A Combination of Captopril Challenge Test After Saline Infusion Test Improves Diagnostic Accuracy for Primary Aldosteronism

Chuan Lin; Jun Yang; Peter J. Fuller; Huan Jing; Ying Song; Wenwen He; Zhipeng Du; Ting Luo; Qingfeng Cheng; Shumin Yang; Hongman Wang; Qifu Li; Jinbo Hu


Clin Endocrinol. 2020;92(2):131-137. 

In This Article

Abstract and Introduction


Context: The saline infusion test (SIT) is a common confirmatory test for primary aldosteronism (PA). According to the guideline, a postinfusion plasma aldosterone concentration (PAC) of 5–10 ng/dL is considered indeterminate, and recommendations for diagnostic strategies are currently limited in this situation.

Objective: To explore whether an addition of the captopril challenge test (CCT) could improve the diagnostic accuracy in patients with indeterminate SIT.

Methods: A total of 280 hypertensive patients with high risk of PA completed this study. Subjects were defined as SIT indeterminate based on their PAC post-SIT. These patients then underwent the CCT where PACs post-CCT >11 ng/dL were considered positive. Using fludrocortisone suppression test (FST) as the reference standard, diagnostic parameters including area under the receiver-operator characteristic curves (AUC), sensitivity and specificity were calculated.

Results: There were 65 subjects (23.2%) diagnosed as PA indeterminate after SIT. With the addition of CCT, true-positive numbers increased from 134 to 147, and false-negative numbers decreased from 27 to 14. Compared to SIT alone, a combination of SIT and CCT showed a higher AUC (0.91 [0.87,0.94] vs 0.87 [0.83,0.91], P = .041) and an increased sensitivity for the diagnosis of PA (0.91 [0.86,0.95] vs 0.83 [0.76,0.89], P = .028), while the specificity remained similar. In the subgroup with indeterminate SIT results, using PAC post-CCT resulted in a 36% higher AUC than using PAC post-SIT alone for the diagnosis of PA.

Conclusion: For patients under investigation for possible PA who have indeterminate SIT results, an addition of CCT improves the diagnostic accuracy.


Primary aldosteronism (PA) is an adrenocortical disease characterized by aldosterone overproduction. Diagnosis of PA involves case detection, case confirmation and subtype classification. Patients with a positive screening test (aldosterone: renin ratio, ARR) should undergo confirmatory testing. Confirmatory tests including the fludrocortisone suppression test (FST), saline infusion test (SIT, also called the saline suppression test) and captopril challenge test (CCT) are recommended by the Endocrine Society's clinical practice guidelines.[1]

Saline infusion test is believed to be a reliable test for PA confirmation and is widely used in clinical practice.[1–3] According to the guidelines, when interpreting the results of SIT (performed in the supine position), a plasma aldosterone concentrations (PAC) post-SIT <5 ng/dL (<140 nmol/L) indicates that PA is unlikely while PAC >10 ng/dL (>277 nmol/L) confirms the diagnosis of PA. A post-SIT PAC between 5 and 10 ng/dL is considered as indeterminate and cannot definitively diagnose or exclude PA. Although a cut-off of 6.8 ng/dL (188 pmol/L) has been found to offer a compromise between sensitivity and specificity, there are limited recommendations for diagnostic strategies following an indeterminate SIT.[1]

Previous studies showed that a combination of two diagnostic tests exhibited higher diagnostic accuracy than a single one.[4,5] Although both CCT and SIT suppress components of the renin-angiotensin-aldosterone system (RAAS) to demonstrate autonomous aldosterone overproduction, their mechanisms of action are different. Saline infusion suppresses renin by salt loading and volume expansion, while captopril administration inhibits the angiotensin-converting enzyme (ACE) and therefore reduces aldosterone production.[1,2] Given their different mechanisms of action, we performed this study to explore whether a combination of CCT and SIT could improve their diagnostic accuracy for PA.