Primary aldosteronism : Genetics and pathology

Abstract

Primary aldosteronism, the excessive production of the steroid hormone aldosterone, is the most common cause of secondary hypertension. Common subforms include bilateral adrenal hyperplasia and aldosterone-producing adenoma. The goal of this review is to summarize important publications on the genetic basis of primary aldosteronism. Somatic mutations in the KCNJ5, CACNA1D, ATP1A1, and ATP2B3 genes have been described as causes of aldosterone-producing adenomas. They eventually all lead to increased cellular calcium influx and aldosterone production. The mechanisms of rare CTNNB1 mutations are less defined. Correlations between mutations and different histologic characteristics as well as gender and ethnicity remain unexplained. Recent publications suggest that bilateral hyperplasia is at least partially due to so-called aldosterone-producing cell clusters, often with mutations in CACNA1D. Rare familial forms show mutations in the CYP11B2, CLCN2, KCNJ5, CACNA1H, or CACNA1D genes. These results suggest that asignificant fraction of primary aldosteronism is due to somatic mutations in single genes.