Inappropriately normal aldosterone levels as the norm for hyperaldosteronism: Use of a modified aldosterone-to-renin ratio to enhance primary aldosteronism detection.

BACKGROUND: The aldosterone-to-renin ratio is the preferred screening test for primary aldosteronism, but its performance may be limited by assay variability and threshold definitions. We evaluated the aldosterone-to-renin ratio in a contemporary cohort of primary aldosteronism and nonsecretory tumors. METHODS: Patients diagnosed with primary aldosteronism were retrospectively identified at our center from January 2016 to January 2024 and compared with nonsecreting adrenal tumors. An aldosterone-to-renin ratio of 5.7 ng/dL/ng/L was used based on previously established thresholds. Plasma aldosterone and direct renin concentration were plotted to determine optimal differentiation between groups. Receiver operating characteristic curve analysis was used to determine optimal performance. RESULTS: Of 169 patients included, 100 had primary aldosteronism (70 unilateral, 30 bilateral) and 69 had nonsecreting tumors. Scatterplot analysis demonstrated 2 distinct biochemical zones separating primary aldosteronism from non-primary aldosteronism patients. Sixty-seven percent with primary aldosteronism had plasma aldosterone <30 ng/dL (45% with a more conservative limit of 20 ng/dL). A guideline-based aldosterone-to-renin ratio cutoff of 5.7 yielded a 73.5% sensitivity and 100% specificity (area under the curve, 0.984; 95% confidence interval, 0.972-0.995). Using a modified formula (aldosterone-to-renin ratio of 4.0, correction factor of 1.8 to plasma aldosterone), sensitivity improved to 93.5% with a specificity of 93.0% (area under the curve, 0.981; 95% confidence interval, 0.968-0.994), although discernment between models did not achieve significance (P = .07). CONCLUSION: Aldosterone-to-renin ratio demonstrates reasonable effectiveness in distinguishing primary aldosteronism from nonsecreting tumors in a modern cohort. As elevated aldosterone levels were seen in a minority of patients, suppressed renin was key in establishing a diagnosis. Modifying the classic aldosterone-to-renin ratio formula increased sensitivity without compromising specificity, which may help with diagnosing nonclassic primary aldosteronism presentations.