Zan Ying, Wei Yedong, Zhang Wenxue, Gao Xiaolu, Si Jigang
Department of Pharmacy, Zibo Central Hospital, Zibo, China.
Department of Pharmacy, Zhangdian Traditional Chinese Medicine Hospital, Zibo, China.
Medicine (Baltimore). 2025 May 16;104(20):e42490. doi: 10.1097/MD.0000000000042490.
Immune checkpoint inhibitors bring hope to cancer patients but may also lead to severe immune-related adverse events (irAEs). Although irAEs during treatment are well-characterized, delayed immune-related events (DIRE) remain underreported. Here, we report a case of sintilimab-induced delayed immune-related diabetes mellitus, accompanied by ICI-related thyroid disease (ICI-TD). Cases involving both ICI-TD and ICI-related diabetes mellitus (ICI-DM) are also relatively rare. This study systematically aggregates dual endocrine irAEs to provide valuable insights for clinical practice.
A 60-year-old Chinese male diagnosed with gastric adenocarcinoma received a multimodal treatment regimen consisting of sintilimab, chemotherapy, and apatinib. He completed 3 cycles of chemotherapy and 4 cycles of sintilimab. Due to disease progression, sintilimab was discontinued, but apatinib was continued for an additional 1 month. No further antitumor therapy was administered afterward. Four months later, he was admitted to the emergency department due to persistent nausea, vomiting, and abdominal pain.
Thyroid dysfunction induced by sintilimab was identified during treatment. His laboratory tests contributed to the diagnosis of diabetes ketoacidosis. Fulminant type 1 diabetes mellitus attributed to sintilimab met diagnostic criteria: plasma glucose 42.01 mmol/L, glycated hemoglobin 7.5%, C-peptide <0.02 µg/L, and negative islet autoantibodies.
Levothyroxine replacement therapy was initiated for hypothyroidism, whereas diabetes ketoacidosis during hospitalization required intensive insulin therapy combined with fluid resuscitation.
The patient exhibited persistent blood glucose fluctuations during hospitalization, including 2 hypoglycemic episodes. Post-treatment stabilization required basal-bolus insulin at discharge, with continued levothyroxine for hypothyroidism.
We report a rare case of concurrent ICI-TD and ICI-DM following sintilimab therapy. This case underscores the potential for DIRE, with onset occurring months posttreatment. Combined with a systematic review of existing cases, this study provides critical insights into surveillance strategies and pathogenesis of irAEs.
免疫检查点抑制剂给癌症患者带来了希望，但也可能导致严重的免疫相关不良事件（irAEs）。尽管治疗期间的irAEs已得到充分描述，但迟发性免疫相关事件（DIRE）的报告仍然不足。在此，我们报告一例信迪利单抗诱导的迟发性免疫相关糖尿病病例，并伴有免疫检查点抑制剂相关甲状腺疾病（ICI-TD）。同时涉及ICI-TD和免疫检查点抑制剂相关糖尿病（ICI-DM）的病例也相对罕见。本研究系统汇总了双重内分泌irAEs，为临床实践提供了有价值的见解。
一名60岁的中国男性被诊断为胃腺癌，接受了由信迪利单抗、化疗和阿帕替尼组成的多模式治疗方案。他完成了3个周期的化疗和4个周期的信迪利单抗治疗。由于疾病进展，信迪利单抗停药，但阿帕替尼继续使用了1个月。此后未再进行进一步的抗肿瘤治疗。4个月后，他因持续的恶心、呕吐和腹痛被收入急诊科。
治疗期间确定为信迪利单抗诱导的甲状腺功能障碍。他的实验室检查有助于糖尿病酮症酸中毒的诊断。信迪利单抗所致暴发性1型糖尿病符合诊断标准：血糖42.01 mmol/L，糖化血红蛋白7.5%，C肽<0.02 μg/L，胰岛自身抗体阴性。
开始使用左甲状腺素替代疗法治疗甲状腺功能减退，而住院期间的糖尿病酮症酸中毒需要强化胰岛素治疗并补充液体。
患者住院期间血糖持续波动，包括2次低血糖发作。出院时需要基础-餐时胰岛素治疗以稳定血糖，同时继续使用左甲状腺素治疗甲状腺功能减退。
我们报告了一例信迪利单抗治疗后并发ICI-TD和ICI-DM的罕见病例。该病例强调了DIRE的可能性，其发病发生在治疗后数月。结合对现有病例的系统综述，本研究为irAEs的监测策略和发病机制提供了关键见解。
