Send to:

Choose Destination
See comment in PubMed Commons below
Curr Opin Nephrol Hypertens. 2013 Mar;22(2):141-7. doi: 10.1097/MNH.0b013e32835cecf8.

New insights into aldosterone-producing adenomas and hereditary aldosteronism: mutations in the K+ channel KCNJ5.

Author information

  • 1Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.



Primary aldosteronism is a major cause of secondary hypertension worldwide. This review describes the recent studies that have provided dramatic new insight into the pathogenesis of aldosterone-producing adenomas (APAs) and inherited primary aldosteronism, revealing the role of mutations in the potassium channel KCNJ5 in these disorders.


Either of two somatic gain-of-function mutations in the inward rectifier potassium channel KCNJ5 (Kir3.4) are present in approximately 40% of APAs. These tumor-causing mutations are heterozygous and alter the channel's selectivity filter. Mutant channels gain permeability to sodium, resulting in cellular depolarization and activation of voltage-gated calcium channels. The resulting calcium influx is sufficient to produce aldosterone secretion and cell proliferation, accounting for APA development. Germline KCNJ5 mutations also result in either of two autosomal-dominant syndromes featuring early-onset primary aldosteronism. Mutations identical or similar to those found in APAs result in massive bilateral adrenal hyperplasia. A different mutation at the same position produces a less severe syndrome without adrenal hyperplasia because this mutation results in Na-dependent cell lethality caused by a drastic increase in Na conductance.


These findings provide fundamental insight into the pathogenesis of APAs and primary aldosteronism, and have implications for new diagnostic and therapeutic strategies.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Lippincott Williams & Wilkins
    Loading ...
    Write to the Help Desk