Systemic Effects of Teprotumumab Treatment on Thyroid Function in Patients With Thyroid Eye Disease: A Retrospective Study

Background: Teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor, has demonstrated significant efficacy in treating thyroid eye disease. While its ophthalmic benefits are well established, limited data exist regarding its effects on thyroid hormone regulation. Objective: To characterize changes in thyroid function associated with teprotumumab therapy in thyroid eye disease patients. Methods: We performed a retrospective comparative study of 46 thyroid eye disease patients treated with teprotumumab and 46 thyroid eye disease patients treated with orbital decompression at a tertiary care facility between January 2020 and December 2023. Thyroid function tests (thyroid-stimulating hormone and free thyroxine) were analyzed at pretreatment and posttreatment. Subgroup analysis was conducted based on prior thyroidectomy or radioactive iodine therapy. Clinical outcomes, including proptosis and Clinical Activity Score, were also evaluated. Results: The teprotumumab cohort had a mean age of 55.9 years, with 80.5% female and 65.2% hyperthyroid at presentation. The orbital decompression cohort mean age was 49.8 years, with 89.1% female and 80.4% hyperthyroid. Both groups showed significant improvements in Clinical Activity Score and proptosis. In the teprotumumab group, free thyroxine levels significantly declined posttreatment (1.7 ± 1.2 to 1.3 ± 0.4, p = 0.049), particularly in patients without prior thyroidectomy/radioactive iodine (1.8 ± 1.4 to 1.2 ± 0.3, p = 0.041). The orbital decompression group showed no significant change in free thyroxine levels ( p = 0.63). Over half (52.2%) of teprotumumab patients required medication adjustments during therapy, compared with 12.5% in the orbital decompression group ( p < 0.001). Conclusions: Teprotumumab may impact thyroid hormone homeostasis, especially in patients with functioning thyroid tissue, suggesting a need for endocrine monitoring with treatment.