Refractory Thyroid Eye Disease Unresponsive to Teprotumumab: A Case Report

Abstract

Thyroid eye disease (TED) is a complex autoimmune condition that can cause proptosis, ophthalmoplegia, diplopia, optic nerve compression, and vision loss. These clinical findings are caused by a complex pathological mechanism characterized by thyroid-stimulating hormone receptor autoantibodies activating thyroid-stimulating hormone receptors (TSH-Rs). Overexpressed insulin-like growth factor 1 (IGF-1) receptors found in orbital fibroblasts form complexes with these TSH-Rs, leading to the inflammation and expansion of these tissues. Teprotumumab, a human monoclonal antibody sold under the brand name Tepezza, is currently the only FDA-approved immunotherapy for the treatment of TED. Given as an intravenous infusion every three weeks, teprotumumab works by suppressing IGF-1 receptors, thereby interfering with TSH-R and IGF-1 complex-mediated actions in these fibroblasts. The efficacy of teprotumumab was established in randomized, placebo-controlled clinical trials, which demonstrated clinically meaningful improvements in proptosis, inflammation, and diplopia. While teprotumumab has been shown to be efficacious, our patient with TSHRAb-positive euthyroid thyroid-associated ophthalmopathy who presented with diplopia did not have any significant improvement following the standard treatment dose of eight infusions over a 24-week period. This case underscores not only barriers to treatment, such as the high cost of teprotumumab but also highlights the importance of identifying risks for nonresponse.