{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:21:57Z","timestamp":1787840517622,"version":"build-2784847793"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy by enhancing T-cell-mediated tumour eradication. However, their use is associated with immune-related adverse events, with endocrinopathies being the most common. Thyroid dysfunction, hypophysitis, primary adrenal insufficiency (PAI), and insulin-dependent diabetes mellitus are well-documented complications. Thyroid dysfunction typically follows a biphasic course, with transient thyrotoxicosis progressing to hypothyroidism. Hypophysitis primarily affects the anterior pituitary, often leading to isolated adrenocorticotropic hormone deficiency. ICI-induced diabetes mellitus results from autoimmune \u03b2-cell destruction, frequently presenting as diabetic ketoacidosis. Primary adrenal insufficiency is rare but requires prompt recognition. Despite these endocrine toxicities, the benefits of ICIs outweigh their risks, and treatment is usually continued with appropriate hormone replacement. Early recognition and management of these endocrinopathies are crucial for optimising patient outcomes. This review summarises the incidence, pathophysiology, diagnosis, and management of ICI-associated endocrine disorders, providing essential insights for oncologists and endocrinologists.<\/jats:p>","DOI":"10.4103\/ijem.ijem_47_25","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T07:00:26Z","timestamp":1756278026000},"page":"408-413","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Endocrine Adverse Events of Immune Checkpoint Inhibitors: A Comprehensive Review"],"prefix":"10.4103","volume":"29","author":[{"given":"Remya","family":"Rajan","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, Christian Medical College Vellore, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devika","family":"Nandakumar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, Christian Medical College Vellore, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"R1-20250827","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.eprac.2024.03.023","article-title":"Endocrinopathies associated with immune checkpoint inhibitor use","volume":"30","author":"Kotwal","year":"2024","journal-title":"Endocr Pract"},{"key":"R2-20250827","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3949\/ccjm.90a.22032","article-title":"Endocrinopathies from checkpoint inhibitors:Incidence, outcomes, and management","volume":"90","author":"Kennedy","year":"2023","journal-title":"Cleve Clin J Med"},{"key":"R3-20250827","doi-asserted-by":"crossref","first-page":"101371","DOI":"10.1016\/j.beem.2019.101371","article-title":"Hypophysitis:An update on the novel forms, diagnosis and management of disorders of pituitary inflammation","volume":"33","author":"Gubbi","year":"2019","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"R4-20250827","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-22-0689","article-title":"Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition:An ESE clinical practice guideline","volume":"187","author":"Husebye","year":"2022","journal-title":"Eur J Endocrinol"},{"key":"R5-20250827","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1001\/jamaoncol.2017.3064","article-title":"Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens:A systematic review and meta-analysis","volume":"4","author":"Barroso-Sousa","year":"2018","journal-title":"JAMA Oncol"},{"key":"R6-20250827","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s12020-024-03718-2","article-title":"Thyroid disorders induced by immune checkpoint inhibitors","volume":"85","author":"Karaviti","year":"2024","journal-title":"Endocrine"},{"key":"R7-20250827","doi-asserted-by":"crossref","first-page":"e3704","DOI":"10.1210\/clinem\/dgab263","article-title":"Thyroid immune-related adverse events following immune checkpoint inhibitor treatment","volume":"106","author":"Muir","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"R8-20250827","doi-asserted-by":"crossref","first-page":"e126","DOI":"10.1093\/oncolo\/oyab043","article-title":"Immune checkpoint inhibitor-related new-onset thyroid dysfunction:A retrospective analysis using the US FDA adverse event reporting system","volume":"27","author":"Lu","year":"2022","journal-title":"Oncologist"},{"key":"R9-20250827","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1210\/js.2017-00432","article-title":"Patients with antithyroid antibodies are prone to develop destructive thyroiditis by nivolumab:A prospective study","volume":"2","author":"Kobayashi","year":"2018","journal-title":"J Endocr Soc"},{"key":"R10-20250827","doi-asserted-by":"crossref","first-page":"e1620","DOI":"10.1210\/clinem\/dgab829","article-title":"Increased risk of thyroid dysfunction by PD-1 and CTLA-4 blockade in patients without thyroid autoantibodies at baseline","volume":"107","author":"Iwama","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"R11-20250827","doi-asserted-by":"crossref","first-page":"e1843","DOI":"10.1210\/clinem\/dgac059","article-title":"Association of antithyroid antibodies in checkpoint inhibitor-associated thyroid immune-related adverse events","volume":"107","author":"Muir","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"R12-20250827","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1089\/thy.2018.0116","article-title":"Immune-related thyroiditis with immune checkpoint inhibitors","volume":"28","author":"Iyer","year":"2018","journal-title":"Thyroid"},{"key":"R13-20250827","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.gendis.2017.11.002","article-title":"Unique cytologic features of thyroiditis caused by immune checkpoint inhibitor therapy for malignant melanoma","volume":"5","author":"Angell","year":"2018","journal-title":"Genes Dis"},{"key":"R14-20250827","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/fcp.12423","article-title":"Thyroiditis and immune check point inhibitors:The post-marketing experience using the French National Pharmacovigilance database","volume":"33","author":"Garon-Czmil","year":"2019","journal-title":"Fundam Clin Pharmacol"},{"key":"R15-20250827","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s11102-015-0671-4","article-title":"Immunotherapy and hypophysitis:Clinical presentation, treatment, and biologic insights","volume":"19","author":"Faje","year":"2016","journal-title":"Pituitary"},{"key":"R16-20250827","doi-asserted-by":"crossref","first-page":"4078","DOI":"10.1210\/jc.2014-2306","article-title":"Ipilimumab-induced