Testing for Exocrine Pancreatic Insufficiency
The fecal elastase-1 (FE-1) test is the recommended initial diagnostic test for exocrine pancreatic insufficiency, with levels <100 μg/g of stool providing good evidence of EPI. 1, 2
When to Suspect EPI
Suspect EPI in patients presenting with:
- Steatorrhea (fatty, foul-smelling stools that float) 3
- Unexplained weight loss despite adequate caloric intake 2
- Chronic diarrhea, bloating, and excessive flatulence 3
- Fat-soluble vitamin deficiencies (A, D, E, K) 2
Risk Stratification Before Testing
High-Risk Conditions (Test Proactively)
- Chronic pancreatitis, cystic fibrosis, pancreatic ductal adenocarcinoma 4, 2
- Recurrent acute pancreatitis or severe acute pancreatitis 4, 3
- Previous pancreatic surgery (total pancreatectomy requires no testing—initiate treatment immediately) 4, 3
Moderate-Risk Conditions (Consider Testing)
- Duodenal diseases, previous intestinal surgery 2
- Long-standing diabetes mellitus 2
- Hypersecretory states (e.g., gastrinoma) 4
Diagnostic Testing Algorithm
Step 1: Fecal Elastase-1 Testing
Perform FE-1 on semi-solid or solid stool specimens only—liquid or watery stool produces false-positive results. 1, 2, 3
Interpretation:
- <100 μg/g = EPI confirmed 1, 3
- 100-200 μg/g = Indeterminate (lower specificity; consider repeat testing) 1, 3
- >200 μg/g = Normal 1
Key advantages: Simple, noninvasive, relatively inexpensive, and can be performed while patient is on pancreatic enzyme replacement therapy (PERT). 4, 2, 3
Step 2: Cross-Sectional Imaging
Obtain pancreatic protocol CT or MRI to identify underlying pancreatic pathology (chronic pancreatitis, pancreatic cancer, structural abnormalities). 1, 3
- Imaging cannot diagnose EPI itself but identifies the cause 2, 3
- Normal imaging correlates with absence of EPI 2
- Endoscopic ultrasound (EUS) is an accurate alternative for detecting structural abnormalities 3
Step 3: Additional Testing (Select Cases Only)
Direct pancreatic function tests (endoscopic secretin stimulation):
- Most accurate but invasive, time-consuming, and available only at specialized centers 4
- Reserved for diagnosing early-stage chronic pancreatitis rather than routine EPI diagnosis 4
Fecal fat testing (72-hour collection):
- Rarely needed and impractical for routine use 1, 2
- Consider only when clinical features are inconclusive or when assessing inadequate response to PERT 1, 2
Baseline Laboratory Studies
Once EPI is suspected or confirmed, obtain:
- Fat-soluble vitamins (A, D, E, K) and micronutrient status 3
- Glucose and HbA1c (assess for concurrent endocrine insufficiency) 3
- Serum amylase or lipase, triglycerides, calcium, liver chemistries 3
Critical Pitfalls to Avoid
Do not use a therapeutic trial of pancreatic enzymes as a diagnostic test—symptomatic improvement with PERT is unreliable and may mask other disorders. 2, 3
Do not perform FE-1 testing on liquid or watery stool—this produces false-positive results. 2, 3
Do not rely on serum pancreatic enzyme levels—they are unreliable if the patient has ongoing pancreatic inflammation. 2
Do not use repeat FE-1 measurements to monitor treatment response—FE-1 does not change with therapy. 3
Management After Positive Test
If FE-1 confirms EPI, initiate pancreatic enzyme replacement therapy (PERT):
- Starting dose: 40,000-50,000 USP units of lipase with each meal (500 units/kg/meal for adults) 4, 5
- 20,000-25,000 USP units with snacks (250 units/kg/snack) 4, 5
- Take PERT during meals, not before or after 5
- Maximum dose: 2,500 units/kg/meal or 10,000 units/kg/day 4, 5
Monitor treatment success by:
- Reduction in steatorrhea and GI symptoms 1
- Weight gain and muscle mass improvement 1
- Improvement in fat-soluble vitamin levels 1
Implement dietary management:
Long-term monitoring: