Case Presentation: A 39 year-old female with a history of hypertriglyceridemia (HTG), IDDM2, and obesity presented to an outside hospital with severe epigastric abdominal pain and was diagnosed with recurrent hypertriglyceridemia-induced pancreatitis (HTGP). Intravenous insulin was started and she was transferred to our hospital for management. On arrival, she was tachycardic and tachypneic with a serum lipase of 1876 U/L, triglyceride (TG) level 8160 mg/dL, ionized calcium 2.8 mg/dL, and lactate 2.9mmol/L. Given concern for end-organ damage and hemodynamic instability, plasma exchange (PLEX) was initiated.The patient’s mother died of CAD at 30 years old, and both her father and paternal uncle had HTG. Neither she nor her family were evaluated for familial causes of HTG. Her initial episode of HTGP was approximately 2 years prior to current hospitalization. At that time, she improved with IV insulin and fluids, followed by initiation of fenofibrate and atorvastatin. She did well until 6 months prior to current hospitalization; she was admitted for 4 separate episodes of pancreatitis during the prior 6 months. She denied alcohol or illicit drug use, and thyroid function tests were normal. Her HbA1c was 8.2, stable for 2+ years. Of note, she reported initiation of estrogen-based oral contraceptive (OCP) medication approximately 1 year prior to admission. The OCP was discontinued as the suspected culprit of recurrent frequent episodes of pancreatitis. She subsequently established with Endocrinology and was started on icosapent ethyl and fenofibrate therapy with normalizing TG levels (<180 mg/dL) and plans to complete outpatient familial HTG genetic testing.
Discussion: Medications are implicated in approximately 2% of cases of acute pancreatitis; disease can occur secondary to direct cellular toxicity, immune-mediated inflammatory response, allergic or idiosyncratic reactions. Drug-induced hypertriglyceridemia (HTG) with resultant pancreatic injury represents a small fraction of drug-induced pancreatitis. We suspect that OCP’s exacerbated an underlying HTG state causing acute HTGP in our patient. Estrogen can induce pancreatitis in one of two ways – by creating a hypercoagulable state and thrombosis leading to necrotizing pancreatitis, or by exacerbating an underlying HTG state, as seen in our case. Estrogen can reduce hepatic lipase activity which is involved in hydrolysis of TGs, and can increase TG synthesis in the liver. Patients are at a significantly increased risk of HTGP at TG level >1000. Though the disease presents clinically similar to other etiologies of pancreatitis, both short and long-term management is unique compared to other etiologies. Acute therapies work to correct the harmful effects of TG breakdown to free fatty acids, and include use of continuous IV insulin or PLEX, depending on severity of disease. Chronic management includes use of lipid-lowering agents and the elimination of risk factors that increase TGs, like uncontrolled DM, hypothyroidism, alcohol-use, and certain medications.
Conclusions: HTGP is a unique disease process, understanding the mechanism behind a patient’s presentation is critical to guiding management and preventing recurrence. Estrogen-based hormone therapies are an easily overlooked cause of HTG exacerbation that can lead to pancreatitis. Thorough review of a patient’s medication regimen is imperative for any individual presenting with HTGP.