When Lipase Lies: Acute Pancreatitis with a Normal Serum Lipase

Background

Acute pancreatitis (AP) is diagnosed when at least two of three criteria are met: characteristic abdominal pain, lipase or amylase >3x the upper limit of normal, or characteristic abdominal imaging findings. Although this framework, derived from the revised Atlanta classification and endorsed by the 2024 American College of Gastroenterology (ACG) guidelines, explicitly permits diagnosis without enzyme elevation, a normal lipase often prompts premature exclusion of AP. We present a case in which imaging and patient symptomatology were used to establish the diagnosis.

Case Presentation

A 21-year-old man with no significant medical history presented with five days of progressive burning non-radiating epigastric pain, with persistent nausea, vomiting, and complete oral intolerance. He denied fever, diarrhea, alcohol use, prior similar episodes, gallstones, abdominal trauma, or family history of pancreatitis. He reported occasional marijuana use, nicotine vaping, and recent methylprednisolone use. He was afebrile and hemodynamically stable, with epigastric and left upper quadrant tenderness without peritoneal signs.

Findings

Laboratory studies were unremarkable: the serum lipase was only 14 U/L, ethanol levels were <10.1 mg/dL, triglycerides were 100 mg/dL, blood cultures were without growth, and the CBC and CMP were normal. CT abdomen/pelvis with contrast showed a mildly edematous pancreas concerning for AP. The patient was admitted for AP based on characteristic pain plus imaging, meeting two of three criteria despite normal lipase. He received aggressive fluids with Lactated Ringer's along with a pain regimen and antiemetics. Pain improved but vomiting persisted until metoclopramide was added. His diet was advanced quickly, which was well tolerated. The patient was later discharged with outpatient follow-up.

Discussion & Conclusion

This case highlights the pitfall of relying on lipase alone to exclude acute pancreatitis: in delayed presentations the enzyme may normalize, and cross-sectional imaging is warranted whenever clinical suspicion remains high. Serum lipase rises within 4-8 hours of symptom onset and normalizes within 8-14 days; in patients presenting days later, it may already have fallen. At the ≥3x threshold, pooled sensitivity of lipase is approximately 80%, so up to 20% of patients fail to meet the enzyme criterion. In one series of 234 patients with confirmed AP, 27% lacked a threefold lipase elevation and would have been underdiagnosed without CT. The 2024 ACG guidelines similarly note amylase may be normal on admission in as many as one-fifth of patients. Contrast-enhanced CT provides greater than 90% sensitivity and specificity for AP and is particularly valuable when there is diagnostic uncertainty. Standard etiologic workup excluded alcohol, biliary disease, and hypertriglyceridemia. Recent corticosteroid exposure was noted; drug-induced pancreatitis is rare but remains a diagnosis of exclusion here.

Acute pancreatitis may present with an entirely normal lipase, particularly with delayed presentation. Diagnosis requires only two of three criteria, and lipase alone should not be used to exclude AP. When clinical suspicion is high, cross-sectional imaging should be obtained to prevent missed or delayed diagnosis.