Levels of DHEA and DHEAS and responses to CRH stimulation and hydrocortisone treatment in chronic fatigue syndrome.
BACKGROUND
An association between chronic fatigue syndrome (CFS) and abnormalities of the hypothalamo-pituitary-adrenal axis has been described, and other adrenal steroid abnormalities have been suggested. Dehydroepiandrostenedione (DHEA) and its sulphate (DHEA-S), apart from being a precursor of sex steroids, have other functions associated with memory, depression and sleep. It has been suggested that CFS may be associated with a state of relative DHEA(-S) deficiency. Therefore we investigated basal levels of DHEA(-S), the cortisol/DHEA molar ratio and the responsiveness of DHEA to stimulation by corticotrophin-releasing hormone (CRH). Recent studies have also suggested that low dose hydrocortisone may be effective at reducing fatigue in CFS. We therefore also assessed these parameters prior to and following treatment with low dose oral hydrocortisone.


METHODS
Basal levels of serum DHEA, DHEAS and cortisol were measured in 16 patients with CFS without depression and in 16 controls matched for age, gender, weight, body mass index and menstrual history. CRH tests (1 g/kg i.v.) were carried out on all subjects and DHEA measured at 0, +30 and +90 min. In the patient group, CRH tests were repeated on two further occasions following treatment with hydrocortisone (5 or 10 mg, p.o.) or placebo for 1 month each in a double-blind cross over study protocol.


RESULTS
Basal levels of DHEA were higher in the patient, compared to the control, group (14.1+/-2.2 vs. 9.0+/-0.90 ng/ml, P=0.04), while levels of DHEAS in patients (288.7+/-35.4 microg/dl) were not different from controls (293.7+/-53.8, P=NS). Higher DHEA levels were correlated with higher disability scores. Basal cortisol levels were higher in patients, and consequently the cortisol/DHEA molar ratio did not differ between patients and controls. Levels of DHEA (8.9+/-0.97 ng/ml, P=0.015) and DHEAS (233.4+/-41.6 microg/dl, P=0.03) were lower in patients following treatment with hydrocortisone. There was a rise in DHEA responsiveness to CRH in the patients after treatment but this did not attain significance (AUCc: 2.5+/-1.7 ng/ml h pre-treatment vs. 6.4+/-1.2 ng/ml h post-hydrocortisone, P=0.053). However, those patients who responded fully to hydrocortisone in terms of reduced fatigue scores did show a significantly increased DHEA responsiveness to CRH (AUCc: -1.4+/-2.5 ng/ml h at baseline, 5.0+/-1.2 ng/ml h after active treatment, P=0.029).


CONCLUSIONS
DHEA levels are raised in CFS and correlate with the degree of self-reported disability. Hydrocortisone therapy leads to a reduction in these levels towards normal, and an increased DHEA response to CRH, most marked in those who show a clinical response to this therapy.
Cleare
A J
AJ
Division of Psychological Medicine, The Institute of Psychiatry and Guy's, King's and St Thomas' School of Medicine, London SE5 8AF, UK. a.cleare@iop.kcl.ac.uk
O'Keane
V
V
Miell
J P
JP
D000328:Adult; D019540:Area Under Curve; D015992:Body Mass Index; D003346:Corticotropin-Releasing Hormone; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000097:blood*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D004311:Double-Blind Method; D015673:Fatigue Syndrome, Chronic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D016555:Matched-Pair Analysis; D010912:Pituitary-Adrenal Function Tests; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D012016:Reference Values; D012720:Severity of Illness Index
D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone