{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T22:42:23Z","timestamp":1775947343390,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Somatic variants in the ubiquitin\u2010specific protease 8 (<jats:italic>USP8<\/jats:italic>) gene are the most common genetic cause of Cushing disease. We aimed to explore the relationship between clinical outcomes and <jats:italic>USP8<\/jats:italic> status in a single centre.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, patients and measurements<\/jats:title><jats:p>We investigated the <jats:italic>USP8<\/jats:italic> status in 48 patients with pituitary corticotroph tumours. A median of 62 months of follow\u2010up was conducted after surgery from November 2013 to January 2015. The clinical, biochemical and imaging features were collected and analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seven <jats:italic>USP8<\/jats:italic> variants (p.Ser718Pro, p.Ser719del, p.Pro720Arg, p.Pro720Gln, p.Ser718del, p.Ser718Phe, p.Lys713Arg) were identified in 24 patients (50%). <jats:italic>USP8<\/jats:italic> variants showed a female predominance (100% vs. 75% in wild type [WT], <jats:italic>p<\/jats:italic>\u2009=\u2009.022). Patients with p.Ser719del showed an older age at surgery compared to patients with the p.Pro720Arg variant (47\u2010 vs. 24\u2010year\u2010olds, <jats:italic>p<\/jats:italic>\u2009=\u2009.033). Patients with p.Pro720Arg showed a higher rate of macroadenoma compared to patients harbouring the p.Ser718Pro variant (60% vs. 0%, <jats:italic>p<\/jats:italic>\u2009=\u2009.037). No significant differences were observed in serum and urinary cortisol and\u00a0adrenocorticotropin hormone (ACTH) levels. Immediate surgical remission (79% vs. 75%) and long\u2010term hormone remission (79% vs. 67%) were not significantly different between the two groups. The recurrence rate was 21% (4\/19) in patients harbouring <jats:italic>USP8<\/jats:italic> variants and 13% (2\/16) in WT patients. Recurrence\u2010free survival presented a tendency to be shorter in <jats:italic>USP8<\/jats:italic>\u2010mutated individuals (76.7 vs. 109.2 months, <jats:italic>p<\/jats:italic>\u2009=\u2009.068).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Somatic <jats:italic>USP8<\/jats:italic> variants accounted for 50% of the genetic causes in this cohort with a significant female frequency. A long\u2010term follow\u2010up revealed a tendency toward shorter recurrence\u2010free survival in <jats:italic>USP8<\/jats:italic>\u2010mutant patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.15065","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T18:23:10Z","timestamp":1714587790000},"page":"32-41","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A long\u2010term prognosis study of human <i>USP8<\/i>\u2010mutated ACTH\u2010secreting pituitary neuroendocrine tumours"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5446-1756","authenticated-orcid":false,"given":"Hui","family":"Miao","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luo","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Translational Medicine Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengying","family":"Gong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Translational Medicine Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian","family":"Duan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Translational Medicine Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Translational Medicine Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1666-2717","authenticated-orcid":false,"given":"Ming","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Pathology, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5172-6870","authenticated-orcid":false,"given":"Huijuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Translational Medicine Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Translational Medicine Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3171\/JNS\/2008\/108\/01\/0009"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61375-1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-013-0511-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05275-5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.20"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa853"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3166"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-0320"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-0689"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-20-0035"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-019-00973-9"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/js.2017-00364"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1453"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-018-1776-0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-00161"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13802"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030871"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa698"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-023-10920-4"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019-00697"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11111761"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2007.07.028"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-17-0634"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0790"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-021-02954-0"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0263-8"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.099663"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2021.03.004"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2008.03404.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noz109"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-022-01437-1"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.05.024"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03647-2"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1679"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-022-01045-0"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-021-06325-1"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1907"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2012.12.008"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203745"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-02332"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21082831"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-017-0829-3"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2924"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-4350"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.15065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T10:20:53Z","timestamp":1747045253000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.15065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/cen.15065"],"URL":"https:\/\/doi.org\/10.1111\/cen.15065","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2023-07-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}