The 1 mug short Synacthen test in Chronic Fatigue Syndrome

OBJECTIVE: 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 mug low

dose short Synacthen test.

DESIGN: Subjects received an

intravenous bolus of 1 mug 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 maximum cortisol attained, the

incremental rise in cortisol over baseline (Deltavalue) and as

the integrated area under the curve.

RESULTS: 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.

Hudson M, Cleare AJ

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