The Impact of Mild Autonomous Cortisol Secretion on Bone Turnover Markers.

CONTEXT: Several studies have reported increased risk of fragility fractures in patients with mild autonomous cortisol secretion (MACS), discordant to the degree of bone density deterioration. OBJECTIVE: To evaluate the effect of MACS on bone metabolism in patients with adrenal adenomas. DESIGN: Cross-sectional study with prospective enrollment, 2014 - 2019. SETTING: Referral center. PATIENTS: 213 patients with adrenal adenomas (22 Cushing syndrome (CS), 92 MACS and 99 nonfunctioning adrenal tumors (NFAT)). RESULTS: Patients with CS demonstrated lower markers of bone formation when compared to patients with MACS and NFAT [CS vs MACS vs NFAT: mean osteocalcin 14.8 vs 20.1 vs 21.3 ng/mL (P<0.0001); mean PINP 34.8 vs 48.7 vs 48.5 microg/L (P=0.003)]. Severity of cortisol excess was inversely associated with sclerostin [CS vs MACS vs NFAT: mean sclerostin 419 vs 538 vs 624 ng/L, (P<0.0001)]. In a multivariable model of age, sex, BMI, cortisol and bone turnover markers, sclerostin was a significant predictor of low bone mass in patients with MACS (OR 0.63 [CI 95% 0.40-0.98] for each 100 ng/L of sclerostin increase).After adrenalectomy, osteocalcin, CTX and sclerostin increased by a mean difference of 6.3 ng/mL, 0.12 ng/mL, and 171 pg/mL (P=0.02 for all), respectively. CONCLUSIONS: Lower sclerostin level in patients with MACS reflects a reduction in osteocyte function or number associated with exposure to chronic cortisol excess. Increase in bone turnover markers after adrenalectomy suggests restoration of favorable bone metabolism.