The 1microg Short Synacthen Test in Chronic Fatigue Syndrome

Clin Endocrinol (Oxf). 1999 Nov;51(5):625-30. doi: 10.1046/j.1365-2265.1999.00856.x.


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 microg low dose short Synacthen test.

Design: Subjects received an intravenous bolus of 1 microg 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., CONCLUSIONS 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Case-Control Studies
  • Cosyntropin*
  • Fatigue Syndrome, Chronic / metabolism
  • Fatigue Syndrome, Chronic / physiopathology*
  • Female
  • Humans
  • Hydrocortisone / blood
  • Hydrocortisone / metabolism*
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Male
  • Pituitary-Adrenal System / physiopathology*


  • Cosyntropin
  • Hydrocortisone