An Extremely Rare Case of Immune Checkpoint Inhibitors–Related Hypoparathyroidism and a Critical Literature Review

Immune checkpoint inhibitors (ICIs) have been approved to treat a variety of malignancies, including melanoma, improving the prognosis of these patients. However, they also cause a wide spectrum of rare immune-related adverse events (irAEs), not well-described yet. Although many endocrinopathies have been recognized as irAEs, primary hypoparathyroidism has rarely been reported, and thus clinical suspicion remains low. Herein, we describe the case of a 68-year-old female patient with metastatic melanoma who was admitted to the emergency department with acute symptomatic hypocalcemia due to immune-related (ir)-hypoparathyroidism after 2 cycles of nivolumab/ipilimumab. The patient was treated symptomatically, and her calcium levels were normalized. Parathyroid hormone levels were partially restored during the 6 months of follow-up. A literature review was conducted, summarizing all other subjects who developed ir-hypoparathyroidism after exposure to ICI-based regimen. The review identified 10 additional cases of hypoparathyroidism during immunotherapy. Interestingly, all melanoma cases with ir-hypoparathyroidism had received nivolumab/ipilimumab; 3 of them were also screened and detected with positive calcium-sensing receptor (CaSR) antibodies. Primary hypoparathyroidism may acutely manifest with symptomatic hypocalcemia and care providers should be aware of this rare irAE.