{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:48:37Z","timestamp":1790171317555,"version":"4.1.0"},"reference-count":125,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Immune checkpoint inhibitors block the checkpoint molecules. Different types of cancer immune checkpoint inhibitors have been approved recently: CTLA-4 monoclonal antibodies (as ipilimumab); anti-PD-1 monoclonal antibodies (as pembrolizumab and nivolumab); and anti-PD-L1 monoclonal antibodies (as atezolizumab, avelumab, and durmalumab). We collect recent published results about autoimmune endocrine dysfunctions associated with cancer antibody immunotherapies. These agents cause a raised immune response leading to immune-related adverse events (irAEs), varying from mild to fatal, based on the organ system and severity. Immune-related endocrine toxicities are usually irreversible in 50% of cases, and include hypophysitis, thyroid dysfunctions, type 1 diabetes mellitus, and adrenal insufficiency. Anti-PD-1-antibodies are more frequently associated with thyroid dysfunctions (including painless thyroiditis, hypothyroidism, thyrotoxicosis, or thyroid storm), while the most frequent irAE related to anti-CTLA-4-antibodies is hypophysitis. The combination of anti-CTLA-4 and anti-PD-1 antibodies is associated with a 30% chance of irAEs. Symptoms and clinical signs vary depending on the target organ. IrAEs are usually managed by an oncological therapist, but in more challenging circumstances (i.e., for new onset insulin\u2013dependent diabetes, hypoadrenalism, gonadal hormones dysfunctions, or durable hypophysitis) an endocrinologist is needed.<\/jats:p>","DOI":"10.3390\/ijms20102560","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T11:20:46Z","timestamp":1558696846000},"page":"2560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Autoimmune Endocrine Dysfunctions Associated with Cancer Immunotherapies"],"prefix":"10.3390","volume":"20","author":[{"given":"Silvia Martina","family":"Ferrari","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poupak","family":"Fallahi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusy","family":"Elia","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ragusa","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Ruffilli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Patrizio","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosaria","family":"Galdiero","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy"},{"name":"WAO Center of Excellence, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-1386","authenticated-orcid":false,"given":"Enke","family":"Baldini","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, \u2018Sapienza\u2019 University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7573-0759","authenticated-orcid":false,"given":"Salvatore","family":"Ulisse","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, \u2018Sapienza\u2019 University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9849-4701","authenticated-orcid":false,"given":"Gianni","family":"Marone","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy"},{"name":"WAO Center of Excellence, 80131 Naples, Italy"},{"name":"Institute of Experimental Endocrinology and Oncology \u201cGaetano Salvatore\u201d (IEOS), National Research Council (CNR), 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Antonelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ejca.2017.01.035","article-title":"Cancer immunotherapy: Opportunities and challenges in the rapidly evolving clinical landscape","volume":"81","author":"Emens","year":"2017","journal-title":"Eur. 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