly.

Comparative Functional Alanine Positional Scanning of the α-Melanocyte Stimulating Hormone and NDP-Melanocyte Stimulating Hormone Demonstrates Differential Structure-Activity Relationships at the Mouse Melanocortin Receptors.

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Todorovic, Aleksandar; Ericson, Mark D; Palusak, Ryan D; Sorensen, Nicholas B; Wood, Michael S; Xiang, Zhimin; Haskell-Luevano, Carrie

2016-07-20

The melanocortin system has been implicated in the regulation of various physiological functions including melanogenesis, steroidogenesis, energy homeostasis, and feeding behavior. Five melanocortin receptors have been identified to date and belong to the family of G protein-coupled receptors (GPCR). Post-translational modification of the proopiomelanocortin (POMC) prohormone leads to the biosynthesis of the endogenous melanocortin agonists, including α-melanocyte stimulating hormone (α-MSH), β-MSH, γ-MSH, and adrenocorticotropic hormone (ACTH). All the melanocortin agonists derived from the POMC prohormone contain a His-Phe-Arg-Trp tetrapeptide sequence that has been implicated in eliciting the pharmacological responses at the melanocortin receptors. Herein, an alanine (Ala) positional scan is reported for the endogenous α-MSH ligand and the synthetic, more potent, NDP-MSH peptide (Ac-Ser(1)-Tyr(2)-Ser(3)-Nle(4)-Glu(5)-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-Lys(11)-Pro(12)-Val(13)-NH2) at the cloned mouse melanocortin receptors to test the assumption that the structure-activity relationships of one ligand would apply to the other. Several residues outside of the postulated pharmacophore altered potency at the melanocortin receptors, most notably the 1560-, 37-, and 15-fold potency loss when the Glu(5) position of α-MSH was substituted with Ala at the mMC1R, mMC3R, and mMC4R, respectively. Importantly, the altered potencies due to Ala substitutions in α-MSH did not necessarily correlate with equivalent Ala substitutions in NDP-MSH, indicating that structural modifications and corresponding biological activities in one of these melanocortin ligands may not be predictive for the other agonist.

Demographic study of pituitary adenomas undergone trans-sphenoidal surgery in Loghman Hakim Hospital, Tehran, Iran 2001–2013

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Farahnaz Bidari Zerehpoosh

2015-01-01

Full Text Available Background: Pituitary adenomas (PAs are abnormal benign tumors that develop in the pituitary gland. This study aimed to assess the prevalence of different types of PAs with an indication for trans-sphenoidal surgery in a well-defined population referred to Loghman Hakim Hospital during 2001–2013. Subjects and Methods: In this retrospective study, the prevalence rate and symptoms associated with pituitary mass and hormone excess in operated patients were investigated. The diagnosis was verified after retrieval of clinical, hormonal, radiological, and pathological data. Demographic data were collected in all cases. Descriptive analysis, t-test, one-way analysis of variance and Fischer exacts test were used. Results: A total of 278 patients with PAs who underwent surgical interventions were evaluated. Most of the patients were aged 40–50 years with an average of 41 ± 14. The most prominent complaint was pressure effect, which was detected in 153 cases (55.2%. At the second place, hormonal disorders were observed in 125 cases (44.8%. Type of pituitary tumors were: Prolactinomas (29.1%, growth hormone (GH-producing tumors (25%, nonfunctioning PAs (28.4%, adrenocorticotropic hormone (ACTH-producing tumors (2.1%, thyroid stimulating hormone (TSH-producing tumors (0.7%, GH/prolactin (13.6%, GH/ACTH (0.3%, and TSH/ACTH (0.3%. Fifty-seven patients presented with recurrent adenomas. Pituitary apoplexy was found in 11 patients. One case of Sheehan syndrome was recorded among these. The correlations between clinical symptoms and patients, age and sex were not significant. Conclusion: The overview of demographic characteristics in Iranian patients with PAs with surgical indication has been discussed in the present investigation. The prevalence of different types of PAs and the most common clinical symptoms have been demonstrated.

The Occurrence of Apparent Bilateral Aldosterone Suppression in Adrenal Vein Sampling for Primary Aldosteronism

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Shibayama, Yui; Wada, Norio; Naruse, Mitsuhide; Kurihara, Isao; Ito, Hiroshi; Yoneda, Takashi; Takeda, Yoshiyu; Umakoshi, Hironobu; Tsuiki, Mika; Ichijo, Takamasa; Fukuda, Hisashi; Katabami, Takuyuki; Yoshimoto, Takanobu; Ogawa, Yoshihiro; Kawashima, Junji; Ohno, Yuichi; Sone, Masakatsu; Fujita, Megumi; Takahashi, Katsutoshi; Shibata, Hirotaka; Kamemura, Kohei; Fujii, Yuichi; Yamamoto, Koichi; Suzuki, Tomoko

2018-01-01

Abstract Context In adrenal venous sampling (AVS) for patients with primary aldosteronism (PA), apparent bilateral aldosterone suppression (ABAS), defined as lower aldosterone/cortisol ratios in the bilateral adrenal veins than that in the inferior vena cava, is occasionally experienced. ABAS is uninterpretable with respect to lateralization of excess aldosterone production. We previously reported that ABAS was not a rare phenomenon and was significantly reduced after adrenocorticotropic hormone (ACTH) administration. Objective To validate the effects of ACTH administration and adding sampling positions in the left adrenal vein on the prevalence of ABAS in the larger Japan Primary Aldosteronism Study. Patients The data from 1689 patients with PA who underwent AVS between January 2006 and October 2016 were studied. All patients in the previous study, the West Japan Adrenal Vein Sampling study, were excluded. Outcome Measurements The prevalence of ABAS was investigated at two sampling positions in the left adrenal vein, the central vein and the common trunk, without and with ACTH administration. Results The prevalence of ABAS with ACTH administration was significantly lower than that without ACTH administration [without ACTH vs with ACTH: 79/440 (18.0%) vs 45/591 (7.6%); P AVS regardless of the sampling position in the left adrenal vein was confirmed in the larger cohort. PMID:29687091

The intramuscular glucagon stimulation test does not provide good discrimination between normal and inadequate ACTH reserve when used in the investigation of short healthy children.

