SAT-362 Persistently Elevated Insulin-like Growth Factor-1 Levels Following Teprotumumab Treatment for Thyroid Eye Disease

Abstract Disclosure: G.S. Schmidt: None. S.C. De La Torre: None. T.S. Knee: None. M.K. Shakir: None. T.D. Hoang: None. Background: Insulin-like growth factor-1 receptor (IGF-1R) signaling plays a role in thyroid eye disease (TED) pathogenesis. Teprotumumab is a monoclonal antibody against IGF-1R approved for treatment of TED. Elevated serum IGF-1 levels are noted in patients treated with teprotumumab but the degree and duration of this elevation is not well characterized. We report the case of a 50-year-old man with Graves’ disease complicated by moderate TED who received treatment with teprotumumab and demonstrated elevated serum IGF-1 levels more than 6 months after the completion of therapy. Clinical Case: A 50-year-old man with no significant past medical history presented to the emergency department with heat intolerance, exertional dyspnea, tachycardia, hyperhidrosis, brain fog, and difficulty in concentrating. Laboratory evaluation demonstrated a suppressed TSH, elevated free T4, and positive thyrotropin receptor antibodies consistent with Graves’ disease. At the time of diagnosis patient had proptosis with a clinical activity score (CAS) of 3. CT scan of the orbits noted moderate bilateral proptosis with mild bilateral enlargement of the extraocular muscles consistent with TED. Patient started treatment with methimazole but one year after initial diagnosis he reported subjective worsening in eye symptoms including worsening lid retraction, exposure keratopathy, and lid edema with CAS increased to 4. Patient elected for therapy with teprotumumab. During treatment, routine labs showed elevated serum IGF-1 levels that remained elevated throughout treatment. Three months after treatment he had an oral glucose tolerance test (OGTT) with appropriate suppression of growth hormone (GH) levels. Patient’s serum IGF-1 level eventually normalized more than 6 months after completion of treatment. Conclusion: Inhibition of IGF-1R reduces feedback inhibition of GH secretion. This results in elevated GH which in turn results in increased production of insulin-like growth factors by the liver and other tissues. This has been implicated in some of the adverse effects with teprotumumab including hyperglycemia and ototoxicity but specific relationships remain unclear. This case demonstrates serum IGF-1 levels can remain elevated for greater than 6 months after completion of treatment with teprotumumab for TED. The clinical significance of persistently elevated serum IGF-1 levels is unclear and requires further characterization. Presentation: Saturday, July 12, 2025