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Increased Osteoprotegerin Levels in Cushing’s Syndrome Are Associated with an Adverse Cardiovascular Risk Profile

Medicina Interna I (A.D., B.A., E.P., M.V., L.S., M.T., A.A.), Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Turin, Italy; Laboratorio Analisi (E.A.), Azienda Sanitaria Ospedaliera San Luigi, I-10043 Orbassano-Turin, Italy; and Endocrinologia (A.P.), Azienda Sanitaria Ospedaliera Santa Croce e Carle, I-12100 Cuneo, Italy

Address all correspondence and requests for reprints to: Andrea Dovio, Medicina Interna I, Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino, Reg. Gonzole 10, 10043 Orbassano-Torino, Italy. E-mail: andrea.dovio{at}unito.it.

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: The aim of the study was to assess serum OPG and soluble receptor activator of nuclear factor-B ligand (sRANKL) levels in CS and their possible relationship with coronary risk profile.

Design and Setting: We conducted a cross-sectional study at a tertiary referral center.

Patients: We studied 48 adult patients with CS and 48 age- and sex-matched controls. Twenty-six patients had pituitary-dependent CS; five patients had CS caused by ectopic ACTH secretion; and 17 patients had adrenal-dependent CS, accounted for by cortisol-secreting adenoma (n = 9), ACTH-independent macronodular bilateral adrenal hyperplasia (n = 4), or World Health Organization stage II cortisol-secreting carcinoma (n = 4). Patients underwent assessment of the absolute coronary risk and measurement of bone mineral density 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.