SUN-400 - Euglycemic Diabetic Ketoacidosis After Teprotumumab: A De Novo Presentation of Type 1 Diabetes

Background
Teprotumumab, an insulin-like growth factor-1 receptor antagonist, has demonstrated substantial clinical efficacy in patients with thyroid eye disease (TED). While hyperglycemia is a common and typically mild adverse effect, severe hyperglycemic emergencies, including hyperosmolar hyperglycemic state and diabetic ketoacidosis (DKA), are infrequently reported.

Clinical Case
A 40-year-old woman with Graves’ disease (GD) and moderate to severe active TED was hospitalized for euglycemic DKA following her third dose of teprotumumab, while on a sodium-glucose cotransporter-2 (SGLT2) inhibitor. She had previously completed a 12-week course of weekly intravenous methylprednisolone for her ocular symptoms, after which her hemoglobin A1c increased from 4.6% (2 years prior) to 6.3%. Due to persistent proptosis and diplopia, teprotumumab infusions were initiated. Four weeks after the 3rd infusion, she presented to the emergency department with abdominal pain following an upper respiratory infection. Laboratory evaluation revealed a hemoglobin A1c of 6.8%, serum glucose 162 mg/dL, anion gap 30 mmol/L, beta-hydroxybutyrate 3.22 mmol/L, bicarbonate 5 mmol/L, and venous pH 7.07, consistent with euglycemic DKA. She was admitted to the intensive care unit and managed with continuous intravenous insulin infusion and discontinuation of the SGLT2 inhibitor. Upon discharge, she was transitioned to a basal-bolus insulin regimen. Three pancreatic autoantibodies returned positive: glutamic acid decarboxylase antibody (GADA) >250 IU/mL (normal < 5), insulinoma-associated-2 antibody (IA-2A) 231 U/mL (normal < 5.4), and insulin antibody (IAA) 35.7 U/mL (normal < 0.4), confirming a new diagnosis of type 1 diabetes. During follow-up, TED symptoms remained stable after discontinuation of teprotumumab, and antihyperglycemic therapy was adjusted accordingly.

Conclusion
We report here the first case of euglycemic DKA associated with teprotumumab, in the setting of a new diagnosis of type 1 DM. Clinicians should recognize hyperglycemic complications, including euglycemic DKA, in teprotumumab-treated patients, who are not only at risk of insulin resistance but also of type 1 diabetes, likely due to shared autoimmune susceptibility underlying their GD/TED. Routine glycemic monitoring in patients receiving teprotumumab and screening for pancreatic autoantibodies in patients with GD/TED may identify patients at risk for such complications and lead to more prompt diagnosis and treatment.

References
1. Carter C, et al. Endocrine. 2023;83:65–68.
2. Cottom S, et al. Case Rep Ophthalmol. 2024;15:246–249.
3. Mehta P, et al. Case Rep Ophthalmol. 2024;15:115–121.
4. Shah K, Charitou M. AACE Clin Case Rep. 2022;8:148–149.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*