A Case of Pembrolizumab-Induced Diabetic Ketoacidosis and Hyperthyroidism in a Patient With Recurrent Esophageal Adenocarcinoma

Abstract

Immune checkpoint inhibitors (ICI) such as program cell death protein 1 (PD-1) inhibitors are widely used for the treatment of patients with recurrent, locally advanced or metastatic, gastric or gastroesophageal (GE) junction adenocarcinoma. Immune-related adverse events (irAE) such as endocrinopathies have been reported after patients received ICI. We report a case of pembrolizumab-induced hyperthyroidism and type 1 diabetes mellitus (DM1) presenting with diabetic ketoacidosis (DKA). A 53-year-old African American male with no history of diabetes or hyperthyroidism was treated with two cycles of pembrolizumab for recurrent GE junction adenocarcinoma after which he was admitted with hyperthyroidism (thyroid stimulating hormone [TSH] 0.070mIU/L, free thyroxine 1.85mIU/L) and DKA (pH 7.06, glucose 583 mg/dL, beta-hydroxybutyrate 8.63 mmol/L, anion gap 27 meq/L). The patient was treated with intravenous insulin and aggressively hydrated. Given the lack of other precipitating factors for the two endocrinopathies, it was determined that the most likely etiology was recent treatment with pembrolizumab (a PD-1 inhibitor). In our case, pembrolizumab monotherapy developed two irAE (hyperthyroidism and DKA), which is unique as most combined immunotherapy regimens are associated with the development of multiple endocrinopathies. Our case emphasizes the importance of baseline monitoring of thyroid function and blood glucose prior to the start of ICI to monitor and evaluate patients with immune-related adverse events, including endocrinopathies.

Immune checkpoint inhibitor– and phosphatidylinositol-3-kinase inhibitor–related diabetes induced by antineoplastic drugs: two case reports and a literature review

“…Available evidence on the association of pancreatic autoantibodies with ICI-related diabetes is inconsistent. Some authors ( 17 ) have reported that most East Asian patients are negative for these autoantibodies, as in our case 1, whereas others have documented positivity for at least one pancreatic autoantibody, most commonly glutamic acid decarboxylase antibody, in 30–50% of cases ( 18 ). In addition, certain human leukocyte antigen (HLA) genotypes (e.g., the DR3-DQ2 and DR4-DQ8 haplotypes) are known to confer susceptibility to (fulminant) type 1 diabetes ( 19 ), and they (mainly DR4) have been detected in about 61% of patients with ICI-related diabetes ( 20 ).…”