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Association of 24-Hour Cortisol Production Rates, Cortisol-Binding Globulin, and Plasma-Free Cortisol Levels with Body Composition, Leptin Levels, and Aging in Adult Men and Women

Oregon Health and Science University, Portland, Oregon 97239

Address all correspondence and requests for reprints to: Jonathan Q. Purnell, M.D., Oregon Health and Science University, Division of Endocrinology, Diabetes, and Clinical Nutrition, L607, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239. E-mail: purnellj{at}ohsu.edu.

The present study was designed to examine the hypothesis that hypothalamic-pituitary-adrenal axis activity as measured by 24-h cortisol production rate (CPR) and plasma levels of free cortisol is linked to increased body fat in adults, and that increased cortisol levels with aging results from increased CPR. Fifty-four healthy men and women volunteers with a wide range of body mass indexes and ages underwent measurement of CPR by isotope dilution measured by gas chromatography-mass spectroscopy, cortisol-binding globulin, and free cortisol in pooled 24-h plasma, body composition, and leptin. Cortisol clearance rates were determined from the 10-h disappearance curves of hydrocortisone after steady-state infusion in a separate group of lean and obese subjects with adrenal insufficiency. Although CPR significantly increased with increasing body mass index and percentage body fat, free cortisol levels remained independent of body composition and leptin levels due to increased cortisol clearance rates. CPR and free cortisol levels were, however, significantly higher in men than women. In addition, 24-h plasma free cortisol levels were increased with age in association with increased CPR, independent of body size. This increase in hypothalamic-pituitary-adrenal axis activity may play a role in the alterations in body composition and central fat distribution in men vs. women and with aging.

This work was supported by the General Clinical Research Centers of the University of Washington (M01-RR00037), Oregon Health and Science University (M01-RR00334), and National Institutes of Health Grant R03-DK61996 (to J.Q.P.).

Abbreviations: AI, Adrenal insufficiency; AUC, area under the curve; BMI, body mass index; CBG, cortisol-binding globulin; CPR, cortisol production rate(s); CPR/BSA, CPR adjusted for body surface area; C(t1/2), half-life of cortisol; FM, fat mass; FFM, fat-free mass; GC/MS, gas chromatography-mass spectrometry; GCRC, General Clinical Research Center; GIP, gastric inhibitory peptide; HPA, hypothalamic-pituitary-adrenal; HRT, hormone replacement therapy; IR, infusion rate; OHSU, Oregon Health and Science University; PS, plasma sample(s).

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