SUN-173 Nivolumab-Induced Fulminant Autoimmune Diabetes Presenting as Diabetic Ketoacidosis in a Patient with Melanoma

Background: Anti PD-1 antibody immunotherapies like nivolumab and pembrolizumab are newer agents used in the treatment of melanoma and multiple other types of advanced cancers. Immune-mediated endocrinopathies triggered by these drugs are increasingly reported in literature and encountered by endocrinologists in their daily practice. Fulminant diabetes characterized by rapid autoimmune destruction of the pancreatic beta cells, is a relatively rare (less than 1% reported incidence with nivolumab) but potentially lethal complication associated with anti PD-1 therapies. Case Presentation: A 44-year-old African American man with metastatic melanoma was treated with nivolumab for 3 months as second line therapy after disease progression on standard therapy. After receiving his third dose of nivolumab (doses q4 weeks), patient started complaining of gradually worsening polyuria, polydipsia, dehydration and blurry vision prompting hospitalization. The patient had no personal or family history of prior diabetes. His outpatient glucose values on office visits 1 month prior to hospitalization were normal, 80 and 82 mg/dL. Admission labs showed significant hyperglycemia with serum glucose of 938 mg/dL (nl 70-100mg/dL), elevated anion gap of 24 mEq/L (nl 7-17 mEq/L), mild acidemia with pH 7.35 (nl 7.32-7.45), elevated serum osmolality at 335 mOsm/kg (nl 281-304mOsm/kg), ketonuria and glucosuria. HbA1c at the time was 9.1% (nl 3.1-6.5%). A diagnosis of diabetic ketoacidosis was made, and the patient was admitted to the medical ICU for intravenous fluids and insulin therapy. Additional work up showed undetectable levels of C-peptide when blood glucose was 215 mg/dL. Patient tested positive for islet cell antibodies and had undetectable titers of anti-GAD antibodies. The patient was medically stabilized and eventually discharged home on a basal-bolus insulin regimen. Conclusion: Our patient is a rare case of nivolumab-induced autoimmune diabetes, clinically significant for the rapid onset and profound nature of DKA on presentation. The use of anti PD-1 immunotherapies like nivolumab is likely to become ubiquitous soon given their efficacy in treating advanced cancers. Clinicians should be aware and educated about monitoring for the potential endocrinopathies including fulminant autoimmune diabetes caused by these drugs. Refrences: Godwin, James Luke, et al. “Nivolumab-Induced Autoimmune Diabetes Mellitus Presenting as Diabetic Ketoacidosis in a Patient with Metastatic Lung Cancer.” Journal for ImmunoTherapy of Cancer, vol. 5, no. 1, 2017, doi:10.1186/s40425-017-0245-2.