Desmopressin augments pituitary-adrenal responsivity to corticotropin-releasing hormone in subjects with chronic fatigue syndrome and in healthy volunteers

Background: Corticotopin-releasing hormone (CRH) and vasopressin (VP) are t he two principal neuropeptide regulators of the hypothalamic-pituitary-adre nal axis in man, with VP serving to augment CH-induced adreno-corticotropic hormone (ACTH) release. Unlike VP, desmopressin (DDAVP), which is a synthe tic analogue of VP, when administered alone, has not been shown in healthy subjects to have consistent ACTH-releasing properties. it has been suggeste d that chronic fatigue syndrome (CFS), characterized by profound fatigue an d a constellation of other symptoms, may be caused by a central deficiency of CRH. Methods: We administered 100 mu g ovine CRH (oCRH) and 10 mu g DDAVP, both alone and in combination, to a group of subjects with CFS, and to a group o f healthy volunteers. Our aim was to establish the effect of DDAVP an CRH-i nduced ACTH release in these two groups, Results: The delta-ACTH responses to oCRH were attenuated in the CFS (21.0 +/- 4.5 ng/L) compared to the control subjects (57.8 +/- 11.0 ng/L; t = 3.2 , df = 21, p <.005). The delta-cortisol responses were also reduced in the CFS (157.6 +/- 40.7 nmol/L) compared to the healthy subjects (303.5 +/- 20. 9 nmol/L; t = 3.1, df = 21, p <.01). The delta-ACTH and delta-cortisol resp onses to DDAVP alone did not differ between the two groups. On administrati on of both CRH and DDAVP no response differences between the two groups for either ACTH (p = .3) or cortisol output (p = .87) were established Compari ng the ACTH and cortisol responses to CRH and CRH/DDAVP in only those indiv iduals from each group who had both tests, the cortisol output to the combi nation was significantly greater in the CFS compared to the healthy group. The ACTH output was also increased in the former group, though this was not significant. Conclusions: DDAVP augments CRH-mediated pituitary-adrenal responsivity in healthy subjects and in patients with CFS. That DDAVP was capable of normal izing the pituitary-adrenal response to oCRH in the CFS group suggests ther e may be increased vasopressinergic responsivity of the anterior pituitary in CFS and/or that DDAVP may be exerting an effect at an adrenal level. (C) 1999 Society of Biological Psychiatry.