An association between hypothalamic‐pituitary dysfunction and peripheral endocrine function in extreme obesity

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Abstract
The aim was to investigate a possible relationship between measures of insulin secretion and glucose disposal and hypothalamic-pituitary function in extreme obesity. A cross-sectional analysis of obese subjects attending the Obesity Clinic at the Royal London Hospital and normal weight volunteers was undertaken. Investigations were performed on separate occasions and in random order. The subjects were 34 extremely obese women, menstruating and with normal glucose tolerance (mean Body Mass Index, BMI = 42) and 15 normal weight female controls (mean BMI = 22). The following were measured: fasting insulin, relative insulin resistance calculated using fasting insulin and plasma glucose by the homeostatic model of assessment, insulin release during a 75-g oral glucose tolerance test (insulin area under the curve), steady-state plasma glucose level achieved during a simultaneous intravenous infusion of dextrose, insulin and somatostatin, and the prolactin and growth hormone (GH) responses to insulin-induced hypoglycaemia. In the obese group an impaired prolactin response to hypoglycaemia (mean area under the curve obese 54 U/l min, controls 155 U/l min; P = 0.0001) was inversely correlated to fasting insulin, r2 = 0.142, P = 0.03; relative insulin resistance, r2 = 0.134, P = 0.03 and steady-state plasma glucose level, r2 = 0.345, P = 0.0004 whereas the impaired GH response (mean GH area under the curve obese 1.9 U/l min, controls 65.7 U/l min; P = 0.0001) was inversely correlated to steady-state plasma glucose level, r2 = 0.196, P = 0.01. Backward procedure for stepwise regression analysis confirmed the steady-state plasma glucose level to be the most important variable associated with the prolactin and growth hormone response among the remaining indices of insulin secretion/resistance. We conclude from these findings that hyperinsulinaemia in obesity is an important association with altered hypothalamic-pituitary function indicated by impaired prolactin and growth hormone secretion to insulin-induced hypoglycaemia.