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

Desmopressin (DDAVP) is a synthetic analogue of AVP, the companion regulator of corticotrophin-releasing hormone (CRH) in the control of ACTH synthesis and release from the pituitary corticotrophs. The body of evidence from human studies suggests that DDAVP alone, unlike AVP, does not bring about ACTH release, although recent evidence suggests idiosyncracies of response in healthy subjects. We examined whether DDAVP exerted any consistent effect on ACTH and cortisol release, and also if this occurred in a dose-dependant manner.

A total of 18 subjects participated in the study. Saline, 5 microg, 10 microg and 15 microg DDAVP were administered as an intravenous bolus 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 120-minutes period.

Significant between group comparisons were demonstrated for both ACTH (P < 0.05) and cortisol responses (P < 0. 005) measured as maximum increment from baseline. The ACTH response to 5, 10 and 15 microg DDAVP was significantly greater than saline at all three doses, whilst maximal responses were seen at 10 microg. The cortisol responses to 10 and 15 microg DDAVP doses, but not 5 microg, were significantly greater than following saline. 11/18 subjects were deemed 'responders' following 10microg DDAVP on the basis of both ACTH and cortisol output.

This data suggests that DDAVP is capable of stimulating ACTH and cortisol release when administered alone as a bolus in over 50% of healthy subjects. This is in contrast to much of the extant literature. The mode of administration may be pertinent to this effect. This finding has implications for the recent focus on DDAVP as a diagnostic tool in disorders such as Cushing's Disease.