Effect of Histamine-2 Receptor Antagonists on Hypocalcemia after Thyroidectomy: A Retrospective Cohort Study and Sensitivity Analysis

Objective: The objective of this study is to examine the risk of hypocalcemia after thyroidectomy in patients taking histamine-2 receptor antagonists. Study Design: Retrospective cohort study. Setting: Multicenter, single database. Methods: Thirty-four thousand two hundred eighteen patients treated with total thyroidectomy from 2011 to 2022 were identified via the TriNetX Research Network. We compared the incidence of transient (0-1 month and 1-6 months following thyroidectomy) and permanent (6-12 months following thyroidectomy) postthyroidectomy hypocalcemia in patients with and without H2 receptor antagonists. Propensity score matching and sensitivity analysis were done to control for additional risk factors. Results: Patients were divided into 2 cohorts: those with an H2 receptor antagonist prescription before surgery (n = 5108) and those without (n = 29,110). 44.9% and 11.6% of thyroidectomy patients taking H2 receptor antagonists had hypocalcemia compared to 38.3% and 8.2% of patients without H2 receptor antagonists at 0 to 1 month and 6 to 12 months, respectively. Patients taking H2 receptor antagonists had a significantly increased risk of experiencing hypocalcemia at 0 to 1 month, 1 to 6 months, and 6 to 12 months. Patients taking H2 receptor antagonists were also at increased risk for visiting the emergency department and receiving intravenous calcium replenishment at 1 and 6 months following surgery. Sensitivity analysis continued to yield significant results at all time points. Conclusion: Patients taking H2 receptor antagonists may be at increased risk of short and long-term hypocalcemia after thyroid surgery. This is the first retrospective cohort study examining the risk of hypocalcemia after thyroidectomy in patients taking H2 receptor antagonists.