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Tenenbaum, Ariel; Phillip, Moshe; de Vries, Liat

2014-01-01

Few studies have addressed the role of the glucagon stimulation test (GST) in evaluating the hypothalamic-pituitary-adrenal axis in children. We investigated the diagnostic value of the GST in evaluating the adrenocortical response in short healthy children. The GST was performed in 190 children investigated for short stature. A peak cortisol >500 nmol/l was considered a normal response. In the 45 (23.7%) with subnormal response, a 250-μg ACTH test was done. The rate of subnormal adrenal response to GST was higher among boys (33.9 vs. 8.9%, p 500 nmol/l in all the patients undergoing an ACTH stimulation test. Since adrenal response to GST is age- and gender-related and the false-positive rate is high, its routine performance in healthy children warrants reconsideration. © 2014 S. Karger AG, Basel.

Nonparaneoplastic anti-N-methyl-D-aspartate receptor encephalitis: a case series of four children.

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Raha, Sarbani; Gadgil, Pradnya; Sankhla, Charulata; Udani, Vrajesh

2012-04-01

A rare, severe form of immune-mediated encephalitis recently has been described, associated with antibodies against N-methyl-D-aspartate receptors. It is reported mostly in women with ovarian tumors. Nonparaneoplastic presentations are less common. We describe four children with a neuropsychiatric and extrapyramidal syndrome associated with the presence of anti-N-methyl-D-aspartate receptor antibodies in cerebrospinal fluid and serum, without evidence of neoplasia. Three children recovered completely after immunomodulatory therapy, i.e., intravenous immunoglobulin and/or steroids, methylprednisolone, and/or adrenocorticotrophic hormone. Copyright © 2012 Elsevier Inc. All rights reserved.

The 11th quality control survey for radioisotopes in vitro tests in Japan, 1989

Energy Technology Data Exchange (ETDEWEB)

1990-10-01

This report presents the results of the 11th quality control nationwide survey. Of 730 facilities performing radioisotopes in vitro tests in November 1989, 422 facilities (60.5%) participated in the present survey. The following 23 items were examined: adrenocorticotropic hormone (ACTH), albumin, carbohydrate antigen 125 (CA 125), carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), calcitonin, cortisol, estradiol, ferritin, free thyroxine (FT{sub 4}), follicle stimulating hormone (FSH), gastrine, cholylglycine, glucagon, insulin, anti-DNA antibody, luteinizing hormone (LH), neuron specific enolase (NSE), parathyroid hormone (PTH), squamous cell carcinoma associated antigen (SCC), thyroxine (T{sub 4}), thyroxine binding globulin (TBG), and antithyroid stimulating hormone (TSH) receptor antibody. 'Within kit variation' between facilities showed large coefficient of variation for ACTH, CA125, CEA, estradiol, ferritin, FSH, glucagon, anti-DNA antibody, LH, PTH, and TSH receptor antibody. Both 'within kit variation' and 'between kit variation' showed small coefficient of variation for cortisol, free T{sub 4}, NSE, SCC, T{sub 4}, and TBG. The present survey was characterized by using immunoradiometric assay (IRMA) and non-isotope techniques, as well as radioimmunoassay. Kits for IRMA greatly varied from facility to facility. (N.K.).

Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder.

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Cooper, Odelia; Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

2017-06-01

Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Prospective controlled study in an outpatient clinic. Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm 3 [standard deviation (SD), 227.3 mm 3 ] in PTSD subjects vs 835.2 mm 3 (SD, 302.8 mm 3 ) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects ( P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches.

Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder

Science.gov (United States)

Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

2017-01-01

Objectives: Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Design: Prospective controlled study in an outpatient clinic. Methods: Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Results: Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm3 [standard deviation (SD), 227.3 mm3] in PTSD subjects vs 835.2 mm3 (SD, 302.8 mm3) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects (P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. Conclusions: The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches. PMID:29264511

Bilateral inferior petrosal sinus sampling using vasopressin

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Narendra Kotwal

2016-01-01

Full Text Available Context: Anatomical localization of pituitary adenoma can be challenging in adrenocorticotropic hormone (ACTH-dependent Cushing's syndrome, and bilateral inferior petrosal sinus sampling (BIPSS is considered gold standard in this regard. Stimulation using corticotrophin-releasing hormone (CRH improves the sensitivity of BIPSS, however, same is not easily available in India. Therefore, we undertook this study of BIPPS using vasopressin as agent for stimulation owing to its ability to stimulate V3 receptors present on corticotrophs. Aims: To study the tumor localization and lateralization in difficult to localize cases of ACTH-dependent Cushing's syndrome by bilateral inferior petrosal sinus sampling using vasopressin for corticotroph stimulation. Settings and Design: Prospective observational study. Subjects and Methods: Six patients (5 females meeting inclusion criteria underwent BIPSS using vasopressin for stimulation. Results: All six patients had nonsuppressible overnight and low dose dexamethasone suppression test with elevated plasma ACTH levels suggestive of ACTH-dependent Cushing's syndrome. High dose dexamethasone suppression test showed suppressible cortisol in two cases, and microadenoma was seen in two patients on magnetic resonance imaging pituitary. Contrast enhanced computed tomography of the abdomen showed left adrenal hyperplasia in one case and anterior mediastinal mass with bilateral adrenal hyperplasia another. Using BIPSS four patients were classified as having Cushing's disease that was confirmed histopathologically following surgery. Of the remaining two, one had primary pigmented nodular adrenocortical disease, and another had thymic carcinoid with ectopic ACTH production as the cause of Cushing's syndrome. No serious adverse events were noted. Conclusions: Vasopressin may be used instead of CRH and desmopressin for stimulation in BIPSS.

A five year prospective investigation of anterior pituitary function after traumatic brain injury: is hypopituitarism long-term after head trauma associated with autoimmunity?

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Tanriverdi, Fatih; De Bellis, Annamaria; Ulutabanca, Halil; Bizzarro, Antonio; Sinisi, Antonio A; Bellastella, Giuseppe; Amoresano Paglionico, Vanda; Dalla Mora, Liliana; Selcuklu, Ahmed; Unluhizarci, Kursad; Casanueva, Felipe F; Kelestimur, Fahrettin

2013-08-15

Traumatic brain injury (TBI) has been recently recognized as a common cause of pituitary dysfunction. However, there are not sufficient numbers of prospective studies to understand the natural history of TBI induced hypopituitarism. The aim was to report the results of five years' prospective follow-up of anterior pituitary function in patients with mild, moderate and severe TBI. Moreover, we have prospectively investigated the associations between TBI induced hypopituitarism and presence of anti-hypothalamus antibodies (AHA) and anti-pituitary antibodies (APA). Twenty five patients (20 men, five women) were included who were prospectively evaluated 12 months and five years after TBI, and 17 of them also had a third-year evaluation. Growth hormone (GH) deficiency is the most common pituitary hormone deficit at one, three, and five years after TBI. Although most of the pituitary hormone deficiencies improve over time, there were substantial percentages of pituitary hormone deficiencies at the fifth year (28% GH, 4% adrenocorticotropic hormone [ACTH], and 4% gonadotropin deficiencies). Pituitary dysfunction was significantly higher in strongly AHA- and APA-positive (titers ≥1/16) patients at the fifth year. In patients with mild and moderate TBI, ACTH and GH deficiencies may improve over time in a considerable number of patients but, although rarely, may also worsen over the five-year period. However in severe TBI, ACTH and GH status of the patients at the first year evaluation persisted at the fifth year. Therefore, screening pituitary function after TBI for five years is important, especially in patients with mild TBI. Moreover, close strong associations between the presence of high titers of APA and/or AHA and hypopituitarism at the fifth year were shown for the first time.

