MSACL 2025 Abstract

Establishment of Screening and Diagnosis Cut-off Values for Primary Aldosteronism Based on LC-MS/MS Method: A Multicenter Prospective Study

Kaijuan Wang (1), Hongying Cong (1), Xiaojing Gao (1), Zhangwei Gao (1), Wei Zhang (1), Wenjun Ma (2), Qifu Li (3), Xiaocui Shi (1), Zhou Zhou (1)
(1) Center of Laboratory Medicine, Beijing Key Laboratory of Cardiovascular Disease Warning and Diagnosis, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College/National Center for Cardiovascular Diseases, Beijing, China. (2) Hypertension Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China (3) Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

Kaijuan Wang, Master's degree (Presenter) Peking Union Medical College

Presenter Bio: Master's degree holder, chief technician, currently responsible for the mass spectrometry platform at the Center of Laboratory Medicine, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College. Undertaking multiple clinical research projects, the main research direction is the application of mass spectrometry technology in the diagnosis and treatment of cardiovascular diseases.

Relevant Financial Disclosures (within past 24 months, reported on Apr 21, 2026) No relevant financial relationship(s) to disclose.

INTRODUCTION:
Primary aldosteronism (PA) is the most frequent form of endocrine hypertension.The target organ damage is earlier and more serious than that associated with essential hypertension. Early diagnosis and causal treatment (like unilateral adrenalectomy or specific drugs antagonizing aldosterone action in uni- or bilateral PA, respectively) are critical to prevent cardiovascular complications and end organ damage. The aldosterone to renin ratio (ARR) is a widely used screening test for PA, and patients with positive screening results need to undergo further confirmatory testing to detect the inhibition rate of aldosterone. At present, aldosterone detection mainly relies on the competitive chemiluminescence method (cCLIA), which is known to be prone to false overestimation in samples with low concentration, and is susceptible to non-specific antibody interference, leading to diagnostic errors. To overcome these limitations, clinical laboratories turned to LC-MS/MS for analysis of aldosterone, an analytical method that does not demonstrate cross-reactivity but an improved diagnostic accuracy compared to traditional chemiluminescence methods. However, the existing diagnostic criteria are based on Immunoassay, and there is no unified screening and confirmation standard for this innovative method, which seriously hinders its clinical application. The establishment of method-specific cut-offs for screening and confirmatory testing of PA is necessary when switching to LC-MS/MS in clinical routine.

OBJECTIVE:
The primary aim of the current study was to establish the method-specific cut-offs for screening and confirmatory testing (sitting saline infusion test and Captopril Challenge Test) of PA in a multicenter prospective cohort.

METHODS:
676 patients (364 males and 312 females) with resistant hypertension from seven clinical medical centers were recruited consecutively, and all patients underwent a standard drug washout and two confirmatory tests: the Captopril Challenge Test (CCT) and the Sitting Saline Infusion Test (sSIT), with a one-day interval between the two tests. Patients were required to maintain a non-supine position and remain quiet for at least 2 hours before baseline venous blood was collected. For CCT, 50 mg of Captopril was administered orally after the first sampling, and blood was collected again 2 hours later. For SIT, 2 L of 0.9% NaCl was infused over 4 hours after the first sampling, and blood was collected after the infusion. cCLIA and LC-MS/MS were used simultaneously for detection, and the consistency between the results of cCLIA and LC-MS/MS was evaluated. Aldosterone standards (GBW09283/09284/09285) and EQA samples for renin and angiotensin I were used to evaluate the accuracy of the LC-MS/MS method. According to existing clinical standards for PA diagnosis, cut-off values for PA screening (ARR) and confirmatory tests (CCT, sSIT) based on LC-MS/MS were established and evaluated.

RESULTS:
A total of 233 cases of primary aldosteronism and 443 cases of essential hypertension were included in the study. Each subject had four detection points: before and after Captopril administration, and before and after saline loading. A total of 676 cases yielded 2,704 results. For aldosterone, the regression equation of cCLIA and LC-MS/MS was y = 1.801191+1.462042x, with a correlation coefficient r = 0.898, Overall, the values measured by cCLIA were 94% higher than those measured by LC-MS/MS, with smaller deviations (50.1%) in the high concentration region (aldosterone>11ng/dL) and more significant deviations (107%) in the low concentration region (aldosterone≤11ng/dL). As eGFR decreases, especially when eGFR is less than 30 mL/min, the consistency between cCLIA and LC-MS/MS becomes increasingly poor.

For LC-MS/MS, the ARR (ratio of aldosterone to renin activity) cut-off value was 7.1 (ng/dL)/(ng/mL/h) (sensitivity 90%, specificity 60%); patients with plasma aldosterone concentration (PAC) > 5.45 ng/dL for post-CCT were considered indicative of PA (sensitivity 62.5%, specificity 90%); patients with PAC > 5.6 ng/dL for post-sSIT were also considered indicative of PA (sensitivity 47%, specificity 90%).

DISCUSSION:
This study innovatively employed the LC-MS/MS method to detect PAC, PRA, and established corresponding ARR screening cut-off values and judgment criteria for the CCT and sSIT. Advantages of this study: Prospective, multicenter consecutive enrollment of patients with resistant hypertension and all participants underwent CCT and sSIT to avoid misdiagnosis bias. For PA screening, sensitivity should be prioritized, while for PA confirmation, specificity should take precedence. Therefore, clinicians should choose the corresponding cut-off value range based on clinical needs rather than relying on a single, fixed value. This study provides more reliable technical means and a diagnostic basis for improving the screening of primary aldosteronism.