Evaluation of Current Screening Thresholds for the Detection of Primary Aldosteronism

BACKGROUND: In 2025, the Endocrine Society (ES) updated the guidelines for primary aldosteronism (PA), introducing more inclusive diagnostic criteria: plasma renin activity (PRA) ≤1 ng/mL per hour, plasma aldosterone concentration (PAC) ≥7.5 ng/dL by liquid chromatography–tandem mass spectrometry, and aldosterone-to-renin ratio >15. We compared PA positivity by comparing these updated criteria against broader permissive criteria (PRA <1 ng/mL per hour, PAC >5 ng/dL, without an aldosterone-to-renin ratio requirement). METHODS: We retrospectively analyzed deidentified adults with PRA and PAC measurements between January and August 2025. Patients were categorized by ES versus permissive criteria. Biochemical and clinical characteristics were compared. RESULTS: Of 60 449 patients, 13.0% (n=7883) met ES screening criteria for PA versus 26.2% (n=15 872) by permissive criteria. Among the 8006 (13.2%) permissive-positive/ES-negative patients, 6325 did not meet ES criteria due to PAC 5 to 7.5 ng/dL, despite 55.2% having a PRA <0.5 ng/mL per hour. An additional 1681 patients were excluded by ES criteria because the aldosterone-to-renin ratio was ≤15, despite a median PAC of 9.00 (8–10) ng/dL. Among permissive-positive/ES-negative patients, PRA ≤ 0.25 ng/mL per hour was associated with higher odds of atrial fibrillation (odds ratio, 2.38; P =0.004), hypertension (odds ratio, 1.27; P =0.0002) and hypokalemia (K<3.5; odds ratio, 1.66; P =0.0012). CONCLUSIONS: Current ES thresholds potentially exclude PA cases with a biochemical phenotype consistent with milder or earlier renin-independent aldosterone production. If validated in cohorts with comprehensive clinical data, the biochemical definition of PA may need to expand to include a greater proportion of individuals with renin-independent aldosterone production.