Desmopressin augments pituitary-adrenal responsivity to corticotropin-releasing hormone in subjects with Chronic Fatigue Syndrome (CFS) & in healthy volunteers

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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


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 LV, Medbak S, Dinan TG

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