Introduction:
Pembrolizumab is an immune checkpoint inhibitor (ICI) of the programmed cell death 1 (PD-1) receptor. The resultant dysregulation in immunologic tolerance is responsible for ICI-related adverse events including endocrinopathy.
Case:
Our patient is a 55-year-old male with a medical history of only an unresectable right pleural mesothelioma treated with chemotherapy followed by three cycles of pembrolizumab 200mg three weekly. He presented with an altered level of consciousness on a background of intermittent vomiting and poor oral intake as well as a one week history of polyuria, polydipsia and 8kg weight loss. He had no focal infective symptoms. His family history is significant for a brother with type 1 diabetes mellitus. On examination, his Glasgow Coma Score was 11 /18. He was tachypnoeic with a respiratory rate of 45/min but was afebrile and normotensive. His cardiorespiratory examination was unremarkable. His venous blood gas confirmed the presence of diabetic ketoacidosis and acute kidney injury. His initial pH was 7.04 with serum bicarbonate 5 mmol/L, serum glucose 87.3 mmol/L, capillary ketone 6.8 mmol/L, serum creatinine 422 umol/L and eGFR 13ml/min/m2. HbA1c was 10.8% (95 mmol/mol) and he had negative insulin, glutamate decarboxylase and islet cell antibodies. His thyroid function and pituitary profile was normal. He was treated with intravenous insulin-dextrose infusion and subsequently discharged on basal/bolus subcutaneous insulin therapy.
Summary:
ICI-induced diabetes is a rare complication with an incidence varying from 0.2 % - 2.2%1,2. There are eight case reports of pembrolizumab-induced diabetes presenting with diabetic ketoacidosis1. It is crucial to monitor patients on ICI therapy for potential life threatening complications.