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Case Reports 2011; 32(4): 421-424 PubMed PMID: 21876495 Citation  Keywords:  ACTH Syndrome, Ectopic:etiology, Adrenocorticotropic Hormone:blood, Biopsy, Carcinoma, Medullary:complications, Carcinoma, Neuroendocrine, Humans, Male, Mediastinal Neoplasms:complications, Middle Aged, Thyroid Neoplasms:complications, Tomography, X-Ray C.   

: A rare case with ectopic adrenocorticotrophic hormone syndrome (EAS) caused by medullar thyroid carcinoma (MTC) in mediastinum was reported. This 49 year-old male patient initially presented with serious and intractable hypokalemia. Endocrine evaluations showed increased levels of adrenocorticotrophic hormone (ACTH) and urinary free cortisol, which could not be suppressed more than 50% by high-dose dexamethasone suppression test. Computed tomography (CT) scan detected a 5×5×5 cm mass at the bottom of thyroid in anterior mediastinum. The patient underwent total thyroidectomy with central compartment and ipsilateral modified radical neck dissection. Pathological examination showed an infiltrating thyroid medullary carcinoma with abundant amyloid deposition, meanwhile immunohistochemical positive for ACTH. After surgery, serum levels of kalium, as well as cortisol and ACTH returned to normal range. During follow-up, the patient's clinical manifestation of Cushing syndrome relieved....

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Journal Article 2009; 30(1): 107-110 PubMed PMID: 19300395 Citation  Keywords:  Acromegaly:etiology, Adenoma:complications, Adrenocorticotropic Hormone:secretion, Adult, Aged, Cell Proliferation:drug effects, Cell Survival:drug effects, Drug Evaluation, Preclinical, Female, Human Growth Hormone:secretion, Humans, Hypoglycemic Agents:.   

OBJECTIVES: Rosiglitazone (RGZ) belongs to thiazolidinediones - new class of antidiabetic drugs which are PPARgamma agonists. It was shown that tumoral tissue, including the pituitary adenomas, posses PPARgamma receptors. The activation of PPARgamma receptors inhibits tumour growth in rodents and induces the oncostatic effect on human cancer cell lines. The aim of the present study was to examine the anti-tumour effect of RGZ on human pituitary adenomas in vitro.

MATERIALS AND METHODS: Cells of eight pituitary adenomas removed neurosurgically were used to our experiment. Before the operation, the hormonal secretion of the tumour was estimated. After the surgery, the histological diagnosis and immunohistochemical detection of pituitary hormones and PPARgamma receptors were performed. The cells of pituitary tumours were exposed in the primary culture to RGZ at the concentrations of 10(-9)-10(-4) M for 24 hours. To measure the cell growth the modified colorimetric Mossman method detecting the cells viability was applied.

RESULTS: On the basis of the pre-operative diagnosis the 6 clinically non-functioning adenomas (CNFPA), one case of acromegaly and one case of Cushing's disease were recognized. In 5 out of 6 CNFPA the immunopositive reaction for different pituitary hormones such as: LH, HGH, PRL, FSH and alpha-subunit was detected. Expression of PPARgamma was found in all examined tumours. Rosiglitazone decreased the cell viability of all CNFPA and corticotropinoma for 20% or more. In somatotropinoma inhibition of the cell growth was about 13%. There is no correlation between PPARgamma expression and efficacy of rosiglitazone. THE MAIN FINDING: The obtained results indicate that RZG exerts a suppressive effect on the cell viability in non-functioning pituitary adenomas. The lack of correlation between PPARgamma expression and anti-tumoral effect of RZG suggests that the above-mentioned action of this compound is independent on PPARgamma expression.

CONCLUSION: Our data suggest that rosiglitazone may be useful in the treatment of non-functioning pituitary adenomas, but its efficacy in Cushing's disease and acromegaly requires further study....

