Endocrine Abstracts

Introduction: Pembrolizumab is an immune checkpoint inhibitor (ICI) used to treat advanced cancers. While improving survival rates, ICIs also cause immune-related adverse events (IRAEs). The endocrine system remains the most vulnerable to IRAEs: thyroid involvement is the commonest while pancreatic involvement is rare, affecting less than 1% of individuals. Risk factors for IRAEs include, personal or family history of autoimmune conditions, presence of another IRAE, most commonly thyroiditis, and being on ICI combination therapy. We describe a man who developed pembrolizumab-induced diabetic ketoacidosis (DKA) a year after developing pembrolizumab-induced hypothyroidism.

Case Presentation: A 62-year-old man presented with three days of weakness, weight loss, polyuria, and polydipsia. His medical history included a recurrence of oropharyngeal cancer and pembrolizumab-induced hypothyroidism. Current medications included intravenous pembrolizumab, started two years ago, levothyroxine 150 mg daily started a year ago, alendronic acid and a calcium-vitamin D supplement. He was a non-smoker and had no family history of diabetes mellitus. His blood glucose levels had been normal prior to this presentation. On examination he was dehydrated and tachypnoeic. Laboratory analysis demonstrated severe hyperglycaemia (glucose 35.3 mmol/l), metabolic acidosis (pH 7.01, bicarbonate 5.5 mmol/l) with ketonaemia (6.6 mmol/l) consistent with DKA. Further tests revealed a slightly raised glycated haemoglobin level (70 mmol/mol), a low C-peptide level (0.13 nmol/l), with negative anti-islet cell and anti-glutamic acid decarboxylase antibodies, consistent with fulminant onset type 1 diabetes. He responded rapidly to treatment according to the DKA treatment guidelines and was discharged on a basal-bolus insulin regimen.

Conclusion: Antibody-positive and antibody-negative endocrine IRAEs can occur even after a year of initiating ICI-therapy. Affected individuals can developed more than one endocrine IRAE. This case highlights the need for clinicians to remain vigilant about the occurrence of life-threatening endocrine IRAEs, even beyond a year after initiating ICI-therapy.