Glucocorticoid replacement duration after unilateral adrenalectomy for mild autonomous cortisol secretion and adrenal Cushing syndrome: a multicenter cohort study

OBJECTIVE: Data on hypothalamic-pituitary-adrenal axis (HPAA) recovery after adrenalectomy are limited by small samples, heterogeneous criteria, and no distinction between mild autonomous cortisol secretion (MACS) and adrenal Cushing syndrome (CS). We investigated HPAA recovery duration and associated factors separately in MACS and adrenal CS. DESIGN: Retrospective, multicenter cohort. METHODS: We analyzed 139 adults with MACS and 280 with adrenal CS who underwent unilateral adrenalectomy and required postoperative glucocorticoid replacement. HPAA recovery was defined as discontinuation of glucocorticoids. Associated factors were evaluated using Cox proportional hazards models and restricted mean survival time (RMST) regression. RESULTS: The Kaplan-Meier-estimated median (95% confidence interval) time to recovery was 8.2 (6.5-9.7) months in MACS and 14.8 (13.2-16.3) months in adrenal CS. In MACS, older age [hazard ratio (HR) = 0.72 per 10 years; +94 days for >61 years, τ = 540 days] and cortisol after 1-mg overnight dexamethasone suppression test [post-overnight dexamethasone suppression test (ODST) cortisol] > 10.0 µg/dL (+113 days) were associated with delayed recovery, whereas higher dehydroepiandrosterone-sulfate ratio (HR = 1.50 per log-unit; -91 days for >0.61) and adrenocorticotropic hormone (ACTH) (HR = 1.61 per log-unit) were associated with faster recovery. In adrenal CS, older age (HR = 0.74 per 10 years; +198 days for >36 years, τ = 1095 days), higher glycated hemoglobin (HR = 0.81 per 1%), and post-ODST cortisol >7.9 µg/dL (+364 days) were associated with delayed recovery, whereas higher ACTH (HR = 1.27 per log-unit; -130 days for >5.1 pg/mL) was associated with faster recovery. CONCLUSIONS: Older age was consistently associated with delayed recovery, while biochemical markers contributed differentially by disease subtypes.