Context: Patients with Cushing's syndrome (CS) have a mortality rate four times higher than age- and sex-matched subjects, mainly due to cardiovascular events. Serum osteoprotegerin (OPG) levels are increased in patients with cardiovascular disease and/or excess bone resorption.

Objective: To assess serum OPG and soluble RANKL (sRANKL) levels in CS and their possible relationship with coronary risk profile.

Design: Cross-sectional study.

Setting: Tertiary referral centre.

Patients: We studied 48 adult patients with CS and 48 age- and sex-matched controls. Twenty-six patients had pituitary-dependent CS; 5 patients had CS caused by ectopic ACTH secretion; 17 patients had adrenal-dependent CS, accounted for by cortisol-secreting adenoma (n = 9), ACTH-independent macronodular bilateral adrenal hyperplasia (n = 4) or WHO stage II cortisol-secreting carcinoma (n = 4). Patients underwent assessment of the absolute coronary risk and measurement of BMD by dual-energy X-ray absorptiometry. Serum OPG and total sRANKL were measured by ELISA.

Results: Serum OPG (but not sRANKL) levels were significantly higher in CS patients than in controls (P < 0.01). In patients, serum OPG showed a positive correlation with age (R = 0.36, P = 0.01). OPG levels were higher in patients with the metabolic syndrome (median 1262 (range 199-2306) pg/ml vs. 867 (412-2479) pg/ml, P = 0.03), and showed a positive correlation with the absolute coronary risk (R = 0.36, P = 0.01). Serum OPG levels were higher in patients with pituitary-dependent CS in comparison with adrenal-dependent CS.

Conclusions: In patients with CS serum OPG levels are increased and appear to be associated with coronary risk.