Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women

Abstract

BackgroundThe ACTH–cortisol axis in women is activated and associated with decreased ACTH potency, estimated by relating ACTH and cortisol pulse masses. Recently, a new accurate method for constructing the endogenous dose–response relationship was introduced, which is based on the relation between ACTH concentrations and associated cortisol secretion rates within cortisol bursts.HypothesisThe endogenous dose–response relation between ACTH and cortisol in obesity is changed, leading to diminished responsiveness.SubjectsTwenty-five obese premenopausal women and 16 normal weight premenopausal women were studied by 10-min blood sampling for 24 h.OutcomesACTH and cortisol secretion rates, analytical dose–response estimates of endogenous ACTH efficacy (maximal cortisol secretion), dynamic ACTH potency, and adrenal sensitivity (slope term) from 24-h ACTH–cortisol profiles were quantified.ResultsThe initial potency (negative logarithm) was −7.83±0.75 (mean±s.e.m.) in obese women and −10.14±1.08 in lean women (P=0.10), and the corresponding values for the recovery phase were −26.62±2.21 and −36.67±1.66 (P=0.004). The sensitivity (curve slope) amounted to 0.468±0.05 in obese women and 0.784±0.09 in normal weight women (P=0.004). The efficacy (maximal value) was 17.6±4.9 nmol/l per min in obese women and 26.3±3.8 nmol/l per min in normal weight women (P=0.009). Basal secretion rate, inflection point, and EC50values were not different. Bromocriptine or acipimox did not change the dose–response curve.ConclusionThe ACTH–cortisol relation in obesity in women is characterized by decreased sensitivity and efficacy, thus explaining non-elevated serum cortisol concentrations despite increased plasma ACTH levels.