{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:15:32Z","timestamp":1783448132308,"version":"3.55.0"},"reference-count":15,"publisher":"Bioscientifica","issue":"4","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":2423,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Introduction: In the last few years, immune checkpoint inhibitors (ICPis) have become a common treatment of cancer. ICPis are associated with peculiar immune side effects, termed immune-related adverse events (irAEs). Thyroid disfunction is a common irAE, but clinical manifestation, severity, and pathogenesis can be variable. While destructive thyroiditis and hypothyroidism are the most common thyroid irAEs induced by ICPis, autoimmune hyperthyroidism (Graves\u2019 disease) is rare. We describe a case of a Graves\u2019 disease induced by anti-PD-1 therapy and we review the previous reports on this issue. Case Presentation: A 51-year-old man developed an overt autoimmune hyperthyroidism 2 months after he had started nivolumab (anti-PD-1) therapy for a metastatic non-small cell lung cancer. Although TSH-receptor autoantibodies (TRAb) were negative, the persistence of hyperthyroidism, the hypervascular pattern at thyroid ultrasound, and the high uptake at thyroid scintigraphy were all features suggestive of Graves\u2019 disease. Methimazole was started with the prompt restoration of euthyroidism. TRAb remained undetectable during the entire follow-up. Conclusions: Autoimmune hyperthyroidism can be induced by anti-PD-1 treatment. TRAb were negative in both cases of nivolumab-induced Graves\u2019 disease described to date. A correct differential diagnosis between destructive thyroiditis and autoimmune hyperthyroidism is crucial for the appropriate treatment.<\/jats:p>","DOI":"10.1159\/000501824","type":"journal-article","created":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T17:00:30Z","timestamp":1563382830000},"page":"192-195","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-17","source":"Crossref","is-referenced-by-count":60,"title":["Graves\u2019 Disease Induced by Immune Checkpoint Inhibitors: A Case Report and Review of the Literature"],"prefix":"10.1530","volume":"8","author":[{"given":"Alessandro","family":"Brancatella","sequence":"first","affiliation":[{"name":"1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Viola","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Brogioni","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Montanelli","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Sardella","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Vitti","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Marcocci","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Lupi","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Latrofa","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2019,7,9]]},"reference":[{"issue":"1","key":"2026070712584926200_ref1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1210\/er.2018-00006","article-title":"Endocrine toxicity of cancer immunotherapy targeting immune checkpoints","volume":"40","author":"Chang","year":"2019","journal-title":"Endocr Rev","ISSN":"https:\/\/id.crossref.org\/issn\/1945-7189","issn-type":"print"},{"issue":"8","key":"2026070712584926200_ref2","doi-asserted-by":"publisher","first-page":"2770","DOI":"10.1210\/jc.2017-00448","article-title":"Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms","volume":"102","author":"Delivanis","year":"2017","journal-title":"J Clin Endocrinol Metab","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"4-5","key":"2026070712584926200_ref3","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.autrev.2014.01.013","article-title":"Diagnosis and classification of Graves\u2019 disease","volume":"13","author":"Menconi","year":"2014","journal-title":"Autoimmun Rev","ISSN":"https:\/\/id.crossref.org\/issn\/1568-9972","issn-type":"print"},{"issue":"8","key":"2026070712584926200_ref4","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.2310\/JIM.0000000000000000","article-title":"Course of graves disease in interferon-treated patients with chronic hepatitis C virus infection and in uninfected patients","volume":"61","author":"Minelli","year":"2013","journal-title":"J Investig Med","ISSN":"https:\/\/id.crossref.org\/issn\/1081-5589","issn-type":"print"},{"key":"2026070712584926200_ref5","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0692-6","volume-title":"The Ocular Manifestations of Drugs Used to Treat Multiple Sclerosis. Drugs","author":"Heath","year":"2017"},{"key":"2026070712584926200_ref6","doi-asserted-by":"crossref","unstructured":"Osorio\n              JC\n            , NiA, ChaftJE, PollinaR, KaslerMK, StephensD, et al. Antibody-Mediated Thyroid Dysfunction During T-cell Checkpoint Blockade in Patients with Non-Small Cell Lung Cancer. Ann Oncol. 