{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T11:49:29Z","timestamp":1775908169659,"version":"3.50.1"},"reference-count":16,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"KAKENHI","doi-asserted-by":"publisher","award":["22K16410"],"award-info":[{"award-number":["22K16410"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recurrence after successful transsphenoidal surgery (TSS) for Cushing disease (CD), caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, remains a major clinical concern. Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have been implicated in corticotroph tumorigenesis and may contribute to recurrence risk. Here, we report a rare case of delayed CD recurrence 19 years after initial surgical remission. A female aged 36 years underwent TSS for CD with typical clinical and biochemical evidence of hypercortisolism. Magnetic resonance imaging showed a 10\u2005mm pituitary adenoma, and histopathology confirmed an ACTH-producing tumor with a low Ki-67 index (&amp;lt;1%). She achieved long-term postoperative remission. At age 55 years, she developed biochemical and radiological findings consistent with recurrence. Inferior petrosal sinus sampling confirmed localization of the ACTH-secreting lesion to the pituitary gland, and repeat surgery was performed. The recurrent tumor demonstrated a high Ki-67 index. Retrospective Sanger sequencing of the initial tumor identified a USP8 c.2159C&amp;gt;G p.(Pro720Arg) mutation, a common variant in CD. This case underscores the potential role of USP8 mutations in long-latency recurrence and highlights the value of genetic profiling. Lifelong endocrine follow-up may be warranted in patients with USP8-mutated CD, even after extended postoperative remission.<\/jats:p>","DOI":"10.1210\/jcemcr\/luag055","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T12:43:06Z","timestamp":1771418586000},"source":"Crossref","is-referenced-by-count":0,"title":["Late recurrence of Cushing disease with\n                    <i>ubiquitin-specific protease 8<\/i>\n                    mutation 19 years after initial surgery"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7575-8487","authenticated-orcid":false,"given":"Keisuke","family":"Kakizawa","sequence":"first","affiliation":[{"name":"Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2176-0749","authenticated-orcid":false,"given":"Miho","family":"Yamashita","sequence":"additional","affiliation":[{"name":"International Center, Hamamatsu University School of Medicine , Hamamatsu, Shizuoka 431-3192 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Yanagida","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuto","family":"Kawauchi","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0363-0695","authenticated-orcid":false,"given":"Yutaka","family":"Oki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hamamatsu Kita Hospital , Hamamatsu, Shizuoka 431-3113 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akio","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"issue":"12","key":"2026041106561723200_luag055-B1","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S2213-8587(21)00235-7","article-title":"Consensus on diagnosis and management of Cushing's disease: a guideline 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for Cushing's disease","volume":"90","author":"Locatelli","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"issue":"7","key":"2026041106561723200_luag055-B5","doi-asserted-by":"crossref","first-page":"E997","DOI":"10.1210\/jc.2015-1453","article-title":"The gene of the ubiquitin-specific protease 8 is frequently mutated in adenomas causing Cushing's disease","volume":"100","author":"Perez-Rivas","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2026041106561723200_luag055-B6","doi-asserted-by":"crossref","first-page":"e0231665","DOI":"10.1371\/journal.pone.0231665","article-title":"CCNB2 and AURKA overexpression may cause atypical mitosis in Japanese cortisol-producing adrenocortical carcinoma with TP53 somatic variant","volume":"15","author":"Ikeya","year":"2020","journal-title":"PLoS 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