{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:09:16Z","timestamp":1792098556947,"version":"4.4.0"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","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"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    Primary aldosteronism (PA) is the most common form of secondary arterial hypertension, with a prevalence of approximately 20% in patients with resistant hypertension. In the last decade, somatic pathogenic variants in\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    ,\n                    <jats:italic>CACNA1D, ATP1A1<\/jats:italic>\n                    and\n                    <jats:italic>ATP2B3<\/jats:italic>\n                    genes, which are involved in maintaining intracellular ionic homeostasis and cell membrane potential, were described in aldosterone-producing adenomas (aldosteronomas). All variants in these genes lead to the activation of calcium signaling, the major trigger for aldosterone production. Genetic causes of familial hyperaldosteronism have been expanded through the report of germline pathogenic variants in\n                    <jats:italic>KCNJ5, CACNA1H<\/jats:italic>\n                    and\n                    <jats:italic>CLCN2<\/jats:italic>\n                    genes. Moreover,\n                    <jats:italic>PDE2A<\/jats:italic>\n                    and\n                    <jats:italic>PDE3B<\/jats:italic>\n                    variants were associated with bilateral PA and increased the spectrum of genetic etiologies of PA. Of great importance, the genetic investigation of adrenal lesions guided by the CYP11B2 staining strongly changed the landscape of somatic genetic findings of PA. Furthermore, CYP11B2 staining allowed the better characterization of the aldosterone-producing adrenal lesions in unilateral PA. Aldosterone production may occur from multiple sources, such as solitary aldosteronoma or aldosterone-producing nodule (classical histopathology) or clusters of autonomous aldosterone-producing cells without apparent neoplasia denominated aldosterone-producing micronodules (non-classical histopathology). Interestingly,\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    mutational status and classical histopathology of unilateral PA (aldosteronoma) have emerged as relevant predictors of clinical and biochemical outcome, respectively. In this review, we summarize the most recent advances in the pathogenesis of PA and discuss their impact on clinical outcome.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2022.927669","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T08:02:13Z","timestamp":1655971333000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Pathogenesis of Primary Aldosteronism: Impact on Clinical Outcome"],"prefix":"10.3389","volume":"13","author":[{"given":"Lucas S.","family":"Santana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto G.","family":"Guimaraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madson 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