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Hypothalamic-Pituitary-Adrenal Axis Activity in Obese Men with and without Sleep Apnea: Effects of Continuous Positive Airway Pressure Therapy

Sleep Research and Treatment Center, Department of Psychiatry (A.N.V., S.P., E.O.B., A.S., M.B.), and Health Evaluation Sciences (H.-M.L., C.M.B.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; and First Department of Pediatrics and Unit on Endocrinology, Metabolism and Diabetes (E.Z., G.P.C.), University of Athens, GR-157-84 Athens, Greece

Address all correspondence and requests for reprints to: Alexandros N. Vgontzas, M.D., Department of Psychiatry, H073, Penn State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033. E-mail: avgontzas{at}psu.edu.

Context: Previous studies on the association between the hypothalamic-pituitary-adrenal axis activity and sleep apnea (SA) and obesity are inconsistent and/or limited.

Objective: In this study, we evaluated the activity of the hypothalamic-pituitary-adrenal axis in nonpsychologically distressed obese subjects with and without SA and examined the impact of continuous positive airway pressure (CPAP) in SA patients.

Design and Participants: In study I, four-night sleep laboratory recordings and serial 24-h plasma measures of cortisol were obtained in 45 obese men with and without apnea and nonobese controls. Sleep apneic patients were reassessed after 3 months of CPAP use. In study II, 38 obese men with and without sleep apnea and nonobese controls were challenged with ovine CRH administration after four nights in the sleep laboratory.

Results: The sleep patterns were similar between obese and nonobese controls. Twenty-four-hour plasma cortisol levels were highest in nonobese controls, intermediate in obese apneic patients, and lowest in obese controls (8.8 ± 0.4 vs. 8.1 ± 0.3 vs. 7.5 ± 0.3 µg/dl, P < 0.05). CPAP tended to reduce cortisol levels in the apneic patients (difference –0.7 ± .4 µg/dl, P = 0.1). CRH administration resulted in a higher ACTH response in both obese groups, compared with nonobese controls; the three groups were not different in cortisol response.

Conclusions: Nonpsychologically distressed, normally sleeping, obese men had low cortisol secretion. The cortisol secretion was slightly activated by SA and returned to low by CPAP use. The low cortisol secretion in obesity through its inferred hyposecretion of hypothalamic CRH might predispose the obese to sleep apnea.