Cosyntropin-Stimulated Aldosterone Reserve of the Nondominant Adrenal Predicts Surgical Outcomes in Primary Aldosteronism.

BACKGROUND Adrenal vein sampling (AVS) is commonly used to direct therapy of primary aldosteronism (PA). We hypothesized that cosyntropin stimulation during AVS exposes the reserve of aldosterone-producing cells in the nondominant adrenal gland and might predict postoperative outcomes. METHODS Patients with PA who underwent successful AVS before and after cosyntropin stimulation between January 2015 and December 2024 in a tertiary-referral center were included. The nondominant adrenal aldosterone reserve was assessed with (1) contralateral aldosterone reserve ratio (=aldosterone postcosyntropin-to-baseline ratio in the nondominant adrenal vein) and (2) lateralization index (LI) ratio (=LIpost-cosyntropin/LIbaseline). Lateralization was based on LI ≥4. RESULTS Four hundred thirty-four patients (57% men; mean age, 53±12 years) were included. AVS lateralized only at baseline in 52 (12%) patients, only after cosyntropin in 46 (11%), and in both protocols in 166 (38%); 170 (39%) patients had bilateral PA. PA severity decreased from cases lateralized in both protocols, to postcosyntropin only, baseline only, and consistently bilateral; conversely, the contralateral aldosterone reserve increased across these groups. The contralateral aldosterone reserve was higher in patients without PA cure and bilateral PA (median [interquartile range], 11.2 [5.0-23.5] and 17.9 [9.1-32.0], respectively, versus 4.9 [2.5-9.4] in those cured; P<0.01) and in Black individuals, those aged ≥45 years, and with CACNA1D mutations. Contralateral aldosterone reserve and postcosyntropin lateralization and contralateral suppression were predictive of residual PA, while baseline parameters were not. CONCLUSIONS Cosyntropin stimulation during AVS unveils the aldosterone reserve in the nondominant adrenal gland, exposing the risk of residual disease after adrenalectomy.