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Recently developed targeted mutational analysis identified aldosterone-driver somatic mutations in aldosterone-producing lesions, including aldosterone-producing adenomas (APAs), aldosterone-producing nodules (APNs), and aldosterone-producing micronodules, formerly known as aldosterone-producing cell clusters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate histologic and genetic characteristics of lateralized PA in young adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Formalin-fixed, paraffin-embedded adrenal tissue sections from 74 young patients with lateralized PA (&amp;lt;35 years old) were used for this study. Immunohistochemistry (IHC) for aldosterone synthase (CYP11B2) was performed to define the histopathologic diagnosis. Somatic mutations in aldosterone-producing lesions were further determined by CYP11B2 IHC-guided DNA sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Based on the CYP11B2 IHC results, histopathologic classification was made as follows: 48 APAs, 20 APNs, 2 multiple aldosterone-producing nodules (MAPN), 1 double APN, 1 APA with MAPN, and 2 nonfunctioning adenomas (NFAs). Of 45 APAs with successful sequencing, 43 (96%) had somatic mutations, with KCNJ5 mutations being the most common genetic cause of young-onset APA (35\/45, 78%). Of 18 APNs with successful sequencing, all of them harbored somatic mutations, with CACNA1D mutations being the most frequent genetic alteration in young-onset APN (8\/18, 44%). Multiple CYP11B2-expressing lesions in patients with MAPN showed several aldosterone-driver mutations. No somatic mutations were identified in NFAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>APA is the most common histologic feature of lateralized PA in young adults. Somatic KCNJ5 mutations are common in APAs, whereas CACNA1D mutations are often seen in APNs in this young PA population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgac408","type":"journal-article","created":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T11:56:52Z","timestamp":1656763012000},"page":"2473-2482","source":"Crossref","is-referenced-by-count":23,"title":["Histopathology and Genetic Causes of Primary Aldosteronism in Young Adults"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6475-5141","authenticated-orcid":false,"given":"Kazutaka","family":"Nanba","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Michigan , Ann Arbor, MI, 48109 ,","place":["USA"]},{"name":"Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center , Kyoto, 612-8555 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