Hypoparathyroidism induced by immune checkpoint inhibitors: a review of literature reports and real-world pharmacovigilance data

Objective: This study aims to comprehensively assess the characteristics of immune checkpoint inhibitor (ICI)-induced hypoparathyroidism (HP) by analyzing published case reports and adverse event data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We identified case reports of HP during ICI treatment through a systematic literature search and extracted clinical data. FAERS data (Q2 2011-Q3 2024) were analyzed for cases where ICIs were the primary suspected cause of HP. Disproportionality and Bayesian analyses were used to evaluate associations between ICI classes and HP. Results: Nine ICI-related HP cases were documented in the literature. Predominant manifestations included neuromuscular symptoms (e.g., weakness, paresthesia). Laboratory findings consistently revealed hypocalcemia and low parathyroid hormone (PTH) levels. Four cases exhibited prolonged QT intervals, and calcium-sensing receptor (CaSR) autoantibodies were detected in four patients. Pharmacovigilance analysis showed the strongest signal for CTLA-4/PD-1 inhibitor combination therapy (ROR (95% CI): 6.04 (2.26-16.13); PRR (χ 2): 6.04 (16.71); EBGM (EBGM05): 6.01 (2.64); IC (IC025): 2.59 (1.29)). Conclusion: ICI-induced HP is a rare endocrine toxicity requiring heightened clinical vigilance. Regular monitoring of serum calcium levels is essential, with PTH measurements recommended in the presence of hypocalcemia to facilitate early diagnosis and appropriate management.