Cardiovascular and metabolic characters of KCNJ5 somatic mutations in primary aldosteronism

Front Endocrinol (Lausanne). 2023 Mar 6:14:1061704. doi: 10.3389/fendo.2023.1061704. eCollection 2023.

Abstract

Background: Primary aldosteronism (PA) is the leading cause of curable endocrine hypertension, which is associated with a higher risk of cardiovascular and metabolic insults compared to essential hypertension. Aldosterone-producing adenoma (APA) is a major cause of PA, which can be treated with adrenalectomy. Somatic mutations are the main pathogenesis of aldosterone overproduction in APA, of which KCNJ5 somatic mutations are most common, especially in Asian countries. This article aimed to review the literature on the impacts of KCNJ5 somatic mutations on systemic organ damage.

Evidence acquisition: PubMed literature research using keywords combination, including "aldosterone-producing adenoma," "somatic mutations," "KCNJ5," "organ damage," "cardiovascular," "diastolic function," "metabolic syndrome," "autonomous cortisol secretion," etc.

Results: APA patients with KCNJ5 somatic mutations are generally younger, female, have higher aldosterone levels, lower potassium levels, larger tumor size, and higher hypertension cure rate after adrenalectomy. This review focuses on the cardiovascular and metabolic aspects of KCNJ5 somatic mutations in APA patients, including left ventricular remodeling and diastolic function, abdominal aortic thickness and calcification, arterial stiffness, metabolic syndrome, abdominal adipose tissue, and correlation with autonomous cortisol secretion. Furthermore, we discuss modalities to differentiate the types of mutations before surgery.

Conclusion: KCNJ5 somatic mutations in patients with APA had higher left ventricular mass (LVM), more impaired diastolic function, thicker aortic wall, lower incidence of metabolic syndrome, and possibly a lower incidence of concurrent autonomous cortisol secretion, but better improvement in LVM, diastolic function, arterial stiffness, and aortic wall thickness after adrenalectomy compared to patients without KCNJ5 mutations.

Keywords: KCNJ5; adrenocortical adenoma; autonomous cortisol secretion (ACS); cardiovascular system; metabolic syndrome; somatic mutation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma* / pathology
  • Adrenocortical Adenoma* / complications
  • Adrenocortical Adenoma* / genetics
  • Adrenocortical Adenoma* / surgery
  • Aldosterone / metabolism
  • Female
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics
  • Humans
  • Hydrocortisone
  • Hyperaldosteronism* / complications
  • Hyperaldosteronism* / genetics
  • Hyperaldosteronism* / surgery
  • Hypertension* / complications
  • Metabolic Syndrome* / complications
  • Metabolic Syndrome* / genetics
  • Mutation

Substances

  • Aldosterone
  • Hydrocortisone
  • KCNJ5 protein, human
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels

Grants and funding

This study was supported by Ministry of Science and Technology (109-2314-B-002 -247 -MY3, 110-2314-B-002-134-MY3, 111-2314-B-002-044), National Taiwan University Hospital (NTUH 110-A141, 110-S5120, 111-N0092, 111UN-0039, 112-UN0077, VN110-14, VN111-11, VN112-03) and Far Eastern Memorial Hospital (FEMH-2023-C-003). The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.