A COMBINED TEST USING DESMOPRESSIN AND CORTICOTROPIN-RELEASING HORMONE IN THE DIFFERENTIAL-DIAGNOSIS OF CUSHINGS-SYNDROME

To assess the ability of desmopressin to differentiate between pituita ry and ectopic ACTH-dependent Cushing's syndrome and to determine whet her diagnostic accuracy could he improved by administering it together with human sequence CRH, we examined its effects on cortisol and ACTH secretion when given alone or in combination with CRH in patients wit h Cushing's syndrome of Oi varied etiology and compared these data to the results of a standard CRH test in the same individuals. Each patie nt was studied on three occasions, in random order, separated by at le ast 48 h. At 0900 h, via an indwelling forearm cannula, 10 mu g desmop ressin, 100 mu g CRH, or a combination of the two were given as an iv bolus; thereafter, blood was drawn every 15 min for 2 h. The responses to the individual agents were determined according to the timing and calculation criteria suggested by Nieman et al. (1993). A total of 25 patients with Gushing's syndrome were studied: 17 patients with pituit ary-dependent Cushin's syndrome, Gushing's disease (CD); 6 patients wi th occult ectopic ACTH secretion (EC): and 3 patients with primary adr enal (ACTH-independent) Cushin's syndrome. In this series, the best di scrimination among ACTH-dependent patient groups was achieved using th e combined test. Using the responses of plasma cortisol. all 17 patien ts with CD showed a rise greater than any of the 5 patients with EC, w hereas 1 patient with CD showed a plasma ACTH response within the rang e seen in the patients with EC. Plasma cortisol responses to desmopres sin alone were seen in 14 of 17 patients with CD and 1 of 5 patients w ith EC and, after CBH alone, in 15 of 17 patients with CD but in no pa tient with EC. In contrast, plasma ACTH responses after CRH alone were seen in 14 of 17 patients with CD and 2 of 5 patients with EC and, af ter desmopressin alone, in 12 or 17 with CD and 3 of 5 with EC, thus i ndicating overlapping responses between the groups and poorer discrimi nation. No responses were seen in the ACTH-independent group.These dat a indicate that desmopressin causes the secretion of ACTH and cortisol in patients with ACTH-dependent Gushing's syndrome, and that in combi nation with CBH, it may provide an improvement over the standard CRH t est in the differential diagnosis of ACTH-dependent Cushing's syndrome . Furthermore, these data suggest that there may be abnormalities in v asopressin receptor function or number in ACTH-secreting tumors.