Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women

Background: The 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. Hypothesis: The endogenous dose–response relation between ACTH and cortisol in obesity is changed, leading to diminished responsiveness. Subjects: Twenty-five obese premenopausal women and 16 normal weight premenopausal women were studied by 10-min blood sampling for 24 h. Outcomes: ACTH 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. Results: The initial potency (negative logarithm) was K7.83G0.75 (meanGS.E.M.) in obese women and K10.14G1.08 in lean women (PZ0.10), and the corresponding values for the recovery phase were K26.62G2.21 and K36.67G1.66 (PZ0.004). The sensitivity (curve slope) amounted to 0.468G0.05 in obese women and 0.784G0.09 in normal weight women (PZ0.004). The efficacy (maximal value) was 17.6G4.9 nmol/l per min in obese women and 26.3G3.8 nmol/l per min in normal weight women (PZ0.009). Basal secretion rate, inflection point, and EC50 values were not different. Bromocriptine or acipimox did not change the dose–response curve. Conclusion: The 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.