Clinical utility of adrenal venous sampling for functional lateralization in ACTH-independent autonomous cortisol secretion: relevance in non-decisive imaging

OBJECTIVE: Determining functional laterality in adrenocorticotropic hormone (ACTH)-independent autonomous cortisol secretion remains challenging when imaging demonstrates bilateral or non-decisive adrenal findings. We evaluated whether adrenal venous sampling (AVS) improves lateralization in this clinically challenging subgroup. METHODS: In this single-center retrospective cohort study, we identified 66 patients with ACTH-independent autonomous cortisol secretion assessed between April 2016 and October 2025. Among them, 21 patients with bilateral or non-decisive imaging findings underwent successful AVS and constituted the study population. All patients underwent contrast-enhanced computed tomography (CT), adosterol scintigraphy, and AVS under low-dose dexamethasone suppression without exogenous ACTH stimulation. Postoperative remission was used as outcome-based evidence of true unilateral disease. Lateralization indices were calculated using cortisol-based and metanephrine-corrected ratios. RESULTS: Among patients with bilateral or non-decisive CT findings (n = 21), AVS identified unilateral cortisol secretion in 11 (52%). Postoperative remission was confirmed in 9 of these 11 patients (82%), supporting true unilateral disease. The median follow-up period was 4.0 years (range, 1.6-7.0 years), and remission status remained unchanged throughout follow-up. Neither adrenal size difference (2.0 mm vs 1.5 mm; p = 0.59) nor adrenal size ratio (1.11 vs 1.10; p = 0.48) on CT predicted AVS-defined lateralization. CONCLUSION: In patients with bilateral or non-decisive CT findings, AVS frequently identified surgically remediable unilateral cortisol secretion that would not have been recognized by imaging alone. These findings support the incremental diagnostic value of AVS and suggest that functional assessment should be considered when imaging alone is insufficient to determine laterality in ACTH-independent autonomous cortisol secretion.