Hormone assay

International Nuclear Information System (INIS)

Eisentraut, A.M.

1977-01-01

An improved radioimmunoassay is described for measuring total triiodothyronine or total thyroxine levels in a sample of serum containing free endogenous thyroid hormone and endogenous thyroid hormone bound to thyroid hormone binding protein. The thyroid hormone is released from the protein by adding hydrochloric acid to the serum. The pH of the separated thyroid hormone and thyroid hormone binding protein is raised in the absence of a blocking agent without interference from the endogenous protein. 125 I-labelled thyroid hormone and thyroid hormone antibodies are added to the mixture, allowing the labelled and unlabelled thyroid hormone and the thyroid hormone antibody to bind competitively. This results in free thyroid hormone being separated from antibody bound thyroid hormone and thus the unknown quantity of thyroid hormone may be determined. A thyroid hormone test assay kit is described for this radioimmunoassay. It provides a 'single tube' assay which does not require blocking agents for endogenous protein interference nor an external solid phase sorption step for the separation of bound and free hormone after the competitive binding step; it also requires a minimum number of manipulative steps. Examples of the assay are given to illustrate the reproducibility, linearity and specificity of the assay. (UK)

[No effect of digitalis on sex and adrenal hormones in healthy subjects and in patients with congestive heart failure].

Science.gov (United States)

Kley, H K; Abendroth, H; Hehrmann, R; Müller, A; Keck, E; Schneitler, H; Elsässer, H; Krüskemper, H L

1984-01-16

Digoxin was studied to see whether it impairs adrenal function and feminizes male subjects by changing plasma sexual hormones; both have been reported on previously. In eight healthy male subjects neither estrone (38.7 +/- 7.7 vs 35.4 +/- 3.2 pg/ml) nor estradiol (35.8 +/- 6.4 vs 32.2 +/- 3.9 pg/ml) nor testosterone (6.32 +/- 0.74 vs 6.45 +/- 0.73 ng/ml) were found to be altered by digoxin administration (plasma levels 1.55 +/0- 0.27 ng/ml) lasting 35 days. The same was true of free testosterone (147 +/- 24 vs 142 +/- 19 pg/ml) and free estradiol (657 +/- 77 vs 615 +/- 78 fg/ml). Even maximal stimulation of the adrenal and gonadal glands by adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) did not exhibit any digoxin-induced alterations in the synthesizing capacity of steroid hormones, as shown by plasma cortisol (increase from 128 +/- 18 to 389 +/- 18 ng/ml) and testosterone (from 5.96 +/- 0.90 to 10.33 +/- 1.19 ng/ml). Furthermore, seven subjects on digoxin were observed over a period of 150-210 days; they did not show any increase of estrogens. This was also found in three subjects when estrogen levels were elevated initially due to extreme obesity. Also, 35 patients who took beta-methyldigoxin (n = 8), beta-acetyldigoxin (n = 20) and digitoxin (n = 7) from 1 to 9 (mean: 1.9) years demonstrated normal plasma concentrations of gonadal and adrenal steroids, irrespective of duration of application or the digitalis compound.(ABSTRACT TRUNCATED AT 250 WORDS)

The ACTH4–9 analog ORG 2766 ‘normalizes’ the changes in motor activities of rats elicited by housing and test conditions

NARCIS (Netherlands)

Wolterink, G.; Ree, J.M. van

1987-01-01

Motor activities of rats were decreased by short-term (7 days) social isolation as well as by intense light test conditions. The ACTH4-9 analog ORG 2766, s.c. administered 50 min before testing, dose-dependently decreased the high motor activities of group-housed housed rats tested under low light

Cryptochrome 2 expression level is critical for adrenocorticotropin stimulation of cortisol production in the capuchin monkey adrenal.

Science.gov (United States)

Torres-Farfan, C; Abarzua-Catalan, L; Valenzuela, F J; Mendez, N; Richter, H G; Valenzuela, G J; Serón-Ferré, M

2009-06-01

Timely production of glucocorticoid hormones in response to ACTH is essential for survival by coordinating energy intake and expenditure and acting as homeostatic regulators against stress. Adrenal cortisol response to ACTH is clock time dependent, suggesting that an intrinsic circadian oscillator in the adrenal cortex contributes to modulate the response to ACTH. Circadian clock gene expression has been reported in the adrenal cortex of several species. However, there are no reports accounting for potential involvement of adrenal clock proteins on cortisol response to ACTH. Here we explored whether the clock protein cryptochrome 2 (CRY2) knockdown modifies the adrenal response to ACTH in a primate. Adrenal gland explants from adult capuchin monkey (n = 5) were preincubated for 6 h with transfection vehicle (control) or with two different Cry2 antisense and sense probes followed by 48 h incubation in medium alone (no ACTH) or with 100 nm ACTH. Under control and sense conditions, ACTH increased cortisol production, whereas CRY2 suppression inhibited ACTH-stimulated cortisol production. Expression of the steroidogenic enzymes steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase at 48 h of incubation was increased by ACTH in control explants and suppressed by Cry2 knockdown. Additionally, we found that Cry2 knockdown decreased the expression of the clock gene brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (Bmal1) at the mRNA and protein levels. Altogether these results strongly support that the clock protein CRY2 is involved in the mechanism by which ACTH increases the expression of steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase. Thus, adequate expression levels of components of the adrenal circadian clock are required for an appropriate cortisol response to ACTH.

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.

