Everolimus-Induced Hypertriglyceridemia Manifesting as Acute Pancreatitis

Abstract

Everolimus is used in the treatment of many advanced cancers like renal and breast cancer. Hypertriglyceridemia (HTG) is a known adverse effect of the drug. However, acute pancreatitis (AP) is not commonly reported. A 46-year-old Hispanic female with recurrent breast cancer had been treated with Everolimus (10 mg/day) for 6 weeks, who then developed elevated triglycerides (TG) and the Everolimus was stopped. Three days later, she presented to the emergency center with nausea and severe, mid-epigastric pain radiating to her back. Lab values included: sodium 127 mEq/L, lipase 795 U/L, blood glucose > 700 mg/dl, with normal calcium. The serum was milky in appearance, with TG > 1590 mg/dL. There was no history of diabetes or alcohol use. She was diagnosed with diabetic ketoacidosis (DKA) and admitted to the medical ICU for intravenous fluids, insulin drip and pain control. Despite resolution of ketoacidosis, her pain worsened and she remained anorexic. Gastroenterology was consulted and diagnosed her with AP due to HTG. After several days, her TG decreased to 336 mg/dL with above treatment, coinciding with improvement of her symptoms (Figure 1). Her diet was advanced and she was discharged with fenofibrates. TG level four months later normalized. Everolimus treatment was not re-attempted. Hypertriglyceridemia and drugs are common causes of AP. There are two main causes of HTG-induced AP (HTG-AP): primary (usually genetic or idiopathic) and secondary. The pathogenesis of HTG associated with mTOR inhibitors is unclear, but may be related to slow degradation of apolipoprotein B100 leading to dyslipidemia. Hyperlipidemia is thought to cause AP when the pancreatic lipase hydrolyzes the excess TGs circulating in the serum damaging the free fatty acids which in turn accumulate in the pancreas leading to severe inflammation of the pancreas. HTG also leads to impaired clearance of chylomicrons leading to pancreatic capillary hyperviscosity causing ischemia. HTG-induced AP may be clinically evident when TG levels exceed 1000 mg/dL. Treatment involves IV insulin, IV heparin, or plasmapheresis (in absence of hyperglycemia) with fenofibrates for long term management. Our patient likely had secondary HTG due to Everolimus. Awareness of Everolimus causing HTG-AP is important for gastroenterologists, especially those who may treat cancer patients.Figure: Timeline showing introduction of Everolimus and development of Hypertriglyceridemia.