{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:46:28Z","timestamp":1786981588294,"version":"build-2736575974"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T00:00:00Z","timestamp":1630627200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T00:00:00Z","timestamp":1630627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006146","name":"F\u00f6rdergemeinschaft Kinderkrebs-Zentrum Hamburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006146","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008792","name":"Novartis Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pfizer Pharma DE"},{"name":"Ipsen Pharma DE"},{"DOI":"10.13039\/501100005711","name":"Universit\u00e4t Hamburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pituitary"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Pituitary adenoma (PA) constitutes the third most common intracranial neoplasm. The mostly benign endocrine lesions express no hormone (null cell PA) or the pituitary hormone(s) of the cell lineage of origin. In 0.5\u20131.5% of surgical specimens and in up to 10% of autopsy cases, two or three seemingly separate PA may coincide. These multiple adenomas may express different hormones, but whether or not expression of lineage-restricted transcription factors and molecular features are distinct within multiple lesions remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Searching the data bank of the German Pituitary Tumor Registry 12 double pituitary adenomas with diverse lineage were identified among 3654 adenomas and 6 hypophyseal carcinomas diagnosed between 2012 and 2020. The double adenomas were investigated immunohistochemically for expression of hormones and lineage markers. In addition, chromosomal gains and losses as well as global DNA methylation profiles were assessed, whenever sufficient material was available (n\u2009=\u20098 PA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In accordance with the literature, combinations of GH\/prolactin\/TSH\u2013FSH\/LH adenoma (4\/12), GH\/prolactin\/TSH\u2013ACTH adenoma (3\/12), and ACTH\u2013FSH\/LH adenoma (3\/12) were observed. Further, two out of 12 cases showed a combination of a GH\/prolactin\/TSH adenoma with a null-cell adenoma. Different expression pattern of hormones were confirmed by different expression of transcription factors in 11\/12 patients. Finally, multiple lesions that were molecularly analysed in 4 patients displayed distinct copy number changes and global methylation pattern.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data confirm and extend the knowledge on multiple PA and suggest that such lesions may origin from distinct cell types.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11102-021-01164-1","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T20:04:45Z","timestamp":1630699485000},"page":"904-913","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Double adenomas of the pituitary reveal distinct lineage markers, copy number alterations, and epigenetic profiles"],"prefix":"10.1007","volume":"24","author":[{"given":"Christian","family":"Hagel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Sch\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Flitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich J.","family":"Knappe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Kellner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Bergmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Buslei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Buchfelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"R\u00fcdiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Herms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3340-8523","authenticated-orcid":false,"given":"Wolfgang","family":"Saeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,3]]},"reference":[{"key":"1164_CR1","first-page":"14","volume-title":"WHO classification of tumours of endocrine organs","author":"RY Osamura","year":"2017","unstructured":"Osamura RY, Grossman A, Korbonits M, Kovacs K, Lopes MBS, Matsuno A, Trouillas J (2017) Pituitary adenoma. 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Knappe, Udo Kellner, Markus Bergmann, Rolf Buslei, Michael Buchfelder, Thomas R\u00fcdiger, Jochen Herms, Wolfgang Saeger) declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards (a separate ethic review and permission of a local committee was not necessary according to \u00a7 12 to the Hamburgisches Krankenhausgesetz, Hamburg, Germany).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}