Pituitary-adrenal axis and peripheral cortisol metabolism in obese patients

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/E^ratio) in a large series of overweight subjects without Cushing's Syndrome.

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/E^ratio were assessed with LC-MS.

We collected 183 LNSC, 176 UFC, 152 1 mg DST and 64 F/E^ratio 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/E^ratio (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.

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/E^ratio), suggesting an effort to counteract hypercortisolism.