BRAF-mutant stage IV lung adenocarcinoma complicated by immunotherapy-induced diabetes

What happened, in summary

This 68-year-old woman was diagnosed in August 2020 with Stage IV lung adenocarcinoma carrying a BRAF V600E mutation. The diagnosis was made through enhanced chest CT and pleural biopsy. She initially received targeted therapy with dabrafenib plus trametinib. In March 2023, CT showed a new metastasis in the left lower lung, and she began tislelizumab immunotherapy after prior targeted treatment.

Her glucose levels stayed normal during much of immunotherapy. In April 2024, however, she developed nausea, vomiting, and electrolyte disturbances and was diagnosed with hypoadrenocorticism. Tislelizumab was suspended, and she started prednisone acetate 5 mg daily. On 20 May 2024, she came to the emergency department with 3 days of sudden dry mouth, excessive thirst, frequent urination, mild nausea, and vomiting. She had no prior history of diabetes. Blood glucose was very high at 33.88 mmol/L, HbA1c was 7%, urine showed glucose and ketones, and beta-hydroxybutyric acid was elevated. GADA was positive, while anti-insulin and anti-islet cell antibodies were negative. Testing also showed failing pancreatic beta-cell function, with very low C-peptide levels, supporting fulminant immune-related diabetes rather than ordinary type 2 diabetes.

She was treated immediately with IV insulin and fluids for diabetic ketosis. Levothyroxine was also started, and after stabilization she transitioned to a continuous subcutaneous insulin pump, then an intensive insulin regimen after discharge. At 3 months, GADA remained positive; by 6 months, it had become negative, but fasting C-peptide remained very low. Her ongoing care centered on living with Stage IV BRAF-mutant lung cancer while managing serious endocrine immune-related effects from immunotherapy.