SAT-366 The Impact of Mild Autonomous Cortisol Secretion on Bone Metabolism

Background: Several studies reported high prevalence of bone disease (osteoporosis/osteopenia) in patients with mild autonomous cortisol secretion (MACS), discordant to the degree of bone density deterioration. Bone turnover marker (BTM) measurements can potentially elucidate the underlying mechanism of MACS-related bone disease. Objective: To describe the relationship between BTMs and glucocorticoid autonomy in patients with adrenal adenomas Methods: Patients were prospectively enrolled from adrenal clinics over 3 years. Inclusion criteria were adults with adrenal adenomas diagnosed with nonfunctioning adrenal tumor (NFAT), MACS (based on cortisol after 1 mg dexamethasone suppression, DST>1.8 mcg/dl) or overt Cushing syndrome (CS). Exclusion criteria were malignancy, exogenous steroid use, bone disease from other causes or receiving therapy for osteoporosis. Osteocalcin, Procollagen I Intact N-Terminal (PINP), C-terminal telopeptide (CTX), and Sclerostin were measured blinded to diagnosis. Ten patients had paired measurements of BTMs before and after adrenalectomy (2 CS, 5 MACS, 3 NFAT). Results: Of 213 patients with adrenal adenomas, CS was diagnosed in 22, MACS in 92 (median DST of 3mcg/dl [1.9-16]) and NFAT in 99, (median DST of 1.2mcg/dl [0.9-1.8]). Median age was 58 years (range, 18-93), 67% were women, median BMI was 31 kg/m(2)(range, 15-53) and median tumor size was 2.5 cm (range, 0.5-14.4). Bone disease was diagnosed in 41% vs 42% vs 23% (P=0.001), osteoporosis in 18% vs 13% vs 6% (P=0.1) and osteopenia in 23% vs 29% vs 17% (P=0.13) of patients with CS, MACS and NFAT, respectively. DST > 1.8 mcg/dl was a significant predictor of bone disease after adjusting for age, sex, and BMI (OR 2.7, P=0.006). Severity of cortisol excess was inversely associated with BTM values; for CS vs MACS vs NFAT: Osteocalcin (median 10 [2.2-80] vs 17 [5-54] vs 19 [2-79] ng/mL (P<0.0001)), PINP (median 29 [12-92] vs 43 [13-123] vs 46 [3-152] µg/L (P=0.003)) and Sclerostin (median 381 [73-935] vs 498 [111-2000] vs 571 [202-1273] ng/L , (P<0.0001)). In MACS patients, Sclerostin was a significant predictor of bone disease in a multivariable model of age, sex, BMI, DST cortisol and BTMs (OR 0.77 [CI95% 0.6-0.99] for each 100 ng/L of sclerostin increase, P=0.03). In 10 patients with available BTM measurements after adrenalectomy, Osteocalcin and CTX increased significantly by mean difference of 11.01 ng/mL (SEM=3.63, P= 0.001) and 0.17 ng/mL (SEM= 0.08, P=0.03), respectively. Conclusion: DST>1.8 mcg/dL significantly predicts bone disease in patients with adrenal adenomas. Sclerostin (secreted by osteocytes only) was decreased in MACS patients and predicted bone disease independent of DST cortisol. Thus, mild chronic hypercortisolism affects osteocyte function, a possible underlying mechanism of bone disease in MACS. Increase in BTMs post-adrenalectomy suggests restoration of favorable bone metabolism.