deamino-arginine-vasopressin and hexarelin

The diagnosis and differential diagnosis of Cushing's syndrome remains a considerable challenge in clinical endocrinology. Investigation is a two-step process, involving first diagnosis followed by differential diagnosis. Traditionally diagnosis has relied upon urinary free cortisol (UFC) collection, low-dose dexamethasone-testing, and assessment of midnight cortisol. More recently, differentiation between mild disease and pseudo-Cushing's states has been achieved using dexamethasone-suppressed corticotropin releasing hormone (CRH) and desmopressin tests. Refinements of tests used for differential diagnosis have been made including optimized response criteria for ovine and human sequence CRH tests, desmopressin tests, GHBP-testing and testing with combinations of peptides. Despite improvements in these non-invasive tests use of inferior petrosal or cavernous sinus sampling is frequently required. Imaging is guided by biochemical assessment. MRI is the investigation of choice for Cushing's disease, but is often negative. Scintigraphic investigation using radionucleotide-labeled agonists for receptors commonly expressed by neuroendocrine tumors the investigation of occult ACTH-dependent disease remains disappointing. In this review we critically analyze the tests used for this most challenging of clinical conditions.

Topics: ACTH Syndrome, Ectopic; Adenoma; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Circadian Rhythm; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Dexamethasone; Diagnosis, Differential; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Magnetic Resonance Imaging; Oligopeptides; Petrosal Sinus Sampling; Pituitary Neoplasms; Pituitary-Adrenal System; Radiography; Radionuclide Imaging; Sheep

Topics: ACTH Syndrome, Ectopic; Adrenocorticotropic Hormone; Anti-Inflammatory Agents; Circadian Rhythm; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Dexamethasone; Diagnosis, Differential; Female; Growth Substances; Humans; Hydrocortisone; Magnetic Resonance Imaging; Male; Metyrapone; Oligopeptides; Petrosal Sinus Sampling; Renal Agents; Tomography, X-Ray Computed; Vasopressins

A challenge in clinical endocrinology is the distinction between Cushing's disease (Cushing's syndrome dependent by adrenocorticotrophic hormone (ACTH)-secreting tumours of pituitary origin) and alcohol-dependent pseudo-Cushing's syndrome. Patients with Cushing's disease are known to have high ACTH/cortisol responses to desmopressin (DDAVP, a vasopressin analogue) and to hexarelin (HEX, a synthetic GH-releasing peptide).. To compare the ACTH/cortisol responses to desmopressin and to hexarelin of subjects with alcohol pseudo-Cushing's syndrome with those obtained in patients with Cushing's disease and in normal controls.. Randomized, single-blind study.. University medical centre.. Eight alcoholics with pseudo-Cushing's syndrome, six patients with Cushing's disease and nine age-matched normal controls.. Three tests at weekly intervals. The dexamethasone (1 mg) suppression test (DST) was carried out first. The desmopressin (10 microg intravenously at 09:00 h) test and hexarelin (2 microgram kg-1 intravenously at 09:00 h) test were carried out in random order.. Plasma ACTH and cortisol levels.. The basal plasma levels of ACTH and cortisol were significantly lower in normal subjects than in patients with Cushing's disease and in alcoholic subjects; these latter groups showed similar basal hormonal values. All normal controls, two patients with Cushing's disease and two alcoholics showed suppression of plasma cortisol levels (<5 microgram dL-1) after dexamethasone administration. Both desmopressin and hexarelin induced striking ACTH/cortisol responses in patients with Cushing's disease, whereas hexarelin, but not desmopressin, slightly increased ACTH/cortisol secretion in the normal controls. Neither desmopressin nor hexarelin administration induced any significant change in ACTH/cortisol secretion in alcoholics.. These data suggest that either the hexarelin or desmopressin test can be used to differentiate patients with Cushing's disease from subjects with alcohol-dependent pseudo-Cushing's syndrome.

