A Novel and Efficient Biochemical Screening Strategy for Glucocorticoid-Remediable Aldosteronism: Combined 1-mg Overnight Dexamethasone Suppression Test and Steroid Profile

Peking Union Medical College Hospital50 enrolled

Overview

This prospective observational study evaluates a simplified biochemical screening strategy to differentiate Glucocorticoid-Remediable Aldosteronism (GRA) from Aldosterone-Producing Adenoma (APA). The approach combines a 1-mg overnight dexamethasone suppression test (ODST) with LC-MS/MS steroid profiling. We aim to establish diagnostic cut-off points for aldosterone and hybrid steroid (18-oxoF, 18-OHF) suppression rates as an efficient screening tool prior to genetic testing.

Background: GRA is a rare form of primary aldosteronism where aldosterone secretion is regulated by ACTH. This study evaluates if a 1-mg ODST can effectively suppress aldosterone and hybrid steroids in GRA patients compared to the autonomous secretion observed in APA.Methods: * Participants: Patients with genetically confirmed GRA or clinically/pathologically confirmed APA are enrolled. * Procedure: Patients undergo a 1-mg ODST (1 mg dexamethasone at midnight). Blood samples are collected at 08:00 AM at baseline and post-suppression. * Analysis: 11 steroids, including ALD, 18-oxoF, and 18-OHF, are measured via LC-MS/MS. * Evaluation: Diagnostic performance is assessed using ROC curves and negative predictive value (NPV) based on a 1% GRA prevalence.Perspective: This initial phase establishes the diagnostic parameters, which will be further validated in a larger cohort to optimize the screening workflow for primary aldosteronism.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Primary Aldosteronism Primary Aldosteronism Due to Aldosterone Producing Adenoma

Interventions

1 mg overnight dexamethasone inhibition testDIAGNOSTIC_TEST

After the patient fasted overnight, venous blood was collected at 08:00 in the morning for baseline steroid profile analysis (including aldosterone, 18-oxycortisol, 18-hydroxy cortisol, etc., a total of 11 types of steroid hormones). At 24:00 that night, the patient took a single oral dose of 1mg dexamethasone tablets. At 08:00 the next morning, venous blood was collected again under the same collection conditions as the baseline to conduct the baseline steroid profile analysis.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients diagnosed with Primary Aldosteronism (PA) according to clinical biochemical screening standards. GRA Group: Genetically confirmed presence of the $CYP11B1/CYP11B2$ chimeric gene. APA group：The patient was diagnosed with PA and the adrenal imaging showed a typical adrenal adenoma on one side. The AVS or Ga68-Pentixafor PET/CT indicated that the adrenal gland on the adenoma side had a dominant secretion of aldosterone. And any of the following conditions was met: (1) The postoperative pathology clearly confirmed an adrenal cortical adenoma, with immunohistochemistry showing aldosterone synthase CYP11B2 (+). (2) After unilateral adrenal resection, the biochemical results of the patient were completely relieved, meeting the surgical outcome criteria for PA. Exclusion Criteria: * Exclude patients with secondary hypertension caused by other reasons (such as Cushing's syndrome, pheochromocytoma), severe cardiac and renal insufficiency (eGFR \< 30 mL/min/1.73m²), or those who are unable to cooperate to complete the trial process for various reasons.

Outcomes

Primary Outcomes

Percent suppression of Plasma Aldosterone Concentration (PAC) after 1-mg ODST

Time frame: Post-1mg ODST (approximately 2 weeks after dexamethasone administration)

Secondary Outcomes

Absolute concentration of Plasma Aldosterone (PAC) post-1mg ODST