(16.03) Hyperlipasemia Associated with Teprotumumab Infusion

Teprotumumab (Tepezza), is a novel therapy used to treat thyroid eye disease, typically associated with Graves' hyperthyroidism. It targets the insulin-like growth factor-1 receptor (IGF-1R) and inhibits signaling within orbital fibroblasts. This therapy revolutionized the treatment of thyroid eye disease by decreasing proptosis, and diplopia and improving patient’s quality of life.  However, several documented adverse effects have been noted by the medication including, hyperglycemia, and hearing impairment. We hereby report the first documented case of transient yet significantly elevated lipase levels associated with teprotumumab infusion.

Case(s) Description : A 36-year-old man with a history of Graves' disease, thyroid eye disease (TED) presented to the emergency department for evaluation of fatigue, and confusion for two days. He also noted a brief episode of self-limiting epigastric discomfort, and diarrhea at the time. Four days before presentation, the patient received Teprotumumab infusion for TED. He denied any overt abdominal pain, nausea, vomiting, headaches, blurred vision, focal weakness, numbness, or tingling. He denied any regular use of alcohol, history of pancreatitis, or intra-abdominal pathology. On physical exam, he was vitally stable, the abdomen was soft, and nondistended, with mild diffuse tenderness in the epigastric region and in the left upper quadrant with some involuntary guarding at that site. The rest of the exam, including the neurological exam, was unremarkable.  His laboratory findings were significant for a lipase of 2,271 U/L. The rest of the labs were within normal limits, including white blood count 6.3x 10^3/µL, hemoglobin 14.0g/dL, triglyceride 118 mg/dL, calcium 8.5 mg/dL, thyroid stimulating hormone 4.92 mIU/L, glucose 123 mg/dL, and normal liver chemistries. Computed tomography of the abdomen was obtained and showed an unremarkable pancreas without evidence of inflammation, or pancreatitis. His repeat lipase levels trended down, and normalized the next day, from 2271 U/L on presentation to 98 U/L on discharge. He received intravenous fluids and was tolerating a low-fat diet the next day. His initial confusional state, fatigue, and mild epigastric tenderness had resolved.

Discussion : This is the first reported case of hyperlipasemia associated with Teprotumumab. The patient notably presented with fatigue, intermittent confusion, mild epigastric tenderness, and significantly elevated lipase levels; without any severe abdominal pain or imaging findings for acute pancreatitis. This case highlights the importance of close monitoring of patients on teprotumumab infusion who may develop side effects not previously documented. The transient elevation of lipase may be a result of possible immunologically mediated intra-abdominal adverse reaction to teprotumumab. Further studies on the effects of teprotumumab and IGF-1R receptor inhibition on multiorgan systems will likely be needed in the future.