2017; 1;28(3):583-589.","DOI":"10.1093\/annonc\/mdw640"},{"issue":"2","key":"2026070712584926200_ref7","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.autrev.2012.07.003","article-title":"TSH receptor autoantibody immunoassay in patients with Graves\u2019 disease: improvement of diagnostic accuracy over different generations of methods. Systematic review and meta-analysis","volume":"12","author":"Tozzoli","year":"2012","journal-title":"Autoimmun Rev","ISSN":"https:\/\/id.crossref.org\/issn\/1568-9972","issn-type":"print"},{"issue":"4","key":"2026070712584926200_ref8","doi-asserted-by":"publisher","first-page":"e87","DOI":"10.1097\/IOP.0b013e3181ef72a1","article-title":"Drug-induced graves disease from CTLA-4 receptor suppression","volume":"27","author":"Borodic","year":"2011","journal-title":"Ophthal Plast Reconstr Surg","ISSN":"https:\/\/id.crossref.org\/issn\/0740-9303","issn-type":"print"},{"issue":"2","key":"2026070712584926200_ref9","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1530\/EJE-10-0833","article-title":"Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy","volume":"164","author":"Min","year":"2011","journal-title":"Eur J Endocrinol","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"6","key":"2026070712584926200_ref10","doi-asserted-by":"publisher","first-page":"424","DOI":"10.3109\/01676830.2014.949792","article-title":"Thyroid-like ophthalmopathy in a euthyroid patient receiving Ipilimumab","volume":"33","author":"McElnea","year":"2014","journal-title":"Orbit","ISSN":"https:\/\/id.crossref.org\/issn\/0167-6830","issn-type":"print"},{"key":"2026070712584926200_ref11","doi-asserted-by":"crossref","unstructured":"Azmat\n              U\n            , LiebnerD, Joehlin-priceA, AgrawalA, NabhanF, ReportC. Case Report Treatment of Ipilimumab Induced Graves \u2019 Disease in a Patient with Metastatic Melanoma. 2016;2016(Table 1):1\u20135.","DOI":"10.1155\/2016\/2087525"},{"key":"2026070712584926200_ref12","doi-asserted-by":"crossref","unstructured":"Gan\n              EH\n            , MitchellAL, PlummerR, PearceS, PerrosP. Tremelimumab-Induced Graves Hyperthyroidism.2017;167\u201370. 10.1159\/000464285","DOI":"10.1159\/000464285"},{"issue":"4","key":"2026070712584926200_ref13","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.jaapos.2018.01.006","article-title":"A case of Graves\u2019 ophthalmopathy associated with pembrolizumab (Keytruda) therapy","volume":"22","author":"Park","year":"2018","journal-title":"J AAPOS","ISSN":"https:\/\/id.crossref.org\/issn\/1091-8531","issn-type":"print"},{"issue":"2","key":"2026070712584926200_ref14","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1159\/000485742","article-title":"Severe Inflammatory Ophthalmopathy in a Euthyroid Patient during Nivolumab Treatment","volume":"7","author":"Campredon","year":"2018","journal-title":"Eur Thyroid J","ISSN":"https:\/\/id.crossref.org\/issn\/2235-0640","issn-type":"print"},{"key":"2026070712584926200_ref15","doi-asserted-by":"crossref","unstructured":"Iadarola\n              C\n            , CroceL, QuaquariniE, TeragniC, PintoS, BernardoA, et al. Nivolumab Induced Thyroid Dysfunction\u202f: Unusual Clinical Presentation and Challenging Diagnosis. Front Endocrinol (Lausanne). 2019; 17;9:813.","DOI":"10.3389\/fendo.2018.00813"}],"container-title":["European Thyroid Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/501824","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/8\/4\/192\/34638\/etj501824.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/8\/4\/192\/34638\/etj501824.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:29:03Z","timestamp":1783445343000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article\/8\/4\/192\/4690\/Graves-Disease-Induced-by-Immune-Checkpoint"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,1]]},"references-count":15,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000501824","relation":{},"ISSN":["2235-0802","2235-0640"],"issn-type":[{"value":"2235-0802","type":"electronic"},{"value":"2235-0640","type":"print"}],"subject":[],"published":{"date-parts":[[2019,7,1]]}}}