Topics: Adrenocorticotropic Hormone; Adult; Alcoholism; Cushing Syndrome; Deamino Arginine Vasopressin; Ethanol; Female; Humans; Hydrocortisone; Male; Oligopeptides; Pituitary Neoplasms; Radioimmunoassay; Single-Blind Method

GH secretagogues (GHSs) act via specific receptors in the hypothalamus and the pituitary gland to release GH. GHSs also stimulate the hypothalamo-pituitary-adrenal (HPA) axis via central mechanisms probably involving CRH or arginine vasopressin (AVP). We studied the effects of hexarelin, CRH, and desmopressin, an AVP analog, on the stimulation of the HPA axis in 15 healthy young male volunteers. Circulating ACTH, cortisol, GH and PRL concentrations were measured for 2 h after the injection of hexarelin, CRH, or desmopressin alone and the combination of hexarelin plus CRH or hexarelin plus desmopressin. Symptoms during the tests were assessed by visual analog scales. Hexarelin significantly increased ACTH and cortisol release (area under the curve, 3,444+/-696 ng/L x 125 min and 45,844+/-2,925 nmol/L x 125 min, respectively), and this effect was augmented by the addition of CRH in a dose that on its own produces maximal stimulation (6,580+/-1,572 ng/mL x 125 min and 63,170+/-2,616 nmol/L x 125 min; P = 0.01 and 0.001, respectively), but was not influenced by the addition of desmopressin (3,540+/-852 ng/mL x 125 min and 35,319+/-3,252 nmol/L x 125 min; not significant). CRH on its own caused similar or slightly higher ACTH and cortisol release than hexarelin alone. Desmopressin given alone elicited a rapid rise in circulating ACTH and cortisol, but its effects were less than those of any other treatment and were not augmented by hexarelin. Hexarelin also caused significant GH and PRL release, but these effects were not influenced by the coadministration of CRH or desmopressin. Visual analog scales showed an acute small increment in appetite with hexarelin. Our data suggest that the effect of GHSs on the HPA axis involve at least in part the stimulation of AVP release. In summary, we have shown that in healthy male volunteers, the effect of hexarelin on the HPA axis does not involve CRH, but may occur through the stimulation of AVP release.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Adult; Arginine Vasopressin; Corticotropin-Releasing Hormone; Deamino Arginine Vasopressin; Double-Blind Method; Growth Substances; Human Growth Hormone; Humans; Hydrocortisone; Hypothalamus; Male; Oligopeptides; Pituitary Gland; Prolactin

Peptide hormones represent an emerging class of potential doping agents. Detection of their misuse is difficult due to their short half-life in plasma and rapid elimination. Therefore, investigating their metabolism can improve detectability. Unfortunately, pharmacokinetic studies with human volunteers are often not allowed because of ethical constraints, and therefore alternative models are needed. This study was performed in order to evaluate in vitro models (human liver microsomes and S9 fraction) for the prediction of the metabolism of peptidic doping agents and to compare them with the established models. The peptides that were investigated include desmopressin, TB-500, GHRP-2, GHRP-6, hexarelin, LHRH and leuprolide. Several metabolites were detected for each peptide after incubation with human liver microsomes, S9 fraction, and serum, which all showed endopeptidase and exopeptidase activity. In vitro models from different organs (liver vs. kidney) were compared, but no significant differences were recorded. Deamidation was not observed in any of the models and was therefore evaluated by incubation with α-chymotrypsin. In conclusion, in vitro models are useful tools for forensic and clinical analysts to detect peptidic metabolic markers in biological fluids.

Topics: Biological Assay; Chymotrypsin; Deamino Arginine Vasopressin; Doping in Sports; Gonadotropin-Releasing Hormone; Humans; Kidney; Leuprolide; Liver; Microsomes, Liver; Models, Biological; Oligopeptides; Substance Abuse Detection

Topics: Athletes; Deamino Arginine Vasopressin; Humans; Oligopeptides