Thyroid function suppression after initiation of teprotumumab treatment

Abstract

Teprotumumab, a monoclonal antibody that inhibits the insulin-like growth factor I receptor (IGF-IR), is newly approved for thyroid eye disease [1]. As IGF-IR forms a complex with the thyrotropin receptor (TSHR), mediating the actions of thyrotropin and Graves’ disease immunoglobulins in the orbital fibroblasts and thyroid epithelial cells [1], and IGF-IR knockout in mouse thyroid reduces circulating thyroxine and raises thyrotropin levels [2], thyroid function may be suppressed by teprotumumab in patients with thyroid eye disease. Clinical trials have not addressed the effects of teprotumumab on thyroid function due to design limits [1]. A case is presented here to provide direct evidence that teprotumumab indeed suppresses thyroid function. A 41-year-old female had been diagnosed with Graves’ disease and thyroid eye disease at age 24 in 2003. Her hyperthyroidism was treated with methimazole. She underwent subtotal thyroidectomy at age 29 in 2008; the goiter recurred a year later. She did not receive radioiodine ablation. The maintenance dose of methimazole was 2.5–5mg daily. She underwent multiple orbital decompression operations and intraorbital corticosteroid injections with residual symptoms of proptosis and double vision. She initiated teprotumumab treatment (540mg every 3 weeks) in mid-September 2020; in the 1.5 years before that, she had been on methimazole 5mg daily with well-controlled thyroid function (Table 1). Her eye symptoms improved with teprotumumab treatment. Two months after starting teprotumumab, she felt fatigued and her free T4 and T3 indices (alternative methods of estimating free T4 and T3 levels) [3] were low and thyrotropin significantly elevated (18.8 μIU/mL, normal range 0.3–4.7) (Table 1). Methimazole was held for 3 days, then resumed at a dose of 2.5mg daily. A month later, free T4 and T3 were normal but thyrotropin was still elevated, albeit lower than before (7.2 μIU/mL) (Table 1). Methimazole was discontinued. Another month later, while still on teprotumumab treatment, free T4 and T3 remained normal while thyrotropin further decreased but still remained slightly elevated (6.2 μIU/mL) (Table 1). The patient had been on stable and typical maintenance dose of methimazole with largely normal free T4 and T3 levels for 1.5 years before the initiation of teprotumumab treatment. She exhibited overt hypothyroidism after 2 months of teprotumumab treatment and she remained slightly hypothyroid even after discontinuation of methimazole. The temporal correlation between the teprotumumab treatment and thyroid function strongly suggests that teprotumumab inhibits thyroid function in patients with Graves’ disease. It is thus important to monitor thyroid function in patients on teprotumumab treatment.