New insights in primary aldosteronism diagnosis: a prospective multicenter study

OBJECTIVES: The high variability in screening and confirmatory cut-off values for primary aldosteronism (PA) largely reflects the insufficient standardization of current analytical methods. Competitive and sandwich immunoassays show variable correlation with the reference liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. This prospective multicenter study aimed to establish diagnostic thresholds for PA using a novel sandwich immunoassay. METHODS: A total of 676 patients suspected of PA were consecutively enrolled from 7 medical centers in China. All participants underwent a captopril challenge test (CCT), followed by a seated saline infusion test (sSIT) on the third day. Plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) were measured using a fully automated chemiluminescent immunoassay platform (Maglumi X8, SNIBE, China). PA was diagnosed according to current clinical guidelines. RESULTS: An aldosterone renin ratio (ARR) cut-off of 11 ng/L/mU/L showed 90 % sensitivity (95 % CI: 85-94 %) and 62 % specificity (95 % CI: 58-67 %) with the area under the receiver-operator characteristic curves (AUC) of 0.843 (95 % CI: 0.81-0.87). PAC post-sSIT and PAC post-CCT exhibited comparable diagnostic performance (AUC 0.818, 95 % CI: 0.79-0.85 vs. AUC 0.848, 95 % CI: 0.82-0.88; p=0.1388). Using cut-off of 56 ng/L and 59 ng/L for post-SIT and post-CCT yielded a specificity of 85 % (95 % CI: 81-88 %). Notably, to achieve a higher specificity of 90 %, the corresponding PAC cut-off values increased to 64 ng/L post-SIT and 66 ng/L post-CCT. CONCLUSIONS: Adjustment of current cut-off values for the screening and confirmation of PA is necessary when a more accurate chemiluminescent sandwich immunoassay is used for measuring PAC and PRC.