Medline Plus

Full Text Available ... stimulates breast tissue in nursing mothers to produce milk ACTH (adrenocorticotropic hormone) - causes the adrenal glands to ... less urine Oxytocin - initiates labor, uterine contractions and milk ejection in mothers

Pituitary tumor with gigantism, acromegaly and preclinical Cushing's disease diagnosed from the 10th row.

Science.gov (United States)

Tourtelot, John B; Vesely, David L

2013-08-01

A 7'3" basketball player was noted to have 2 to 3 times thicker tissue in his hands than 6'10" players by an endocrinologist sitting 10 rows above the player in a basketball arena. This led to the diagnosis of pituitary gigantism where the history revealed that he was 7'3" at 15 years of age. At age 19 when the acryl enlargement was noted, a diagnostic workup revealed elevated growth hormones and insulin-like growth factor 1 (IGF-1) with a 2 × 1.3 cm pituitary tumor. His history suggested that his epiphyseal plates had closed at age 15, and because he continued to produce IGF-1, he now has acromegaly. His elevated adrenocorticotropic hormone (ACTH) before surgery suggests that he also had preclinical Cushing's disease. After pituitary transsphenoidal surgery, all acryl enlargement in hands and ligaments disappeared. His growth hormone, IGF-1 and ACTH returned to normal 2 weeks after surgery.

Reduced steroidogenesis in patients with PCDH19-female limited epilepsy.

Science.gov (United States)

Trivisano, Marina; Lucchi, Chiara; Rustichelli, Cecilia; Terracciano, Alessandra; Cusmai, Raffaella; Ubertini, Grazia Maria; Giannone, Germana; Bertini, Enrico Silvio; Vigevano, Federico; Gecz, Jozef; Biagini, Giuseppe; Specchio, Nicola

2017-06-01

Patients affected by protocadherin 19 (PCDH19)-female limited epilepsy (PCDH19-FE) present a remarkable reduction in allopregnanolone blood levels. However, no information is available on other neuroactive steroids and the steroidogenic response to hormonal stimulation. For this reason, we evaluated allopregnanolone, pregnanolone, and pregnenolone sulfate by liquid chromatographic procedures coupled with electrospray tandem mass spectrometry in 12 unrelated patients and 15 age-matched controls. We also tested cortisol, estradiol, progesterone, and 17OH-progesterone using standard immunoassays. Apart from estradiol and progesterone, all the considered hormones were evaluated in basal condition and after stimulation with adrenocorticotropic hormone (ACTH). A generalized decrease in blood levels of almost all measured neuroactive steroids was found. When considering sexual development, cortisol and pregnenolone sulfate basal levels were significantly reduced in postpubertal girls affected by PCDH19-FE. Of interest, ACTH administration did not recover pregnenolone sulfate serum levels but restored cortisol to control levels. In prepubertal girls with PCDH19-FE, by challenging adrenal function with ACTH we disclosed defects in the production of cortisol, pregnenolone sulfate, and 17OH-progesterone, which were not apparent in basal condition. These findings point to multiple defects in peripheral steroidogenesis associated with and potentially relevant to PCDH19-FE. Some of these defects could be addressed by stimulating adrenocortical activity. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Detection of tetracosactide in plasma by enzyme-linked immunosorbent assay (ELISA).

Science.gov (United States)

Martin, Laurent; Chaabo, Ayman; Lasne, Françoise

2015-06-01

As a synthetic analogue of adrenocorticotropic hormone (ACTH), tetracosactide is prohibited in sport by the World Anti-Doping Agency (WADA). An enzyme-linked immunosorbent assay (ELISA) method is proposed for detection of this drug in plasma. Since its structure corresponds to the 24 N-terminal of the 39 amino acids of the natural endogenous peptide ACTH, tetracosactide can be detected with a commercial ELISA kit for ACTH that uses antibodies, the epitopes of which are located in the 1-24 part of ACTH. However, an essential condition for detection specificity is the preliminary total clearance of endogenous ACTH in the plasma samples. This is achieved by a preparative step based on cation-exchange chromatography before ELISA. The method is specific and sensitive (LOD: 30 pg/mL) and may be used as a screening analysis in anti-doping control. The pre-analytical conditions are shown to be of the upmost importance and recommendations for blood collection (EDTA tubes), sample transport (4 °C) and plasma sample storage (-20 °C) are presented. Copyright © 2014 John Wiley & Sons, Ltd.

Cushing's disease due to mixed pituitary adenoma-gangliocytoma of the posterior pituitary gland presenting with Aspergillus sp. sinus infection.

Science.gov (United States)

Bridenstine, Mark; Kerr, Janice M; Lillehei, Kevin O; Kleinschmidt-DeMasters, Bette K

2013-01-01

Gangliocytic lesions of the pituitary gland producing Cushing's disease are extremely rare entities that may exist with or without a pituitary adenoma. The latter have been designated mixed pituitary adenoma-gangliocytomas, the majority of which produce growth hormone, not adrenocorticotropin (ACTH), and are localized to the anterior gland. We now report an immunocompetent woman with hypercortisolism who presented with an intranasal aspergilloma eroding the bony sellar floor. The fungal ball was contiguous with, and extended into, a large neurohypophyseal-centered mass. Transsphenoidal resection revealed a gangliocytic lesion of the posterior gland with small clusters of intimately admixed ACTH-immunoreactive adenoma cells as the cause of her Cushing's disease. Rare transitional sizes and shapes of cells coupled with immunohistochemical findings supported interpretation as advanced neuronal metaplasia within an ACTH adenoma. This mixed ACTH adenoma-gangliocytoma is the first example to present clinically with an opportunistic infection.

Factitious Cushing's syndrome masquerading as Cushing's disease.

Science.gov (United States)

Thynne, Tilenka; White, Graham H; Burt, Morton G

2014-03-01

Factitious Cushing's syndrome is extremely rare. The diagnosis is challenging as cross-reactivity of synthetic corticosteroids or their metabolites in immunoassay measurements of plasma or urinary cortisol can make distinguishing between true and factitious Cushing's syndrome difficult. Adrenocorticotropin (ACTH) is usually suppressed in factitious Cushing's syndrome. A 54-year-old woman presented with clinical and biochemical features of Cushing's syndrome and an unsuppressed ACTH concentration. She denied recent exogenous corticosteroid use. Initial investigations revealed a markedly elevated urinary free cortisol, mildly elevated midnight salivary cortisol and normal morning cortisol concentration. Plasma ACTH was not suppressed at 13 ng/l (RR 10-60 ng/l). A pituitary MRI was normal, but inferior petrosal sinus sampling (IPSS) revealed a post corticotrophin releasing hormone ACTH ratio >20:1 in the left petrosal sinus. Ketoconazole therapy amplified discordance between the urinary free and morning plasma cortisol concentrations. Further investigation of this discordance using high-pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) revealed a urinary free cortisol excretion of only 20 nmol/24 h, but prednisolone excretion of 16,200 nmol/24 h. Factitious Cushing's syndrome can mimic endogenous ACTH-dependent hypercortisolism during initial investigations and IPSS. This case highlights the importance of (i) recognizing the significance of discordant results; (ii) using an ACTH assay capable of reliably differentiating ACTH-dependent from ACTH-independent Cushing's syndrome; and (iii) appreciating that IPSS is only useful to localize the source of ACTH in confirmed ACTH-dependent Cushing's syndrome. In this case, measurement of corticosteroids by HPLC-MS/MS was essential in reaching the correct diagnosis. © 2013 John Wiley & Sons Ltd.

