deamino-arginine-vasopressin and Alcoholism

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

Abnormal baseline hypothalamic-pituitary-adrenal axis function and dexamethasone suppressibility seen in withdrawing alcoholics returns to normal on abstinence, but some studies report blunting of the ACTH response to CRH persisting during the early abstinence phase. Reduced central levels of endogenous opioid peptides have been postulated to have an aetiological role in alcohol addiction.. To evaluate hypothalamic-pituitary-adrenal axis function in a group of recently abstinent alcoholics using basal hormone data, naloxone (an opioid receptor antagonist), and ovine CRH.. Nine alcoholics (age 41.4 +/- 3.1 years) studied more than one week after the acute withdrawal period but within 6 weeks of cessation of drinking, and nine age and sex matched non-alcoholic controls.. Cortisol, ACTH, CRH and AVP levels were measured every 20 minutes for 2 hours between 0900 and 1100h Twenty mg naloxone i.v. was administered at 1100h (0 minutes) and further samples for the above hormones were taken at 15, 30, 45, 60, 90 and 120 minutes. On a separate occasion, again at 1100h, oCRH 1 microgram/kg (n = 7 alcoholics, n = 6 controls) was administered, with samples for cortisol, ACTH and AVP taken at the same times.. Results were examined by analysis of variance for repeated measures (ANOVA), while incremental hormone response and area under the secretory curve (AUC) in alcoholics versus controls were compared by the two-tailed Student's t-test. Linear regression analysis was carried out to examine the relation between basal cortisol and hormone responses to naloxone and oCRH.. Basal hormone levels did not differ between the groups. The alcoholics had a blunted ACTH incremental response to naloxone (11.4 +/- 3.0 vs 21.1 +/- 2.5 pmol/l, P < 0.05) but the cortisol response was not significantly different (205 +/- 51 vs 305 +/- 42 nmol/l, P = 0.15). The alcoholics also had a blunted ACTH incremental response to oCRH (28.7 +/- 4.2 vs 41.2 +/- 3.7 pmol/l, P = 0.052) and by ANOVA a significant main effect of group (alcoholic vs control) was seen (P < 0.02) for the ACTH response to oCRH. There was no difference between the groups in the cortisol incremental response to oCRH. In the control subjects, a negative correlation was found between basal cortisol and the cortisol increment (r = -0.82, P < 0.05) and ACTH increment (r = -0.81, P = 0.052) following oCRH, while in contrast, basal cortisol correlated positively with cortisol increment (r = 0.72, P < 0.05) following naloxone. There was also a trend for basal cortisol to correlate positively with ACTH increment following naloxone in the controls (r = 0.63, P < 0.07). In the alcoholics, the normal negative effect of basal cortisol on the cortisol increment after oCRH was reversed, with a positive correlation between basal cortisol and cortisol increment (r = 0.75, P = 0.05).. Recently abstinent alcoholics with normal basal HPA axis hormone levels have a blunted ACTH response to naloxone and oCRH. While reduced levels of central endogenous opioid peptides may be a factor in the blunted ACTH response to naloxone in the alcoholics, it is proposed that the alcoholics have reduced pituitary responsiveness to CRH. This may be via a direct pituitary effect of the chronic ethanol exposure or by a reduction in hypothalamic-hypophyseal vasopressin levels.

Topics: Adrenocorticotropic Hormone; Adult; Alcoholism; Corticotropin-Releasing Hormone; Deamino Arginine Vasopressin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Naloxone; Opioid Peptides; Pituitary-Adrenal System

Alcohol administration in drinking water to mother rats during gestation resulted in a permanent learning deficit of the offspring when behavioural reactions were tested in active avoidance conditioned reflex situation in adult age. A similar deficit of learning capacity was observed in adult rats following alcohol administration for two weeks; the acquisition of active avoidance response was tested later. Administration of arginine-vasopressin and ACTH 4-10 during behavioural test led to a significant improvement of learning ability of the animals pretreated with alcohol. The observations indicate that the ethanol-induced deficit of learning capacity involves peptidergic mechanisms and the behavioural manifestations following chronic alcohol treatment are not irreversible processes.

Topics: Adrenocorticotropic Hormone; Alcoholism; Animals; Avoidance Learning; Deamino Arginine Vasopressin; Female; Learning Disabilities; Male; Maternal-Fetal Exchange; Peptide Fragments; Pregnancy; Pregnancy Complications; Rats