SAT-556 Use of ACTH-Stimulated Lateralization Indices Underestimates Surgically Curable Primary Aldosteronism

Introduction: Adrenal venous sampling (AVS) is recommended to assess laterality in primary aldosteronism to determine whether a patient has unilateral, or surgically curable, disease. Institutional practices differ in whether ACTH stimulation is used or not and if so, whether values are obtained after a single injection of ACTH or during an ACTH infusion. Studies have demonstrated appreciable discordance between lateralization based on unstimulated versus stimulated AVS. Objective: To assess the influence of ACTH-stimulation on lateralization indices. Methods: We performed a retrospective cross-sectional analysis of 140 patients who underwent AVS between 2012–2019. We then validated these findings in a separate cohort of 233 patients who underwent AVS between 2008–2016. AVS was performed using simultaneous, unstimulated, and triplicate sampling from the inferior vena cava (IVC) and bilateral adrenal veins, followed by repeated sampling in duplicate or triplicate from each site following a bolus of 250 ug of ACTH (cosyntropin). The lateralization index (LI) was defined as the quotient of the aldosterone-to-cortisol ratios from each adrenal vein, and the categorical definition of lateralization was defined as a LI ≥ 2 (unstimulated) and LI ≥ 4 post-ACTH. Results: The median unstimulated LI was 8.7 compared to 8.9 post-ACTH. Seventy-one of 140 patients (51%) had a decrease in LI following the ACTH bolus. Overall lateralization discordance was 21.4%, with the majority of this discordance (90%) attributed to situations where there was an unstimulated LI ≥ 2 that became a post-ACTH LI < 4, thereby transforming a unilateral interpretation into one of bilateral disease. Comparing the group that had an increase in LI after ACTH to the group that had a decrease in LI, the latter had significantly higher rates of lateralization pre-ACTH (89% vs 74%, p=0.02) and significantly lower rates of lateralization post-ACTH (50% vs 78%, p=0.001). All of these general findings were validated in the separate cohort of 233 patients. The discordance rate between pre-ACTH lateralization and available imaging data was 32%; the same discordance rate was found when comparing post-ACTH lateralization to imaging. Conclusions: The administration of ACTH during AVS causes an increase in LI in half of patients and a decrease in LI in the other half. Using conventional cut-offs, pre-ACTH and post-ACTH lateralization indices disagree on laterality more than 20% of the time and almost always involve pre-ACTH unilateral disease that is classified as bilateral disease post-ACTH. These findings underscore that while ACTH stimulation may be useful for confirming adrenal vein selectivity, the decrease in post-ACTH LI may result in misclassification of surgically curable primary aldosteronism in a substantial proportion of patients.