Increased osteoprotegerin levels in Cushing's syndrome are associated with an adverse cardiovascular risk profile.
BACKGROUND
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-kappaB ligand (sRANKL) levels in CS and their possible relationship with coronary risk profile.


METHODS
We conducted a cross-sectional study at a tertiary referral center.


METHODS
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.
Dovio
Andrea
A
Medicina Interna I, Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino, Reg. Gonzole 10, 10043 Orbassano-Torino, Italy. andrea.dovio@unito.it.
Allasino
Barbara
B
Palmas
Enrico
E
Ventura
Massimo
M
Pia
Anna
A
Saba
Laura
L
Aroasio
Emiliano
E
Terzolo
Massimo
M
Angeli
Alberto
A
D015502:Absorptiometry, Photon; D000311:Adrenal Glands / Q000503:physiopathology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000209:etiology*; D003430:Cross-Sectional Studies; D003480:Cushing Syndrome / Q000097:blood* / Q000150:complications* / Q000453:epidemiology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D010901:Pituitary Function Tests; D010902:Pituitary Gland / Q000503:physiopathology; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000097:blood; D012306:Risk
D053244:Osteoprotegerin; D053246:Receptor Activator of Nuclear Factor-kappa B; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone