Primary Aldosteronism LC-MS/MS-specific Cutoffs (PM)

LC-MS/MS-specific Cutoffs for Screening and Confirmatory Testing of Primary Aldosteronism: A Multi-center Study

Aims to evaluation the LC-MS/MS-specific cutoffs of PA screening and CCT test.

Study Overview

• Status: Completed
• Conditions: Primary Aldosteronism
• Intervention / Treatment: Diagnostic test: Captopril Challenge Test

Detailed Description

Plasma aldosterone concentration and plasma renin activity / concentration measurement are important for early screening and diagnosis of Primary Aldosteronism (PA), most measurement methods are currently based on chemiluminescence, which may be cross-reactivity with other compounds and metabolites, leading to misdiagnosis or missed diagnosis of PA patients. Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been introduced into the clinical routine analysis of steroid hormones due to its higher specificity and is increasingly used for the diagnosis of adrenal diseases. However, it is unknown for the cut-offs of PA screening and CCT test based on this technology in China. Therefore, the purpose of this study is to establish the screening and CCT cut-off point for primary aldosteronism based on LC-MS/MS technique at multicenter in China.

• Study Type: Observational
• Enrollment (Actual): 396

Contacts and Locations

Study Locations

• China
  • Chongqing, China, 400016
    • Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University
  • Chongqing
    • Chongqing, Chongqing, China, 400016
      • Qifu Li

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

This study intends to include patients taking hypertension medication at each center between June 2023 and July 2024 with subjects signing written informed consent.

Description

Inclusion Criteria:

1. Age is between 18-75 years old.
2. Hypertension patients with high risk factors for PA (meeting one of the following criteria): a.Persistent hypertension (> 150 / 100mmHg); b. Refractory hypertension (combined with 3 antihypertensive drugs and one used as a diuretic,Blood pressure is still greater than 140 / 90 mmHg or four antihypertensive drugs are needed to control blood pressure of less than 140 / 90 mmHg); c.Hypertension with adrenal accidental tumor; d.Hypertension is associated with hypokalaemia;
3. Recent and stable use of antihypertensive drugs for more than 2 weeks, The drug types may include: β receptor blockers, CCB(calcium channel blockers), angiotension converting enzyme inhibitors(ACEi), Angiotensin Receptor Blocker(ARB), mineralocorticoid receptor antagonists(MRA), and other diuretics.

Exclusion Criteria:

1. Patients who are unwilling to participate and complete the study or refuse to sign a written informed consent for the study;
2. Patients diagnosed with other secondary hypertension (such as renal hypertension, renal artery stenosis, pheochromocytoma, Cushing's syndrome, etc.);
3. Combined with severe renal insufficiency eGFR <30 ml/min / 1.73 m2, Or patients with liver insufficiency OR liver failure (Alanine aminotransferase and / or aspartate aminotransferase increased 2.5 times above the upper limit of normal);
4. Clinical assessment of a dressing change risk, Including: Heart failure (NYHA stage grade II or above), any one or more of the stroke, myocardial infarction, and unstable angina pectoris diagnosed within three months;
5. Patients who are pregnant or who are currently being treated with sex hormones and glucocorticoids;
6. incurable malignancy;
7. Other reasons make it difficult to change or stop the drug to complete the diagnosis.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Primary Aldosteronism Group; Patients diagnosed with primary aldosteronism	Diagnostic test: Captopril Challenge Test; Patients received 50 mg captopril orally in the morning after sitting or standing for at least two hours. PAC and PRC were measured using mass spectrometry two hours after administration of capopril.
Essential Hypertension Group; Patients diagnosed with essential hypertension	Diagnostic test: Captopril Challenge Test; Patients received 50 mg captopril orally in the morning after sitting or standing for at least two hours. PAC and PRC were measured using mass spectrometry two hours after administration of capopril.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish a LC-MS/MS assay-specific cut-off point of CCT without medication interfering for primary aldosteronism.	Measure the plasma aldosterone concentration by LC-MS/MS.	2 hours after the captopril challenge test without medication interfering.
Establish a LC-MS/MS assay-specific cut-off point of screening without medication interfering for primary aldosteronism.	Measure the plasma aldosterone concentration and plasma renin activity by LC-MS/MS.Plasma aldosterone concentration and plasma renin activity will be combined and reported as an aldosterone-to-renin ratio.	At baseline without medication interfering.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish a LC-MS/MS assay-specific cut-off point of screening with medication interfering for primary aldosteronism.	Measure the plasma aldosterone concentration and plasma renin activity by LC-MS/MS. Plasma aldosterone concentration and plasma renin activity will be combined and reported as an aldosterone-to-renin ratio.	At baseline with medication interfering.
compare the different criteria of Captopril Challenge Test for the diagnosis of primary aldosteronism.	plasma aldosterone concentration were measured using automated chemiluminescence immunoassays.	2 hours after the captopril challenge test without medication interfering.

