Teprotumumab Induced Type 1 Diabetes Mellitus

Introduction:
Thyroid Eye disease is a potentially vison impairing condition for which Teprotumumab has emerged as a premier option in managing disease activity. The primary mechanism of action is monoclonal antibody against the insulin-like growth factor-I receptor but a large portion remains unknown. In the original trial for Teprotumumab about 10% of patients developed hyperglycemia which was described as self limited and mild. Since commercial release there has been great heterogeneity of hyperglycemia shown with case reports of HHS and DKA despite a third of trial patients returning to baseline after completion of therapy. We present a case of type 1 diabetes after starting Teprotumumab which may help advise decisions for therapy, monitoring, and surveillance.

Case Description:
A 52-year-old female with prediabetes (A1C 6.1%), mild hypothyroidism and tobacco use who presents with diplopia, proptosis, palpitations in January of 2022 to PCP. She had lab work performed in March 2022 with TSH 0.007, FT4 2.45, TPO antibodies 219 positive. Last normal TFTs in Feb of 2020. Her levothyroxine was stopped by PCP and she was started on methimazole 10 mg tid and propranolol ER 60 mg daily. April 2022 referred to Endocrinology, Labs: TSI index of 2.9, TSH now of 13, Free T4 of 0.56 (0.93 - 1.7) while on methimazole 10 mg tid. She was reduced to 10 mg bid and referred to Ophthalmology for co-management of thyroid eye disease with plan for Teprotumumab for moderate to severe disease. Subsequent follow up in June 2022, she had been tapered down to 5 mg bid between visits and labs showed: TSH 0.074, FT4 1.08, FT3 3.8. Methimazole was further reduced to 5 mg daily. She was started on metformin XR 500 mg bid given her diagnosis of prediabetes and plan for Teprotumumab therapy. She achieved smoking cessation with varenicline. CBC and LFT monitoring was remarkable for chronic mild ALP elevation. Teprotumumab was started and her eye symptoms improved significantly by the second infusion. Hyperglycemia worsened and A1C increased to 7.5%.TSH was 6.32 and Free T4 1.1 on 5 mg of methimazole. Subsequently methimazole was decreased to 2.5 mg daily and Metformin increased to 1g bid and addition of glimepiride 2 mg daily. She had continued hyperglycemia. Subsequent labs we obtained GAD antibodies with continued hyperglycemia and monitoring labs for remission. GAD antibodies >125 exceeding beyond the upper limit of normal for the assay and subsequent thyroid tests with c-peptide are pending at this time.

Discussion:
Teprotumumab has revolutionized thyroid eye disease treatment. This case demonstrates there are multiple modalities of hyperglycemia that may be non-reversible after completion of Teprotumumab. The importance of monitoring and perhaps a role in evaluating antibodies and insulin reserve in Teprotumumab induced hyperglycemia surveillance. This case supports that this group is heterogenous and needs further studies. Further evaluation for this patient is still pending with initiation of insulin therapy. We hope that this case can help guide research, safety protocols, and awareness in the management of thyroid eye disease.