Screening Cutoff Values for the Detection of Aldosterone Producing Adenoma by LC-MS/MS and a Nobel Non-competitive CLEIA

Abstract Context Detecting patients with surgically curable aldosterone-producing adenoma (APA) among hypertensive subjects is clinically pivotal. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the ideal method of measuring plasma aldosterone concentration (PAC) because of the inaccuracy of conventional chemiluminescent enzyme immunoassay (CLEIA). However, LC-MS/MS is expensive and requires expertise. We have developed a novel non-competitive CLEIA (NC-CLEIA) for measuring PAC in 30 min. Objective To validate NC-CLEIA PAC measurements by comparing them with LC-MS/MS measurements and determining screening cutoffs for both measurements detecting APA. Method We retrospectively measured PAC using LC-MS/MS and NC-CLEIA in 133 patients with APA, 100 with bilateral hyperaldosteronism, and 111 with essential hypertension to explore the accuracy of NC-CLEIA PAC measurements by comparing with LC-MS/MS measurements and determined the cutoffs for detecting APA. Results Passing-Bablok analysis revealed that the values by NC-CLEIA (the regression slope, intercept, and correlation coefficient were 0.962, -0.043, and 0.994, respectively) were significantly correlated and equivalent to those by LC-MS/MS. Bland-Altman plot analysis of NC-CLEIA and LC-MS/MS also demonstrated smaller systemic errors (a bias of -0.348 ng/dL with limits of agreement of -4.390 and 3.694 within a 95% confidence interval) in NC-CLEIA than LC-MS/MS. The receiver-operating characteristic analysis demonstrated that cutoff values for aldosterone/renin activity ratio obtained by LC-MS/MS and NC-CLEIA were 31.2 and 31.5 (ng/dL per ng/mL/hr), with a sensitivity of 91.0% and 90.2% and specificity of 75.4% and 76.8%, respectively, to differentiate APA from non-APA. Conclusion This newly developed NC-CLEIA for measuring PAC could serve as a clinically reliable alternative to LC-MS/MS.