Endocrine Abstracts

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized oncological treatment and substantially improved a prognosis for patients with advanced malignancy. ICIs inhibit the immunological pathways controlling T-cell activation or anergy. The most frequently used classes of ICIs are those that targeted and inhibit cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death receptor 1 (PD-1) or its ligand PD-L1. The initiation of ICIs therapy is often associated with immune-related adverse events that can lead to destruction and permanent loss of function of various tissues, including the endocrine glands, with the thyroid gland being the most commonly affected. The overall incidence of ICI-induced diabetes mellitus ranges from 0.4% to 2%, resembling type 1 diabetes. It is characterized by the acute onset of hyperglycaemia with severe insulin deficiency and diabetic ketoacidosis very frequent at diagnosis. Autoantibodies and HLA genotypes associated with type 1 diabetes are often present. The standard treatment mode is a multiple insulin injection regimen.

Case presentation: A 71-year-old woman was admitted to the emergency department due to hyperglycaemic hyperosmolar syndrome, metabolic acidosis, and diarrhoea. Prior to admission, she had received eight cycles of nivolumab therapy for metastatic skin melanoma, and had been on glucocorticoid therapy for more than 10 years due to seropositive rheumatoid arthritis. She had no history of diabetes. Upon assessment, she was found to have severe hyperglycaemia [plasma glucose level of 55.2 mmol/l (993.6 mg/dl)] with positive urine ketones, acute renal insufficiency (urea level of 17.0 mmol/l, creatinine level of 269 umol/l), and hyperkalaemia (potassium level of 6.6 mmol/l). HbA1c was 9.4% (79 mmol/mol). She was treated per standard-of-care fluid resuscitation and insulin infusion protocols, and discharged as fully recovered to the outpatient diabetes clinic with basal insulin, a DPP-4 inhibitor, and repaglinide. During the follow-up visit, the glycaemic control was unsatisfactory with high glycaemic variability, and ICI-induced diabetes was suspected. Additional laboratory examinations showed immeasurable C-peptide level of < 0.02 nmol/l (normal range: 0.27 – 1.28) while GAD, ICA, and IA-2 autoantibodies were negative. A multiple insulin injection regimen was initiated, and glycaemic control significantly improved.

Conclusions: ICI-related diabetes is a rare but often life-threatening condition. As the increasing number of patients will be exposed to ICIs, healthcare professionals and patients should be aware of ICI-mediated endocrinopathies, with the regular monitoring of plasma glucose level being a part of comprehensive care for all patients treated with ICIs.