ArticleProceedings of the National Academy of Sciences of the United States of America2015
Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
169 citing papers in PubMed, 1 synthesis or guideline pooled it, 316 citations in OpenAlex.
- Identification of risk loci for primary aldosteronism in genome-wide association studies.Nature communications · 2022Pooled it
- [Nature medicine · 2023Trial
- ACTH Stimulation Maximizes the Accuracy of Peripheral Steroid Profiling in Primary Aldosteronism Subtyping.The Journal of clinical endocrinology and metabolism · 2021Trial
- Renalase stimulates aldosterone production via PMCA4b/cAMP in NCI-H295R cells.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- From bench to bedside: primary aldosteronism revisited.Endocrine connections · 2026Article
- Integrated Transcriptomics Reveals Evolutionary Trajectories and Cell Density-Dependent Mechanisms in Aldosterone-Producing Adenomas.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Familial Hyperaldosteronism Type IV (FH-IV)-Clinical Phenotypes, Genetics and Management ofJournal of clinical medicine · 2026Review
- Increased Frequency and Distinct Genotypic Patterns of Somatic Aldosterone-Driver Mutations in Aldosterone-Producing Micronodules from Primary Aldosteronism Patients.Endocrine pathology · 2026Article
- The genetics of hypertension.Nature reviews. Nephrology · 2026Review
- Emerging methods for subtype differentiation in primary aldosteronism.Journal of internal medicine · 2026Review
- Subclinical primary aldosteronism and major adverse cardiovascular events: evidence for a continuum of renin-independent aldosterone excess and a proposal for early detection.Frontiers in cardiovascular medicine · 2026Review
- Subclinical primary aldosteronism: toward a conceptual framework linking primary aldosteronism and low-renin hypertension.Frontiers in endocrinology · 2026Review
- Coexistence of primary aldosteronism and micro-pheochromocytoma: a case report with pathological analysis and literature review.Frontiers in medicine · 2026Article
- Case Report: SomaticFrontiers in medicine · 2026Article
- Subclinical primary aldosteronism.Archives of endocrinology and metabolism · 2025Review
- Osmolarity Controls Oscillatory Calcium Signaling to Reduce Autonomous Aldosterone Production in Zona Glomerulosa Cells.Endocrinology · 2025Article
- Subclinical Primary Aldosteronism Is Characterized by Maladaptive Natriuretic Peptide and Adrenal Hormonal Physiology.The Journal of clinical endocrinology and metabolism · 2025Observational
- Cosyntropin-Stimulated Aldosterone Reserve of the Nondominant Adrenal Predicts Surgical Outcomes in Primary Aldosteronism.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Review
- Advancements in the research of the structure, function, and disease-related roles of ARMC5.Frontiers of medicine · 2025Review
109 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Primary aldosteronism (PA) represents the most common cause of secondary hypertension, but little is known regarding its adrenal cellular origins. Recently, aldosterone-producing cell clusters (APCCs) with high expression of aldosterone synthase (CYP11B2) were found in both normal and PA adrenal tissue. PA-causing aldosterone-producing adenomas (APAs) harbor mutations in genes encoding ion channels/pumps that alter intracellular calcium homeostasis and cause renin-independent aldosterone production through increased CYP11B2 expression. Herein, we hypothesized that APCCs have APA-related aldosterone-stimulating somatic gene mutations. APCCs were studied in 42 normal adrenals from kidney donors. To clarify APCC molecular characteristics, we used microarrays to compare the APCC transcriptome with conventional adrenocortical zones [zona glomerulosa (ZG), zona fasciculata, and zona reticularis]. The APCC transcriptome was most similar to ZG but with an enhanced capacity to produce aldosterone. To determine if APCCs harbored APA-related mutations, we performed targeted next generation sequencing of DNA from 23 APCCs and adjacent normal adrenal tissue isolated from both formalin-fixed, paraffin-embedded, and frozen tissues. Known aldosterone driver mutations were identified in 8 of 23 (35%) APCCs, including mutations in calcium channel, voltage-dependent, L-type, α1D-subunit (CACNA1D; 6 of 23 APCCs) and ATPase, Na(+)/(K+) transporting, α1-polypeptide (ATP1A1; 2 of 23 APCCs), which were not observed in the adjacent normal adrenal tissue. Overall, we show three major findings: (i) APCCs are common in normal adrenals, (ii) APCCs harbor somatic mutations known to cause excess aldosterone production, and (iii) the mutation spectrum of aldosterone-driving mutations is different in APCCs from that seen in APA. These results provide molecular support for APCC as a precursor of PA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.