Case Presentation: 90-year-old female presented with generalized weakness, nausea, vomiting, and diarrhea of 3 days duration. She also reported anorexia but denied any fever, chills, abdominal pain, chest pain, shortness of breath and cough. Vital signs were unremarkable. Physical exam was remarkable for dry oral mucous membranes, the presence of bilateral nephrostomy tubes and costovertebral angle tenderness. CBC was remarkable for mild anemia with Hb 11.8 gm/dL. BMP revealed conspicuous abnormalities including hyponatremia (127 mMol/L), hypochloremia (91 mMol/L), significant hyperglycemia blood glucose (482 mg/dl), and an elevated creatine (1.24 mg/dl ). Potassium (4.4 mMol/L), bicarbonate (26 mMol/L) and the anion gap (14 mEq/L) were within normal limits. Sodium, when adjusted for hyperglycemia, was 133 mMol/L. Urinalysis was remarkable for positive leukocyte esterase, nitrites, bacteria and >182 WBCs The clinical presentation was consistent with new onset diabetes mellitus and UTI. The patient was managed with intravenous fluids, insulin, and antibiotics with clinical improvement. In the meanwhile, HbA1c came back elevated at 9.7% consistent with the diagnosis of DM. The c-peptide level was low normal at 1.2 despite being hyperglycemic. The patient had no prior personal or family history of diabetes mellitus. Of note, 5 months before this presentation, the patient was diagnosed with Urothelial bladder cancer for which she underwent TURBT procedure with placement of bilateral nephrostomy tubes and had been on Atezolizumab, a monoclonal antibody against PD-L1. Atezolizumab is rarely associated with autoimmune endocrinopathies including Insulin-dependent diabetes mellitus and was likely the inciting factor for the onset of diabetes mellitus in this elderly patient. The patient was ultimately discharged home on Insulin and follow-up with endocrinology.
Discussion: Atezolizumab is anti-PD-L1 (programmed cell death- ligand 1) monoclonal antibody which is FDA approved for locally advanced or metastatic urothelial carcinoma and previously treated metastatic non-small cell lung cancer. The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death receptor-1 (PD-1) immune checkpoints play an integral role in the maintenance of immune tolerance to self through negative regulation of the immune system. PD-1 and PD-L1 inhibitors are able to induce an anti-tumor response by interrupting this negative regulation and hence boosting the immune response against cancer cells. However, an unintended consequence is a deleterious autoimmune response which might potentially involve the endocrine organs. Insulin-dependent diabetes mellitus triggered by Atezolizumab, an aftermath of immune-mediated pancreatic burnout and beta cell depletion, is one such example. In absence of any other known risk factors and relatively abrupt onset, it is likely that diabetes mellitus in our patient was an autoimmune sequela of Atezolizumab. She was managed successfully with insulin.
Conclusions: It is not unusual in a hospital setting to come across patients admitted with hyperglycemia or DKA secondary to new-onset diabetes mellitus. As our case exemplifies, a few patients might have an iatrogenic etiology. It is imperative for the hospitalists to be aware of autoimmune Insulin-dependent diabetes mellitus as a consequence of immune checkpoint inhibitors like Atezolizumab.