Assessing Lateralization Index of Adrenal Venous Sampling for Surgical Indication in Primary Aldosteronism

Context: Clinical practice guidelines recommend the lateralization index (LI) as the standard for determining surgical eligibility in primary aldosteronism (PA). Objective: Our goal was to identify the optimal LI cutoffs in adrenal venous sampling (AVS) for diagnosing PA that is amenable to surgical cure. Methods: We conducted a retrospective international cohort study across 16 institutions in 11 countries, including 1550 patients with PA who underwent AVS, with and/or without adrenocorticotropin (ACTH) stimulation. The establishment of optimal cutoffs was informed by a survey of 82 patients with PA in Japan, aimed at determining the LI cutoff aligned with patient expectations for a surgical cure rate. Results: The survey revealed that a median cure rate expectation of 80% would motivate patients with PA towards undergoing adrenalectomy. The optimal LI cutoffs achieving an adjusted positive predictive value (PPV) of 80% were identified as 3.8 for unstimulated AVS and 3.4 for ACTH-stimulated AVS. Furthermore, a contralateral ratio of less than 0.4 and the detection of an adrenal nodule on computed tomography imaging were identified as independent predictors of surgically curable PA. Incorporating these factors with the optimal LI cutoffs, the adjusted PPV increased to 96.6% for unstimulated AVS and 89.6% for ACTH-stimulated AVS. No clear differences in predictive ability between unstimulated and ACTH-stimulated LI were found. Conclusion: The present study clarified the optimal LI cutoffs for without and with ACTH stimulation. The presence of contralateral suppression and adrenal nodule on CT imaging seems to provide additional available information besides LI for surgical indication.