The 1mcg short Synacthen Test in Chronic Fatigue Syndrome.


Results from this study do not confirm the assumption that patients with chronic fatigue syndrome have a low adrenal reserve. It is suggested that many other factors may be contributing to irregularities in hormone/stress/adrenal function in CFS. These factors may include disturbed sleep, inactivity, disruptions in circadian rhythm, other illnesses, medication and psychiatric issues. This array of factors may explain the surprising findings.


Many studies suggest mild hypocortisolism in chronic fatigue syndrome (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 mcg low dose short Synacthen test [a serial cortisol test]. DESIGN: Subjects received an intravenous bolus of 1 mcg 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.


We calculated the cortisol responses to the test as the maximum cortisol attained, the incremental rise in cortisol over baseline (Deltavalue) and as the integrated area under the curve.


There were no significant differences in baseline cortisol or cortisol responses between patients and controls. However, responses generally were low, and many subjects’ peak responses were prior to the standard 30 minute sampling time.


These results do not lend support to the theory that patients with chronic fatigue syndrome have a low adrenal reserve. However, results from studies assessing the HPA axis are proving to be inconsistent. We suggest that many other factors may be contributing to HPA axis alterations in chronic fatigue syndrome, including sleep disturbance, inactivity, altered circadian rhythmicity, illness chronicity, concomitant medication and comorbid psychiatric disturbance. These sources of heterogeneity need to be considered in future studies, and may explain the inconsistent findings to date.


Clin Endocrinol (Oxf) 1999 Nov;51(5):625-630.

Department of Psychological Medicine, Guy’s King’s and St Thomas’ School of Medicine and the Institute of Psychiatry, London, UK.

PMID: 10594524

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