Beyond the Lateralization Threshold: Outcomes in Primary Aldosteronism with Borderline Adrenal Vein Sampling Lateralization Index

Background: A lateralization index (LI) ≥4 on adrenal vein sampling (AVS) commonly distinguishes unilateral primary aldosteronism treated surgically from bilateral disease treated medically. Whether patients with LI<4 benefit from adrenalectomy remains uncertain. We evaluated clinical outcomes after surgical versus medical management across LI-defined groups. Study Design: We performed a retrospective cohort study of patients with primary aldosteronism undergoing AVS from 2002–2022. Patients were classified as Classic Medical (CM; LI<4 without adrenalectomy, n=101), Classic Surgical (CS; LI≥4 with adrenalectomy, n=367), or Non-Classic Surgical (NCS; LI<4 with adrenalectomy, n=23). Outcomes were systolic blood pressure (SBP) and antihypertensive medication number at 6–12 months. Inverse probability treatment weighting (IPTW) and propensity score matching (PSM) compared NCS with CM. Results: Among 491 patients, NCS patients were younger and more frequently male than CS and CM patients. Baseline SBP and hypertension duration did not differ across groups. Adrenalectomy was associated with greater antihypertensive medication reduction (p<0.001), greatest among NCS patients. After IPTW, NCS was associated with a greater medication reduction than CM (−0.88, 95% CI −1.64 to −0.13, p=0.022), without a significant difference in SBP. PSM sensitivity analysis confirmed these findings. Conclusions: In selected patients with primary aldosteronism and LI<4, adrenalectomy was associated with reduced antihypertensive medication burden compared with medical management. These findings support individualized surgical consideration beyond a strict LI≥4 threshold.