{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:42:30Z","timestamp":1792269750649,"version":"4.4.0"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) are widely used in tumor therapy, and the immune-related adverse events (irAEs) they induce can involve multiple organs. As an organ with both endocrine and exocrine functions, pancreatic involvement may manifest as acute pancreatitis, new-onset diabetes mellitus, or even a combination of both. Among these, ICI-induced acute pancreatitis concurrent with fulminant type 1 diabetes mellitus (FT1DM) is extremely rare but highly critical and easily missed in clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A 59-year-old male patient with squamous cell carcinoma of the left base of the tongue received toripalimab combined with chemotherapy. On day 7 after treatment, he presented with nausea, vomiting, and altered mental status. Emergency examination revealed hyperglycemia (17.4 mmol\/L), severe diabetic ketoacidosis (blood ketones 9.52 mmol\/L, pH 7.28), and significantly elevated serum amylase (370 U\/L). Abdominal CT showed swelling of the body and tail of the pancreas with surrounding exudation, consistent with acute pancreatitis. His glycated hemoglobin (HbA1c) was normal (5.4%), pancreatic autoantibodies were negative, and islet function was completely lost. He was diagnosed with toripalimab-associated acute pancreatitis (Grade 3) concurrent with FT1DM. ICIs were permanently discontinued immediately. The patient was treated with fasting, fluid replacement, somatostatin to inhibit pancreatic enzyme secretion, and intensive insulin pump therapy for glycemic control. Glucocorticoids were not administered. After 11 days of comprehensive treatment, his symptoms resolved, and he was discharged upon normalization of pancreatic enzymes and blood glucose levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PD-1 inhibitors can simultaneously impair both the endocrine and exocrine functions of the pancreas, leading to the coexistence of acute pancreatitis and FT1DM. Clinicians must maintain a high index of suspicion for this dual injury. For patients receiving ICI therapy, emergency evaluation of pancreatic function is warranted once gastrointestinal symptoms or unexplained hyperglycemia\/ketosis occur. Early drug withdrawal and individualized management centered on supportive care can effectively prevent life-threatening complications. Notably, this case represents the first report of such dual pancreatic injury in a patient with locally advanced tongue base squamous cell carcinoma receiving first-cycle toripalimab combined with paclitaxel plus cisplatin chemoimmunotherapy, with distinct atypical clinical manifestations and a faster steroid-free recovery trajectory compared with the single previously published toripalimab-associated case.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1906731","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:33:37Z","timestamp":1789450417000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune checkpoint inhibitor\u2013related pancreatitis with fulminant type 1 diabetes mellitus: a case report"],"prefix":"10.3389","volume":"17","author":[{"given":"Li","family":"Niu","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Zhongnan Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Zhongnan Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Zhongnan Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiazhong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Zhongnan Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-related adverse events associated with immune checkpoint blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.3923","article-title":"Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis","volume":"4","author":"Wang","year":"2018","journal-title":"JAMA Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.627612","article-title":"Immunotherapy-associated pancreatic adverse events: current understanding of their mechanism, diagnosis, and management","volume":"11","author":"Liu","year":"2021","journal-title":"Front Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.currproblcancer.2017.05.001","article-title":"Risk of pancreatitis with the use of immune checkpoint inhibitors: a meta-analysis","volume":"41","author":"Abdel-Rahman","year":"2017","journal-title":"Curr Probl Cancer"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.25.9.1529","article-title":"Fulminant type 1 diabetes: a nationwide survey in Japan","volume":"25","author":"Imagawa","year":"2002","journal-title":"Diabetes Care"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.77.6385","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline","volume":"36","author":"Brahmer","year":"2018","journal-title":"J Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17071080","article-title":"Immune checkpoint inhibitor-induced pancreatic injury in adult cancer patients: a systematic review and meta-analysis","volume":"17","author":"Lee","year":"2025","journal-title":"Cancers"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.817662","article-title":"Pancreatic adverse events associated with immune checkpoint inhibitors: a large\u2011scale pharmacovigilance analysis","volume":"13","author":"Zhang","year":"2022","journal-title":"Front Pharmacol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-011271","article-title":"Hyperglycemia in patients treated with immune checkpoint inhibitors: key clinical challenges and multidisciplinary consensus recommendations","volume":"13","author":"Wu","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.20384","article-title":"Immune checkpoint inhibitor-induced pancreatic enzyme elevation in melanoma patients: incidence, management and therapy","volume":"39","author":"Brandlmaier","year":"2025","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1159\/000527541","article-title":"Fulminant Type 1 diabetes mellitus caused by long\u2011term nivolumab administration followed by nivolumab plus cabozantinib combination","volume":"68","author":"Homma","year":"2023","journal-title":"Chemotherapy"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1243773","article-title":"Immune checkpoint inhibitors-related pancreatitis with fulminant type 1 diabetes mellitus: case report and literature review","volume":"14","author":"Fang","year":"2023","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022125","article-title":"The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice","volume":"198","author":"Ansari","year":"2003","journal-title":"J Exp Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1906731\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:33:38Z","timestamp":1789450418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1906731\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":13,"alternative-id":["10.3389\/fimmu.2026.1906731"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1906731","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"article-number":"1906731"}}