Endocrine Abstracts

JOINT2227

Background: Immunotherapy displays a prominent role in the current treatment of many malignancies. However, several adverse events of immune checkpoint inhibitors (ICIs) have been described so far. We present a rare case report of pembrolizumab–induced autoimmune diabetes mellitus (DM) concomitantly with myositis.

Case presentation: A 65-year-old Caucasian male, with no personal or family history of DM, was treated with pembrolizumab for squamous lung cancer. Two months after the 1^st dose of treatment, he presented to the emergency department due to muscle weakness, fatigue and high plasma glucose levels (>500mg/dl). The patient also reported polyuria, polydipsia, mouth dryness, weight loss and abdominal pain over the last three days. Physical examination revealed tachycardia, tachypnea, dehydration, numbness of the lower extremities and left eyelid ptosis. The patient did not experience any cardiac symptoms and the electrocardiogram was normal. Laboratory tests were indicative of diabetic ketoacidosis concomitantly with myositis. Further investigation, for DM, revealed low c-peptide (0,55 ng/dl), and insulin concentration (<1,6 μUI/ml). Immediate treatment was initiated, including hydration, intravenous insulin infusion and high-dose intravenous methylprednisolone of 1gr daily with significant clinical and biochemical improvement. He was subsequently switched to subcutaneous insulin therapy and to 1mg/kg methylprednisolone orally which was slowly tapered over the next two months. The patient tested positive for autoantibodies against glutamic acid decarboxylase (anti-GAD) and islet cell autoantibodies (ICA). These data established the diagnosis of new-onset autoimmune DM. The antibodies for myasthenia Gravis were negative. Six months later, the patient presented within glycemic targets along with a significant improvement of the left eyelid movement and fatigue.

Discussion: Pembrolizumab is an ICI, widely used in cancer treatment. Its main action is to inhibit lymphocytes’ PD-1 receptors and elicit an immune response. This allows the immune system to target and destroy cancer cells, but also, leads to immune-related adverse events (irAEs) in various organ systems. Immune-mediated destruction of pancreatic β-cells and myositis by pembrolizumab are rare disorders. This is the first case report of pembrolizumab-induced autoimmune DM concomitantly with myositis, described so far. Monitoring of early signs of these adverse events and medical professional awareness are crucial, as some of these could be life-threatening. The exact mechanisms are yet to be elucidated.