{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:09:12Z","timestamp":1788491352927,"version":"build-2803163510"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"GW consulted for Novartis and Theramex and received punctual compensations."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immune control point (ICI) inhibitors represent a significant advance in the management and survival of cancers such as melanoma or non-small cell bronchial carcinoma. However, they induce unusual side effects, such as hypophysitis, which are rarely described elsewhere. This nationwide retrospective study describes the characteristics of hypophysitis reported in the French pharmacovigilance database (FPVD). We requested for all cases of ICI-related hypophysitis registered in the FPVD before May 2018. An endocrinologist and a pharmacologist reviewed all cases. About 94 pituitary cases were selected, involving 49 females and 45 men. Ipilimumab alone or in combination was the most represented ICI (56%). Most cases (61%) were grade 3 severity and the majority (90%) were corticotropic deficiency cases. Cases with thyroid and\/or gonadotropic involvement were 21% and 1% respectively. Five patients (8%) had panhypopituitarism. Pituitary MRI, when performed, was in favor of hypophysitis in 50%. No patient recovered his previous hormonal function. The mean time of onset was significantly shorter with ipilimumab than other ICIs. ICI-related hypophysitis generate deficits that do not spontaneously recover, even at a distance from the event, unlike thyroiditis. Patients must then benefit from long-term coordinated onco-endocrinological management, adapted to their own specific deficits.<\/jats:p>","DOI":"10.1038\/s41598-019-56026-5","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T11:02:52Z","timestamp":1576753372000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Immune check point inhibitors-induced hypophysitis: a retrospective analysis of the French Pharmacovigilance database"],"prefix":"10.1038","volume":"9","author":[{"given":"Julie","family":"Garon-Czmil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Petitpain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Rouby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Sassier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samy","family":"Babai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lissa","family":"Y\u00e9l\u00e9h\u00e9-Okouma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Weryha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0598-7508","authenticated-orcid":false,"given":"Pierre","family":"Gillet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,19]]},"reference":[{"issue":"7","key":"56026_CR1","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1634\/theoncologist.2015-0509","volume":"21","author":"E Gonzalez-Rodriguez","year":"2016","unstructured":"Gonzalez-Rodriguez, E. & Rodriguez-Abreu, D. Spanish Group for Cancer, I.-B.: Immune Checkpoint Inhibitors: Review and Management of Endocrine Adverse Events. Oncologist 21(7), 804\u2013816, https:\/\/doi.org\/10.1634\/theoncologist.2015-0509 (2016).","journal-title":"Oncologist"},{"key":"56026_CR2","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.ejim.2017.08.019","volume":"47","author":"P Iglesias","year":"2018","unstructured":"Iglesias, P. Cancer immunotherapy-induced endocrinopathies: Clinical behavior and therapeutic approach. Eur J Intern Med 47, 6\u201313, https:\/\/doi.org\/10.1016\/j.ejim.2017.08.019 (2018).","journal-title":"Eur J Intern Med"},{"issue":"6","key":"56026_CR3","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1002\/cncr.31200","volume":"124","author":"R Barroso-Sousa","year":"2018","unstructured":"Barroso-Sousa, R. et al. Endocrine dysfunction induced by immune checkpoint inhibitors: Practical recommendations for diagnosis and clinical management. Cancer 124(6), 1111\u20131121, https:\/\/doi.org\/10.1002\/cncr.31200 (2018).","journal-title":"Cancer"},{"issue":"3","key":"56026_CR4","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1111\/cen.13063","volume":"85","author":"MN Joshi","year":"2016","unstructured":"Joshi, M. N., Whitelaw, B. C., Palomar, M. T., Wu, Y. & Carroll, P. V. Immune checkpoint inhibitor-related hypophysitis and endocrine dysfunction: clinical review. Clin Endocrinol (Oxf) 85(3), 331\u2013339, https:\/\/doi.org\/10.1111\/cen.13063 (2016).","journal-title":"Clin Endocrinol (Oxf)"},{"key":"56026_CR5","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.ejca.2015.11.016","volume":"54","author":"JM Michot","year":"2016","unstructured":"Michot, J. M. et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. 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Eur J Endocrinol 179(3), R151\u2013R163, https:\/\/doi.org\/10.1530\/EJE-17-0009 (2018).","journal-title":"Eur J Endocrinol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-56026-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-56026-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-56026-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T17:42:22Z","timestamp":1671298942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-56026-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,19]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["56026"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-56026-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,19]]},"assertion":[{"value":"17 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.G.C., N.P., F.R., M.S., S.B., M.Y.O., M.K. and P.G. declare no financial competing interests. GW consulted for Novartis and Theramex and received punctual compensations. Nadine PETITPAIN: unpaid membership as expert of the French Drug Agency (ANSM), Unpaid member of the coordination committee of an academic interventional clinical trial (NCT02250729) funded by a consortium of 15 companies marketing pholcodine containing drugs (Bouchara-Recordati, Hepatoum, Biocodex\/Leurquin, Pierre Fabre, Sanofi, Urgo, Zambon, Alliance, Bells healthcare, Boots, Ernest Jackson, GSK, Medgenix, Pinewood, Vemedia). Franck ROUBY: unpaid membership as expert of the French Drug Agency (ANSM), unpaid expert (Co-investigator) for clinical Trials (Biogen, Theranexus, Inflectis Bioscience, Roche Genentech, Abbvie, Roche). Marion SASSIER: unpaid membership as expert of the French Drug Agency (ANSM), Samy BABAI: unpaid membership as expert of the French Drug Agency (ANSM), unpaid expert in a multicentric academic study on tranexamic acid. M\u00e9lissa YELEHE-OKOUMA: unpaid membership as expert of the French Drug Agency (ANSM), Pierre GILLET: unpaid membership as expert of the French Drug Agency (ANSM), Unpaid member of the coordination committee of an academic interventional clinical trial (NCT02250729) funded by a consortium of 15 companies marketing pholcodine containing drugs (Bouchara-Recordati, Hepatoum, Biocodex\/Leurquin, Pierre Fabre, Sanofi, Urgo, Zambon, Alliance, Bells healthcare, Boots, Ernest Jackson, GSK, Medgenix, Pinewood, Vemedia).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19419"}}