KCNJ5 -Negative Primary Aldosteronism: Histopathology and Surgical Outcomes

BACKGROUND: Unilateral primary aldosteronism (uPA) is the most common surgically curable secondary hypertension. KCNJ5 mutations are frequent in aldosterone-producing adenomas, but the clinical significance of KCNJ5 -negative uPA remains unclear. We investigated whether histopathologic subtypes defined by the HISTALDO (Histopathology of Primary Aldosteronism) consensus are associated with postoperative outcomes in KCNJ5 -negative uPA. METHODS: We analyzed 171 KCNJ5 -negative uPA patients from the Taiwan Primary Aldosteronism Investigation registry who underwent adrenalectomy. Somatic mutations were identified by Sanger sequencing and targeted next-generation sequencing. Adrenal histopathology was classified as classical (solitary adenoma or dominant nodule) or nonclassical (multiple nodules, micronodules, or diffuse hyperplasia) per the HISTALDO criteria. Postsurgical outcomes at 12 months were assessed using the Primary Aldosteronism Surgical Outcome consensus criteria. RESULTS: The cohort (mean age, 55.0±11.3 years; 53.8% women) comprised 90 (52.6%) patients with classical histopathology and 81 (47.4%) with nonclassical features. Complete clinical success was achieved in 40.9% of patients at 12 months. Patients with classical histopathology had significantly higher complete clinical success (50%) than those with nonclassical histopathology (30.9%; P =0.01). On multivariate analysis, nonclassical histopathology (odds ratio, 0.33 [95% CI, 0.16–0.68]; P =0.003), higher preoperative serum creatinine (odds ratio, 0.24; P =0.022), and higher diastolic blood pressure (odds ratio, 0.97; P =0.017) independently predicted failure to achieve complete clinical success. CONCLUSIONS: Nearly half of KCNJ5 -negative uPA cases exhibit nonclassical adrenal histopathology, which is associated with significantly lower complete clinical success rates. These findings underscore the prognostic value of histopathologic classification in KCNJ5 -negative uPA and support integrating histology and genetics to improve patient management.