Genetics and Primary Aldosteronism: Disease Phenotype and Demographic Implications for Hypertension

Detecting secondary forms of hypertension is key to targeted management and prevention of cardiovascular complications. Primary aldosteronism (PA) is the most common form of secondary arterial hypertension, resulting from excess adrenal unilateral or bilateral aldosterone production. Its prevalence rises with hypertension severity, reaching 25% in treatment-resistant patients. Understanding the genetic basis of PA provides key insights into its pathophysiology and improves strategies for diagnosing and managing hypertension in the general population. Genetic studies performed over the last few years have unraveled the genetic spectrum of PA. Somatic and germline mutations have been identified in most aldosterone-producing adenomas and familial forms of the disease. Recent studies have also uncovered genetic loci that increase susceptibility to PA that are common to lateralized and bilateral forms of PA and shared with blood pressure loci. Together with the clinical and biochemical description of a continuum of aldosterone dysregulation in hypertension, these findings mark a shift in our understanding of disease pathogenesis, indicating that common genetic variants may contribute to dysregulated aldosterone production in hypertension and to the development of PA in extreme cases. Different genetic susceptibility and genotype-phenotype correlations may shape the demographic distribution and clinical recognition of PA, influencing both its apparent prevalence and the likelihood of timely diagnosis.