{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:45:31Z","timestamp":1790696731102,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,1]]},"abstract":"\nObjective<\/jats:title>\nSomatic mutations in the ubiquitin-specific protease 8 (USP8<\/jats:italic>) gene are frequent in corticotroph tumors causing Cushing\u2019s disease (CD). Corticotroph tumor progression, the so-called Nelson\u2019s syndrome (NS), is a potentially life-threatening complication of bilateral adrenalectomy in patients with refractory CD that is caused by the development of an ACTH-secreting tumor of the pituitary gland. Whether USP8<\/jats:italic> alterations are also present in progressive Nelson\u2019s tumors has not been studied in detail so far.<\/jats:p><\/jats:sec>\n\nDesign and Methods<\/jats:title>\nRetrospective, multicenter study involving tumors from 33 patients with progressive corticotroph tumors (29 females) and screening for somatic mutations on the mutational hotspot of the USP8<\/jats:italic> gene in the exon 14 with Sanger sequencing.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nFifteen out of 33 tumors (45%) presented with a mutation in the exon 14 of USP8<\/jats:italic>, with c.2159C>A (p.Pro720Gln) being the most frequent (9\/33), followed by c.2155_2157delTCC (p.Ser718del, 4\/33) and c.2152T>C (p.Ser718Pro, 2\/33). This prevalence is similar to that previously reported for CD. Mutations were found exclusively in females. Other variables, such as age at diagnosis with NS, body mass index, hyperpigmentation, visual field defects, adenoma size or mortality, did not significantly differ between patients with wild-type and mutant tumors. Patients with USP8<\/jats:italic> mutant tumors exhibited higher levels of plasma ACTH after surgery (median: 640 vs 112\u2009pg\/mL, P<\/jats:italic>\u2009=\u20090.03). No differences were observed in ACTH normalization (<50\u2009pg\/mL) and tumor control after surgery for Nelson\u2019s tumor.<\/jats:p><\/jats:sec>\n\nConclusion<\/jats:title>\nSomatic mutations in USP8<\/jats:italic> are common in Nelson\u2019s tumors, indicating that they do not drive the corticotroph tumor progression that leads to NS, and may be associated with a less favorable biochemical outcome after surgery for Nelson\u2019s tumor.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-17-0634","type":"journal-article","created":{"date-parts":[[2017,10,6]],"date-time":"2017-10-06T00:10:43Z","timestamp":1507248643000},"page":"57-63","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":46,"title":["Somatic USP8 mutations are frequent events in corticotroph tumor progression causing Nelson\u2019s tumor"],"prefix":"10.1093","volume":"178","author":[{"given":"Luis G","family":"P\u00e9rez-Rivas","sequence":"first","affiliation":[{"name":"1Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marily","family":"Theodoropoulou","sequence":"additional","affiliation":[{"name":"1Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany"},{"name":"2Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy H","family":"Puar","sequence":"additional","affiliation":[{"name":"3Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Centre, Nijmegen, The Netherlands"},{"name":"4Department of Endocrinology, Changi General Hospital, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Fazel","sequence":"additional","affiliation":[{"name":"1Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mareike R","family":"Stieg","sequence":"additional","affiliation":[{"name":"2Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Ferra\u00f9","sequence":"additional","affiliation":[{"name":"5Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Assi\u00e9","sequence":"additional","affiliation":[{"name":"6Department of Endocrinology, Cochin Hospital, Assistance Publique H\u00f4pitaux de Paris; Inserm Unit\u00e9 1016, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche, Institut Cochin, Universit\u00e9 Paris Descartes, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica R","family":"Gadelha","sequence":"additional","affiliation":[{"name":"7Division of Endocrinology, Hospital Universit\u00e1rio Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Deutschbein","sequence":"additional","affiliation":[{"name":"8Division of Endocrinology and Diabetology, Department of Internal Medicine, University Hospital W\u00fcrzburg, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C","family":"Fragoso","sequence":"additional","affiliation":[{"name":"9Unidade de Neuroendocrinologia, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular\/LIM42, Disciplina de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benno","family":"Kusters","sequence":"additional","affiliation":[{"name":"10Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Saeger","sequence":"additional","affiliation":[{"name":"11Institut f\u00fcr Neuropathologie der Universit\u00e4t Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Honegger","sequence":"additional","affiliation":[{"name":"12Department of Neurosurgery, Eberhard Karls University T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Buchfelder","sequence":"additional","affiliation":[{"name":"13Neurochirurgische Klinik, Klinikum der Universit\u00e4t Erlangen, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rta","family":"Korbonits","sequence":"additional","affiliation":[{"name":"5Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Bertherat","sequence":"additional","affiliation":[{"name":"6Department of Endocrinology, Cochin Hospital, Assistance Publique H\u00f4pitaux de Paris; Inserm Unit\u00e9 1016, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche, Institut Cochin, Universit\u00e9 Paris Descartes, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter K","family":"Stalla","sequence":"additional","affiliation":[{"name":"2Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad R","family":"Hermus","sequence":"additional","affiliation":[{"name":"3Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Beuschlein","sequence":"additional","affiliation":[{"name":"1Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany"},{"name":"14Klinik f\u00fcr Endokrinologie, Diabetologie und Klinische Ern\u00e4hrung, Universit\u00e4tsspital Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Reincke","sequence":"additional","affiliation":[{"name":"1Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"ref251","first-page":"2647","article-title":"Risk factors and long-term outcome in pituitary-dependent Cushing\u2019s disease","volume":"81","year":"1996","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref151","first-page":"1","article-title":"The genome-wide mutational landscape of pituitary adenomas","volume":"10","year":"2016","journal-title":"Cell Research"},{"key":"ref211","first-page":"22","article-title":"First report of an AIP mutation in Nelson\u2019s syndrome successfully treated with the novel multireceptor-targeted somatostatin analogue pasireotide 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