Seated Saline Infusion Test in Predicting Subtype Diagnosis of Primary Aldosteronism

Hiroki Kaneko; Hironobu Umakoshi; Yuki Ishihara; Taku Sugawa; Kazutaka Nanba; Mika Tsuiki; Toru Kusakabe; Noriko Satoh-Asahara; Akihiro Yasoda; Tetsuya Tagami


Clin Endocrinol. 2019;91(6):737-742. 

In This Article

Abstract and Introduction


Context: Although saline infusion test is widely used as a confirmatory test for primary aldosteronism (PA), it is reportedly less sensitive in patients in whom aldosterone is responsive to the upright position by performing it in recumbent position. Based on a single-centre experience, seated saline infusion test (SSIT) has been reported to be highly sensitive and superior to recumbent testing in identifying both unilateral and bilateral forms of PA. However, due to limited participants number, the utility of SSIT needs to be validated in other series.

Objective: This study aimed to evaluate the accuracy of SSIT in determining the PA subtypes compared with adrenocorticotropic hormone stimulation test under dexamethasone suppression (Dex-AT).

Patients and Setting: Sixty-four patients with PA who underwent both SSIT and Dex-AT were included. Subtype diagnosis of PA was determined by adrenal venous sampling (AVS) (16 unilateral and 48 bilateral forms).

Main Outcome Measure: Plasma aldosterone concentrations (PACs) were measured after SSIT and Dex-AT.

Results: The area under the receiver operating characteristic (ROC) curve for diagnosing unilateral PA was greater in SSIT than that in Dex-AT (0.907 vs. 0.755; P = .023). ROC curve analysis predicted optimal cut-off PACs of 13.1 ng/dL (sensitivity, 93.8%; specificity, 79.2%) for SSIT and 34.2 ng/dL (sensitivity, 75.0%; specificity, 68.8%) for Dex-AT.

Conclusions: Seated saline infusion test has superior accuracy in subtype diagnosis of PA compared with Dex-AT. SSIT can be a sensitive test for determining patients who require AVS prior to surgery.


Primary aldosteronism (PA) is the most common cause of secondary hypertension and develops in 5%–10% of patients with hypertension.[1–3] Since patients exhibit various cardiometabolic complications associated with aldosterone excess,[4,5] early diagnosis of PA is important. Hypertensive patients with positive screening test undergo confirmatory tests, such as saline infusion test (SIT), captopril challenge test, oral sodium loading test, and fludrocortisone suppression test, to definitively confirm or exclude the diagnosis of PA.[6] If they are diagnosed with having PA and desire surgery, adrenal venous sampling (AVS) is performed to determine two major subtypes: unilateral forms, such as an aldosterone-producing adenoma (APA), and bilateral forms, such as idiopathic hyperaldosteronism. Although AVS is the standard procedure for subtype diagnosis of PA, it is invasive, expensive, and technically difficult and requires expertise of limited facilities.[7] It is desirable to predict subtypes prior to AVS with alternative procedures.

The SIT is widely used as a confirmatory test of PA because it is safe and requires a short time at the outpatient clinic.[8] A previous study[9] showed that seated saline infusion test (SSIT) was highly sensitive and superior to recumbent SIT in identifying both unilateral and bilateral forms of PA. Since recumbent SIT has the possibility of missing patients with PA in whom aldosterone production was responsive to the upright position, SSIT might be a reliable alternative to recumbent SIT. In contrast, the usefulness of recumbent SIT for predicting PA subtypes was demonstrated,[10,11] and it can be helpful in omitting unnecessary diagnostic procedures because PA subtype can be predicted with recumbent SIT as an established confirmatory test. Since plasma aldosterone concentrations (PACs) in unilateral forms were higher than those in bilateral forms for SSIT in a previous study,[9] SSIT may also be useful for predicting PA subtypes. However, due to the limited number of participants and a single-centre experience, endocrine clinical practice guidelines suggested to validate the utility of SSIT in other cohorts.[6]

The present study was performed to test the hypothesis that SSIT could be useful in the diagnosis of unilateral forms among patients suspected of PA because accurate diagnosis of unilateral forms of PA is crucial in clinical practice. To address this hypothesis, we compared the accuracy of subtype diagnosis between SSIT and adrenocorticotropic hormone (ACTH) stimulation test under dexamethasone suppression (Dex-AT), which was reported to be useful in the diagnosis of unilateral forms among East Asian patients suspected of PA.[12,13]