Mortality and clinical outcomes in patients with mild autonomous cortisol secretion: Adrenalectomy versus nonoperative management.

Abstract

Mild autonomous cortisol secretion (MACS) is the most common hormonal abnormality in adrenal incidentalomas, but the benefits of adrenalectomy remain unclear. We conducted a retrospective cohort study using a multi-institutional database (2011-2024) to analyze patients with adrenal incidentalomas and mild autonomous cortisol secretion, defined as cortisol levels between 1.8 and 5 μg/dL after a 1 mg dexamethasone suppression test. Cox proportional hazards models with propensity score matching for demographic and comorbidities were used to compare hazard ratios and 95% confidence intervals for mortality and metabolic outcomes between adrenalectomy and nonoperative management. We identified 1,954 patients with mild autonomous cortisol secretion. Among them, 296 (15.1%) underwent adrenalectomy, whereas 1,658 (84.9%) received nonoperative management. After 1:1 propensity score matching, 291 patients remained in each group with balanced baseline characteristics. The cohort was predominantly female (64.9%) and White (71.1%), with a mean age of 62 ± 13 years. The mean follow-up duration was 1,367 ± 1,185 days in the adrenalectomy group and 1,315 ± 1,227 days in the nonoperative group. Adrenalectomy was associated with a lower hazard of mortality (hazard ratio, 0.34; 95% confidence interval, 0.27-0.36) and new-onset diabetes (hazard ratio, 0.49; 95% confidence interval, 0.25-0.97). No significant differences were observed in the incidence of cerebral infarction (hazard ratio, 0.58; 95% confidence interval, 0.24-1.43), ischemic heart disease (hazard ratio, 0.83; 95% confidence interval, 0.54-1.28), fractures (hazard ratio, 0.72; 95% confidence interval, 0.37-1.41), or hypertension (hazard ratio, 1.23; 95% confidence interval, 0.79-1.93). However, in a sensitivity analysis excluding patients with adrenocorticotropic hormone >20 pg/mL, adrenalectomy was not associated with a survival benefit. Adrenalectomy in mild autonomous cortisol secretion patients with cortisol levels between 1.8 and 5 μg/dL after a 1-mg dexamethasone suppression test is associated with reduced mortality and a lower risk of new-onset diabetes.