Histopathology and Molecular Profiling of Primary Aldosteronism

Area of Science:

• Endocrinology
• Nephrology
• Surgical Pathology

Background:

• Primary aldosteronism is the leading surgically treatable cause of hypertension.
• Surgically treatable forms involve lateralized aldosterone overproduction, ranging from unilateral hypersecretion to asymmetrical bilateral production.
• Historically, solitary adenomas were implicated, but now a spectrum of lesions, including micronodules, is recognized.

Purpose of the Study:

• To review recent evidence linking histopathology, genetics, and cellular mapping to surgical outcomes in primary aldosteronism.
• To explain the heterogeneity observed in surgical outcomes for this condition.
• To advance a pathophysiology-based framework for improved diagnosis and management.

Main Methods:

• Synthesis of recent evidence from histopathology, genetics, and cellular mapping studies.
• Application of the Histopathology of Primary Aldosteronism consensus classification.
• Analysis of somatic driver mutations and single-cell/spatial omics data.

Main Results:

• Lateralized primary aldosteronism is classified into classical (adenoma-predominant) and nonclassical (micronodule-predominant) forms.
• Classical forms correlate with biochemical remission, while nonclassical forms are linked to persistent or recurrent aldosteronism.
• Somatic mutations and omics data reveal distinct pathogenic trajectories and metabolic profiles influencing tumor progression.

Conclusions:

• Histopathology, genetics, and omics collectively explain heterogeneity in surgical outcomes for primary aldosteronism.
• A precise, pathophysiology-based framework enhances diagnosis, subtyping, and outcome prediction.
• These advances facilitate tailored management strategies for patients with primary aldosteronism.