{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:05:51Z","timestamp":1791389151941,"version":"4.3.3"},"reference-count":121,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"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 (ICIs) have revolutionized cancer treatment by reactivating T cell-mediated anti-tumor immunity. However, this enhanced immune activity can lead to immune-related adverse events (irAEs). This narrative review focuses on endocrine irAEs, including thyroid dysfunction, hypophysitis, adrenal insufficiency, and diabetes mellitus. It also explores infectious complications and their underlying mechanisms. These mechanisms include immune dysregulation resulting directly from ICI-induced T-cell activation and indirectly from the immunosuppressive therapies used to treat irAEs. Furthermore, potential role of endocrine irAEs in predisposing patients to infectious complications is analyzed. The objective is to provide non-oncology specialists with the clinical insight necessary to recognize and manage these complex side effects. This narrative review synthesizes current literature on the diagnosis, management, and pathophysiology of endocrine irAEs and infections associated with different classes of ICIs (anti-CTLA-4, anti-PD-1, and anti-PD-L1). Endocrine irAEs are common, with incidence varying by ICI type; combination therapies pose the highest risk. Thyroid dysfunction is the most frequent, followed by hypophysitis, which often leads to permanent secondary adrenal insufficiency. ICI-induced diabetes mellitus is a rare but serious complication, frequently presenting as diabetic ketoacidosis. ICIs are believed to induce a distinct array of infections resulting from immunological dysregulation, unrelated to immunosuppressive medication. The phenomenon is increasingly called ICI therapy-induced dysregulated immunity. Moreover, evidence suggests that endocrine irAEs can compromise immune function and lead to a significantly higher risk of bacterial and fungal infections. Identifying infections that imitate irAEs is particularly important because the therapy is significantly distinct. Greater interdisciplinary awareness is crucial for the early recognition and appropriate management of both the endocrine and infectious complications, ultimately improving the safety and outcomes for patients receiving immunotherapy.<\/jats:p>","DOI":"10.3390\/ijms262311619","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T08:13:49Z","timestamp":1764576829000},"page":"11619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Beyond Tumor Immunity: The Disruption of Endocrine and Infectious Homeostasis by Immune Checkpoint Inhibitors"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7605-7095","authenticated-orcid":false,"given":"Ema","family":"Sch\u00f6nberger","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Internal Medicine Clinic, University Hospital Centre Osijek, 31000 Osijek, Croatia"},{"name":"Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0208-5821","authenticated-orcid":false,"given":"Luka","family":"\u0160vitek","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"Clinic of Infectious Diseases, University Hospital Centre Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6668-7744","authenticated-orcid":false,"given":"Barbara","family":"Grubi\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"Clinic of Infectious Diseases, University Hospital Centre Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5234-7557","authenticated-orcid":false,"given":"Tara","family":"Cviji\u0107 Peri\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"Clinic of Oncology, University Hospital Centre Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0392-2943","authenticated-orcid":false,"given":"Romana","family":"Maru\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"National Memorial Hospital \u201cDr. Juraj Njavro\u201d Vukovar, 32000 Vukovar, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1109-039X","authenticated-orcid":false,"given":"Nika","family":"Vlahovi\u0107 Vla\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"Clinic of Infectious Diseases, University Hospital Centre Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2523-6007","authenticated-orcid":false,"given":"Tomislav","family":"Kizivat","sequence":"additional","affiliation":[{"name":"Clinical Institute of Nuclear Medicine and Radiation Protection, University Hospital Osijek, 31000 Osijek, Croatia"},{"name":"Department for Nuclear Medicine, Faculty of Medicine, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9535-7915","authenticated-orcid":false,"given":"Silvija","family":"Canecki Var\u017ei\u0107","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Internal Medicine Clinic, University Hospital Centre Osijek, 31000 Osijek, Croatia"},{"name":"Department of Pathophysiology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5523-0426","authenticated-orcid":false,"given":"Lorna","family":"Stemberger Mari\u0107","sequence":"additional","affiliation":[{"name":"Department of Pediatric Infectious Diseases, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia"},{"name":"Department of Infectious Diseases, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8861-5987","authenticated-orcid":false,"given":"Ines","family":"Bili\u0107 \u0106ur\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Internal Medicine Clinic, University Hospital Centre Osijek, 31000 Osijek, Croatia"},{"name":"Department of Pharmacology, Faculty of Medicine Osijek, J. J. 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