{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:51:00Z","timestamp":1790297460635,"version":"4.1.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Co-secretion of cortisol and aldosterone can be observed in adrenal adenomas. The aim of this study was to investigate the molecular characteristics of a co-existing aldosterone- and a cortisol-producing adenoma (CPA) in the same patient.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Design and methods<\/jats:title>\n<jats:p>Two different adenomas within the same adrenal gland from a 49-year-old female patient with primary aldosteronism (PA) and Cushing's syndrome (CS) were studied. Multiple formalin-fixed paraffin-embedded tumor blocks were used for the analysis. Immunohistochemistry (IHC) was performed using a specific antibody against aldosterone synthase (CYP11B2). DNA and RNA were isolated separately from CYP11B2-positive and -negative tumor regions based on CYP11B2 IHC results.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>CYP11B2 IHC clearly demonstrated that three pieces from one adenoma were positive for CYP11B2 and the remaining three from the other adenoma were negative for CYP11B2. In quantitative real-time RT-PCR, <jats:italic>CYP11B2<\/jats:italic> mRNA was upregulated in CYP11B2-positive tumor specimens (219-fold vs CYP11B2-negative tumor specimens). Targeted next-generation sequencing (NGS) detected novel <jats:italic>KCNJ5<\/jats:italic> gene mutations (p.T148I\/T149S, present in the same reads) and a <jats:italic>PRKACA<\/jats:italic> gene hotspot mutation (p.L206R) in the CYP11B2-positive and -negative tumors, respectively. Sanger sequencing of DNA from each tumor specimen (CYP11B2-positive tumor, <jats:italic>n<\/jats:italic>=3; CYP11B2-negative tumor, <jats:italic>n<\/jats:italic>=3) showed concordant results with targeted NGS.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our findings illustrate the co-existence of two different adrenocortical adenomas causing the concurrent diagnosis of PA and CS in the same patient. Molecular analysis was able to demonstrate that the two diseases resulted from independent somatic mutations seen in double adrenocortical adenomas.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-16-0262","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T02:50:58Z","timestamp":1462935058000},"page":"K1-K6","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":37,"title":["Double adrenocortical adenomas harboring independent KCNJ5 and PRKACA somatic mutations"],"prefix":"10.1093","volume":"175","author":[{"given":"Kazutaka","family":"Nanba","sequence":"first","affiliation":[{"name":"1Departments of Molecular and Integrative Physiology & Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Omata","sequence":"additional","affiliation":[{"name":"2Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A","family":"Tomlins","sequence":"additional","affiliation":[{"name":"2Department of Pathology"},{"name":"3Comprehensive Cancer Center"},{"name":"4Michigan Center for Translational Pathology"},{"name":"5Department of Urology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Giordano","sequence":"additional","affiliation":[{"name":"2Department of Pathology"},{"name":"3Comprehensive Cancer Center"},{"name":"6Division of Metabolism, Endocrinology, and Diabetes"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D","family":"Hammer","sequence":"additional","affiliation":[{"name":"1Departments of Molecular and Integrative Physiology & Internal Medicine"},{"name":"6Division of Metabolism, Endocrinology, and Diabetes"},{"name":"7Endocrine Oncology ProgramCenter for Organogenesis, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E","family":"Rainey","sequence":"additional","affiliation":[{"name":"1Departments of Molecular and Integrative Physiology & Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Else","sequence":"additional","affiliation":[{"name":"6Division of Metabolism, Endocrinology, and 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