Endocrine Abstracts

Atezolizumab, a programmed death-ligand 1 (PD-L1) inhibitor, has been associated with development of several immune-related adverse events. Type 1 diabetes mellitus (T1DM) is considered a rare adverse event, described in 0.2-0.9% of patients treated with PD-L1 inhibitors. We present the case of a 67-year-old lady, who was diagnosed with extensive-disease small cell lung cancer. She received four cycles of carboplatin, etoposide and atezolizumab, and thereafter maintenance therapy of atezolizumab was initiated. Four months into treatment she was diagnosed with primary hypothyroidism due to auto-immune thyroiditis. Nine months after her first dose of atezolizumab, she presented to the emergency department with four days of polyuria, polydipsia, and abdominal pain. Laboratory investigations demonstrated hyperglycaemia (glucose 25 mmol/l), profound ketonaemia (ketones 7.7 mmol/l), and severe metabolic acidosis (pH 7.14, HCO3 11 mmol/l). Subsequent investigations revealed low C-peptide level (30 pmol/l) but only modest elevation of HbA1c (50 mmol/mol). Her presentation was consistent with rapid-onset diabetic ketoacidosis (DKA) as the presenting feature of auto-immune diabetes mellitus, akin to T1DM. DKA resolved with appropriate treatment, but she experienced rapid relapse with recurrent DKA 4 hours after IV insulin was stopped. She required prolonged IV insulin therapy, before transitioning to basal-bolus insulin treatment. Atezolizumab inhibits the binding of PD-1 to PD-L1. A rare side effect involves the activation of T-cells against pancreatic β-cells, leading to β-cell destruction. This can cause complete insulin deficiency, manifesting as fulminant T1DM. This subtype of T1DM is characterised by rapid onset ketoacidosis within days of development of hyperglycaemia symptoms, pronounced hyperglycaemia despite modest HbA1c elevations, and the near-complete destruction of β-cell at onset of disease evidenced by low C-peptide levels. When PDL1 inhibitors are administered, clinicians and patient should be aware of the potential for development of fulminant T1DM in addition to other auto-immune endocrine complications.