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A Randomized Controlled Trial

Robin McKenzie, MD; Ann O'Fallon, RN; Janet Dale, RN, MPH; Mark Demitrack, MD; Geetika Sharma, MD; Maria Deloria; Diego Garcia-Borreguero, MD; William Blackwelder, PhD; Stephen E. Straus, MD

JAMA. 1998;280:1061-1066.

Context.— Chronic fatigue syndrome (CFS) is associated with a dysregulated hypothalamic–pituitary adrenal axis and hypocortisolemia.

Objective.— To evaluate the efficacy and safety of low-dose oral hydrocortisone as a treatment for CFS.

Design.— A randomized, placebo-controlled, double-blind therapeutic trial, conducted between 1992 and 1996.

Setting.— A single-center study in a tertiary care research institution.

Patients.— A total of 56 women and 14 men aged 18 to 55 years who met the 1988 Centers for Disease Control and Prevention case criteria for CFS and who withheld concomitant treatment with other medications.

Intervention.— Oral hydrocortisone, 13 mg/m² of body surface area every morning and 3 mg/m² every afternoon, or placebo, for approximately 12 weeks.

Main Outcome Measures.— A global Wellness scale and other self-rating instruments were completed repeatedly before and during treatment. Resting and cosyntropin-stimulated cortisol levels were obtained before and at the end of treatment. Patients recorded adverse effects on a checklist.

Results.— The number of patients showing improvement on the Wellness scale was 19 (54.3%) of 35 placebo recipients vs 20 (66.7%) of 30 hydrocortisone recipients (P=.31). Hydrocortisone recipients had a greater improvement in mean Wellness score (6.3 vs 1.7 points; P=.06), a greater percentage (53% vs 29%; P=.04) recording an improvement of 5 or more points in Wellness score, and a higher average improvement in Wellness score on more days than did placebo recipients (P<.001). Statistical evidence of improvement was not seen with other self-rating scales. Although adverse symptoms reported by patients taking hydrocortisone were mild, suppression of adrenal glucocorticoid responsiveness was documented in 12 patients who received it vs none in the placebo group (P<.001).

Conclusions.— Although hydrocortisone treatment was associated with some improvement in symptoms of CFS, the degree of adrenal suppression precludes its practical use for CFS.

From the Laboratory of Clinical Investigation (Drs McKenzie, Sharma, and Straus and Mss O'Fallon and Dale) and Division of Microbiology and Infectious Diseases (Ms Deloria and Dr Blackwelder), National Institute of Allergy and Infectious Diseases, and Clinical Psychobiology Branch, National Institute of Mental Health (Dr Garcia-Borreguero), National Institutes of Health, Bethesda, Md; and Department of Psychiatry, University of Michigan, Ann Arbor (Dr Demitrack).

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