Case Presentation: The patient is a 54 year old male with multifactorial chylomicronemia syndrome (MFCS), one prior episode of pancreatitis, hemochromatosis, cirrhosis, and alcohol use disorder (last drink 2 days prior to admission) who presented with a 2 week history of abdominal pain, chest pain, and malaise. Outpatient blood work one day prior to presentation revealed AST 686 IU/L, ALT 164 IU/L, ALP 452 IU/L, total bilirubin 3.5 mg/dL, direct bilirubin 2.4 mg/dL (increased from six days prior), and highly elevated triglycerides at 3766 mg/dL. Initial exam was notable for epigastric tenderness and jaundice. Other labs included normal troponin, lipase, BUN, and lactate. CT abdomen/pelvis showed new ascites with severe hepatic steatosis, pericholecystic fluid, and normal pancreas without evidence of inflammation. Workup for causes including viral hepatitis and spontaneous bacterial peritonitis was negative. Alcoholic hepatitis was considered, however, Maddrey score was 2.5, so steroids were deferred. Despite not meeting Atlanta criteria for pancreatitis, the patient was started on an insulin drip for empiric treatment of hypertriglyceridemia-induced pancreatitis due to high degree of suspicion. With only insulin and a low-dose pain regimen, his symptoms resolved, and his labs improved with AST 304 IU/L, ALT 102 IU/L, ALP 297 IU/L, and triglycerides 319 mg/dL by hospital day three. He was discharged that day with a diagnosis of hypertriglyceridemia-induced pancreatitis from uncontrolled MFCS. He was restarted on fenofibrate and counseled on alcohol cessation with close follow-up with his lipid specialist. Repeat triglycerides one month post-discharge were normal at 92 mg/dL with no recurrence of symptoms.
Discussion: In diagnosing acute pancreatitis, the Atlanta classification is often used requiring 2 of 3 criteria: acute persistent epigastric abdominal pain that can radiate to the back, lipase or amylase at least 3 times the upper limit of normal, and characteristic findings on imaging (1). This patient presented with classic pain but had normal lipase and CT imaging findings, which did not meet diagnostic criteria. Lipase can be normal with chronic pancreatitis, delayed presentation, or with marked hypertriglyceridemia (2). The mechanism for normal lipase in the setting of hypertriglyceridemia is unclear. One theory hypothesizes that high levels of triglycerides interfere with enzymatic assays, possibly due to the presence of inhibitors (3,4). In MFCS, triglyceride levels are persistently >1000 mg/dL. One of the most common complications of MFCS is acute pancreatitis, with at least a 7-fold increased risk compared to the general population. In addition, triglyceride-induced pancreatitis is noted to have worse prognosis compared to other causes of pancreatitis (5). As such despite a high negative predictive value, a normal lipase in the context of classic symptoms and known hypertriglyceridemia should still prompt pancreatitis treatment.
Conclusions: Acute pancreatitis is a well-established complication of MFCS due to hypertriglyceridemia that has poorer prognosis compared to other causes of pancreatitis. Clinicians should maintain a high index of suspicion for hypertriglyceridemia-induced pancreatitis even with a normal lipase, as elevated triglycerides can cause falsely lower levels due to lab assay limitations, which will help limit delays in diagnosis and treatment.