Impact of Adiposity and Fat Distribution on the Dynamics of Adrenocorticotropin and Cortisol Rhythms.

Obesity impacts many hormonal systems, including pituitary hormones, as well as insulin and leptin. In this review we discuss articles which investigate the influence of obesity on the hypothalamic-pituitary-adrenal (HPA) axis. Different techniques have been used to assess the function of the HPA-axis in obesity, including measuring fasting and/or late evening levels of adrenocorticotropic hormone (ACTH) and (free) cortisol in plasma and saliva, studying feedback with dexamethasone or cortisol, and evaluating responsiveness of the system to corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) or ACTH 1-29. In addition, more elaborate studies investigated 24-h secretion patterns, analyzed with deconvolution techniques to quantitate pulsatile secretion rates of cortisol and less often ACTH. Other investigators used timed infusions of labeled cortisol for the estimation of the 24-h secretion rate, clearance rate and distribution volume. Many studies relied on the 24-h urinary excretion of free cortisol, but for quantitation of the 24-h secretion, measurement of all cortisol-derived metabolites is required. Several studies have applied modern liquid chromatography-tandem-mass spectrometry techniques to measure these metabolites. The picture emerging from all these studies is that, first, ACTH secretion is amplified, likely via enhanced forward drive; and, second, serum cortisol levels are normal or even low, associated with a normal 24-h cortisol secretion per liter distribution volume determined by deconvolution, but enhanced when based on the increased total distribution volume associated with obesity. Increased cortisol secretion was also established by isotope dilution studies and reports based on the measurement of all urinary cortisol metabolites. The responsiveness of the adrenal gland to ACTH is diminished. The studies do not address quantitative aspects of cortisol-cortisone metabolism on individual organs, including liver, central and peripheral fat, intestine, skin, and muscle.