Recent Advances in the Molecular and Genetic Landscape of Primary Aldosteronism

Primary aldosteronism (PA) is the leading cause of endocrine hypertension and a significant contributor to cardiovascular and renal morbidity. Advances in adrenal endocrinology have uncovered a growing spectrum of somatic and germline mutations that drive autonomous aldosterone production in aldosterone-producing adenomas (APAs) and bilateral adrenal hyperplasia. These discoveries have reshaped our understanding of adrenal tumorigenesis, highlighting distinct molecular subtypes of PA with varying clinical presentations, biochemical profiles, and therapeutic responses.

Despite substantial progress, the pathogenesis of PA remains incompletely understood. It involves a complex interplay between genetic mutations, signaling pathway dysregulation, epigenetic modifications, and microenvironmental factors. Together, these processes govern adrenal cell fate, zonation, and steroidogenic function—ultimately influencing disease progression and treatment outcomes. The integration of molecular genetics with adrenal physiology offers new opportunities for improved diagnostic accuracy, subtype classification, and personalized therapeutic strategies.

This Research Topic aims to showcase cutting-edge studies that investigate the genetic and molecular basis of PA, particularly those bridging mechanistic insights with translational and clinical relevance. We encourage contributions that explore how molecular alterations influence adrenal cell behavior, tumor biology, and patient management, with a focus on leveraging genomics to inform endocrine practice.

We welcome submissions including, but not limited to:

- Discovery and functional validation of novel somatic or germline mutations in APAs and familial PA
- Molecular regulation of aldosterone biosynthesis and adrenal cortex zonation
- Cellular and developmental origins of APAs, including stem/progenitor cell dynamics
- Single-cell transcriptomic, spatial omics, and multi-omics approaches in adrenal tissue
- Aberrant activation of signaling pathways (e.g., calcium, Wnt/β-catenin) and ion channelopathies
- Epigenetic regulation and post-transcriptional networks involved in PA pathogenesis
- In vivo and in vitro models elucidating adrenal tumor development and aldosterone excess
- Translational research linking molecular diagnostics to targeted treatment strategies