Desmopressin and hexarelin tests in alcohol-induced pseudo-Cushing's syndrome

BACKGROUND: 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). OBJECTIVE: 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. DESIGN: Randomized, single-blind study. SETTING: University medical centre. SUBJECTS: Eight alcoholics with pseudo-Cushing's syndrome, six patients with Cushing's disease and nine age-matched normal controls. INTERVENTION: 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. MEASUREMENTS: Plasma ACTH and cortisol levels. RESULTS: 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. CONCLUSIONS: 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.