The Occurrence of Apparent Bilateral Aldosterone Suppression in Adrenal Vein Sampling for Primary Aldosteronism.

Science.gov (United States)

Shibayama, Yui; Wada, Norio; Naruse, Mitsuhide; Kurihara, Isao; Ito, Hiroshi; Yoneda, Takashi; Takeda, Yoshiyu; Umakoshi, Hironobu; Tsuiki, Mika; Ichijo, Takamasa; Fukuda, Hisashi; Katabami, Takuyuki; Yoshimoto, Takanobu; Ogawa, Yoshihiro; Kawashima, Junji; Ohno, Yuichi; Sone, Masakatsu; Fujita, Megumi; Takahashi, Katsutoshi; Shibata, Hirotaka; Kamemura, Kohei; Fujii, Yuichi; Yamamoto, Koichi; Suzuki, Tomoko

2018-05-01

In adrenal venous sampling (AVS) for patients with primary aldosteronism (PA), apparent bilateral aldosterone suppression (ABAS), defined as lower aldosterone/cortisol ratios in the bilateral adrenal veins than that in the inferior vena cava, is occasionally experienced. ABAS is uninterpretable with respect to lateralization of excess aldosterone production. We previously reported that ABAS was not a rare phenomenon and was significantly reduced after adrenocorticotropic hormone (ACTH) administration. To validate the effects of ACTH administration and adding sampling positions in the left adrenal vein on the prevalence of ABAS in the larger Japan Primary Aldosteronism Study. The data from 1689 patients with PA who underwent AVS between January 2006 and October 2016 were studied. All patients in the previous study, the West Japan Adrenal Vein Sampling study, were excluded. The prevalence of ABAS was investigated at two sampling positions in the left adrenal vein, the central vein and the common trunk, without and with ACTH administration. The prevalence of ABAS with ACTH administration was significantly lower than that without ACTH administration [without ACTH vs with ACTH: 79/440 (18.0%) vs 45/591 (7.6%); P sampling position, at the central vein and at the common trunk [33/591 (5.6%) vs 32/591 (5.4%); P = 1.00]. The effectiveness of ACTH administration for the reduction of ABAS in AVS regardless of the sampling position in the left adrenal vein was confirmed in the larger cohort.

Combined Ovarian and Adrenal Venous Sampling in the Localization of Adrenocorticotropic Hormone-Independent Ectopic Cushing Syndrome.

Science.gov (United States)

Chen, Shi; Li, Ran; Zhang, Xiaobo; Lu, Lin; Li, Ji; Pan, Hui; Zhu, Huijuan

2018-03-01

Cushing syndrome is rarely caused by the secretion of cortisol from ovarian tumors. In clinical decision-making, it is important to determine whether the ovarian tumor is capable of secreting cortisol. Selective ovarian and adrenal venous sampling is scarcely reported in the localization of ACTH-independent ectopic Cushing syndrome. We present a case of 40-year-old Chinese woman who had weight gain, hirsutism, hypertension, and menstrual disorder over 6 months. Her physical examination and biochemical assessment revealed adrenocorticotropic hormone-independent Cushing syndrome. Adrenal computed tomography scan indicated no abnormality. A mass of 5.7 cm × 4.2 cm × 3.4 cm was discovered by pelvic ultrasonography. Somatostatin receptor scintigraphy revealed no abnormal radioactivity intake. Combined ovarian and adrenal venous sampling together with a cortisol assay were conducted. Results revealed cortisol concentration of the right-side ovarian vein, left-side ovarian vein, and peripheral vein of 268.60, 29.00, and 35.18 μg/dL, respectively, suggesting a right-side ovarian origin. A right-side salpingo-oophorectomy was performed and the pathological diagnosis revealed ovarian steroid cell tumor, not otherwise specified. The cortisol level was substantially lower after the patient underwent surgery and symptoms of Cushing syndrome disappeared. At 3-year follow-up, the patient remained disease free, and no tumor was observed on pelvic ultrasonogram. Combined ovarian and adrenal venous sampling is valuable in the localization of adrenocorticotropic hormone-independent ectopic Cushing syndrome.

Live Staining and Isolation of Specific Hormone-Producing Cells from Rat Anterior Pituitary by Cytochemistry with Lectins and Cholera Toxin B Subunit

International Nuclear Information System (INIS)

Kikuchi, Motoshi; Kusumoto, Kenji; Fujiwara, Ken; Takahashi, Kozue; Tando, Yukiko; Yashiro, Takashi

2011-01-01

Anterior pituitary glands contain five types of hormone-producing cells. Distinguishing and isolating specific types of living cells are essential for studying their function. Although many such attempts have been made, the results have been disappointing. In the present study, we labeled specific types of living hormone-producing cells by using potential differences in sugar chains on the cell surfaces. Cytochemical analysis with lectins and cholera toxin B subunit revealed that PNA, S-WGA, and cholera toxin B subunit recognized sugar chains specific to prolactin cells, ACTH cells, and GH cells, respectively, and that UEA-I recognized most of prolactin cells and GH cells. Next, fluorescence-activated cell sorting was used to isolate GH cells labeled by fluoresceinated cholera toxin B. The purity of the GH cell fraction estimated by immunocytochemistry and quantitative real-time PCR for cell type-specific genes was more than 98%, which was higher than that reported in earlier studies, including those using transgenic animals. We conclude that cytochemistry with lectins and cholera toxin B subunit is a straightforward, acceptable method of isolating specific types of anterior pituitary cells and that the cells isolated by this method can serve as useful materials in the study of anterior pituitary cells

Sublethal effects of manganese on the carbohydrate metabolism of ...

