Investigation of the hypothalamopituitary-adrenal axis by low-dose (1 mu g) adrenocorticotrophic hormone test and metyrapone test in patients with chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is a disease characterized by debilitating fatigue of at least 6 months' duration. The pathophysiology and the localization of the underlying HPA axis disturbance are a matter of debate. Our aim was to evaluate the hypothalamopituitary-adrenal (HPA) axis by the 1 mu g adrenocorticotrophic hormone (ACTH) test and metyrapone test in patients with CFS and to compare the size of the adrenal glands of the patients with that of the control subjects. Twenty patients (14 females, 6 males) with CFS were included in the study. Fifteen healthy subjects (12 females, 3 males) served as matched controls. ACTH stimulation test was carried out by using 1 mu g ACTH, intravenously, as a bolus injection after an overnight fast, and blood samples for cortisol were drawn at 0, 30, and 60 minutes. Metyrapone at a dosage of 30 mg/kg was taken orally at 11:00 PM with a snack. The following morning, blood was sampled for serum 11-deoxycortisol between 8:00 and 9:00 AM. Peak cortisol responses to 1 mu g ACTH test were significantly lower in the CFS group (620.7 +/- 146.2 nmol/L) than in the control group (838.7 +/- 129.6 nmol/L) (P 0.05). We conclude that the perturbation of the HPA axis in CFS is characterized by underactivation of the HPAaxis