MON-505 - Skeletal Health in Endogenous Hypercortisolism: Baseline Characteristics and Early Changes Following Treatment

Background
Endogenous hypercortisolism is associated with adverse skeletal outcomes, yet comparative baseline bone characteristics and early post-treatment trajectories across cortisol excess phenotypes remain incompletely defined.

Objective
To characterize baseline bone health and early longitudinal changes following treatment in patients with overt Cushing syndrome (CS) and mild autonomous cortisol secretion (MACS).

Design and Participants
Prospective cohort study of patients with CS or MACS achieving sustained surgical remission and undergoing baseline and follow-up dual-energy X-ray absorptiometry (DXA) with trabecular bone score (TBS) measurement.

Main Outcomes and Measures
Bone mineral density (BMD) at lumbar spine, total hip, femoral neck, and forearm, and TBS, assessed at baseline and 8–18 months following treatment. Multivariable analyses evaluated predictors of change in TBS.

Results
A total of 223 patients (n=100 with CS and n=123 with MACS) with endogenous hypercortisolism were enrolled. Patients with CS were younger than those with MACS (median age 46 [IQR 38–57] vs 59 [50–68] years; P< 0.001), with similar sex distribution. CS was associated with greater clinical and biochemical severity (P < 0.001 for both). Postoperative glucocorticoid therapy was more common in CS (87% vs 62%).
At baseline, BMD did not differ between groups at any skeletal site. However, TBS was lower in CS compared with MACS (median [IQR] 1.3 [1.3–1.4] vs 1.4 [1.3–1.5]; P=0.016), indicating a more impaired bone microarchitecture despite similar BMD.
Longitudinal follow-up was available in 45 patients (27 CS, 18 MACS). At 8–18 months post-treatment, femoral neck BMD decreased modestly (median change −0.03 g/cm² [IQR −0.05 to 0.01]; P=0.008), while TBS improved (median change +0.04 [−0.01 to 0.10]; P=0.005). In multivariable analysis, adjusting for age, BMI, time from surgery, and biochemical severity, higher baseline biochemical severity was independently associated with greater improvement in TBS (β 0.01; 95% CI 0.00–0.03; P=0.04).

Conclusions
Despite similar BMD, patients with CS exhibit greater baseline impairment in bone microarchitecture than those with MACS. Following treatment, early improvements in TBS occur alongside modest declines in femoral neck BMD, suggesting differential recovery of bone quality versus density. Greater baseline biochemical severity predicts more pronounced microarchitectural improvement, highlighting the dynamic skeletal response to resolution of hypercortisolism.

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