{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:37:04Z","timestamp":1791286624046,"version":"4.1.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Cortisol excess due to adrenal adenomas or hyperplasia causes Cushing's syndrome. Recent genetic studies have identified a somatic<jats:italic>PRKACA<\/jats:italic><jats:sup><jats:italic>L206R<\/jats:italic><\/jats:sup>mutation as a cause of cortisol-producing adenomas. We aimed to compare the clinical features of<jats:italic>PRKACA<\/jats:italic>-mutant lesions with those of<jats:italic>CTNNB1<\/jats:italic>mutations, and to search for similar mutations in unilateral hyperplasia or tumors co-secreting aldosterone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, patients, and methods<\/jats:title><jats:p>In this study, 60 patients with cortisol excess who had adrenalectomies at our institution between 1992 and 2013 were assessed, and somatic mutations were determined by Sanger sequencing. A total of 36 patients had overt Cushing's syndrome, the remainder were subclinical: 59 cases were adenomas (three bilateral) and one was classified as hyperplasia. Four tumors had proven co-secretion of aldosterone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among cortisol-secreting unilateral lesions without evidence of co-secretion (<jats:italic>n<\/jats:italic>=52), we identified somatic mutations in<jats:italic>PRKACA<\/jats:italic>(L206R) in 23.1%,<jats:italic>CTNNB1<\/jats:italic>(S45P, S45F) in 23.1%,<jats:italic>GNAS<\/jats:italic>(R201C) in 5.8%, and<jats:italic>CTNNB1<\/jats:italic>+<jats:italic>GNAS<\/jats:italic>(S45P, R201H) in 1.9%.<jats:italic>PRKACA<\/jats:italic>and<jats:italic>GNAS<\/jats:italic>mutations were mutually exclusive. Of the co-secreting tumors, two (50%) had mutations in<jats:italic>KCNJ5<\/jats:italic>(G151R and L168R). The hyperplastic gland showed a<jats:italic>PRKACA<\/jats:italic><jats:sup><jats:italic>L206R<\/jats:italic><\/jats:sup>mutation, while patients with bilateral adenomas did not have known somatic mutations.<jats:italic>PRKACA<\/jats:italic>-mutant lesions were associated with younger age, overt Cushing's syndrome, and higher cortisol levels vs non-<jats:italic>PRKACA<\/jats:italic>-mutant or<jats:italic>CTNNB1<\/jats:italic>-mutant lesions.<jats:italic>CTNNB1<\/jats:italic>mutations were more significantly associated with right than left lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>PRKACA<\/jats:italic><jats:sup><jats:italic>L206R<\/jats:italic><\/jats:sup>is present not only in adenomas, but also in unilateral hyperplasia and is associated with more severe autonomous cortisol secretion. Bilateral adenomas may be caused by yet-unknown germline mutations.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-14-1113","type":"journal-article","created":{"date-parts":[[2015,3,7]],"date-time":"2015-03-07T02:53:35Z","timestamp":1425696815000},"page":"677-685","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":71,"title":["PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia: a single-center study of 60 cases"],"prefix":"10.1093","volume":"172","author":[{"given":"Anne","family":"Thiel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Carinna","family":"Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Haase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Goh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger S","family":"Willenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute I","family":"Scholl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"6186","key":"1_47918752","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1126\/science.1254901","volume":"344","author":"Kirschner","year":"2014","journal-title":"Science","ISSN":"https:\/\/id.crossref.org\/issn\/0036-8075","issn-type":"print"},{"issue":"12","key":"2_15774042","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1056\/NEJM199503233321207","volume":"332","author":"Orth","year":"1995","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"key":"3_47918755","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1056\/NEJMoa1310359","volume":"370","year":"2014","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"issue":"6186","key":"4_47675163","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1126\/science.1249480","volume":"344","year":"2014","journal-title":"Science","ISSN":"https:\/\/id.crossref.org\/issn\/0036-8075","issn-type":"print"},{"issue":"6186","key":"5_47918754","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1126\/science.1252328","volume":"344","author":"Sato","year":"2014","journal-title":"Science","ISSN":"https:\/\/id.crossref.org\/issn\/0036-8075","issn-type":"print"},{"key":"6_48476730","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/ng.2956","volume":"46","year":"2014","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"key":"7_50396883","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1507\/endocrj.EJ14-0282","volume":"61","year":"2014","journal-title":"Endocrine