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Genetic Spectrum and Clinical Correlates of Somatic Mutations in Aldosterone-Producing Adenoma
Open accessAbstract
Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D have been described in aldosterone-producing adenomas (APAs). Our aim was to investigate the prevalence of somatic mutations in these genes in unselected patients with APA (n=474), collected through the European Network for the Study of Adrenal Tumors. Correlations with clinical and biochemical parameters were first analyzed in a subset of 199 patients from a single center and then replicated in 2 additional centers. Somatic heterozygous KCNJ5 mutations were present in 38% (180/474) of APAs, whereas ATP1A1 mutations were found in 5.3% (25/474) and ATP2B3 mutations in 1.7% (8/474) of APAs. Previously reported somatic CACNA1D mutations as well as 10 novel CACNA1D mutations were identified in 44 of 474 (9.3%) APAs. There was no difference in the cellular composition of APAs or in CYP11B2, CYP11B1, KCNJ5, CACNA1D, or ATP1A1 gene expression in APAs across genotypes. Patients with KCNJ5 mutations were more frequently female, diagnosed younger, and with higher minimal plasma potassium concentrations compared with CACNA1D mutation carriers or noncarriers. CACNA1D mutations were associated with smaller adenomas. These associations were largely dependent on the population structure of the different centers. In conclusion, recurrent somatic mutations were identified in 54% of APAs. Young women with APAs are more likely to be KCNJ5 mutation carriers; identification of specific characteristics or surrogate biomarkers of mutation status may lead to targeted treatment options.
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Pizzo, A., Paccagnella, M., & Bernardi, S. (2024) · L Endocrinologo · doi:10.1007/s40619-024-01557-x
Genetic causes of aldosterone-producing adenomas
Nanba, K., & Rainey, W. E. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00140-0
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Self-citationZuo, R., Chen, Z., Wang, Z., Li, S., Li, W., Xia, Z., Pang, H., & Xu, L. (2026) · EJNMMI Research · doi:10.1186/s13550-026-01389-w
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Fayad, M., Cosentino, T., Faedda, N., Boulkroun, S., Zennaro, M., & Fernandes-Rosa, F. L. (2026) · Annales d Endocrinologie · doi:10.1016/j.ando.2026.102520
Self-citation
Metadata
- Authors
- Fernandes-Rosa, F. L., Williams, T. A., Riester, A., Steichen, O., Beuschlein, F., Boulkroun, S., Strom, T. M., Monticone, S., Amar, L., Meatchi, T., Mantero, F., Cicala, M.-V., Quinkler, M., Fallo, F., Allolio, B., Bernini, G., Maccario, M., Giacchetti, G., Jeunemaitre, X., Mulatero, P., Reincke, M., & Zennaro, M.-C.
- Affiliations
- Inserm (FR)
- From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d’Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension,...
- ORCID
- Venue
- Hypertension
- Published
- 2014-08
- Volume
- 64
- Issue
- 2
- Pages
- 354-361
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2111582520
- Cited by
- 310
- References
- 30
- Citations by year
- 2026: 21 · 2025: 18 · 2024: 14 · 2023: 15 · 2022: 16 · 2021: 28 · 2020: 27 · 2019: 33 · 2018: 25 · 2017: 31 · 2016: 34 · 2015: 33 · 2014: 12
- FWCI
- 29.40
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- aldosterone-producing adenoma, primary aldosteronism, somatic mutations, KCNJ5, ATP1A1, ATP2B3, CACNA1D, secondary hypertension, plasma potassium, adenoma size, mutation prevalence, genetic spectrum, clinical correlates
- MeSH terms
- Sodium-Potassium-Exchanging ATPase, Adrenal Cortex Neoplasms, Adult, Age Factors, Aldosterone, Female, Humans, Hyperaldosteronism, Male, Middle Aged, Mutation, Potassium, Sex Factors, Adrenocortical Adenoma, Genetic Predisposition to Disease, Calcium Channels, L-Type, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Plasma Membrane Calcium-Transporting ATPases, Genetic Association Studies
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