Aldosterone synthase expression vs cross-sectional imaging in lateralized primary aldosteronism

Adrenal vein sampling 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.

Single referral-center retrospective cohort study of patients with PA who underwent unilateral adrenalectomy between 2012 and 2024. Blinded cross-sectional imaging interpretation was corroborated with aldosterone synthase (CYP11B2) immunohistochemistry (IHC) of formalin-fixed paraffin-embedded adrenal tissue.

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 nonfunctional 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.

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.