MON-288 Aldosterone Response to Cosyntropin Stimulation in the Non-dominant Adrenal Predicts Postoperative Outcomes in Primary Aldosteronism

Abstract Disclosure: P. Vibhatavata: None. J. Shields: None. J. Rege: None. A. Udager: None. W.E. Rainey: None. A. Turcu: None. Background: In patients with primary aldosteronism (PA), adrenal vein sampling (AVS) is commonly used to direct surgical vs. medical therapy. Cosyntropin [ACTH N-terminal 24 amino acids (1–24)] stimulation boosts the confidence of successful adrenal vein (AV) catheterization, by amplifying the AV-peripheral cortisol gradient. In addition, both normal zona glomerulosa cells and autonomous aldosterone sources respond acutely to cosyntropin stimulation, due to variable expression of ACTH receptors (MC2R). We hypothesized that cosyntropin exposes the reserve of aldosterone-producing cells in the non-dominant adrenal gland. Objective: To assess the association between contralateral aldosterone response to cosyntropin during AVS and post-operative outcomes. Methods: Patients with PA who underwent successful AVS both before and after cosyntropin stimulation between January 2015 and December 2024 in a tertiary-referral center were included. The aldosterone reserve in the non-dominant adrenal gland was assessed with: 1. Contralateral Aldosterone Reserve Ratio (CARR), defined by a ratio of aldosterone in the non-dominant AV post-cosyntropin/baseline; and 2. Lateralization Index Ratio (LIR= LIpost-cosyntropin : LIbaseline). CYP11B2-guided aldosterone-driver mutations and postoperative outcomes were assessed in available cases. Results: In total, 434 patients (57% men), with mean age of 53 + 12 years, 66% White, and 25% Black were included. AVS lateralization (LI ≥4) occurred only at baseline in 52 (12%) of patients (Unilateral/Bilateral; UB), only after cosyntropin in 46 (11%, BU), and in both protocols in 166 (38%, UU); 170 (39%) patients had bilateral PA (BB). Aldosterone reserve in the non-dominant adrenal was similarly high in UB and BB cases (high CARR, low LIR), while BU and UU patients had lower CARR and higher LIR. Of 169 patients treated with adrenalectomy, 78% had persistent hypertension, and 15% had residual PA. Median CARR increased gradually from patients with PA cure (4.9; IQR 2.5-9.4), to those without cure (11.2; IQR 5.0-23.5), and to bilateral PA (17.9; IQR 9.1-32.0, p<0.01). Conversely, LIR decreased progressively across these groups. CARR was higher in Black vs. White individuals, in those older than 45 years vs. younger individuals, and in those with CACNA1D vs. other aldosterone-driver mutations. ROC curves analysis showed that CARR and post-cosyntropin LI were predictive of residual PA (AUC=0.73, p<0.001 for both), while baseline LI and LIR were not useful predictors of postoperative outcomes. Conclusion: Cosyntropin stimulation during AVS unveils the aldosterone reserve in the non-dominant adrenal gland, exposing the risk of residual disease after adrenalectomy. Presentation: Monday, July 14, 2025