What are the diagnostic steps and treatment options for exocrine pancreatic insufficiency (EPI)?

Diagnosis of Exocrine Pancreatic Insufficiency

The fecal elastase-1 test is the most appropriate initial diagnostic test for EPI, with levels <100 μg/g of stool providing good evidence of EPI, and this test must be performed on semi-solid or solid stool specimens. 1

Clinical Suspicion: When to Test

High-Risk Conditions (Test These Patients)

• Chronic pancreatitis 1
• Relapsing acute pancreatitis 1
• Pancreatic ductal adenocarcinoma 1
• Cystic fibrosis 1
• Previous pancreatic surgery 1

Moderate-Risk Conditions (Consider Testing)

• Duodenal diseases (celiac disease, Crohn's disease) 1
• Previous intestinal surgery 1
• Longstanding diabetes mellitus 1, 2
• Hypersecretory states (Zollinger-Ellison syndrome) 1

Clinical Features Suggesting EPI

• Steatorrhea with or without diarrhea 1
• Weight loss 1
• Bloating and excessive flatulence 1
• Fat-soluble vitamin deficiencies 1
• Protein-calorie malnutrition 1

Diagnostic Algorithm

Step 1: Fecal Elastase-1 Testing

This is your first-line test. 1

Interpretation:

• FE-1 <100 μg/g stool = Good evidence of EPI 1
• FE-1 100-200 μg/g stool = Indeterminate for EPI 1
• FE-1 >200 μg/g stool = Normal 1

Critical technical requirements:

• Must be performed on semi-solid or solid stool (not liquid/watery stool, which gives false positives) 1
• Can be performed while patient is on pancreatic enzyme replacement therapy (PERT does not alter results) 1
• Repeat FE-1 measurements are not helpful for assessing treatment response 1

Important caveat: Patients with initial FE-1 <15 μg/g are unlikely to be reclassified as normal on repeat testing, whereas those with borderline values (100-200 μg/g) may normalize 3

Step 2: Cross-Sectional Imaging

Imaging cannot diagnose EPI but identifies underlying pancreatic pathology. 1

Order CT, MRI, or endoscopic ultrasound to:

• Evaluate for pancreatic cancer, chronic pancreatitis, or structural abnormalities 1
• End-stage calcific pancreatitis or significant pancreatic atrophy correlates with EPI presence 1
• Normal pancreatic imaging correlates with absence of EPI 1
• Patients with abnormal pancreatic imaging are 10 times more likely to respond to PERT 3

Key limitation: Moderate pancreatic imaging changes on CT, MRI, or endoscopic ultrasound do not correlate with EPI 1

Step 3: Additional Testing (When Needed)

Fecal fat testing:

• Rarely needed and generally not practical for routine clinical use 1
• Must be performed on a high-fat diet 1
• Requires 5-day diet with known fat content and 3-day stool collection 1
• Consider only when clinical features are inconclusive or when assessing inadequate response to PERT 1
• Steatorrhea defined as coefficient of fat absorption <93% (>7% of ingested fat in stool) 1

Direct pancreatic function tests:

• