Impact of mild autonomous cortisol secretion on bone density, metabolism, and microstructure: a cross-sectional study

CONTEXT: Patients with mild autonomous cortisol secretion (MACS) have higher rates of vertebral fractures compared to patients with non-functioning adrenal nodules, yet bone density is not always reduced. OBJECTIVE: To characterize the effect of MACS on bone density, metabolism, and microstructure as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). DESIGN: Cross-sectional study, 2019-2022. SETTING: Tertiary referral center. PARTICIPANTS: 75 patients with MACS and 75 age-, sex-, and gonadal status matched referent subjects. MEASUREMENTS: Bone turnover markers, dual-energy x-ray absorptiometry (DXA) scan, and HR-pQCT. OUTCOMES: Areal and volumetric bone mineral density (aBMD, vBMD), trabecular bone score (TBS), microstructural parameters including trabecular bone volume to total volume (BV/TV) ratio. RESULTS: While no differences in aBMD were observed at any skeletal site, patients with MACS had decreased TBS (1.389 vs 1.475, P < 0.001) and lower osteocalcin concentration (17.1 vs 19.5 ng/mL, P = 0.030) than referent subjects. On HR-pQCT at the tibia, patients with MACS had reduced trabecular BV/TV (0.220 vs 0.233, P = 0.015) compared to referent subjects. On multivariable analysis, MACS was associated with lower TBS (OR per SD decrease 2.87 [1.65-5.00]), lower trabecular BV/TV at the radius (OR per SD decrease 2.58 [1.33-5.00]), and lower trabecular BV/TV at the tibia (OR per SD decrease 4.06 [2.10-7.86]). CONCLUSION: Patients with MACS have microstructural deterioration that may not be evident on routine DXA aBMD testing.