Study on Cutoff Revision Effects and Evaluation of NNT in Primary Aldosteronism (SCREEN-PA)

Impact of the Revised Aldosterone-Renin Ratio (ARR) Cutoff in the 2025 Primary Aldosteronism Guideline in Real-World Practice: A Prospective Study

The goal of this observational study is to evaluate the real-world impact of applying the revised aldosterone-to-renin ratio (ARR) cutoff recommended in the 2025 primary aldosteronism guideline in adults with hypertension and biochemical findings suggestive of an intermediate probability of lateralizing primary aldosteronism (PA). The main questions it aims to answer are:

• What is the number needed to test (NNT) to diagnose one case of primary aldosteronism when using the revised ARR cutoff (>20)?
• What is the optimal ARR cutoff for diagnosing PA in Korean patients?
• What is the biochemical treatment response rate at 6 months after treatment for confirmed PA?

Participants will:

• Undergo standardized ARR testing after protocol-based medication adjustment and controlled sampling conditions.
• Undergo confirmatory testing using the saline infusion test (SIT).
• Receive standard clinical management for confirmed PA according to institutional practice.
• Be followed for assessment of biochemical outcomes after treatment.

Study Overview

• Status: Recruiting
• Conditions: Primary Aldosteronism
• Intervention / Treatment: Diagnostic test: Saline Infusion Test

Detailed Description

Primary aldosteronism (PA) is one of the most common causes of secondary hypertension and is associated with an increased risk of cardiovascular, renal, and metabolic complications independent of blood pressure levels. Despite its clinical importance and the availability of effective targeted treatments such as adrenalectomy or mineralocorticoid receptor antagonists, PA remains substantially underdiagnosed in routine clinical practice, with estimates suggesting that only a small proportion of eligible hypertensive patients undergo appropriate screening.

The aldosterone-to-renin ratio (ARR) is the most widely used screening tool for PA. Traditionally, an ARR cutoff of >30 has been used to define a positive screening result. However, recent evidence suggests that this threshold may lack sufficient sensitivity and may miss a considerable number of patients with clinically relevant PA. In response, recent international hypertension and endocrine society guidelines have proposed lowering the ARR cutoff to >20 in order to improve case detection and broaden screening indications.

However, lowering the ARR threshold may also increase the number of false-positive results, potentially leading to an increased burden of aldosterone suppression test. Therefore, the clinical utility of the revised cutoff must be evaluated in real-world settings, particularly with regard to diagnostic yield and testing efficiency.

This study is a multicenter, prospective observational cohort study designed to evaluate the impact of applying the revised ARR cutoff (>20) in routine clinical practice in Korea. Patients with hypertension who meet predefined biochemical screening criteria indicating an intermediate probability of lateralizing PA will be enrolled.

Participants will undergo standardized pre-analytical preparation, including medication adjustment and controlled sampling conditions. All eligible participants will undergo confirmatory testing using the saline infusion test (SIT), performed under standardized protocols (supine or seated depending on institutional practice).

The primary objective of this study is to determine the number of confirmatory tests required to diagnose one case of PA (number needed to test, NNT) when using the revised ARR cutoff (>20). Secondary outcomes include biochemical treatment response at 6 months (complete biochemical success), and identification of an optimal ARR cutoff value using receiver operating characteristic (ROC) analysis.

The findings of this study are expected to provide real-world evidence regarding the diagnostic efficiency and clinical implications of lowering the ARR cutoff in Korean patients, and may inform future guideline updates and clinical decision-making strategies for the screening and diagnosis of primary aldosteronism.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Yun Mi Choi; Phone Number: +82-31-8086-3655; Email: ymchoi@hallym.or.kr

Study Locations

• South Korea
  • Korea, Republic of
    • Seoul, Korea, Republic of, South Korea, 03080
      • Recruiting
      • Seoul National University Hospital
      • Contact: Jung Hee Kim; Phone Number: +82-02-2072-0694; Email: jhee1@snu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults with hypertension who have an aldosterone-to-renin ratio (ARR) >20 and meet criteria for intermediate probability of lateralizing primary aldosteronism.

Description

Inclusion Criteria:

• Adults aged 18 years or older
• Diagnosis of hypertension or current use of antihypertensive medications
• Plasma renin activity (PRA) ≤1 ng/mL/hr
• Plasma aldosterone concentration (PAC) ≥10 ng/dL by immunoassay or ≥7.5 ng/dL by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
• Aldosterone-to-renin ratio (ARR) >20 by immunoassay or >15 by LC-MS/MS
• Participants meeting criteria for intermediate probability of lateralizing primary aldosteronism
• For participants with ARR values between 20 and 30, repeat ARR measurement within 26 weeks demonstrating persistent ARR >20

Exclusion Criteria:

• Current use of mineralocorticoid receptor antagonists or amiloride that cannot be discontinued according to study protocol
• Previous adrenalectomy
• Chronic kidney disease stage 4 or higher (estimated glomerular filtration rate <30 mL/min/1.73 m²)
• Pregnancy
• Current use of combined estrogen- and progesterone-containing oral contraceptive pills or hormone replacement therapy
• High probability primary aldosteronism defined as hypokalemia with PRA <0.2 ng/mL/hr and PAC >20 ng/dL by immunoassay or >15 ng/dL by LC-MS/MS
• Low probability primary aldosteronism defined as PAC <11 ng/dL by immunoassay or <8 ng/dL by LC-MS/MS
• Inability to undergo saline infusion test according to investigator judgment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ARR >20 Cohort; Adults with hypertension who have an aldosterone-to-renin ratio (ARR) >20 and meet criteria for intermediate probability of lateralizing primary aldosteronism.	Diagnostic test: Saline Infusion Test; Standardized saline infusion test performed for confirmatory diagnosis of primary aldosteronism.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number Needed to Test for Diagnosis of Primary Aldosteronism	Number of saline infusion tests required to confirm one case of primary aldosteronism among participants meeting the revised aldosterone-to-renin ratio screening cutoff criteria.	Through study completion, an average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Biochemical Success After Treatment	Proportion of participants with confirmed primary aldosteronism who achieve complete biochemical success after treatment.	Through study completion, an average of 6 months
Optimal Aldosterone-to-Renin Ratio Cutoff for Diagnosis of Primary Aldosteronism	Diagnostic performance and optimal cutoff value of aldosterone-to-renin ratio for identifying confirmed primary aldosteronism using receiver operating characteristic (ROC) analysis.	Through study completion, an average of 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adrenal Vein Sampling Lateralization Rate	Proportion of participants with confirmed primary aldosteronism demonstrating lateralization on adrenal vein sampling.	Perioperative/Periprocedural
Phenotypic Differences According to Aldosterone-to-Renin Ratio Range	Comparison of clinical and biochemical characteristics between participants with aldosterone-to-renin ratio values of 20-30 and those with higher aldosterone-to-renin ratio values.	Baseline

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Samsung Medical Center; Asan Medical Center; Chonnam National University Hospital; Korea University Guro Hospital; Ajou University School of Medicine; Kangbuk Samsung Hospital; Chungnam National University Hospital; DongGuk University; Inha University Hospital; Gangneung Asan Hospital; Nowon Eulji Medical Center; Eunpyeong St. Mary's Hospital; Hallym University Dongtan Sacred Heart Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: May 31, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 31, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Screening; Primary Aldosteronism; Aldosterone-to-Renin Ratio; Number Needed to Test
• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Adrenocortical Hyperfunction; Hyperaldosteronism
• Other Study ID Numbers: SCREEN-PA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No