Spatial Proteomics Profiles of Aldosterone-producing Adenoma and Unilateral Hyperplasia

Third Military Medical University30 enrolled

Overview

Primary aldosteronism (PA) is a common cause of secondary hypertension, which is characterized by excessive aldosterone production by the adrenal gland. Excessive aldosterone can significantly increase the risk of cardiovascular disease and stroke. Patients with aldosterone-producing adenoma (APA) or unilateral hyperplasia (UAH) can be cured by unilateral adrenalectomy. The adrenal cortex is the outer part of the adrenal gland and is subdivided into three layers- the zona glomerulosa, the zona fasciculata, and the zona reticularis. And the outermost layer is the zona glomerulosa, and it's full of cells that make the hormone aldosterone. Although it has been investigated that the main cause of APA or UAH is the mutations of different calcium ion channels, including KCNJ5, CACNA1D, CLCN2 et al, it is still unknown whether there are any other changes of other proteins in different layers. Therefore, the investigators designed the study to characterize the proteomics profiles of adrenal adenoma/hyperplasia leading to primary aldosterone and identify biomarkers for early identification of PA by using spatial proteomics. The samples from adrenal adenoma or hyperplasia will be collected and analyzed by spatial proteomics in Hangzhou Jingjie Biotechnology Co., Ltd. The differentially expressed proteins in different layers will be screened out between APA and UAH, APA and its adjacent normal tissues, and UAH and its adjacent normal tissues, respectively. And KEGG analysis will be conducted to determine enriched pathway in these differentially expressed protein, respectively.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Primary Aldosteronism Due to Aldosterone Producing Adenoma Primary Aldosteronism Due to Adrenal Hyperplasia (Bilateral)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * According to the 2020 guidelines for primary aldosteronism, patients with positive primary aldosteronism confirmed test; * Patients with predominant unilateral aldosterone secretion at AVS; adrenal CT suggesting unilateral adrenal adenoma (\> 0.8cm diameter) and no abnormalities in contralateral adrenal morphology. * Patients who agreed to do the adrenalectomy. Exclusion Criteria: * adrenal CT suggests abnormal bilateral adrenal morphology or unilateral nodules. * glucocorticoids can treat aldosteronism (GRA) and familial aldosteronism. * other secondary hypertension: renal parenchymal hypertension, renal artery stenosis, Cushing syndrome, adrenal myeloid hyperplasia, aortic narrowing, obstructive sleep apnea hypoventilation syndrome. * any other unsuitable condition for surgery. * Patients who refused to perform adrenalectomy.

Outcomes

Primary Outcomes

Screening for the biomarkers.

Histological validation of the CYP11B2 positive area in APA and UAH by immunohistochemical staining (IHC). Some specimens will be characterized more deeply with advanced spatial proteomics technologies to identify the biomarkers.

Time frame: After APA/UAH resection/biopsy, usually within 6 months

Secondary Outcomes

Incorporate biomarkers into the accurate and early diagnosis of PA.

Verifying the relationship between biomarkers and clinical presentations, including plasma aldosterone concentrations (PAC), aldosterone to rein ratio (ARR), direct renin concentration (DRC), and serum potassium, etc. Comparing the relationships between biomarkers and risk factors, including osas and family history, etc. Establishing a mathematical model for diagnosing PA through machine learning and studying the pathogenesis of PA through corresponding animal models.

Time frame: 12 months

Identifying the relationship between biomarkers and the prognosis of PA.

The alteration of blood pressure and medication status are investigated through 3 months followed up. Verifying the relationship between the biomarkers and the function of APA and UAH, as well as the prognosis of PA.