Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial

Background Reports of mild hypocortisolism in chronic fatigue syndrome led us to postulate that tow-dose hydrocortisone therapy may be an effective tr eatment. Methods In a randomised crossover trial, we screened 218 patients with chro nic fatigue. 32 patients met our strict criteria for chronic fatigue syndro me without co-morbid psychiatric disorder. The eligible patients received c onsecutive treatment with low-dose hydrocortisone (5 mg or 10 mg daily) for 1 month and placebo for 1 month;the order of treatment was randomly assign ed. Analysis was by intention to treat. Findings None of the patients dropped out. Compared with the baseline self- reported fatigue scores (mean 25.1 points), the score fell by 7.2 points fo r patients on hydrocortisone and by 3.3 points for those on placebo (paired difference in mean scores 4.5 points [95% CI 1.2-7.7], p = 0.009). In nine (28%) of the 32 patients on hydrocortisone, fatigue scores reached a prede fined cut-off value similar to the normal population score, con;pared with three (9%) of the 32 on placebo (Fisher's exact test p = 0.05). The degree of disability was reduced with hydrocortisone treatment, but not with place bo. Insulin stress tests showed that endogenous adrenal function was not su ppressed by hydrocortisone. Minor side-effects were reported by three patie nts after hydrocortisone treatment and by one patient after placebo. Interpretation In some patients with chronic fatigue syndrome, low-dose hyd rocortisone reduces fatigue levels in the short term. Treatment for a longe r time and follow-up studies are needed to find out whether this effect cou ld be clinically useful.