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 mu g intravenously at 09:00 h) test and hexarelin (2 mu g 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 mu g 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.