Histopathology and Molecular Profiling of Primary Aldosteronism

Primary aldosteronism is the most common surgically treatable form of hypertension. Surgically amenable forms are characterized by lateralized aldosterone overproduction, which may occur along a spectrum ranging from true unilateral hypersecretion to asymmetrical bilateral production. Historically attributed to solitary aldosterone-producing adenomas, lateralized primary aldosteronism is now recognized to encompass a range of histopathologic lesions, including aldosterone-producing micronodules, reflecting a continuum from subclinical autonomous secretion to overt primary aldosteronism. This review synthesizes recent evidence demonstrating how histopathology, genetics, and cellular mapping can collectively explain some of the heterogeneity in surgical outcomes. The Histopathology of Primary Aldosteronism consensus classifies lateralized primary aldosteronism into classical (aldosterone-producing adenoma-predominant) and nonclassical (aldosterone-producing micronodule-predominant) forms, with the former linked to biochemical remission and the latter associated with persistent or recurrent aldosteronism. Somatic driver mutations further correlate with histology and outcomes, while single-cell and spatial omics data reveal distinct pathogenic trajectories and metabolic profiles underlying tumor progression. Together, these advances offer a more precise, pathophysiology-based framework to improve diagnosis, subtyping, and outcome prediction, advancing tailored management for this disease.