Plasma leptin in chronic fatigue syndrome and a placebo-controlled study of the effects of low-dose hydrocortisone on leptin secretion

OBJECTIVE Previous studies have suggested that chronic fatigue syndrome (CF S) is associated with changes in appetite and weight, and also with mild hy pocortisolism. Because both of these features may be related to leptin meta bolism, we undertook a study of leptin in CFS. DESIGN (i) A comparison of morning leptin concentration in patients with CF S and controls and (ii) a randomized, placebo-controlled crossover study of the effects of hydrocortisone on leptin levels in CFS. PATIENTS Thirty-two medication free patients with CFS but not comorbid depr ession or anxiety. Thirty-two age, gender, weight, body mass index and mens trual cycle matched volunteer subjects acted as controls. MEASUREMENTS We measured basal 0900 h plasma leptin levels in patients and controls. All 32 patients were taking part in a randomized, placebo-control led crossover trial of low dose (5 or 10 mg) hydrocortisone as a potential therapy for CFS. We measured plasma leptin after 28 days treatment with hyd rocortisone and after 28 days treatment with placebo. RESULTS At baseline, there was no significant difference in plasma leptin b etween patients [mean 13.8, median 7.4, interquartile range (IQR) 18.0 ng/m l] and controls (mean 10.2, median 5.5, IQR 11.3 ng/ml). Hydrocortisone tre atment, for both doses combined, caused a significant increase in leptin le vels compared to placebo. When the two doses were analysed separately, only 10 mg was associated with a significant effect on leptin levels. We also c ompared the hydrocortisone induced increase in leptin between those who wer e deemed treatment-responders and those deemed nonresponders. Responders sh owed a significantly greater hydrocortisone-induced rise in leptin than non responders. This association between a clinical response to hydrocortisone and a greater rise in leptin levels may indicate a greater biological effec t of hydrocortisone in these subjects, perhaps due to increased glucocortic oid receptor sensitivity, which may be present in some patients with CFS. CONCLUSIONS We conclude that, while we found no evidence of alterations in leptin levels in CFS, low dose hydrocortisone therapy caused increases in p lasma leptin levels, with this biological response being more marked in tho se CFS subjects who showed a positive therapeutic response to hydrocortison e therapy. Increases in plasma leptin levels following low dose hydrocortis one therapy may be a marker of pretreatment physiological hypocortisolism a nd of response to therapy.