Presentations

Abstract

Introduction: Immune checkpoint inhibitors (ICIs) like Pembrolizumab have been revolutionary in treating cancer, but they can cause severe side effects. In this case report, we will discuss immune-related adverse events (irAEs) due to ICIs

Case Information: Our patient is a 61-year-old man with a history of Renal Cell Carcinoma with pancreatic metastases. The patient presented to the ER with fatigue, polyuria, polydipsia, and poor oral intake two days after completing his third monthly infusion of Pembrolizumab. The exam revealed new onset Atrial Fibrillation with rapid ventricular response. His labs were significant for a blood sugar of 780 mg/dl (normal range 70-99mg/dl), moderate Acetone levels in the blood, glucosuria, and ketonuria. He had a low TSH (<0.01 mcU/mL) and high FT4 (>2.0 ng/dl, with the normal range being 0.9 to 1.8 ng/dl)). Thyroid Stimulating Immunoglobulins were elevated. His Diabetic ketoacidosis was resolved with fluids and an insulin drip, and he was transitioned to a basal-bolus insulin regimen, which controlled his glucose well. His tachycardia was controlled with beta-blockade. He was discharged on propranolol, apixaban, and methimazole. His final diagnoses were Pembrolizumab-induced new onset Type 1 Diabetes Mellitus and Pembrolizumab-induced Graves' Disease.

Discussion/Clinical Findings: Immune checkpoint inhibitors (ICIs), also known as checkpoint inhibitor immunotherapy, are immunomodulatory antibodies that enhance the immune system. These agents have substantially improved the prognosis for patients with many advanced malignancies. Despite important clinical benefits, ICIs are associated with a unique spectrum of side effects known as immune-related adverse events (irAEs). IrAEs include dermatologic, gastrointestinal, hepatic, endocrine, and other less common inflammatory events. IrAEs are believed to arise from general immunologic enhancement. Temporary immunosuppression with glucocorticoids and other immunosuppressants is effective in treating irAEs in most cases. Although rare, fulminant and even fatal toxicities may occur with ICIs. Therefore, prompt recognition and management of irAEs is important. The most common endocrinopathies due to ICIs are hypothyroidism, hyperthyroidism, and hypophysitis. The incidence rate for Pembrolizumab-induced hyperthyroidism is 0.6 %. Autoimmune thyroid disease due to ICIs can be manifested as primary hypothyroidism secondary to destructive thyroiditis or rarely as hyperthyroidism associated with Graves' disease. ICI-related Graves' disease is treated similarly to non-ICIs-related Graves' disease, and thyroid function should be monitored before each dose of an ICI for early detection of thyroid dysfunction.

Conclusion: Treatment with ICIs has also been associated with acute onset of type 1 diabetes mellitus in approximately 0.2 to 0.9 % of cases. Patients who develop immunotherapy-induced type 1 diabetes mellitus are typically treated with insulin therapy and, unfortunately, will remain Insulin-dependent. In contrast to other immune-related adverse events from ICIs, treatment with glucocorticoids or other immunosuppressive agents is not effective in these patients due to the almost complete destruction of the pancreatic beta cells by immunotherapy. It is recommended to monitor glucose with each dose of ICI for early detection of new-onset Diabetes mellitus due to ICIs. A brief literature review did not show other cases of Pembrolizumab-related combined new-onset Diabetes and Graves' disease.