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.