What tests are used to evaluate pancreas function?

Tests for Pancreatic Function Evaluation

Fecal elastase-1 is the recommended first-line test for evaluating pancreatic exocrine function, with values <200 mg/g of stool considered abnormal and <100 mg/g more consistent with exocrine pancreatic insufficiency. 1

Clinical Context Determines Testing Approach

The appropriate pancreatic test depends critically on whether you're evaluating acute versus chronic pancreatic disease:

For Acute Pancreatitis

• Serum lipase is the first-line test, with diagnostic threshold ≥3 times the upper limit of normal 2
• Serum amylase can be used but lipase is preferred for superior sensitivity and specificity 2
• Additional acute phase markers include:
  • Liver function tests (bilirubin, AST, ALT, alkaline phosphatase) to identify biliary etiology 2
  • Fasting triglycerides to exclude hypertriglyceridemia 2
  • Serum calcium to detect hypercalcemia 2
  • C-reactive protein at 48-72 hours (≥150 mg/L predicts severe disease) 2
  • Hematocrit >44% (independent risk factor for pancreatic necrosis) 2
  • BUN >20 mg/dL (predicts mortality) 2

For Chronic Pancreatitis and Exocrine Insufficiency

The testing algorithm follows a stepwise progression from noninvasive to invasive:

First-Line: Fecal Elastase-1 (FE-1)

• Most frequently used indirect pancreatic function test because it is simple, noninvasive, and relatively inexpensive 1
• Interpretation thresholds 1:
  • <200 mg/g: abnormal
  • <100 mg/g: more consistent with exocrine pancreatic insufficiency (EPI)
  • <50 mg/g: most reliable for severe EPI
• Key advantage: Not affected by pancreatic enzyme replacement therapy (PERT), so can be done while patient is on treatment 1
• Important limitation: Poor sensitivity in mild/early pancreatic disease—requires significant loss of pancreatic function before becoming positive 1

Alternative Indirect Tests

• Serum trypsin can be measured as an alternative that is also not affected by PERT 1
• Critical caveat: Serum pancreatic enzymes (lipase, amylase, trypsin) are unreliable if ongoing pancreatic inflammation is present 1
• Do NOT use serum enzymes to diagnose chronic pancreatitis or EPI—they lack sensitivity until disease is very advanced 2

Fecal Fat Testing

• Rarely needed in routine practice 1
• Requires high-fat diet and 3-day stool collection after 5 days of known fat intake 1
• Steatorrhea defined as coefficient of fat absorption <93% (>7% of ingested fat in stool) 1
• Reserve for: Inconclusive clinical features or inadequate response to PERT 1
• Sudan stain is nonspecific for EPI 1

Direct Pancreatic Function Tests

• Most accurate but invasive, time-consuming, and available only at specialized centers 1
• Involves stimulating pancreas (with secretin/cholecystokinin) and aspirating duodenal secretions for 30-60 minutes 1
• Analyzes bicarbonate concentration and pancreatic digestive enzymes 1
• Primary use: Diagnosing early-stage chronic pancreatitis rather than established EPI 1
• Not recommended in UK/European practice despite American guidelines mentioning them 1

Obsolete Tests

• N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA/NBTP) and pancreolauryl test: No longer in use in UK due to poor sensitivity and specificity 1
• C13 mixed triglyceride breath test: Not widely available with poor sensitivity in mild/moderate disease 1

Imaging Studies for Underlying Pancreatic Disease

Cross-sectional imaging cannot identify EPI itself but plays a crucial role in diagnosing underlying pancreatic pathology: 1

Imaging Modality Selection

• Abdominal ultrasound: Initial test to detect cholelithiasis/choledocholithiasis in acute pancreatitis 2
• CT scan: Best initial cross-sectional imaging with good sensitivity for severe chronic pancreatitis; may obviate need for other tests 3
• MRCP with secretin (MRCP-S): More detailed evaluation of pancreatic parenchyma and ducts when CT is equivocal 1, 2, 3
• Endoscopic ultrasound (EUS): Sensitivity 68-100%, specificity 78-97% for chronic pancreatitis; complementary to MRCP-S 1, 2
• Both EUS and MRCP-S are effective and best used complementarily, with local availability dictating choice 1

Critical Clinical Pitfalls

Do NOT Use Therapeutic Trial for Diagnosis

• Response to PERT is unreliable for diagnosing EPI 1
• Nonspecific symptoms (bloating, gas, foul-smelling stools) may improve with PERT due to placebo effect or masking of other disorders like celiac disease 1
• Always perform appropriate testing (fecal elastase) before initiating PERT 1

When Testing is Unnecessary

• Total pancreatectomy patients: No testing needed—initiate PERT directly 1
• Definite high-risk conditions: Severe chronic pancreatitis, cystic fibrosis, pancreatic head malignancy—can proceed directly to treatment 1

Test Limitations to Remember

• Fecal elastase has poor sensitivity for mild/early disease 1
• All noninvasive tests require significant pancreatic function loss before becoming positive 1
• Repeat FE-1 measurements are NOT helpful for assessing treatment response 1