Abstract

Title: Sex differences in in the screening cutoffs of primary aldosteronism Objective: In screening for primary aldosteronism (PA), simultaneous measurements of plasma aldosterone concentration (PAC; pg/mL) and plasma renin activity (PRA; ng/mL/hr) and the resulting PAC/PRA ratio (ARR) > 200 have been actively employed. Because of the low stability and reproducibility of PRA, screening using active renin concentration (ARC; pg/mL), which can overcome these problems, is desirable but has not become a mainstream screening method in practice. This study will clarify the association between ARC and PRA and examine the impact of sex differences on PA screening. Methods: 1631 consecutive patients (1018 inpatients (51.5%; male) and 613 outpatients (58.1%; male)) who had measured PRA and ARC simultaneously at Osaka University Hospital from February 2017 to December 2020 were analyzed retrospectively. In the inpatients, blood samples were taken in the supine position at rest in the early morning. In outpatients, blood was collected without specifying the blood collection conditions. PRA, ARC, and PAC if blood was collected at the same time were analyzed. PRA was measured by enzyme immunoassay. Each of PAC and ARC was measured by chemiluminescent immunoassay. All results are represented as median (25th to 75th percentile). For the analysis of variables association Mann Whitney`s U t test was used for comparison of each measurement between the two groups, with 5% significance level. Results: PRA and ARC were correlated in the overall population and by sex (overall; r = 0.78 p < 0.0001, male r = 0.90 p < 0.0001, female r = 0.71, P < 0.0001). Analysis of covariance showed a significant difference in the regression line between PRA and ARC by sex (p < 0.0001) and PRA/ARC was significantly lower in males (0.17 [0.13–0.22] vs 0.19 [0.14–0.26] p < 0.0001). In the inpatients, PRA, ARC and PAC was significantly higher in males (PRA; 1.1 [0.4–2.9] vs 0.7 [0.3–1.7] p < 0.0001, ARC; 6.6 [3.0–16.8] vs 4.4 [1.8–8.3] p < 0.0001, PAC; 137 [100–196] vs 130 [88–185], p = 0.003,). PAC/PRA, PAC/ARC were significantly lower in males (PAC/PRA; 120 [47–307] vs 179 [81–335] p = 0.0002, PAC/ARC; 20 [8–45] vs 32 [16–63] p < 0.0001). In the outpatients, both PRA and ARC, PAC were also significantly higher, and PAC/PRA and PAC/ARC were significantly lower in males(PRA; 1.3 [0.6–3.4] vs 0.8 [0.4–2.4] p < 0.0001, ARC; 6.8 [3.4–15.1] vs 4.4 [2.0–11.1] p < 0.0001, PAC; 137 [98–198] vs 158 [116–220] p = 0.003, PAC/PRA; 106 [44–226] vs 179 [70–380] p < 0.0001, PAC/ARC; 20 [10–40] vs 36 [15–72] p < 0.0001). Conclusion: Significant differences in PRA, ARC, PAC, PRA/ARC, PAC/PRA, and PAC/ARC were observed by the sex. Sex differences should be considered in screening for PA by ARR and PAC/ARC.

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