SUN-240 High Discordance between Imaging and Aldosterone Synthase Immunohistochemistry in Lateralized Primary Aldosteronism

Abstract Disclosure: L.M. Mermejo: None. Y. Liu: None. E. Caoili: None. D. Rooyen: None. J. Rege: None. T. Giordano: None. W. Rainey: None. A.F. Turcu: None. Background: Primary aldosteronism (PA) can originate in one or both adrenal glands. The classic PA subtypes, aldosterone-producing adenomas (APA) and bilateral adrenal hyperplasia, emerged from morphological findings on cross-sectional imaging and histology. The use of highly specific antibodies against human aldosterone synthase (CYP11B2) has revealed that aldosterone sources often do not correspond with morphological findings. Emerging molecular imaging for PA subtyping use radioisotopes that are not specific to APA and rely on correspondence with nodules identified on cross-sectional imaging. Objective: To corroborate cross-sectional imaging findings with CYP11B2 immunohistochemistry (IHC) in patients with PA who underwent adrenal vein sampling-guided adrenalectomy. Methods: This single, referral center study included consecutive patients with PA who underwent unilateral adrenalectomy between 2012-2024 if both cross-sectional imaging and formalin-fixed paraffin-embedded (FFPE) adrenal tissue were available. Hematoxylin-eosin, CYP11B2, and 17α-hydroxylase/17,20-lyase (CYP17A1) IHC were performed on 5 µm FFPE tissue sections. Radiologic studies were reviewed by an expert radiologist, who was blinded to clinical and IHC data. Results: The cohort included 133 patients, 91 (68.4%) men, with mean age 51±12 years; 103 (77.4%) White, 23 (17.3%) Black, and 3 (2.3%) Asian. We observed single APA or aldosterone-producing nodules on both IHC and imaging in 68 (51.1%) patients; corresponding APA on imaging and IHC, but with additional CYP11B2-positive areas in 19 (14.3%) patients; corresponding IHC and imaging nodules in the removed adrenal, but additional nodules/enlargement of the other adrenal gland in 25 (18.8%) patients; adrenal hyperplasia on imaging/histology, but discrete CYP11B2-positive nodules in 13 (9.8%) patients. In 25 (18.8%) patients, the dominant nodule identified on imaging was CYP11B2 negative. Patients with discrepant IHC-imaging findings were more often Black (24.6% vs. 10.3%) and had a higher proportion of CACNA1D mutations (58.8% vs. 31.0%) compared to those with concordant imaging-IHC. Conversely, KCNJ5 mutations and ATPase mutations were more prevalent in patients with concordant imaging-IHC findings (27.6% vs. 13.7%, and 36.2% vs. 19.6%, respectively). Lack of biochemical cure following adrenalectomy was more frequent in patients with discrepant vs. concordant IHC-imaging findings (31.7% vs. 15.6%). Conclusions: Even in patients with lateralized PA, functional mapping of aldosterone sources corresponded with radiologic findings in only half of the cases. Discordant CYP11B2-imaging findings were more frequent in Black individuals and in those harboring CACNA1D aldosterone-driver mutations. Non-specific molecular imaging agents designed for PA subtyping should recognize the limited value of cross-sectional imaging. Presentation: Sunday, July 13, 2025