African Journals Online (AJOL)

Carbohydrate metabolism provides (1) energy,. (2) precursors for synthetic reactions ... as a response to the adrenal corticotrophic hormone (ACTH) from the ... During the exposure experiments, control groups were also set-up. The control fish ...

Radioimmunological and radiochemical analysis of postradiation injuries of the hypophysis-adrenal cortex system

International Nuclear Information System (INIS)

Petrova, G.A.

1979-01-01

It has been established in experiments on Wistar male rats that total irradiation with 60 Co in a dose of 600 R brings about disorders in the nature of interaction between the components of the hypophysis-adrenal cortex system. Hypersecretion of the adrenocorticotropic hormone (ACTH) does not correspond to the increased corticosterone content in the blood plasma of the irradiated animals. A slowed down elimination of ACTH- 131 I from the blood plasma of the irradiated animals evidences deficiency of endogenous corticotropine in the peripheral blood. It was recorded that increased glucocorticoid activity of adrenal cortex in irradiation-induced deficiency of ACTH is provided, on one binding capacity of the adrenocortical cells and on the other side, by slowing down the dissositation speed of binded corticotropine

Model approach for stress induced steroidal hormone cascade changes in severe mental diseases.

Science.gov (United States)

Volko, Claus D; Regidor, Pedro A; Rohr, Uwe D

2016-03-01

Stress was described by Cushing and Selye as an adaptation to a foreign stressor by the anterior pituitary increasing ACTH, which stimulates the release of glucocorticoid and mineralocorticoid hormones. The question is raised whether stress can induce additional steroidal hormone cascade changes in severe mental diseases (SMD), since stress is the common denominator. A systematic literature review was conducted in PubMed, where the steroidal hormone cascade of patients with SMD was compared to the impact of increasing stress on the steroidal hormone cascade (a) in healthy amateur marathon runners with no overtraining; (b) in healthy well-trained elite soldiers of a ranger training unit in North Norway, who were under extreme physical and mental stress, sleep deprivation, and insufficient calories for 1 week; and, (c) in soldiers suffering from post traumatic stress disorder (PTSD), schizophrenia (SI), and bipolar disorders (BD). (a) When physical stress is exposed moderately to healthy men and women for 3-5 days, as in the case of amateur marathon runners, only few steroidal hormones are altered. A mild reduction in testosterone, cholesterol and triglycerides is detected in blood and in saliva, but there was no decrease in estradiol. Conversely, there is an increase of the glucocorticoids, aldosterone and cortisol. Cellular immunity, but not specific immunity, is reduced for a short time in these subjects. (b) These changes are also seen in healthy elite soldiers exposed to extreme physical and mental stress but to a somewhat greater extent. For instance, the aldosterone is increased by a factor of three. (c) In SMD, an irreversible effect on the entire steroidal hormone cascade is detected. Hormones at the top of the cascade, such as cholesterol, dehydroepiandrosterone (DHEA), aldosterone and other glucocorticoids, are increased. However, testosterone and estradiol and their metabolites, and other hormones at the lower end of the cascade, seem to be reduced. 1

A Challenging Case of an Ectopic Cushing Syndrome

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Joana Menezes Nunes

2014-01-01

Full Text Available Bronchopulmonary carcinoids are rare pulmonary neoplasms although they account for most cases of ectopic ACTH syndromes. When feasible, the mainstay treatment is surgical resection of the tumor. We report the case of a 52-year-old woman with signs and symptoms suggestive of hypercortisolism for 12 months, admitted to our department because of community acquired pneumonia. Blood hormone analysis showed increased levels of ACTH and urinary free cortisol and nonsuppressibility to high- and low-dose dexamethasone tests. Pituitary MRI showed no lesion and no central-to-peripheral ACTH gradient was present in bilateral inferior petrosal sinus sampling. CRH stimulation test suggested an ectopic ACTH source. Thoracic CT scan revealed a nodular region measuring 12 mm located in the inferior lingular lobule of the left superior lung with negative uptake by 18-FDG-PET scan and negative SRS. The patient was successfully treated with an atypical lung resection and histology revealed an atypical bronchial carcinoid tumor with positive ACTH immunoreactivity. This was an interesting case because the patient was admitted due to pneumonia that may have been associated with her untreated and chronic hypercortisolism and a challenging case of ectopic ACTH syndrome due to conflicting results on the diagnostic exams.

Cortisol secretion in patients with normoprolactinemic amenorrhea

DEFF Research Database (Denmark)

Boesgaard, S; Hagen, C; Andersen, A N

1988-01-01

with normoprolactinemic amenorrhea have elevated basal serum cortisol, the reason probably being hypersecretion of corticotropin-releasing hormone. Secondly that dopaminergic blockade with metoclopramide stimulates ACTH and cortisol secretion in patients presumed to have raised dopaminergic activity....

A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report

Directory of Open Access Journals (Sweden)

Joo Hee Lim

2016-03-01

Full Text Available A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease.

A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report.

Science.gov (United States)

Lim, Joo Hee; Kim, Soo Jung; Jung, Mo Kyung; Kim, Ki Eun; Kwon, Ah Reum; Chae, Hyun Wook; Kim, Duk Hee; Kim, Ho-Seong

2016-03-01

A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS) was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease.

Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Science.gov (United States)

Rossi, Emanuela; Morabito, Alessandro; De Maio, Ermelinda; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; Piccirillo, Maria Carmela; D'Aiuto, Giuseppe; D'Aiuto, Massimiliano; Rinaldo, Massimo; Botti, Gerardo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2008-01-10

To compare the endocrine effects of 6 months of adjuvant treatment with letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with early breast cancer within an ongoing phase 3 trial (Hormonal Adjuvant Treatment Bone Effects study). Prospectively collected hormonal data were available for 81 premenopausal women, of whom 30 were assigned to receive tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin +/- zoledronate. Serum 17-beta-estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), Delta4-androstenedione, testosterone, dehydroepiandrosterone-sulfate, progesterone, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline and after 6 months of treatment. For each hormone, 6-month values were compared between treatment groups by the Wilcoxon-Mann-Whitney exact test. Median age was 44 years for both groups of patients. Letrozole + triptorelin (+/- zoledronate) induced a stronger suppression of median E2 serum levels (P = .0008), LH levels (P = .0005), and cortisol serum levels (P < .0001) compared with tamoxifen + triptorelin. Median FSH serum levels were suppressed in both groups, but such suppression was lower among patients receiving letrozole, who showed significantly higher median FSH serum levels (P < .0001). No significant differences were observed for testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone between the two groups of patients. Letrozole in combination with triptorelin induces a more intense estrogen suppression than tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Prognosis of Cyclic Vomiting Syndrome

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J. Gordon Millichap

2016-03-01

Full Text Available Investigators from Teikyo University School of Medicine, Tokyo, Japan, evaluated the clinical features, prognosis, and prophylaxis of cyclic vomiting syndrome and the relationship between the syndrome and levels of adrenocorticotropic/antidiuretic hormones (ACTH/ADH.

