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 ax is. There are no studies on basal daily secretory pattern of ACTH and cortisol in subjects with different obesity phenotypes. DESIGN AND PAT IENTS In this study we examined daytime pulsatile secretion of ACTH an d 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) b ody fat distribution (measured by CT scan) and in a group of normal we ight healthy controls (BMI 21.1 +/- 0.5). After an overnight fast, blo od samples were taken at 15-minute intervals for 12h (49 samples, from 0800h until 2000h). All women avoided breakfast but had a normal lunc h and dinner, both containing similar food, energy and nutrient compos ition. ACTH and cortisol responses to mixed meals at noon and in the e vening were also investigated. RESULTS Mean values of ACTH and cortiso l 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 tha n in S-BFD obese (P<0.02) and control (P<0.05) groups. Cortisol episod ic characteristics did not differ between V-BFD and S-BFD obese and co ntrols. 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 par ameters during the three periods of the day between the various groups , apart from late afternoon cortisol pulse frequencies, which were sig nificantly lower in V-BFD than in controls. After lunch, ACTH and cort isol levels significantly increased in all groups, but the cortisol in crease 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 n ot in the S-BFD group, whereas cortisol rose significantly in all grou ps, but significantly less in S-BFD than in V-BFD and controls. Cortis ol(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 wer e 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 w omen with visceral obesity and a reduced activation of the hypothalami c-pituitary-adrenal axis after dinner in women with subcutaneous obesi ty.