hypophysitis:A detailed longitudinal analysis in a large cohort of patients with metastatic melanoma","volume":"99","author":"Faje","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"R17-20250827","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.1016\/j.ajpath.2016.08.020","article-title":"Hypophysitis secondary to cytotoxic T-Lymphocyte-associated protein 4 blockade:Insights into pathogenesis from an autopsy series","volume":"186","author":"Caturegli","year":"2016","journal-title":"Am J Pathol"},{"key":"R18-20250827","doi-asserted-by":"crossref","first-page":"19419","DOI":"10.1038\/s41598-019-56026-5","article-title":"Immune check point inhibitors-induced hypophysitis:A retrospective analysis of the french pharmacovigilance database","volume":"9","author":"Garon-Czmil","year":"2019","journal-title":"Sci Rep"},{"key":"R19-20250827","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1080\/17446651.2019.1701434","article-title":"Hypophysitis induced by immune checkpoint inhibitors:A 10-year assessment","volume":"14","author":"Di","year":"2019","journal-title":"Expert Rev Endocrinol Metab"},{"key":"R20-20250827","doi-asserted-by":"crossref","first-page":"bvad012","DOI":"10.1210\/jendso\/bvad012","article-title":"Spectrum of clinical presentations, imaging findings, and HLA types in immune checkpoint inhibitor-induced hypophysitis","volume":"7","author":"Quandt","year":"2023","journal-title":"J Endocr Soc"},{"key":"R22-20250827","doi-asserted-by":"crossref","first-page":"5499","DOI":"10.1210\/jc.2019-00423","article-title":"Checkpoint inhibitor-associated autoimmune diabetes is distinct from type 1 diabetes","volume":"104","author":"Tsang","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"R23-20250827","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.2337\/dbi18-0002","article-title":"Collateral damage:Insulin-dependent diabetes induced with checkpoint inhibitors","volume":"67","author":"Stamatouli","year":"2018","journal-title":"Diabetes"},{"key":"R24-20250827","doi-asserted-by":"crossref","first-page":"8295","DOI":"10.1038\/s41598-018-26471-9","article-title":"Interferon-gamma drives programmed death-ligand 1 expression on islet ? cells to limit T cell function during autoimmune diabetes","volume":"8","author":"Osum","year":"2018","journal-title":"Sci Rep"},{"key":"R25-20250827","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1007\/s00262-017-2033-8","article-title":"Autoimmune diabetes induced by PD-1 inhibitor-retrospective analysis and pathogenesis:A case report and literature review","volume":"66","author":"Gauci","year":"2017","journal-title":"Cancer Immunol Immunother"},{"key":"R26-20250827","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1053\/j.seminoncol.2023.11.003","article-title":"Primary adrenal insufficiency induced by immune checkpoint inhibitors:Biological, clinical, and radiological aspects","volume":"50","author":"Martella","year":"2023","journal-title":"Semin Oncol"},{"key":"R27-20250827","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1634\/theoncologist.2019-0555","article-title":"Immune checkpoint inhibitor-associated primary adrenal insufficiency:Who vigibase report analysis","volume":"25","author":"Grouthier","year":"2020","journal-title":"Oncologist"},{"key":"R28-20250827","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.mayocpiqo.2020.07.006","article-title":"Hypoparathyroidism:An uncommon complication associated with immune checkpoint inhibitor therapy","volume":"4","author":"El","year":"2020","journal-title":"Mayo Clin Proc Innov Qual Outcomes"},{"key":"R29-20250827","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1210\/jc.2018-01151","article-title":"Immune checkpoint inhibitor-induced hypoparathyroidism associated with calcium-sensing receptor-activating autoantibodies","volume":"104","author":"Piranavan","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"R30-20250827","first-page":"e40","article-title":"A case of acquired generalized lipodystrophy associated with pembrolizumab in a patient with metastatic malignant melanoma","volume":"6","author":"Bedrose","year":"2020","journal-title":"AACE Clin Case Rep"},{"key":"R31-20250827","doi-asserted-by":"crossref","first-page":"luad025","DOI":"10.1210\/jcemcr\/luad025","article-title":"Marked hypoleptinemia precedes overt fat loss in immune checkpoint inhibitor-induced acquired generalized lipodystrophy","volume":"1","author":"Dhanasekaran","year":"2023","journal-title":"JCEM Case Rep"},{"key":"R32-20250827","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ejca.2021.04.031","article-title":"Male fertility during and after immune checkpoint inhibitor therapy:A cross-sectional pilot study","volume":"152","author":"Salzmann","year":"2021","journal-title":"Eur J Cancer"},{"key":"R33-20250827","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1200\/OP.22.00469","article-title":"Minding the bathwater:Fertility and reproductive toxicity in the age of immuno-oncology","volume":"18","author":"Kim","year":"2022","journal-title":"JCO Oncol Pract"},{"key":"R34-20250827","doi-asserted-by":"crossref","first-page":"102134","DOI":"10.1016\/j.ctrv.2020.102134","article-title":"Association between immune-related side effects and efficacy and benefit of immune checkpoint inhibitors-A systematic review and meta-analysis","volume":"92","author":"Hussaini","year":"2021","journal-title":"Cancer Treat Rev"},{"key":"R35-20250827","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1007\/s00262-021-03128-7","article-title":"Associations between immune-related thyroid dysfunction and efficacy of immune checkpoint inhibitors:A systematic review and meta-analysis","volume":"71","author":"Cheung","year":"2022","journal-title":"Cancer Immunol Immunother"}],"container-title":["Indian Journal of Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/ijem.ijem_47_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:24:17Z","timestamp":1787837057000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/ijem.ijem_47_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/ijem.ijem_47_25","relation":{},"ISSN":["2230-8210","2230-9500"],"issn-type":[{"value":"2230-8210","type":"print"},{"value":"2230-9500","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2025-01-31","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-18","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}