A-081 From Immunoassays to LC-MS/MS: Re-evaluating conventional Aldosterone cut-off values for Primary Aldosteronism Screening

Background Given that the conventional aldosterone cut-offs for primary aldosteronism (PA) screening are derived from immunoassays and vary from study to study, the applicability of traditional cut-offs in patients with aldosterone detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method remains to be investigated. Thus, the study aims to compare the differences in PA screening based on traditional aldosterone cut-offs using LC-MS/MS and radioimmunoassay (RIA), respectively. Intra-individual variability and seasonal variations in aldosterone were also assessed based on cohort data. Methods Proportions of patients below traditionally adopted aldosterone cut-offs (10, 12, 15, and 20 ng/dL), intra-individual variability, and seasonal changes in aldosterone were calculated among patients with aldosterone detected using LC-MS/MS and RIA assays. The Bland-Altman plot and the kappa were used to assess the agreement around the cut-offs (15, and 20ng/dL) and the continuous measurements. To explore the intra-individual variability of aldosterone, the coefficient of variation (CV), measured as the ratio of standard deviation to the mean value, was calculated in patients with at least two aldosterone measurements. Results This retrospective cohort study included 608 patients with PA, 208 of whom 208 had at least two aldosterone measurements based on the LC-MS/MS assay. The median values of aldosterone measured for the first time by LC-M/MS and RIA were 14.53 and 21.48 ng/dL. The proportion of patients with at least one aldosterone measurement below 5, 10, 12, 15, and 20 ng/dL was 12.8%, 36.5%, 45.6%, 56.7%, and 70.7% by LC-MS/MS, and only 0.2%, 3.7%, 7.5%, 18.2% and 48.4% by RIA. The Bland-Altman plot and the kappa value 0.127 showed a low agreement between LC/MS/MS and RIA assays. High intra-individual variability was found in LC-MS/MS-detected plasma aldosterone, with a median CV of 30.3%. The plasma aldosterone concentrations were significantly lower in spring and summer than in autumn and winter (median, 13.1, 14.0 vs 15.4, 16.2 ng/dL, p=0.028). Conclusion Significant discrepancies in plasma aldosterone measurements between assays have been observed, and the conventional cut-offs derived from immunoassays are not applicable in patients with aldosterone measured by LC-MS/MS. An assay-specific cut-off for aldosterone is required to achieve accurate PA screening.