The hypothalamic-pituitary-adrenal axis in obese women with different patterns of body fat distribution

To investigate whether obese subjects with abdominal obesity may be characterized by hyperactivity of the hypothalamic-pituitary-adrenal axis, we examined two groups of obese women with a waist to hip ratio (WHR) lower than 0.80 (n = 13), therefore having peripheral body fat distribution (P-BFD), or a WHR higher than 0.85 (n = 12), thus having abdominal body fat distribution (A-BFD). A group of seven normal weight healthy women served as controls. All subjects underwent the following protocol study that included 1) measurement of daily urinary free cortisol excretion rate; 2) a CRF test (human CRF, 1 microgram/kg BW, as iv bolus), with blood samples taken at regular intervals for ACTH and cortisol determination; and 3) an ACTH test, performed by administering two boli of ACTH (Synacthen, 0.2 microgram/kg BW, iv), at 90-min intervals, with blood samples taken for cortisol determination. Each woman also had a control saline study. Basal levels of both ACTH and cortisol rose significantly after CRF administration in all groups, but this increase was significantly higher in A-BFD than in P-BFD and control women. A significant correlation was found between the incremental area of cortisol and that of ACTH during the CRF test (r = 0.502), but not between these parameters and WHR values. Although the cortisol increase after the ACTH test was higher in A-BFD than in the other groups, these differences were only significant at 60 min during the test and when the analysis for repeated measures was applied. On the contrary, the incremental cortisol area after the ACTH test was not significantly different in the three groups. Moreover, it was not significantly correlated with the incremental cortisol area after CRF test or WHR values. Daily urinary free cortisol excretion rates (per g creatinine), however, were significantly higher in A-BFD than in P-BFD and control women. These results, therefore, suggest that obese women with A-BFD may have hyperactivity of the hypothalamic-pituitary-adrenal axis. This abnormality could be central in origin, due to hypersecretion of CRF or ACTH; alternatively, it could represent an adaptive phenomenon secondary to a state of functional cortisol resistance.