Pembrolizumab-Associated Hypoparathyroidism: A Single Case Report

Objective: To evaluate a case of pembrolizumab-induced hypoparathyroidism leading to hypocalcemia.

Methods: The diagnostic tests performed included calcium and parathyroid hormone level detection and calcium-sensing receptor gene analysis.

Results: A 71-year-old Caucasian man was diagnosed with stage IIIB adenocarcinoma of the lung and received radiation therapy but had no other exposure to radiation. Pembrolizumab 200 mg intravenous every 3 weeks was started 5 years after the initial diagnosis. The patient's corrected calcium level was 9.2 mg/dL (normal, 8.5-10.5 mg/dL) at the start of pembrolizumab therapy. The calcium level after the 13th dose of pembrolizumab was 8.1 mg/dL (normal, 8.5-10.2 mg/dL), leading to endocrinology referral. The patient's parathyroid hormone and corrected calcium levels after the 22nd dose were 4.3 mg/dL (normal, 14-72 pg/mL) and 6.5 mg/dL (normal, 8.5-10.2 mg/dL), respectively. He denied symptoms of latent tetany on presentation while on pembrolizumab for 15 months but complained of fatigue and weakness. The patient had no history of autoimmune diseases or neck injuries. Calcium-sensing receptor gene analysis was negative for genetic mutations. Immunotherapy-mediated hypoparathyroidism was diagnosed. He was treated with daily oral calcium carbonate (2000 mg), calcitriol 0.5 μg, 1 dose of calcium gluconate 2 g intravenous, and 3 doses of calcium chloride 1 g intravenous. His fatigue, weakness, and calcium levels improved with therapy.

Conclusion: Pembrolizumab treatment may have resulted in immune-mediated hypoparathyroidism, leading to hypocalcemia. It is important to report such cases to understand its presentation and timing in relation to pembrolizumab, which further facilitates its timely treatment.