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

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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. DESIGN AND SUBJECTS

A total of 18 subjects participated in the study. Saline, 5 μg, 10 μg and 15 μg 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. RESULTS

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 μg DDAVP was significantly greater than saline at all three doses, whilst maximal responses were seen at 10 μg. The cortisol responses to 10 and 15 μg DDAVP doses, but not 5 μg, were significantly greater than following saline. 11/18 subjects were deemed ‘responders’ following 10μg DDAVP on the basis of both ACTH and cortisol output. CONCLUSIONS

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.
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Document Type: Research Article

Affiliations: 1: Department of Psychiatry, Trinity College Medical School, St. James' Hospital, Dublin, Eire, 2: Department of Chemical Pathology, Queen Alexandra Hospital, Portsmouth, 3: Department of Psychological Medicine, St. Bartholomew's Hospital, London, UK

Publication date: November 1, 1999

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