Primary maternal preoccupation revisited: circuits, genes, and the ...

African Journals Online (AJOL)

QuickSilver

2003-05-08

May 8, 2003 ... need to increase their caloric intake as well as to remain well hydrated. There is ... tation showed a persistent deficit in pup retrieval but were not im- .... adrenocorticotropic hormone (ACTH) and corticosterone responses to.

Cushing's Syndrome

Science.gov (United States)

... person cured of Cushing’s syndrome might have some memory loss and slight mental decline. But the change is ... Categories: Family Health, Infants and Toddlers, Kids and Teens, Men, Seniors, WomenTags: acth, adenomas, hormone, sickness September ...

Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

DEFF Research Database (Denmark)

Bork, E; Hansen, M; Urdal, P

1988-01-01

Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...

LONG-TERM OUTCOME OF THE DIFFERENT TREATMENT ALTERNATIVES FOR RECURRENT AND PERSISTENT CUSHING DISEASE.

Science.gov (United States)

Espinosa-de-Los-Monteros, Ana Laura; Sosa-Eroza, Ernesto; Espinosa, Etual; Mendoza, Victoria; Arreola, Rocio; Mercado, Moises

2017-07-01

Treatment alternatives for persistent and recurrent Cushing disease (CD) include pituitary surgical re-intervention, radiation therapy (RT), pharmacotherapy, and bilateral adrenalectomy (BA). The decision of which of these alternatives is better suited for the individual patient rests on clinical judgment and the availability of resources. This retrospective cohort study was performed at a referral center to evaluate the long-term efficacy of different secondary interventions for persistent and recurrent CD. We evaluated the hospital charts of 84 patients (77 female, median age 34 years, median follow up 6.3 years) with CD diagnosed, treated, and followed at our multidisciplinary clinic according to a pre-established protocol. Of the 81 patients who were initially treated with transsphenoidal surgery (TSS), 61.7% had a long-lasting remission, 16% had persistent disease, and 22% achieved remission but relapsed during follow-up. The most frequently used secondary treatment was pituitary re-intervention, followed by ketoconazole, RT, and BA. Early remissions were observed in 66.6% of the re-operated and in 58.3% of the radiated patients; long-lasting remission was achieved in 33.3% and 41.6% of these patients, respectively. Nelson syndrome developed in 41.6% of the patients who underwent BA. Upon last follow-up, 88% of all the patients are in remission, and 9.5% are biochemically controlled with ketoconazole. The efficacy of treatment alternatives for recurrent or persistent CD varies considerably among patients and multiple interventions are often required to achieve long-lasting remission. ACTH = adrenocorticotrophic hormone; BA = bilateral adrenalectomy; CBG = cabergoline; CD = Cushing disease; CV = coefficient of variation; DXM = dexamethasone; IQR = interquartile range; RT = radiation therapy; SRS = stereotactic radiosurgery; TSS = transsphenoidal surgery; UFC = urinary free cortisol; ULN = upper limit of normal.

Effects of cytokines on the pituitary-adrenal axis in cancer patients.

Science.gov (United States)

Nolten, W E; Goldstein, D; Lindstrom, M; McKenna, M V; Carlson, I H; Trump, D L; Schiller, J; Borden, E C; Ehrlich, E N

1993-10-01

Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate glucocorticoid secretion. In this study, the effects of variable doses and repetitive administration of IFNs and TNF on secretion of pituitary hormones and cortisol were measured. Patients were given for a period of 15 days on alternating days injections of IFN-beta (IFN-beta ser), 90 or 450 x 10(6) IU, IFN-gamma, 0.1-100 x 10(6) IU, or TNF 125-275 micrograms/m2. Sixty to 120 min after IFN-beta ser injection median levels of cortisol, adrenocorticotropin (ACTH), prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol excretion increased significantly during the day following IFN-beta ser administration. IFN-gamma > or = 30 x 10(6) IU caused a comparable rise in plasma cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact that increased cortisol secretion was associated with a rise in the level of ACTH as well as PRL and GH suggests that the cytokines increased cortisol by stimulating the anterior pituitary. The hormonal response induced by cytokines was unrelated to their pyrogenic effect, undiminished with repetitive treatment, and not dose-dependent above a threshold level. These observations reinforce the concept of a physiologic link between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis.

Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH

Science.gov (United States)

... Were Treated with hGH Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH ... Adrenal crisis is a serious condition that can cause death in people who lack the pituitary hormone ACTH. ...

Lack of Ubiquitin Specific Protease 8 (USP8) Mutations in Canine Corticotroph Pituitary Adenomas

NARCIS (Netherlands)

Sbiera, Silviu; Tryfonidou, Marianna A; Weigand, Isabel; Grinwis, Guy C M; Broeckx, Bart; Herterich, Sabine; Allolio, Bruno; Deutschbein, Timo; Fassnacht, Martin; Meij, Björn P

2016-01-01

PURPOSE: Cushing's disease (CD), also known as pituitary-dependent hyperadrenocorticism, is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumours. Affected humans and dogs have similar clinical manifestations, however, the incidence of the canine disease is thousand-fold higher.

Atrazine Does Not Induce Pica Behavior at Doses that Increase Hypothalamic-Pituitary-Adrenal Axis Activation and Cause Conditioned Taste Avoidance.

Science.gov (United States)

Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH), serum corticosterone (CORT) and progesterone. The mechanism for these effects is unknown. To tes...

Prospective investigation of the hypothalamo-pituitary-adrenal axis in patients with tularemia.