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Journal Article 2009; 30(4): 511-514 PubMed PMID: 20010499 Citation  Keywords:  Adrenocorticotropic Hormone:blood, Animals, Blood Glucose:drug effects, Cholinergic Fibers:drug effects, Cholinesterase Inhibitors:pharmacology, Hippocampus:cytology, Male, Microinjections, Motor Activity, Neostigmine:pharmacology, Neural Pathways, Rats, .   

OBJECTIVE: In our previous study, a lesion in the lateral bed nucleus of the stria terminalis (BNSTL) was found to significantly attenuate the elevation of adrenocorticotropic hormone (ACTH) in plasma during microinjectin of neostigmine, an inhibitor of acetylcholine esterase, into the rat hippocampus. The current study was designed to examine the role of the BNSTL in regulation of blood glucose elevation induced by hippocampal neostigmine injection.

MATERIALS AND METHODS: Ibotenic acid (15 microg/microl) was stereotaxically bilaterally injected into the BNSTL of rats. Two weeks after the injections, neostigmine methylsulfate (sigma, 5 x 10-8 mol) was microinjected into the rat hippocampus in a volume of 1 microl for 1 min using a CMA/100 microinjection pump. Plasma ACTH and glucose concentrations were examined using radioimmunoassay and immobilized enzyme casing/H2O2 method techniques, respectively.

RESULTS: Compared with sham-operated control rats, rats with BNSTL lesions produced by ibotenic acid showed significantly attenuated the elevations of plasma ACTH evoked by the microinjection of neostigmine into the hippocampus. However, no significant difference of blood glucose in response to the injection was observed between the BNSTL-lesioned rats and controls.

CONCLUSION: The results of the present study indicate that the BNSTL plays a role in ACTH regulation and not in blood glucose regulation when the hippocampal cholinergic system is activated....

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Journal Article 2008; 29(3): 341-346 PubMed PMID: 18580851 Citation  Keywords:  Adrenocorticotropic Hormone:blood, Adult, Biomarkers, Body Mass Index, Cohort Studies, Female, Glycopeptides:analysis, Humans, Hydrocortisone:blood, Hypothalamus:metabolism, Male, Middle Aged, Sex Characteristics, Stress, Psychological:metabolism, Vasopre.   

BACKGROUND: During stress, vasopressin is a potent synergistic factor of CRH as a hypothalamic stimulator of the HPA axis. The measurements of CRH and vasopressin levels are cumbersome because of their instability and short half-life. Copeptin is a more stable peptide stoichiometrically released from the same precursor molecule. The aim of our study was to compare copeptin and cortisol levels in different stress situations.

METHODS: Three groups of patients with increasing stress levels were investigated: a) healthy controls without apparent stress (n=20), b) hospitalized medical patients with moderate stress (n=25) and c) surgical patients 30 minutes after extubation, with maximal stress (n=29). In all patients we assessed cortisol and copeptin levels. Copeptin levels were measured with a new sandwich immunoassay.

RESULTS: Cortisol levels in controls were (median, IQ range, 486 [397-588] nmol/L), not significantly different as compared to medical patients (438 [371-612] nmol/L, p=0.69). Cortisol levels in surgical patients after extubation were higher (744 [645-1062] nmol/L p<0.01 vs controls and medical patients). Copeptin levels in controls were 4.3 [3.2-5.5] pmol/L, which was lower as compared to medical patients (17.5 [6.4-24.1], p<0.001) and surgical patients after extubation (67.5 [37.8-110.0] pmol/L, p<0.001). The correlation between copeptin levels and cortisol was r=0.46, p<0.001.

CONCLUSION: Copeptin is a novel marker of the individual stress level. It more subtly mirrors moderate stress as compared to cortisol values....

