ACTH and cortisol release following intravenous desmopressin: a dose-response study

OBJECTIVE Desmopressin (DDAVP) is a synthetic analogue of AVP, the companio n regulator of coptico-trophin-releasing hormone (CRH) in the control of AC TH synthesis and release from the pituitary corticotrophs. The body of evid ence from human studies suggests that DDAVP alone, unlike AVP, does not bri ng about ACTH release, although recent evidence suggests idiosyncracies of response in healthy subjects. We examined whether DDAVP exerted any consist ent effect on ACTH and cortisol release, and also if this occurred in a dos e-dependant manner. DESIGN AND SUBJECTS A total of 18 subjects participated in the study. Salin e, 5 mu g, 10 mu g and 15 mu g DDAVP were administered as an intravenous bo lus at 1300 h; 5, 7, 18 and 8 subjects, respectively, participated in each arm of the study. Plasma ACTH and cortisol responses were measured over a 1 20-minutes period. RESULTS Significant between group comparisons were demonstrated for both AC TH (P < 0.05) and cortisol responses (P < 0.005) measured as maximum increm ent from baseline. The ACTH response to 5, 10 and 15 mu g DDAVP was signifi cantly greater than saline at all three doses, whilst maximal responses wer e seen at 10 mu g, The cortisol responses to 10 and 15 mu g DDAVP doses, bu t not 5 mu g, were significantly greater than following saline. 11/18 subje cts were deemed 'responders' following 10 mu g DDAVP on the basis of both A CTH and cortisol output. CONCLUSIONS This data suggests that DDAVP is capable of stimulating ACTH an d cortisol release when administered alone as a bolus in over 50% of health y subjects. This is in contrast to much of the extant literature. The mode of administration may be pertinent to this effect. This finding has implica tions for the recent focus on DDAVP as a diagnostic toot in disorders such as Gushing's Disease.