Pituitary-adrenal axis and peripheral cortisol metabolism in obese patients

Abstract

Background and aim: A close relationship between adiposity and increased cortisol levels is well established in patients with endogenous hypercortisolism. Nevertheless, hypothalamic-pituitary-adrenal (HPA) axis regulation in overweight subjects is still a matter of concern. We studied free cortisol (urinary free cortisol, UFC and late night salivary cortisol, LNSC), pituitary feedback (serum cortisol after 1 mg dexamethasone suppression test, 1 mg DST) and peripheral cortisol metabolism (urinary cortisol to cortisone ratio, F/Eratio) in a large series of overweight subjects without Cushing’s Syndrome. Materials and methods: We considered 234 patients divided in 5 BMI classes, matched for age and gender (BMI ≤ 25 kg/m2n = 38; 25–30 n = 58; 30–35 n = 52; 35–40 n = 52; >40 n = 34). UFC, LNSC and urinary F/Eratio were assessed with LC-MS. Results: We collected 183 LNSC, 176 UFC, 152 1 mg DST and 64 F/Eratio tests. UFC levels were higher in lean subjects, and they decreased according to the BMI classes (p = 0.022). Non-suppressed cortisol levels (>50 nmol/L) after 1 mg DST were observed especially in patients with normal weight or mild obesity. Patients with BMI ≥ 35 kg/m2 revealed a reduced F/Eratio (0.39 vs. 0.61, p = 0.006). The specificity of tests (false positive results) was higher considering 1 mg DST or UFC in obese patients, on the contrary impaired cortisol rhythm (LNSC above normality) was observed in 47 subjects, irrespective of weight. Conclusions: Overweight and obese subjects are characterised by an original regulation of HPA axis (reduced UFC levels, increased suppression after 1 mg DST) and peripheral cortisol metabolism (reduced F/Eratio), suggesting an effort to counteract hypercortisolism.