Thyroid eye disease with teprotumumab-related hyperglycemia associated with increased growth hormone secretion
Abstract Teprotumumab, an insulin-like growth factor-1 (IGF-1) receptor antibody, has been approved for thyroid eye disease (TED) treatment. However, teprotumumab is associated with adverse events such as hyperglycemia, and the underlying mechanisms of teprotumumab-related hyperglycemia remain unclear. We report a case of teprotumumab-related hyperglycemia with endocrinological evaluation. A 60-year-old woman with Graves disease developed active TED and was treated with teprotumumab. The patient had preexisting type 2 diabetes managed with oral hypoglycemic agents. At 6 weeks after teprotumumab initiation, glycemic control deteriorated, necessitating temporary teprotumumab discontinuation and insulin therapy initiation. Serum growth hormone (GH) level changed minimally, whereas serum IGF-1 level increased markedly, suggesting increased integrated GH secretion. Fasting plasma glucose level substantially increased, whereas serum immunoreactive insulin level only modestly increased, indicating insufficient endogenous insulin secretion. Following glycemic improvement with insulin therapy, teprotumumab was resumed, and 8 infusions were completed. Despite persistently elevated serum IGF-1 levels, insulin was gradually tapered with concomitant weight loss and was discontinued at 9 weeks after the final infusion. In patients with reduced endogenous insulin secretory capacity, teprotumumab-related hyperglycemia may develop when endogenous insulin secretion is insufficient to compensate for GH-mediated increases in hepatic gluconeogenesis and insulin resistance.