{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:47:20Z","timestamp":1787021240906,"version":"build-2736575974"},"reference-count":41,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Sao Paulo Research Foundation","doi-asserted-by":"publisher","award":["2019\/15873-6"],"award-info":[{"award-number":["2019\/15873-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FAPESP fellowship","award":["2021\/10101-5"],"award-info":[{"award-number":["2021\/10101-5"]}]},{"name":"FAPESP fellowship","award":["2024\/16029-2"],"award-info":[{"award-number":["2024\/16029-2"]}]},{"name":"FAPESP fellowship","award":["2024\/18510-0"],"award-info":[{"award-number":["2024\/18510-0"]}]},{"name":"FAPESP fellowship","award":["2021\/11240-9"],"award-info":[{"award-number":["2021\/11240-9"]}]},{"name":"FAPESP fellowship","award":["2021\/10363-0"],"award-info":[{"award-number":["2021\/10363-0"]}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["304091\/2021-9"],"award-info":[{"award-number":["304091\/2021-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The Brazilian population represents a mosaic of genetic diversity resulting from admixture ancestries. Given reported disparities in primary aldosteronism (PA) genetics across ethnicities, we investigated the genetic spectrum of aldosterone-producing adenomas (APAs) and nodules (APNs) with classical histology in a Brazilian cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 62 lesions (1 case with bilateral APAs) from 61 consecutive patients (median age at PA diagnosis 49 years, 59% women) with PA and classical histology, defined by CYP11B2 immunostaining (HISTALDO consensus). Somatic DNA was extracted from CYP11B2-positive areas of the dominant lesions. Hotspot regions of KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 were initially analyzed by Sanger sequencing. Whole-exome sequencing of paired somatic and germline DNA was subsequently performed in cases without driver variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Histopathology showed combined APA + aldosterone-producing micronodules as the most frequent subtype (n = 29, 47.54%), followed by isolated APA (n = 20, 32.79%) and APN (n = 5, 8.2%). Somatic pathogenic variants were identified in 82.26% of lesions: KCNJ5 (n = 35, 56.45%), ATP2B3 (n = 7, 11.29%), CACNA1D (n = 5, 8.06%), and ATP1A1 (n = 4, 6.45%). Nine novel variants were identified, including 3 in ATP2B3 (2 exon 8 in-frame deletions and 1 missense), 3 in KCNJ5, 2 in CACNA1D, and 1 in CTNNB1. The frequency of ATP2B3 variants (11.29%) was significantly higher than that reported in other cohorts (4.06%) from different ethnicities (p = .0053). ATP2B3-mutated tumors occurred predominantly in older men and were smaller in size compared with wild-type tumors. Rare germline CACNA1H variants were also detected in 3 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We confirmed the predominance of known somatic drivers and identified a uniquely high frequency of ATP2B3 variants, refining their clinical phenotype. These findings underscore the influence of population-specific genetic backgrounds and expand the global understanding of PA genetics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag002","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:31:15Z","timestamp":1767702675000},"page":"1584-1595","source":"Crossref","is-referenced-by-count":5,"title":["Somatic Drivers in Aldosterone-producing Adenomas and Nodules: Insights from a Brazilian Cohort of Primary Aldosteronism"],"prefix":"10.1210","volume":"111","author":[{"given":"Augusto G","family":"Guimaraes","sequence":"first","affiliation":[{"name":"Unidade de Adrenal, Laborat\u00f3rio de Endocrinologia Molecular e Celular LIM25, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana S","family":"Goldbaum","sequence":"additional","affiliation":[{"name":"Unidade de Adrenal, Laborat\u00f3rio de Endocrinologia Molecular e Celular LIM25, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe L","family":"Ledesma","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Freitas-Castro","sequence":"additional","affiliation":[{"name":"Unidade de Adrenal, Laborat\u00f3rio de Endocrinologia Molecular e Celular LIM25, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas S","family":"Santana","sequence":"additional","affiliation":[{"name":"Unidade de Adrenal, Laborat\u00f3rio de Endocrinologia Molecular e Celular LIM25, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Antonio B L","family":"Sobrinho","sequence":"additional","affiliation":[{"name":"Unidade de Adrenal, Laborat\u00f3rio de Endocrinologia Molecular e Celular LIM25, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas B","family":"Rossetti","sequence":"additional","affiliation":[{"name":"Unidade de Adrenal, Laborat\u00f3rio de Endocrinologia Molecular e Celular LIM25, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Okubo","sequence":"additional","affiliation":[{"name":"Unidade de Adrenal, Laborat\u00f3rio de Endocrinologia Molecular e Celular LIM25, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Z","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Unidade de Adrenal, Laborat\u00f3rio de Endocrinologia Molecular e Celular LIM25, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz A","family":"Bortolotto","sequence":"additional","affiliation":[{"name":"Unidade de Hipertens\u00e3o, Instituto do Cora\u00e7\u00e3o (InCor), Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 05403-900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8346-3833","authenticated-orcid":false,"given":"Victor","family":"Srougi","sequence":"additional","affiliation":[{"name":"Divis\u00e3o de Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio Y","family":"Tanno","sequence":"additional","affiliation":[{"name":"Divis\u00e3o de Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Williams C","family":"Nahas","sequence":"additional","affiliation":[{"name":"Divis\u00e3o de Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L","family":"Chambo","sequence":"additional","affiliation":[{"name":"Divis\u00e3o de Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Adelaide A","family":"Pereira","sequence":"additional","affiliation":[{"name":"Unidade de Adrenal, Laborat\u00f3rio de Endocrinologia Molecular e Celular LIM25, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pio-Abreu","sequence":"additional","affiliation":[{"name":"Unidade de Hipertens\u00e3o, Disciplina de Nefrologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanio V","family":"Silva","sequence":"additional","affiliation":[{"name":"Unidade de Hipertens\u00e3o, Disciplina de Nefrologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano F","family":"Drager","sequence":"additional","affiliation":[{"name":"Unidade de Hipertens\u00e3o, Instituto do Cora\u00e7\u00e3o (InCor), Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 05403-900 ,","place":["Brazil"]},{"name":"Unidade de Hipertens\u00e3o, Disciplina de Nefrologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Candida B V","family":"Fragoso","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]},{"name":"Unidade de Oncologia End\u00f3crina, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia","family":"Latronico","sequence":"additional","affiliation":[{"name":"Unidade de Adrenal, Laborat\u00f3rio de Endocrinologia Molecular e Celular LIM25, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice B","family":"Mendonca","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7408-9816","authenticated-orcid":false,"given":"Maria Claudia N","family":"Zerbini","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2957-6148","authenticated-orcid":false,"given":"Madson Q","family":"Almeida","sequence":"additional","affiliation":[{"name":"Unidade de Adrenal, Laborat\u00f3rio de Endocrinologia Molecular e Celular LIM25, Divis\u00e3o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 ,","place":["Brazil"]},{"name":"Unidade de Oncologia End\u00f3crina, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-000 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