ODP159 A Rare Case of Pembrolizumab Induced Diabetic Ketoacidosis
Authors: Durrani Jawahar , Sood Aayushi , Sharma Brihant , Khattar Khyati , Buradkar Ajinkya 
Published: November 2022

Abstract

Introduction
Immune checkpoint inhibitors (ICI), such as Pembrolizumab, have demonstrated excellent clinical outcomes in numerous solid organ malignancies. However, this new drug comes with unpredictable adverse reactions which are still under review in the medical literature. We are showcasing a cancer patient treated with an ICI and presenting to the hospital in diabetic ketoacidosis (DKA), despite no significant history of a formal diagnosis of Diabetes Mellitus.

Case description
The patient is a 69 year old male who presented to the hospital with generalized weakness. His past medical history was significant but not limited to, Hypothyroidism, Tobacco use disorder, Stage IV Siewert type 2 gastroesophageal junction adenocarcinoma (cT4N2M1, HER2/FGFR negative, PD-L1 positive) after completion of one year of chemotherapy. He was now undergoing immunotherapy with Pembrolizumab, with his first dose three weeks ago. Reviews of systems including fever, abdominal pain, nausea, vomiting, polyuria, polydipsia were negative. Vital signs were grossly normal. He gave no personal or family history of diabetes. On admission venous blood gas demonstrated a high anion gap metabolic acidosis (pH 7. 096, Blood glucose 762 mg/dL, Anion Gap 29 mmol/L, bicarbonate 9 mmol/L, Plasma osmolality 337 mOsm/kg). Serum Lipase was 23 U/L. HbA1c was found to be 5.9%. Urinalysis was significant for glucose &gt;500 mg/dl and &gt;80 mg/dl of ketones. The physical exam was only remarkable for dry mucous membranes. Given the presentation and lab findings, he was subsequently diagnosed with DKA. The patient was treated with standard guideline therapy for DKA including bolus fluids, maintenance fluids and intravenous (IV) Insulin. The Anion gap closed and glucose decreased to under 200. He was transitioned to a subcutaneous insulin regimen, and discharged on the same.

Discussion
Based on diagnostic workup and exclusion of probable aetiologies, the patient was diagnosed with pembrolizumab-induced DKA. In the acute care setting, an autoimmune workup was not done in our patient. A meta analysis review of 71 such cases from 56 publications showed the average HbA1c concentration was 7.84% + 1. 0% at presentation. The A1c finding of 5.9%, defined at pre-diabetes, in represents an outlier. Another meta-analysis of such patients demonstrated DKA as the first sign of diabetes in 30 out of 35. The pathophysiology of this side effect of ICI's remains unknown, however several mouse studies have shown PD-1/PD L1 blockade precipitating diabetes in prediabetic non-obese mice. Anti -PD-1 drugs might have the same effect, and the reduction of PD-1 might activate autoreactive T cells, resulting in an autoimmune response against pancreatic islet cells. As the use of immunotherapy is expected to increase, it is essential that clinicians become aware of DKA as a rare and life threatening side effects of immunotherapy and that blood glucose monitoring is strongly considered as a method of prevention.
Presentation: No date and time listed