Case detection in primary aldosteronism: High-diagnostic value of the aldosterone-to-renin ratio when performed under standardized conditions

Objective: The aldosterone-to-renin ratio is widely used and is the recommended screening modality for primary aldosteronism by the Endocrine Society Guideline. However, studies on its diagnostic accuracy have been inconsistent, which is mainly because of methodological limitations. We set out to evaluate this diagnostic value by using a highly standardized study protocol, which is in line with the Endocrine Society Guideline recommendations regarding indications for screening, testing conditions and reference standards in daily clinical practice. Methods: In this prospective study, 233 consecutive patients referred to the University Medical Center Utrecht with difficult-to-control hypertension were enrolled. In addition to aldosterone-to-renin ratio measurements, all patients underwent a saline infusion test as a reference standard. A plasma aldosterone concentration greater than 280pmol/l after saline infusion was considered diagnostic for aldosteronism and the plasma renin activity was assessed to exclude patients with secondary aldosteronism from the final primary aldosteronism diagnosis. Results: Correlation of the aldosterone-to-renin ratio (cut-off >5) with primary aldosteronism diagnosis showed 16 true positive, 29 false positive, 188 true negative and 0 false negative aldosterone-to-renin ratios, resulting in a sensitivity of 100% (CI 75.9-100), specificity of 86.7% (CI 81.2-90.7), positive-predictive value of 35.6% (CI 22.3-51.3) and negative-predictive value of 100% (CI 97.5-100.0). The corresponding area under the curve was 0.933 (CI 0.900-0.966). Conclusion: These findings show that the aldosterone-to-renin ratio is a good screening modality for primary aldosteronism and is without a high risk of missing a primary aldosteronism diagnosis whenever performed under well standardized conditions.