Immune Checkpoint Inhibitors and Endocrine Disruption: A Case of Hyponatremia and Adrenal Insufficiency

Abstract

Immune checkpoint inhibitors, such as pembrolizumab, have transformed cancer therapy by enhancing the immune system's ability to combat tumors, but they can also lead to immune-related adverse events, including adrenal insufficiency. This case report presents a 52-year-old male with a history of malignant melanoma who developed adrenal insufficiency after four months of pembrolizumab therapy. The patient was admitted with symptoms of malaise, vomiting, abdominal pain, and poor appetite. Laboratory tests revealed significant metabolic abnormalities including hyponatremia, hypokalemia, and elevated thyroid-stimulating hormone. Further endocrine evaluation confirmed the diagnosis of secondary adrenal insufficiency, likely due to pembrolizumab-induced inflammation of the pituitary gland. The patient was treated with corticosteroid replacement therapy, leading to clinical improvement, and pembrolizumab was discontinued due to the risk of worsening adrenal insufficiency. This case underscores the importance of early recognition and management of adrenal insufficiency in patients receiving pembrolizumab. While the exact cause of pembrolizumab-induced adrenal insufficiency is not fully understood, it may involve an autoimmune attack on cells in the pituitary gland. Prompt identification and treatment are essential to prevent potentially life-threatening complications, and this case highlights the need for clinicians to maintain a high level of awareness for adrenal insufficiency in patients presenting with nonspecific symptoms during or after immunotherapy.