NEW SCREENING CUTOFF VALUES FOR DETECTION OF ALDOSTERONOMA EXAMINED BY LC-MS/MS AND NEWLY DEVELOPED NON-COMPETITIVE CLEIA

Abstract

Objective: Thinking of the poor accuracy of conventional CLEIA measurements of aldosterone, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the ideal method but it is costly, labor intensive and time consuming. A novel non-competitive chemiluminescent enzyme immunoassay (sandwich assay) (NC-CLEIA) for measuring aldosterone was recently developed. We validated the accuracy and diagnostic ability of the NC-CLEIA and compared the results obtained with those by LC-MS/MS and also determined the new screen cutoffs by both measurements, respectively, detecting aldosterone-prodcuing adenoma (APA) in hypertensive patients. Design and method: We measured plasma renin activity by enzyme assay and plasma aldosterone concentrations (PAC) using LC-MS/MS and NC-CLEIA in 133 APA, 100 bilateral hyperaldosteronism and 111 essential hypertension patients to examine the accuracy of the values of PAC measured by this new NC--CLEIA as compared with those by LC-MS/MS, and determine the new screen cutoff values by both measurements to detect APA, respectively. Results: Passing-Bablok analysis revealed that NC-CLEIA (regression slope, intercept and correlation coefficient were 0.962, -0.043, and 0.994, respectively), was significantly correlated and equivalent to LC-MS/MS than RIA. Bland-Altman plot analysis of NC-CLEIA by LC-MS/MS also demonstrated much smaller systemic errors (a bias of -0.348 ng/dL with limits of agreement of -4.390 and 3.694 and 95% confidence interval). The receiver-operating characteristics analysis demonstrated that cut-off values of 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 a specificity of 75.4% and 76.8%, respectively, in terms of discriminating APA from non-APA. Therefore, we can recommend an ARR > 30.0 ng/dL per ng/mL/hr as a screening cut-off by both LC-MS/MS and NC-CLEIA, which would discriminate APA with a sensitivity of 91.7% in both assays, and with a specificity of 73.0% and 73.9 %, respectively. Conclusions: This novel NC-CLEIA assay for PAC could serve as a clinically reliable alternative to LC-MS/MS to detect APA among hypertensive patients with more accuracy than the conventional methods.