SUN-398 - Worsening Glycemic Control in A Prediabetic Female after Teprotumumab Therapy

Background:
Thyroid Eye Disease (TED) is a serious vision threatening autoimmune disease with reported 20 per 100,000 yearly cases. Teprotumumab, a monoclonal antibody against insulin-like growth factor-1 receptor (IGF-1R), is now an effective option. Hyperglycemia has been reported with treatment.
Case report
A 50 year old female with a past medical history of Graves disease on methimazole, polycystic ovarian syndrome, and prediabetes presented to the clinic for follow up. She had experienced worsening diplopia and periorbital swelling. She was evaluated by Neuro-Ophthalmology which confirmed the diagnosis of TED with Orbit measurements. The patient was started on Teprotumumab with an infusion every 3 weeks for 8 cycles as per protocol. The patient's fasting glucose before treatment was between 110-120 and her HbA1c was 5.8-6%. At the next visit after completing the first infusion,her fasting glucose raised to 130s with her HbA1c of 6.5%. After 3 treatment cycles her glucose increased to 180 and her HbA1c increased to 7.5%. At this visit she was initiated on Metformin and Tirzepatide.

Discussion:
The Teprotumumab trials showed transient increase of blood glucose and HbA1c in 10% of patients, especially in patients with pre-existing impaired glucose tolerance and diabetes. Of those reported cases most were described as mild with return to baseline after finishing the treatment course. An observational study showed a higher prevalence of hyperglycemia with a report of 52% compared to the clinical trial with only 38% of patients returning to their baseline. The hyperglycemia is theorized to be due to the monoclonal antibody binding to the Insulin Receptors due to the same binding site as IGF-1R affecting glucose regulation especially in patients with underlying risk factors. Another possible mechanism is increased growth hormone concentration resulting in increased hepatic gluconeogenesis.

Conclusion:
Teprotumumab, while effective for the treatment of moderate and severe TED, has been shown to have a risk factor of hyperglycemia especially in diabetics and patients with impaired glucose tolerance. This case and previous cases and studies emphasize the need for guidelines for screening and management of Teprotumumab related hyperglycemia. We recommend patient education of potential hyperglycemia with the use of this agent and close endocrine follow up in patients with risk factors and at risk of developing significant hyperglycemia and glycemic decompensation.

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