Association of the Primary Aldosteronism Severity Classification with Lateralization and Treatment Outcomes

CONTEXT: The 2025 clinical guideline for primary aldosteronism (PA) recommends a diagnostic and therapeutic pathway stratified by lateralization risk. The PA severity classification (PASC) integrates biochemical and clinical features and is intended to inform graded recommendations for adrenal venous sampling (AVS). OBJECTIVE: We examined whether PASC is associated with AVS-defined lateralization and treatment outcomes. DESIGN: A retrospective multicenter cohort study. SETTING: Eight tertiary centers. PATIENTS: A total of 833 patients with PA who underwent AVS. PASC severity was classified as mild, moderate, or severe. MAIN OUTCOME MEASURES: We evaluated associations between severity, AVS-defined lateralization, and outcomes using the Primary Aldosteronism Surgical Outcome (PASO) and Primary Aldosteronism Medical Treatment Outcome (PAMO) criteria. RESULTS: Among 833 patients, 52 (6.1%), 563 (67.6%) and 218 (26.2%) had mild, moderate, and severe PA, respectively. Higher severity was associated with a stepwise increase in AVS-defined lateralizing PA (19.2%, 48.0%, and 76.1%, respectively; p < 0.001). In unilateral PA treated surgically, PASO clinical outcomes differed by severity (p = 0.002), with complete clinical success in 40.2% (moderate) and 31.3% (severe), and a marked increase in partial clinical success in severe disease (55.1%). PASO biochemical outcomes were similar across severity groups (p = 0.389). In bilateral PA treated medically, PAMO clinical outcomes varied by severity (p = 0.005), with complete clinical response decreasing from mild to severe disease (36.8%, 27.0%, and 8.8%), whereas biochemical outcomes were comparable (p = 0.993). CONCLUSIONS: PASC-defined severity correlated with AVS-defined lateralization. Greater severity was associated with lower rates of complete clinical success/response despite preserved biochemical outcomes, supporting a severity-informed framework to complement AVS in PA management.