THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN OBESE WOMEN WITH DIFFERENTPATTERNS OF BODY-FAT DISTRIBUTION

To investigate whether obese subjects with abdominal obesity may be ch aracterized by hyperactivity of the hypothalamic-pituitary-adrenal axi s, we examined two groups of obese women with a waist to hip ratio (WH R) lower than 0.80 (n = 13), therefore having peripheral body fat dist ribution (P-BFD), or a WHR higher than 0.85 (n = 12), thus having abdo minal body fat distribution (A-BFD). A group of seven normal weight he althy women served as controls. All subjects underwent the following p rotocol study that included 1) measurement of daily urinary free corti sol excretion rate; 2) a CRF test (human CRF, 1 mug/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 bo li of ACTH (Synacthen, 0.2 mug/kg BW, iv), at 90-min intervals, with b lood samples taken for cortisol determination. Each woman also had a c ontrol saline study. Basal levels of both ACTH and cortisol rose signi ficantly after CRF administration in all groups, but this increase was significantly higher in A-BFD than in P-BFD and control women. A sign ificant correlation was found between the incremental area of cortisol and that of ACTH during the CRF test (r = 0.502), but not between the se parameters and WHR values. Although the cortisol increase after the ACTH test was higher in A-BFD than in the other groups, these differe nces were only significant at 60 min during the test and when the anal ysis for repeated measures was applied. On the contrary, the increment al cortisol area after the ACTH test was not significantly different i n the three groups. Moreover, it was not significantly correlated with the incremental cortisol area after CRF test or WHR values. Daily uri nary free cortisol excretion rates (per g creatinine), however, were s ignificantly higher in A-BFD than in P-BFD and control women. These re sults, therefore, suggest that obese women with A-BFD may have hyperac tivity of the hypothalamic-pituitary-adrenal axis. This abnormality co uld be central in origin, due to hypersecretion of CRF or ACTH; altern atively, it could represent an adaptive phenomenon secondary to a stat e of functional cortisol resistance.