Immune Checkpoint Inhibitor-Induced Hypoparathyroidism Associated With Calcium-Sensing Receptor-Activating Autoantibodies

Abstract

Context: Whereas therapy with immune checkpoint inhibitors (ICIs), such as nivolumab, have substantially improved survival in several types of cancer, increased attention has been given to adverse immune events associated with their use, including the development of endocrine autoimmunity.

Objectives: First, to describe a patient with a 2-year history of metastatic small cell lung cancer who had been treated with nivolumab a few months before presentation with the signs and symptoms of severe hypocalcemia and hypoparathyroidism. Second, to investigate the etiology of the patient's hypoparathyroidism, including the presence of activating autoantibodies against the calcium-sensing receptor (CaSR), as humoral and cellular immune responses against the CaSR have been reported in patients with autoimmune hypoparathyroidism.

Participants: A 61-year-old female was admitted with persistent nausea, vomiting, epigastric pain, constipation, and generalized weakness. Laboratory analyses showed low total serum calcium, ionized calcium, and parathyroid hormone (PTH). The patient was diagnosed with severe hypocalcemia as a result of autoimmune hypoparathyroidism after testing positive for CaSR-activating autoantibodies.

Interventions: She was treated with intravenous calcium gluconate infusions, followed by a transition to oral calcium carbonate, plus calcitriol, which normalized her serum calcium.

Results: Her serum PTH remained low during her hospitalization and initial outpatient follow-up, despite adequate repletion of magnesium.

Conclusions: This case illustrates autoimmune hypoparathyroidism induced by ICI blockade. As ICIs are now used to treat many cancers, clinicians should be aware of the potential risk for hypocalcemia that may be associated with their use.