When “right” goes wrong: poor accuracy of calculated right adrenal vein aldosterone levels in subtyping primary aldosteronism

Abstract Background The purpose of this study is to externally validate a published ratio of left adrenal aldosterone to calculated-right adrenal aldosterone (Aldosterone LAV :cAldosterone RAV ) proposed to determine disease subtype when right-sided adrenal vein sampling is unsuccessful. Materials and methods This single-center retrospective study included 199 post-adrenocorticotropic hormone stimulation adrenal vein sampling cases (2016–2025). A selectivity index ≥ 5 was considered diagnostic and lateralization index ≥ 4 indicated unilateral disease. The cAldosterone RAV was calculated as cAldosterone RAV  = [2 × Aldosterone IVC  × (Cortisol LAV /Cortisol IVC )]–Aldosterone LAV . The ratio of Aldosterone LAV :cAldosterone RAV determined disease subtype; published thresholds were ≥ 3 for left-sided and ≤ 0.33 for right-sided disease. Intermediate values were deemed bilateral disease. Sensitivities and specificities of this metric were calculated using standard AVS interpretation as the gold standard reference. Receiver operating characteristic curve analysis performed on the Aldosterone LAV :cAldosterone RAV ratio derived institution-optimized thresholds by maximizing the Youden’s J statistic. Results Adrenal vein sampling was technically successful with determinate lateralization indices in 164 patients (41 left, 35 right, 88 bilateral). Using the published thresholds of 3 and 0.33, the Aldosterone LAV :cAldosterone RAV ratio had an overall accuracy of 43.3% (95% CI 35.9–50.9%). Institution-optimized thresholds of ≥ 32.43 (left-sided) and ≤ 0.56 (right-sided) improved the accuracy to 65.9% (95% CI 58.3–72.7%). Using institution-optimized thresholds, the sensitivities/specificities for the calculated right-sided, left-sided, and bilateral disease were 88.6%/95.3%, 92.7%/63.4%, and 44.3%/93.4%, respectively. Conclusions The Aldosterone LAV :cAldosterone RAV ratio can help to rule in right-sided disease with high specificity, but otherwise has poor overall accuracy in disease subtyping, underscoring the importance of meticulous technique to achieve diagnostic samples during adrenal vein sampling.