Pathogenesis and treatment of primary aldosteronism

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 last 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 familiar 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.

A Bibliometric Analysis of Primary Aldosteronism Research From 2000 to 2020

“…Adrenal adenoma is considered a benign neoplasm of the adrenal cortex. In addition, genetic studies have helped to understand the relationship between benign aldosterone-producing adrenocortical proliferation and ion channel mutations ( 2 , 39 , 40 ). Cluster 3 is related to hypertension associated with PA. PA accounts for 5–10% of all hypertension patients and exist in 20% of those with resistant hypertension.…”

“…Cluster 3 is related to hypertension associated with PA. PA accounts for 5–10% of all hypertension patients and exist in 20% of those with resistant hypertension. Our understanding of PA-related hypertension has increased tremendously during the last two decades and exploring how PA leads to hypertension is the key to improve the outcome of long-term diseases and improve the quality of life of PA patients ( 2 , 6 , 41 ). Cluster 4 is related to clinical monitoring parameters and diagnosis in PA patients.…”

“…Adrenal vein sampling (AVS), the most recommended procedure for lateralization in PA, has many limitations such as required technical expertise, increased costs, and potential complications ( 42 ). As a consequence, the development of new non-invasive imaging techniques and monitoring parameters is conducive to timely diagnosis, provides appropriate treatment, and prevents deleterious cardiovascular outcomes of PA, which is also a challenge for doctors and researchers in the future ( 2 , 43 ).…”

“…PA was first described by Jerome Conn in 1955 in a patient ( 14 ). During the past 65 years, especially in the last two decades, great progress has been made in the field of PA research regarding genetic and genomic mechanisms, pathophysiology, diagnostics, and therapeutics ( 2 , 15 , 16 ). However, there is still a lack of comprehensive reports that can assist researchers in obtaining an intuitive overview and reveal research trends in the PA research field.…”

“…Primary aldosteronism (PA), characterized by an increased aldosterone production, is the most frequent form of secondary hypertension (1,2). PA patients have an increased risk of stroke, heart failure, coronary artery disease, atrial fibrillation (1,(3)(4)(5), renal damage (6,7), diabetes (8,9), metabolic syndrome (9,10).…”