Case Report: Tislelizumab-induced delayed-onset diabetic ketoacidosis and hypothyroidism in esophageal adenocarcinoma

Immune checkpoint inhibitor-related diabetes ketoacidosis (ICI-DKA) and hypothyroidism are rare but serious adverse events of Anti-programmed cell death-1 (anti-PD-1) therapy, previously unreported in patients with EAC receiving tislelizumab. A 53-year-old man with well-controlled type 2 diabetes and human epidermal growth factor receptor 2 (HER2)-positive metastatic EAC completed 8 cycles of tislelizumab combined with trastuzumab and capecitabine-oxaliplatin (XELOX) chemotherapy, achieving a partial response. Eleven months after the last tislelizumab dose, he presented with fatigue and was diagnosed with DKA and hypothyroidism. Laboratory testing revealed severe insulin deficiency and negative diabetes-related autoantibodies. This was the first reported case of tislelizumab-induced concurrent DKA and hypothyroidism in an EAC patient. This case demonstrates the potential for severe, delayed-onset endocrine toxicity with tislelizumab, even in patients with pre-existing diabetes. It underscores the necessity for extended monitoring of glucose, C-peptide, and thyroid function beyond active therapy in programmed cell death protein 1 (PD-1) inhibitor recipients to mitigate life-threatening complications like ICI-DKA. Given the expanding global use of tislelizumab for EAC and the life-threatening nature of ICI-DKA, this case provides critical safety evidence necessitating urgent protocol revisions for long-term endocrine monitoring.