Pathogenesis of primary aldosteronism

Primary aldosteronism (PA) is the most common cause of endocrine hypertension, characterized by autonomous aldosterone production, unregulated by sodium balance or renin-angiotensin system activity. Once considered a rare, PA is now recognized as a spectrum that includes subclinical forms in normotensive individuals. Aldosterone synthesis, normally regulated by angiotensin II, extracellular potassium, and adrenocorticotropic hormone (ACTH), undergoes dysregulated in PA, often due to somatic or germline mutations affecting ion channels or intracellular signaling pathways. This disruption promotes morphological alteration in the adrenal cortex, including aldosterone-producing cell clusters (APCCs), micronodules, and aldosterone-producing adenomas (APAs). These lesions contribute to renin-independent aldosterone secretion and inappropriate ACTH sensitivity. Aldosterone acts through the mineralocorticoid receptor (MR), triggering both genomic and non-genomic effects. MR activation in multiple tissues promotes cardiovascular and metabolic damage, often independent of blood pressure. These insights support early detection and a broader clinical approach to PA, incorporating its genetic, structural, and molecular basis.