Collaborators and Investigators

• Sponsor: Chongqing Medical University
• Collaborators: Chinese PLA General Hospital; Tianjin Medical University General Hospital; Chinese Academy of Medical Sciences, Fuwai Hospital
• Investigators: Study Chair: Qifu Li, First Affiliated Hospital of Chongqing Medical University

Publications and helpful links

General Publications

• Young WF Jr. Diagnosis and treatment of primary aldosteronism: practical clinical perspectives. J Intern Med. 2019 Feb;285(2):126-148. doi: 10.1111/joim.12831. Epub 2018 Sep 25.
• Xu Z, Yang J, Hu J, Song Y, He W, Luo T, Cheng Q, Ma L, Luo R, Fuller PJ, Cai J, Li Q, Yang S; Chongqing Primary Aldosteronism Study (CONPASS) Group. Primary Aldosteronism in Patients in China With Recently Detected Hypertension. J Am Coll Cardiol. 2020 Apr 28;75(16):1913-1922. doi: 10.1016/j.jacc.2020.02.052.
• Mulatero P, di Cella SM, Monticone S, Schiavone D, Manzo M, Mengozzi G, Rabbia F, Terzolo M, Gomez-Sanchez EP, Gomez-Sanchez CE, Veglio F. 18-hydroxycorticosterone, 18-hydroxycortisol, and 18-oxocortisol in the diagnosis of primary aldosteronism and its subtypes. J Clin Endocrinol Metab. 2012 Mar;97(3):881-9. doi: 10.1210/jc.2011-2384. Epub 2012 Jan 11.
• Fuss CT, Brohm K, Kurlbaum M, Hannemann A, Kendl S, Fassnacht M, Deutschbein T, Hahner S, Kroiss M. Confirmatory testing of primary aldosteronism with saline infusion test and LC-MS/MS. Eur J Endocrinol. 2021 Jan;184(1):167-178. doi: 10.1530/EJE-20-0073.
• Olsen MH, Angell SY, Asma S, Boutouyrie P, Burger D, Chirinos JA, Damasceno A, Delles C, Gimenez-Roqueplo AP, Hering D, Lopez-Jaramillo P, Martinez F, Perkovic V, Rietzschel ER, Schillaci G, Schutte AE, Scuteri A, Sharman JE, Wachtell K, Wang JG. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet. 2016 Nov 26;388(10060):2665-2712. doi: 10.1016/S0140-6736(16)31134-5. Epub 2016 Sep 23. No abstract available.
• Rehan M, Raizman JE, Cavalier E, Don-Wauchope AC, Holmes DT. Laboratory challenges in primary aldosteronism screening and diagnosis. Clin Biochem. 2015 Apr;48(6):377-87. doi: 10.1016/j.clinbiochem.2015.01.003. Epub 2015 Jan 22.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Actual): July 31, 2024
• Study Completion (Actual): July 31, 2024

Study Registration Dates

• First Submitted: June 26, 2023
• First Submitted That Met QC Criteria: July 24, 2023
• First Posted (Actual): July 25, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Diagnostic; Multicenter study
• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Adrenocortical Hyperfunction; Hyperaldosteronism; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Antihypertensive Agents; Angiotensin-Converting Enzyme Inhibitors; Captopril
• Other Study ID Numbers: PM-China 2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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