The 1 mu g short Synacthen test in chronic fatigue syndrome

OBJECTIVE Many studies suggest mild hypocortisolism in chronic fatigue synd rome (CFS), usually assumed to be due to reduced suprahypothalamic drive to the hypothalamo-pituitary-adrenal (HPA) axis. We wished to explore further the state of the HPA axis in CFS using the 1 ag low dose short Synacthen t est. DESIGN Subjects received an intravenous bolus of 1 mu g Synacthen; samples for cortisol estimation were taken at baseline and 2, 10, 20, 30, 40 and 60 minutes after injection. PATIENTS We tested 20 subjects suffering from CFS according to the criteria of the Center for Diseases Control without psychiatric comorbidity and 20 matched healthy controls. All subjects were drug free for at least 1 month. MEASUREMENTS We calculated the cortisol responses to the test as the maximu m cortisol attained, the incremental rise in cortisol over baseline (Delta value) and as the integrated area under the curve. RESULTS There were no significant differences in baseline cortisol or corti sol responses between patients and controls. However, responses generally w ere low, and many subjects' peak responses were prior to the standard 30 mi nute sampling time, CONCLUSIONS These results do not lend support to the theory that patients w ith chronic fatigue syndrome have a low adrenal reserve. However, results f rom studies assessing the HPA axis are proving to be inconsistent. We sugge st that many other factors may be contributing to HPA axis alterations in c hronic fatigue syndrome, including sleep disturbance, inactivity, altered c ircadian rhythmicity, illness chronicity, concomitant medication and comorb id psychiatric disturbance. These sources of heterogeneity need to be consi dered in future studies, and may explain the inconsistent findings to date.