Cardiometabolic benefits after adrenalectomy for mild autonomous cortisol secretion.

Background

Mild autonomous cortisol secretion causes substantial cardiometabolic morbidity, yet evidence for benefits following adrenalectomy remains mixed. Prior studies are limited by small sample sizes and heterogeneous definitions. This study evaluates the metabolic impact of adrenalectomy compared with nonoperative management in mild autonomous cortisol secretion using standardized biochemical criteria from the Epic Cosmos database.

Methods

Mild autonomous cortisol secretion was defined biochemically using dexamethasone suppression test cortisol 1.8-10 μg/dL, dexamethasone, and adrenocorticotropic hormone levels. Surgical patients underwent unilateral adrenalectomy with biochemical resolution of hypercortisolism. Inverse probability of treatment weighting was performed, adjusting for demographics, baseline cardiometabolic parameters, dexamethasone suppression test cortisol level, and glucagon-like peptide-1 receptor agonist use. The starting time point was the adrenalectomy date or, for nonoperative patients, the dexamethasone suppression test date plus the median time to surgery. Follow-up outcomes (A1C, lipid profile, body mass index, and blood pressure) were assessed for categorical improvement at last follow-up within 3 years using a weighted logistic regression model.

Results

From 2018 to 2025, 395 patients met inclusion criteria (54 surgical, 341 nonoperative). Surgical patients had a higher adjusted likelihood of categorical improvements in A1C (25.6% vs 9.5%, odds ratio, 3.30; P = .002), total cholesterol (14.6% vs 3.9%, odds ratio, 4.25; P = .004), and body mass index (24.9% vs 12.1%, odds ratio, 2.42; P = .018). There were no differences in blood pressure between groups (28.4% vs 26.7%, odds ratio, 1.09; P = .803).

Conclusion

This is the largest cohort study to date evaluating metabolic outcomes after surgery for mild autonomous cortisol secretion. Adrenalectomy was associated with categorical improvement in A1C, body mass index, and total cholesterol, supporting more widespread consideration for selective operative management.