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

  [ 32 votes ]   [ Discuss This Article ]
www.ProHealth.com • June 1, 1999


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 LV, Medbak S, Dinan TG




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