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Journal Article 2008; 29(3): 359-365 PubMed PMID: 18580846 Citation  Keywords:  Adrenal Cortex Hormones:metabolism, Adrenocorticotropic Hormone:blood, Animals, Cell Proliferation:drug effects, Cells, Cultured, Corticosterone:blood, Immunity, Cellular:physiology, Indicators and Reagents, Injections, Intraventricular, Leukocytes:drug e.   

OBJECTIVE: Cocaine-amphetamine regulated transcript peptides (CART) belong to a neuropeptide family expressed in the central nervous system, especially in the hypothalamus, and also in peripheral tissues. The physiological functions of CART include modulation of pituitary hormone release, regulation of body weight, and the control of feeding behavior and metabolic activity. The reciprocal relationships between CART and immune system function have to be established. Therefore, in the present study we aimed to investigate the influence of CART, administered intracerebroventricularly (icv), on selected immune parameters and pituitary-adrenal axis hormone secretion in the rat.

RESEARCH METHODS: In rats submitted to icv infusion of CART or artificial cerebrospinal fluid (aCSF, control) selected immune parameters: splenocyte proliferation (spontaneous and mitogen-stimulated) and peritoneal leukocyte (PTL) activity (spontaneous and phorbol myristate acetate (PMA)-stimulated) were examined 60 and 120 min after treatment. The direct effect of CART on splenocytes in culture in vitro was also examined. Concentration of adrenocorticotrophic hormone (ACTH) and corticosterone was also measured in serum of control and CART infused rats.

RESULTS: Splenocytes isolated 60 min after CART infusion exhibited a decreased, albeit non-significant, ability to proliferate spontaneously and were unable to answering to the mitogenic stimulation. This effect was not seen 120 min after CART treatment, which restored splenocyte proliferation decreased by aCSF infusion. CART addition in vitro did not influence proliferation of splenocytes from control rats. Spontaneous activity of peritoneal leukocytes was not modified by CART infusion. PMA-stimulated PTL activity was significantly decreased in aCSF-infused rats 120 min after treatment and CART infusion antagonized this effect. Non-significant increase in serum cortisol after 60 min followed by a significant decrease after 120 min with no change in ACTH concentration was found.

CONCLUSION: The immunomodulatory activity of icv-infused CART appears to consist in the creation of a short-lasting immunosuppressive internal milieu, followed by the immunostimulatory one. This first effect was most probably due to the activation of the HPA axis and/or other immunosuppressive peptides, but not through the direct action of CART on immune cells. Thus, CART appears to be short-lasting and indirect modulator of immunity....

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Journal Article 2008; 29(3): 347-350 PubMed PMID: 18580839 Citation  Keywords:  ACTH-Secreting Pituitary Adenoma:metabolism, Adenoma:metabolism, Adrenocorticotropic Hormone:metabolism, Adult, Cushing Syndrome:blood, Female, Humans, Immunohistochemistry, Ki-67 Antigen:blood, Male, Nelson Syndrome:blood, Paraffin Embedding, Pituitary H.   

OBJECTIVES: The aim of the study was to evaluate the ACTH-immunopositive pituitary adenomas, especially those without manifestation of Cushing's disease

MATERIAL AND METHODS: 148 pituitary adenomas removed surgically in years 1994--2007 were studied. The paraffin sections were immunostained with antibodies against the pituitary hormones. In 79 adenomas the immunostaining with anti-ACTH antibody was performed Additionally, 23 tumors were also immunostained with anti-Ki-67 (MIB-1) antibody. Visualization of reactions was done by means of streptavidin-biotin-peroxidase technique with use of 3,3'-diaminobenzidine as chromogen.

