The ratio of cortisol/DHEA in chronic fatigue syndrome

Abstract

Introduction: Hypoactivity of the hypothalamic-pituitary-adrenal axis (HPA axis) has been one of the most consistent biological findings in chronic fatigue syndrome (CFS). However, it has been hypothesised that the adrenal steroid dehydroepiandrosterone (DHEA) may counteract the effects of cortisol in the brain (Kroboth et al., 2003) and that consequently a true measure of the “net” effect of cortisol on the brain is better obtained by calculating the ratio of cortisol to DHEA. Studies have not attempted to measure this pre and post Cognitive Behavioural Therapy (CBT), an effective treatment for CFS (Whiting et al., 2000) also recommended byNational UK guidelines. Methods: Basal (0900 h) plasma levels of cortisol, DHEA and their ratio were measured in 41 patients with CFS without depression and in 28 matched controls. In 33 of the above patients this ratio was repeated following a 6 month course of CBT. Furthermore diurnal salivary cortisol profiles were measured at 0800, 1200, 1600 and 2000 h pre- and post-CBT in all 41 patients. Results: The plasma ratio of cortisol/DHEA (mean±SD) did not differ between patients and controls (5.91±0.46 vs 5.86±0.46, p=0.97). Although there was no difference comparing the 0900 h plasma cortisol/DHEA ratio before and after CBT, 0900 h plasma DHEA was significantly lower after CBT (34.7±18.4 vs. 31.2± 21.0 nmol/l, p=0.001). While total daily salivary cortisol output from 0800–2000 h (measured as the area under the curve) increased significantly from 68.2±19.6 to 79.4±21.8 nmol/l h (t=2.62, p<0.05) after CBT. Conclusions: The combined novel findings of increased total daily salivary cortisol output and reduced plasma DHEA suggest that ‘functional’ cortisol is increased following CBT for CFS. We suggest that there disavantages in using single plasma levels and that further clarity will be obtained in future research by measuring both cortisol and DHEA concurrently in saliva throughout the day.