MON-425 - From Orbitopathy Relief to Glycemic Risk: A Unique Case of Self Resolving Diabetes Following Teprotumumab Therapy in Thyroid Eye Disease

Teprotumumab is a human monoclonal antibody inhibitor of insulin-like growth factor I receptor, used to treat thyroid eye disease (TED) commonly associated with Graves' disease. Teprotumumab carries a risk of hyperglycaemia with reported incidence of 8 – 10%. It causes an upregulation of growth hormone production by blocking the receptor of IGF -1, which leads to increased glucose production and insulin resistance. We present a case of severe hyperglycaemia as a side effect of teprotumumab requiring insulin therapy.​
A 72-year-old male presented for weight loss, tremors, bilateral eye puffiness, redness and left eye protrusion. Test results at that time showed TSH of 0.01 IU/L (0.49-4.67 IU/L), Free T4 of 2.62 ng/dl (0.61 – 1.60 ng/dl), Free T3 of 10.57 pg/ml (2.50 – 3.90 pg/ml) and thyroid stimulating immunoglobulin of 16.30 IU/L ( < 0.55 IU/L) consistent with Grave’s disease. Methimazole was prescribed with further dose adjustment that eventually controlled hyperthyroidism. Later, teprotumumab was initiated for worsening TED. After a total of 8 doses of teprotumumab every 3 weeks, TED improved. One month later he began experiencing progressive fatigue, weight loss of 4 Kg and light-headedness along with polydipsia and polyuria. At the emergency room plasma glucose was measured at 714 mg/dl and HbA1c at >15% without ketoacidosis. This drastic increase emphasized how much his blood sugars had increased since starting teprotumumab. Insulin therapy consisting of glargine 15 units daily and aspart 5 units with each meal was implemented. One year ago, patient was noted to have fasting glucose intolerance with fasting blood glucose of 120 mg/dl. Antibodies for autoimmune diabetes were all negative and C-peptide measured at 3.5 ng/ml (1.1 – 4.4 ng/ml) with concurrent glucose of 148 mg/dl, indicating low residual endogenous production. At 3 and 6 month follow up glucose levels improved, and insulin dose was decreased overtime and eventually discontinued as he began experiencing hypoglycaemia and spontaneous resolution of hyperglycaemia.
Teprotumumab was a trigger for this transient case of symptomatic and severe diabetes and hence detecting those who have underlying glucose intolerance ahead of time is crucial. Additionally, it shows that not only diabetic patients, but all with impaired fasting glucose should undergo close supervision while on teprotumumab therapy. Clinical guidelines are needed around monitoring and treatment of this complication. We recommend obtaining a baseline HbA1c prior to treatment initiation, followed by periodic fasting glucose or HbA1c assessments during therapy, and continued glucose monitoring for several months post-treatment, especially in patients with risk factors for dysglycemia. Hence the importance of following thyroid eye disease patients with multidisciplinary team with an ophthalmologist and an Endocrinologist cannot be overemphasized.

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