Salangsang Jonathan, Sapkota Surendra, Kharel Sanjeev, Gupta Prakash, Kalla Abhishek
Internal Medicine, Ascension Saint Agnes Hospital, Baltimore, USA.
Internal Medicine, Tribhuvan University Institute of Medicine, Kathmandu, NPL.
Cureus. 2023 Feb 21;15(2):e35276. doi: 10.7759/cureus.35276. eCollection 2023 Feb.
Immune checkpoint inhibitors (ICI) such as program cell death protein 1 (PD-1) inhibitors are widely used for the treatment of patients with recurrent, locally advanced or metastatic, gastric or gastroesophageal (GE) junction adenocarcinoma. Immune-related adverse events (irAE) such as endocrinopathies have been reported after patients received ICI. We report a case of pembrolizumab-induced hyperthyroidism and type 1 diabetes mellitus (DM1) presenting with diabetic ketoacidosis (DKA). A 53-year-old African American male with no history of diabetes or hyperthyroidism was treated with two cycles of pembrolizumab for recurrent GE junction adenocarcinoma after which he was admitted with hyperthyroidism (thyroid stimulating hormone [TSH] 0.070mIU/L, free thyroxine 1.85mIU/L) and DKA (pH 7.06, glucose 583 mg/dL, beta-hydroxybutyrate 8.63 mmol/L, anion gap 27 meq/L). The patient was treated with intravenous insulin and aggressively hydrated. Given the lack of other precipitating factors for the two endocrinopathies, it was determined that the most likely etiology was recent treatment with pembrolizumab (a PD-1 inhibitor). In our case, pembrolizumab monotherapy developed two irAE (hyperthyroidism and DKA), which is unique as most combined immunotherapy regimens are associated with the development of multiple endocrinopathies. Our case emphasizes the importance of baseline monitoring of thyroid function and blood glucose prior to the start of ICI to monitor and evaluate patients with immune-related adverse events, including endocrinopathies.
免疫检查点抑制剂（ICI），如程序性细胞死亡蛋白1（PD-1）抑制剂，被广泛用于治疗复发、局部晚期或转移性胃癌或胃食管（GE）交界腺癌患者。有报道称，患者接受ICI治疗后出现了免疫相关不良事件（irAE），如内分泌病。我们报告了一例帕博利珠单抗诱发的甲状腺功能亢进症和1型糖尿病（DM1），并伴有糖尿病酮症酸中毒（DKA）。一名53岁的非裔美国男性，既往无糖尿病或甲状腺功能亢进症病史，因复发性GE交界腺癌接受了两个周期的帕博利珠单抗治疗，之后因甲状腺功能亢进症（促甲状腺激素[TSH]0.070mIU/L，游离甲状腺素1.85mIU/L）和DKA（pH值7.06，血糖583mg/dL，β-羟丁酸8.63mmol/L，阴离子间隙27meq/L）入院。患者接受了静脉胰岛素治疗并积极补液。鉴于这两种内分泌病缺乏其他诱发因素，确定最可能的病因是近期使用帕博利珠单抗（一种PD-1抑制剂）治疗。在我们的病例中，帕博利珠单抗单药治疗引发了两种irAE（甲状腺功能亢进症和DKA），这很独特，因为大多数联合免疫治疗方案与多种内分泌病的发生有关。我们的病例强调了在开始ICI治疗前对甲状腺功能和血糖进行基线监测的重要性，以便监测和评估免疫相关不良事件患者，包括内分泌病患者。