Science.gov (United States)

Demiraslan, Hayati; Şimşek, Yasin; Tanriverdi, Fatih; Doğanay, Mehmet; Keleştemur, Hasan Fahrettin

2015-01-01

To investigate prospectively the hypothalamo-pituitary-adrenal (HPA) axis by adrenocorticotropic hormone (ACTH) stimulation test. Tularemia was diagnosed according to guidelines. An ACTH stimulation test (1 µg) and a dexamethasone suppression test (DST; 1 mg) were performed in patients in the acute phase of tularemia before antibiotic treatment and in the chronic phase. Nineteen patients (mean age: 41.0 ± 13.2 years; 57.9% female) with tularemia were enrolled in the study in 2011 and 2012. Cortisol response to ACTH stimulation test was sufficient in all patients during the acute phase. After the DST, the cortisol was not suppressed during the acute phase in only one patient. The median control time of 11 patients after acute tularemia was 13 months. During the chronic phase, cortisol response to ACTH stimulation was normal in all patients, and after DST cortisol was suppressed in all patients. The peak cortisol level after the ACTH stimulation test in the acute phase was higher than that in the chronic phase, but the difference was not statistically significant. The HPA axis of patients with tularemia was not significantly affected in the acute and chronic phases.

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

Adrenal failure due to bilateral adrenal metastasis of rectal cancer: A case report.

Science.gov (United States)

Imaoka, Yuki; Kuranishi, Fumito; Ogawa, Yoshiteru; Okuda, Hiroshi; Nakahara, Masahiro

2017-01-01

It is rare for a patient to present with adrenal insufficiency secondary to bilateral adrenal metastases from a malignant colorectal tumor. An 82-year-old Japanese man presented to our hospital with high fever and malaise. He was receiving oral chemotherapy for the treatment of rectal cancer with multiple metastases. Computed tomography showed new bilateral adrenal gland metastases. A rapid adrenocorticotropic hormone (ACTH) test showed adrenal insufficiency. Treatment with hydrocortisone provided immediate symptom improvement. Adrenal insufficiency secondary to bilateral adrenal metastases from rectal cancer is rare. A rapid ACTH test is useful to diagnose adrenal insufficiency. The incidence of adrenal insufficiency may be underestimated in patients with multiple metastasis. Appropriate therapy with adrenal corticosteroid hormone supplementation may lead to a significant improvement in the patient's symptoms and quality of life. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Effect of inhibitory avoidance trainning, ACTH, beta-endorphin and adrenaline on the incorporation of 14C-leucine into synaptosomal proteins of rat hypothalamus, amygdala and hippocampus

International Nuclear Information System (INIS)

Dalmaz, C.; Maia, H.M.M.; Izquierdo, I.

1986-01-01

'In vitro' incorporation of leucine to protein was studied in synaptosomes isolated from the hypothalamus, amygdala and hippocampus of rats submitted to inhibitory avoidance training or to the i.p. injection of ACTH, beta-endorphin or adrenaline; or in synaptosomes incubated with these substances. (M.A.C.) [pt

A Large PROP1 Gene Deletion in a Turkish Pedigree

Directory of Open Access Journals (Sweden)

Suheyla Gorar

2018-01-01

Full Text Available Pituitary-specific paired-like homeodomain transcription factor, PROP1, is associated with multiple pituitary hormone deficiency. Alteration of the gene encoding the PROP1 may affect somatotropes, thyrotropes, and lactotropes, as well as gonadotropes and corticotropes. We performed genetic analysis of PROP1 gene in a Turkish pedigree with three siblings who presented with short stature. Parents were first degree cousins. Index case, a boy, had somatotrope, gonadotrope, thyrotrope, and corticotrope deficiency. However, two elder sisters had somatotroph, gonadotroph, and thyrotroph deficiency and no corticotroph deficiency. On pituitary magnetic resonance, partial empty sella was detected with normal bright spot in all siblings. In genetic analysis, we found a gross deletion involving PROP1 coding region. In conclusion, we report three Turkish siblings with a gross deletion in PROP1 gene. Interestingly, although little boy with combined pituitary hormone deficiency has adrenocorticotropic hormone (ACTH deficiency, his elder sisters with the same gross PROP1 deletion have no ACTH deficiency. This finding is in line with the fact that patients with PROP1 mutations may have different phenotype/genotype correlation.

E2F1-mediated human POMC expression in ectopic Cushing's syndrome.

Science.gov (United States)

Araki, Takako; Liu, Ning-Ai; Tone, Yukiko; Cuevas-Ramos, Daniel; Heltsley, Roy; Tone, Masahide; Melmed, Shlomo

2016-11-01

Cushing's syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing's syndrome). Hypercortisolemic features of ectopic Cushing's syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing's syndrome. We show that ectopic hPOMC transcription proceeds independently of pituitary-specific Tpit/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating hPOMC We identify an E2F1 cluster binding to the proximal hPOMC promoter region (-42 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337. hPOMC mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed hPOMC gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing's cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated hPOMC transcription is a potential target for suppressing ACTH production in ectopic Cushing's syndrome. © 2016 Society for Endocrinology.

Changes in Plasma Prolactin and Growth Hormone Level and Visual Problem after radiation Therapy(RT) of Pituitary Adenoma

International Nuclear Information System (INIS)

Yoon, Sei Chul; Kwon, Hyung Chul; Oh, Yoon Kyeong; Bahk, Yong Whee; Son, Ho Young; Kang, Joon Ki; Song, Jin Un

1985-01-01

Twenty-four cases of pituitary adenoma, 13 males and 11 females with the age ranging from 11 to 65 years, received radiation therapy(RT) on the pituitary area with 6MV linear accelerator during past 25 months at the Division of Radiation Therapy, Kangnam St. Mary Hospital, Catholic Medical College. Of 24 case of RT, 20 were postoperative and 4 primary. To evaluate the effect of RT, we analyzed the alteration of the endocrinological tests, neurologic abnormalities, major clinical symptoms, endocrinological changes and improvement in visual problems after RT. The results were as follows ; 1. Major clinical symptoms were headache, visual defects, diabetes insipidus, hypogonadisms and general weakness in decreasing order of frequency. 2. All but the one with Nelson syndrome showed abnormal neuroradiologic changes in the sella turcica with an invasive tumor mass around supra and para-sellar area. 3. Endocrinological classifications of the patient were 11 prolactinoma, 4 growth hormonesecreting tumors, 3 ACTH-secreting tumors consisting of one Cushing disease and two Nelson syndrome, and 6 nonfunctioning tumors. 4. Eleven of 14 patients, visual problems were improved after treatment but remaining 3 were unchanged. 5. Seven of 11 prolactinomas returned to normal hormonal level after postoperative and primary RT and 3 patients are being treated with bromocriptine (BMCP) but on lost case. 6. Two of 4 growth hormone-secreting tumor returned to normal level after RT but the remaining 2 are being treated with BMCP, as well

Up-regulation of corticotropin releasing hormone is associated with ...