Desmopressin augments pituitary-adrenal responsivity to corticotropin-releasing hormone in subjects with chronic fatigue syndrome and in healthy volunteers.
BACKGROUND
Corticotropin-releasing hormone (CRH) and vasopressin (VP) are the two principal neuropeptide regulators of the hypothalamic-pituitary-adrenal axis in man, with VP serving to augment CRH-induced adrenocorticotropic hormone (ACTH) release. Unlike VP, desmopressin (DDAVP), which is a synthetic analogue of VP, when administered alone, has not been shown in healthy subjects to have consistent ACTH-releasing properties. It has been suggested that chronic fatigue syndrome (CFS), characterized by profound fatigue and a constellation of other symptoms, may be caused by a central deficiency of CRH.


METHODS
We administered 100 micrograms ovine CRH (oCRH) and 10 micrograms DDAVP, both alone and in combination, to a group of subjects with CFS, and to a group of healthy volunteers. Our aim was to establish the effect of DDAVP on CRH-induced 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 responses to DDAVP alone did not differ between the two groups. On administration of both CRH and DDAVP no response differences between the two groups for either ACTH (p = .3) or cortisol output (p = .87) were established. Comparing the ACTH and cortisol responses to CRH and CRH/DDAVP in only those individuals from each group who had both tests, the cortisol output to the combination 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 normalizing the pituitary-adrenal response to oCRH in the CFS group suggests there may be increased vasopressinergic responsivity of the anterior pituitary in CFS and/or that DDAVP may be exerting an effect at an adrenal level.
Scott
L V
LV
Department of Psychiatry, Trinity College Medical School, St. James' Hospital, Dublin, Ireland.
Medbak
S
S
Dinan
T G
TG
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects; D003894:Deamino Arginine Vasopressin; D004347:Drug Interactions; D015673:Fatigue Syndrome, Chronic / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D012076:Renal Agents
D012076:Renal Agents; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003894:Deamino Arginine Vasopressin; D006854:Hydrocortisone