RESULTS: ACTH immunopositivity was found in 34 cases (23%). Fourteen ACTH-immunopositive tumors manifested themselves as Cushing's disease (including 1 case of Nelson's syndrome). In the remaining 20 cases in spite of the positive immunostaining for ACTH of the tumor cells, no features of hypercortisolism were observed (in several cases even hypocortisolism was found). Thus, those tumors represented so-called "silent" corticotropinomas. Over one third (37%) of "clinically" nonfunctioning pituitary adenomas, when immunostained with anti-ACTH antibody, showed ACTH immunopositivity. Three adenomas in patients with Cushing's disease (21.4%) and 7 "silent" corticotropinomas (35%) were recurrent tumors. In contrast, the recurrence rate in the group of ACTH-immunonegative clinically nonfunctioning pituitary adenomas was 14.7%. The "silent" corticotropinomas exhibited a tendency towards the higher expression of a proliferation marker, Ki-67 antigen as compared to the "active" corticotropinomas.

CONCLUSIONS: (i) "Silent" corticotropinomas are rather frequent. (ii) This adenoma type should be considered as aggressive. (iii) It is hypothetized that--like in Nelson's syndrome--the lack of hypercortisolism or even presence of hypocortisolism favorizes the exaggerated growth of tumoral corticotrophs....

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Comparative Study 2008; 29(1): 141-145 PubMed PMID: 18283269 Citation  Keywords:  Adolescent, Adrenocorticotropic Hormone:blood, Blood Pressure:physiology, Child, Child, Preschool, Female, Humans, Hydrocortisone:blood, Lipids:blood, Male, Metabolic Syndrome X:blood, Obesity:blood, Risk Factors,.   

OBJECTIVES: The aim of this study was to investigate the relationship between the varying degrees of obesity and blood glucocorticoid levels in obese children and adolescents with and without metabolic syndrome features.

METHODS: We studied 241 obese children and adolescents aged between 2 and 17.6 years; 127 boys and 114 girls. All children underwent an oral glucose tolerance test. Measurements included blood pressure, cortisol, ACTH, and lipid profiles. The diagnosis of metabolic syndrome was defined according to the criteria adapted from World Health Organisation and National Cholesterol Education Program Adult Treatment Panel-III guidelines.

RESULTS: Blood cortisol and ACTH levels were higher in patients with MS than without MS (p = 0.02). ACTH levels increased with weight (r = 0.13, p = 0.02), systolic blood pressure (r = 0.21, p = 0.002), diastolic blood pressure (r = 0.17, p = 0.01), fasting glucose (r = 0.17, p = 0.01). Cortisol production was only correlated with systolic blood pressure (r = 0.12, p = 0.05).

CONCLUSIONS: Results from the present study indicates that there may be a link between cortisol production and the metabolic syndrome in obese children and adolescents....

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Journal Article 2008; 29(1): 159-162 PubMed PMID: 18283263 Citation  Keywords:  Adrenocorticotropic Hormone:blood, Animals, Body Weight:physiology, Central Nervous System:physiology, Circadian Rhythm:physiology, Corticosterone:blood, Entorhinal Cortex:physiology, Hypothalamo-Hypophyseal System:physiology, Male, Pituitary-Adrenal Syst.   

OBJECTIVE: In our previous study, a lesion in the entorhinal cortex was found to significantly attenuate the elevation of adrenocorticotropic hormone (ACTH) in plasma during immobilization stress. The aim of the present study was to investigate whether the entorhinal cortex exerts a modulatory effect on circadian ACTH and corticosterone release.

MATERIALS AND METHODS: Ibotenic acid (15 microg/microl) was stereotaxically bilaterally injected into the entorhinal cortex of rats. Two weeks after the injections, ACTH and corticosterone levels in plasma were measured at 0800 h, 1300 h and 1800 h.

RESULTS: Compared with sham-operated control rats, rats with entorhinal cortex lesions produced by ibotenic acid showed either significantly elevated plasma ACTH or plasma corticosterone levels at 0800 h, but no difference at 1300 h or 1800 h.

CONCLUSION: The results of the present study indicate that the entorhinal cortex plays a certain role in the regulation by the central nervous system of the circadian rhythm of the hypothalamic-pituitary-adrenal (HPA) axis....

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