Pembrolizumab- and ipilimumab-induced diabetic ketoacidosis and isolated adrenocorticotropic hormone deficiency: a case report

Background: Several human monoclonal antibodies directed against immune checkpoints, including T lymphocyte antigen 4 and programmed cell death protein 1, have been implemented for cancer treatment in order to promote effector T cell response to tumors. Despite the antitumor activity of these agents, a significant number of patients demonstrated immune-related adverse events that affected the functions of multiple organs, including the endocrine system. We report the first case of immune checkpoint inhibitor-induced simultaneous diabetic ketoacidosis and isolated adrenocorticotropic hormone deficiency following combination treatment with immune checkpoint inhibitors.

Case presentation: A 70-year-old Thai man with no previous history of diabetes mellitus was diagnosed with stage IVB non-small cell lung with pleural and liver metastases. After 14 weeks of combination treatment with pembrolizumab and ipilimumab, he presented with fatigue, nausea, and vomiting. Laboratory investigation revealed random plasma glucose 794 mg/dl, serum ketone 6.3 mmol/L, bicarbonate 13 mmol/L, and high anion gap 24 mmol/L. New-onset diabetes mellitus and diabetic ketoacidosis were diagnosed. Insulin therapy was initiated a favorable outcome within 10 hours. Despite improvement of hyperglycemia, the patient had persistent nausea and hyponatremia. Further investigation revealed cortisol 0.8 μg/dl and adrenocorticotropic hormone 21.7 pg/ml. His other pituitary hormone levels were normal, except for mild elevation of gonadotropin hormone. Magnetic resonance imaging of the pituitary showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, resulting in an improvement of his symptoms.

Conclusion: Our patient developed new-onset diabetes mellitus, diabetic ketoacidosis, and isolated adrenocorticotropic hormone deficiency during cancer treatment with pembrolizumab and ipilimumab. The present case highlights the need for physicians to be aware that immune-related adverse events can occur in multiple organs at the same time.

Keywords: Diabetic ketoacidosis; Immune checkpoint inhibitors; Immune-related adverse event; Immunotherapy; Isolated adrenocorticotropic hormone deficiency.