Urinary Cortisol and Cortisol Metabolite Excretion in Chronic Fatigue Syndrome

Objectives: Reduced basal hypothalamic–pituitary–adrenal (HPA) axis output in chronic fatigue syndrome (CFS) has been inferred from low cortisol levels in blood, saliva, and urine in some studies. Because > 95% of cortisol is metabolized before excretion, we assessed cortisol output by assay of both cortisol metabolites and free cortisol in 24-hour urine collections and also investigated sex differences in these between CFS and control groups. Method: We calculated total urinary cortisol metabolites (TCM) and cortisol metabolite ratios from individual steroid data in 40 patients (20 males and 20 females) with CFS who were free of medication or comorbid psychiatric disorder likely to influence the HPA axis. Results were compared with those of 40 healthy volunteers (20 males and 20 females) well matched for age and body mass index. Data for free cortisol was obtained on 28 of the patients and 27 of the controls. Results: The mean of TCM and cortisol metabolite ratios was not significantly different between patients and controls for either sex (p > .05 for all parameters). Previously established sex differences were confirmed in our controls and were found to be similar in CFS for TCM and the ratios 11OH/11OXO, 5&agr;/5&bgr; THF, and 20OH/20OXO (see text) (p < .005, p < .05, p < .05, and p < .005, respectively). Urinary free cortisol values were numerically (but not statistically) lower in patients with CFS than controls, and correlated inversely with fatigue levels in patients. Conclusion: The finding of normal urinary cortisol metabolite excretion in patients with CFS is at variance with earlier reports that CFS is a hypocortisolemic state. If serum and saliva cortisol levels are lower in CFS, this would suggest that metabolic clearance of cortisol is faster in patients with CFS than controls. This study also demonstrates that sex differences must be taken into account when interpreting results in patients with CFS. HPA = hypothalamic–pituitary–adrenal; UFC = urinary free cortisol; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; CDC = Centers for Disease Control and Prevention; CBG = cortisol binding globulin; 11&bgr; HSD = 11&bgr; hydroxysteroid dehydrogenase activity; TCM = total urinary cortisol metabolites; THE = tetrahydrocortisone; THF = tetrahydrocortisol; 5&agr;THF = allo-tetrahydrocortisol; &agr;-Cort = &agr;-cortolone; &bgr;&&bgr; = &bgr;-cortolone and &bgr;-cortol; &agr;-cortol = &agr;-cortol.

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