Risk of significant liver enzyme elevation after switching antithyroid drugs.

Clinically significant liver enzyme elevation is a recognized adverse effect of antithyroid drugs (ATDs) and often necessitates treatment discontinuation and switching to an alternative agent. Using TriNetX, we conducted a retrospective cohort study of patients with hyperthyroidism who initiated methimazole/carbimazole (MMI) or propylthiouracil (PTU), developed significant liver enzyme elevation within 4 months, and switched to the alternate ATD within 12 months. Baseline characteristics were indexed to the initial prescription, and outcomes were assessed for 120 days following the second prescription. The cohort included 276 patients who switched from MMI to PTU and 82 patients who switched from PTU to MMI. Significant liver enzyme elevation occurred in 111/276 (40%) and 25/82 (30%) of patients, respectively. Hepatocellular-pattern elevation occurred in 48/276 (17%) and 13/82 (16%), while cholestatic-pattern elevation occurred in 91/276 (33%) and 15/82 (18%). These findings demonstrate that significant liver injury after ATD switching is frequent but not inevitable and occurs at comparable rates across switch groups, underscoring the need for close biochemical monitoring and individualized treatment decisions.