Aldosterone Synthase Expression vs. Cross-Sectional Imaging in Lateralized Primary Aldosteronism

CONTEXT: Adrenal vein sampling (AVS) is the standard of care for guiding surgery in primary aldosteronism (PA). Because of its technical complexity and limited availability, however, many centers still use cross-sectional imaging for surgical guidance. DESIGN: Single referral-center retrospective cohort study of patients with PA who underwent unilateral adrenalectomy between 2012-2024. Blinded cross-sectional imaging interpretation was corroborated with CYP11B2 immunohistochemistry (IHC) of formalin-fixed paraffin-embedded adrenal tissue. RESULTS: Of 173 patients, age 52.6±11.8 years, 119 (68.8%) were men, 134 (77.5%) White, 30 (17.3%) Black, and 9 (5.2%) other races. CYP11B2 IHC identified a single aldosterone-producing adenoma (APA) or nodule (APN) in 87 (50.3%) and 38 (22.0%) patients, respectively; multiple CYP11B2-positive foci in 45 (26.0%) patients, and no CYP11B2-positive lesions in 3 patients. A single corresponding APA or APN on both IHC and imaging was found in only 53/173 (31%) patients, and an additional 38/173 (22%) patients also had adrenal thickening. Discrepant IHC-imaging findings were observed in 82 (47.4%) patients, including: 1) additional nodule(s) on imaging (ipsilateral non-functional adenoma, n=21; bilateral nodules, n=29; or contralateral nodule(s), n=6); 2) normal adrenals (n=2) or unilateral adrenal hyperplasia (n=4), but discrete CYP11B2-positive foci on IHC; and 3) corresponding APA/APN on imaging-IHC with additional CYP11B2-positive area(s) (n=20). Patients with IHC-imaging concordance had the highest proportion of women and KCNJ5 mutations, while CACNA1D mutations were most frequent in the discordant group. CONCLUSIONS: Even in patients with lateralized PA, IHC mapping of aldosterone sources corresponded with imaging findings in approximately half of the cases. These data caution against targeted therapy guided by cross-sectional imaging.