HYPERACTIVITY OF THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS IN OBESITY - A STUDY OF ACTH, AVP, BETA-LIPOTROPHIN AND CORTISOL RESPONSES TO INSULIN-INDUCED HYPOGLYCEMIA

OBJECTIVE The purpose of this study was to determine whether alteratio ns in the hypothalamo-pituitary-adrenal axis and arginine vasopressin secretion, which have been associated with animal obesity, also occur in man. DESIGN Cross-sectional analysis of extremely obese women and n ormal weight controls. PATIENTS Thirty-three obese premenopausal, non- diabetic women (mean age 31 years, mean body mass index (BMI) 41), and 15 normal weight controls (mean age 24 years, mean BMI 22). MEASUREME NTS AND RESULTS Arginine vasopressin (AVP), ACTH, beta-lipotrophin and cortisol responses to insulin-induced hypoglycaemia (0.2 units Actrap id/kg body weight for obese; 0.15 unit/kg for controls) were measured. The obese women were further characterized by anthropometric measurem ents (weight, body mass index, fat distribution) and indices of insuli n secretion/resistance: fasting insulin, insulin secretion during 75-g oral glucose tolerance test area under curve, insulin-stimulated gluc ose disposal and an index of insulin resistance. No significant differ ences were found in the basal levels of ACTH, AVP, beta-lipotrophin or cortisol. An augmented peak beta-LPH (n=16, P < 0.02, the difference of the mean 3.65, 95% confidence interval 1.33-10) and ACTH (n=16, P=0 .05, the difference of the mean 2.12, 95% CI 1.0-4.5) response were fo und in obese as compared with normal weight controls. Both ACTH and AV P areas under the curve were similar in both groups studied. There was additionally a direct positive association between the integrated ACT H response (area under the curve) and the weight of the obese subjects (P < 0.05, r2=0.265). The cortisol response was negatively correlated with insulin stimulated glucose disposal (P < 0.01, r2=0.23), but not with other indices of insulin secretion/resistance (fasting insulin, oral glucose tolerance test area under the curve index of insulin resi stance) or fat distribution. Comparable responses to hypoglycaemia wer e seen for AVP and cortisol. There was no correlation between the ACTH , AVP or cortisol responses. CONCLUSION Obesity is associated with inc reased activity of the hypothalamo-pituitary-adrenal axis as supported by augmented ACTH and beta-lipotrophin secretion in response to insul in-induced hypoglycaemia and the positive association between the ACTH response and the body weight of obese women studied.