journal","ISSN":"https:\/\/id.crossref.org\/issn\/0918-8959","issn-type":"print"},{"key":"8_49236968","doi-asserted-by":"crossref","first-page":"E2093","DOI":"10.1210\/jc.2014-2152","volume":"99","year":"2014","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"1","key":"9_40812503","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.mce.2011.09.009","volume":"351","author":"Berthon","year":"2012","journal-title":"Molecular and cellular endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0303-7207","issn-type":"print"},{"issue":"2","key":"10_30302159","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/j.1365-2265.2007.03033.x","volume":"68","author":"Tadjine","year":"2008","journal-title":"Clinical endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0300-0664","issn-type":"print"},{"issue":"8","key":"11_36460522","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1093\/hmg\/ddq029","volume":"19","year":"2010","journal-title":"Human Molecular Genetics","ISSN":"https:\/\/id.crossref.org\/issn\/0964-6906","issn-type":"print"},{"issue":"5","key":"12_17611046","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1210\/jc.2002-021362","volume":"88","author":"Fragoso","year":"2003","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"key":"13_41383128","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.beem.2006.07.006","volume":"20","year":"2006","journal-title":"BEST PRACTICE RESEARCH CLINICAL ENDOCRINOLOGY METABOLISM"},{"key":"14_50396884","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1159\/000314315","volume":"92","year":"2010","journal-title":"Neuroendocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0028-3835","issn-type":"print"},{"issue":"5","key":"15_36705115","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/hr.2010.18","volume":"33","author":"Willenberg","year":"2010","journal-title":"Hypertension research : official journal of the Japanese Society of Hypertension","ISSN":"https:\/\/id.crossref.org\/issn\/0916-9636","issn-type":"print"},{"issue":"8","key":"16_43367495","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1507\/endocrj.EJ12-0247","volume":"59","author":"Yamada","year":"2012","journal-title":"Endocrine journal","ISSN":"https:\/\/id.crossref.org\/issn\/0918-8959","issn-type":"print"},{"issue":"4","key":"17_39039008","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1530\/EJE-10-1070","volume":"164","year":"2011","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"6018","key":"19_39182913","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1126\/science.1198785","volume":"331","author":"Choi","year":"2011","journal-title":"Science","ISSN":"https:\/\/id.crossref.org\/issn\/0036-8075","issn-type":"print"},{"key":"20_45695426","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/ng.2550","volume":"45","year":"2013","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"key":"21_46521413","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/ng.2716","volume":"45","year":"2013","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"key":"22_47043124","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/ng.2695","volume":"45","year":"2013","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"key":"23_50396885","first-page":"81","volume":"45","year":"2013","journal-title":"Hormone and metabolic research. Hormon- und Stoffwechselforschung. Hormones et m&#x00A0;&#x00A0;tabolisme","ISSN":"https:\/\/id.crossref.org\/issn\/0018-5043","issn-type":"print"},{"issue":"4","key":"24_41746512","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1210\/en.2011-1733","volume":"153","year":"2012","journal-title":"Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0013-7227","issn-type":"print"},{"issue":"7","key":"25_43336849","doi-asserted-by":"publisher","first-page":"e41926","DOI":"10.1371\/journal.pone.0041926","volume":"7","author":"Akerstrom","year":"2012","ISSN":"https:\/\/id.crossref.org\/issn\/1932-6203","issn-type":"print"},{"issue":"2","key":"26_11035444","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1046\/j.1440-1827.2001.01169.x","volume":"51","author":"Takamura","year":"2001","journal-title":"Pathology international","ISSN":"https:\/\/id.crossref.org\/issn\/1320-5463","issn-type":"print"},{"key":"27_50396886","doi-asserted-by":"crossref","first-page":"77","DOI":"10.4158\/EP.1.2.77","volume":"1","year":"1995","journal-title":"ENDOCRINE PRACTICE"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/172\/6\/677.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/172\/6\/677.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T17:40:39Z","timestamp":1717782039000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/172\/6\/677\/6671070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6]]},"references-count":26,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.1530\/eje-14-1113","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6]]}}}