Pulsatile secretion of ACTH and cortisol in premenopausal women: effect of obesity and body fat distribution

OBJECTIVE There is emerging evidence that women with visceral obesity may have hyper-responsiveness of the hypothalamic-pituitary-adrenal axis. There are no studies on basal daily secretory pattern of ACTH and cortisol in subjects with different obesity phenotypes. DESIGN AND PATIENTS In this study we examined daytime pulsatile secretion of ACTH and cortisol in two groups of premenopausal obese women with visceral (V-BFD) (BMI 37.1 +/- 1.7) and subcutaneous (S-BFD) (BMI 38.8 +/- 1.5) body fat distribution (measured by CT scan) and in a group of normal weight healthy controls (BMI 21.1 +/- 0.5). After an overnight fast, blood samples were taken at 15-minute intervals for 12h (49 samples, from 0800h until 2000h). All women avoided breakfast but had a normal lunch and dinner, both containing similar food, energy and nutrient composition. ACTH and cortisol responses to mixed meals at noon and in the evening were also investigated. RESULTS Mean values of ACTH and cortisol did not differ between the groups. However, ACTH pulse frequency was significantly higher in V-BFD (P<0.06) and S-BFD (P<0.02) obese women than in controls, without any significant differences between the two obese subgroups. Mean ACTH pulse amplitude was lower in the V-BFD than in S-BFD obese (P<0.02) and control (P<0.05) groups. Cortisol episodic characteristics did not differ between V-BFD and S-BFD obese and controls. All differences in ACTH pulsatile parameters between obese and controls and between the two obese subgroups were evident only in the morning, with no further significant differences during the early and late afternoon. There were no significant differences in cortisol parameters during the three periods of the day between the various groups, apart from late afternoon cortisol pulse frequencies, which were significantly lower in V-BFD than in controls. After lunch, ACTH and cortisol levels significantly increased in all groups, but the cortisol increase tended to be more rapid in V-BFD than in the other two groups. After dinner, ACTH significantly increased in V-BFD and controls but not in the S-BFD group, whereas cortisol rose significantly in all groups, but significantly less in S-BFD than in V-BFD and controls. Cortisol(AUC) (but not ACTH(AUC)) after lunch was significantly higher than after dinner in all groups. ACTH response after each meal was similar in all groups, but cortisol(AUC) after dinner was significantly lower in S-BFD than in V-BFD women. CONCLUSION This study demonstrates that in premenopausal women, obesity, particularly the visceral phenotype, is associated with several abnormalities of ACTH pulsatile secretion, particularly in the morning. On the contrary, no major differences were present in either blood concentrations, diurnal rhythm or secretory pattern of cortisol between obese and controls. The responses to meals seem to indicate a much more rapid cortisol response after lunch in women with visceral obesity and a reduced activation of the hypothalamic-pituitary-adrenal axis after dinner in women with subcutaneous obesity.