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Pathogenesis and treatment of primary aldosteronism

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Early diagnosis and appropriate treatment of primary aldosteronism, the most frequent cause of secondary hypertension, are crucial to prevent deleterious cardiovascular outcomes. In the past decade, the discovery of genetic… Click to show full abstract

Early diagnosis and appropriate treatment of primary aldosteronism, the most frequent cause of secondary hypertension, are crucial to prevent deleterious cardiovascular outcomes. In the past decade, the discovery of genetic abnormalities responsible for sporadic and familial forms of primary aldosteronism has improved the knowledge of the pathogenesis of this disorder. Mutations in genes encoding ion channels and pumps lead to increased cytosolic concentrations of calcium in zona glomerulosa cells, which triggers CYP11B2 expression and autonomous aldosterone production. Improved understanding of the mechanisms underlying the disease is key to improving diagnostics and to developing and implementing targeted treatments. This Review provides an update on the genetic abnormalities associated with sporadic and familial forms of primary aldosteronism, their frequency among different populations and the mechanisms explaining excessive aldosterone production and adrenal nodule development. The possible effects and uses of these findings for improving the diagnostics for primary aldosteronism are discussed. Furthermore, current treatment options of primary aldosteronism are reviewed, with particular attention to the latest studies on blood pressure and cardiovascular outcomes following medical or surgical treatment. The new perspectives regarding the use of targeted drug therapy for aldosterone-producing adenomas with specific somatic mutations are also addressed. This Review outlines the latest understanding of the pathogenesis of primary aldosteronism. Current treatment options are also discussed, including the potential for targeted therapies. Primary aldosteronism is the most frequent form of secondary hypertension and is curable. The condition is largely underdiagnosed, preventing patients from receiving targeted treatment and preventing cardiovascular complications. Different genetic abnormalities have been identified in aldosterone-producing adenoma and familial forms of the disease. Most genetic abnormalities increase intracellular calcium signalling in the adrenal zona glomerulosa, increasing aldosterone production. New approaches are currently being developed to achieve more rapid and precise diagnosis of the condition and for more efficient targeted treatment.

Keywords: genetic abnormalities; aldosteronism; primary aldosteronism; treatment primary; pathogenesis

Journal Title: Nature Reviews Endocrinology
Year Published: 2020

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