From the Guidelines
Investigation of mildly elevated lipase should begin with a thorough clinical assessment to determine if the patient has symptoms of pancreatic disease, and the first step is to repeat the lipase test to confirm the elevation, as isolated mild elevations can occur transiently or due to laboratory error. According to the 2019 guidelines for the management of severe acute pancreatitis 1, serum lipase is considered a more reliable diagnostic marker of acute pancreatitis than serum amylase, with a sensitivity of 79% and specificity of 89%. The diagnosis of acute pancreatitis should be established within 48 hours of admission, based on compatible clinical features and elevations in amylase or lipase levels, with elevations in lipase levels greater than 3 times the upper limit of normal being most consistent with acute pancreatitis 1.
If the elevation persists, evaluate for common non-pancreatic causes including renal insufficiency, certain medications (thiazide diuretics, steroids, opiates), and macrolipasemia. Additional laboratory tests should include comprehensive metabolic panel, complete blood count, triglycerides, and amylase. Imaging studies are warranted if symptoms are present or if lipase elevation is significant; an abdominal ultrasound is typically the initial imaging modality, followed by contrast-enhanced CT or MRI/MRCP if pancreatic pathology is suspected.
Key points to consider in the investigation of mildly elevated lipase include:
- Repeating the lipase test to confirm the elevation
- Evaluating for common non-pancreatic causes of elevated lipase
- Performing additional laboratory tests, such as comprehensive metabolic panel and triglycerides
- Considering imaging studies, such as abdominal ultrasound or contrast-enhanced CT, if symptoms are present or if lipase elevation is significant
- Periodic monitoring of lipase levels every 3-6 months in asymptomatic patients with persistent mild elevations despite negative initial workup, as recommended by the AGA institute medical position statement on acute pancreatitis 1.
The investigation is important because while lipase is primarily produced by the pancreas and elevations often indicate pancreatic inflammation, mild elevations can occur in various non-pancreatic conditions and may not always represent clinically significant disease. As stated in the 2019 guidelines for the management of severe acute pancreatitis 1, numerous biomarkers have been studied as potential early predictors of the severity of acute pancreatitis, but no laboratory test is practically available or consistently accurate to predict severity in patients with acute pancreatitis.
From the Research
Investigation of Mildly Elevated Lipase
- Mildly elevated lipase levels can be associated with various conditions, not just pancreatitis 2, 3
- A study found that extensive investigation of patients with mild elevations of serum amylase and/or lipase is 'low yield' 4
- The diagnostic yield in patients with mild elevations of lipase alone was particularly poor, with 78.9% of patients having a normal pancreas 4
- A systematic approach to patients with elevated levels of serum amylase or lipase is critical to making an accurate diagnosis and initiating appropriate treatment 5
Differential Diagnoses
- Reduced clearance of lipase caused by renal impairment or macrolipase formation 3
- Other hepatobiliary, gastroduodenal, intestinal, and neoplastic causes 3
- Critical illness, including neurosurgical pathology 3
- Alternative pancreatic diagnoses, such as non-pathological pancreatic hyperenzymaemia 3
- Miscellaneous causes such as diabetes, drugs, and infections 3
- Uremic patients with or without dialysis can have elevated pancreatic enzymes, including lipase 6
Clinical Implications
- Emergency physicians should be aware of other potential causes of elevated lipase and not assume that all cases of elevated lipase are associated with pancreatitis 2
- Clinicians should utilize knowledge of alternative diagnoses for significant serum lipase elevations in the interpretation and management of patients 3
- A systematic approach to patients with elevated amylase and/or lipase can help avoid unnecessary admission and initiate appropriate treatment 5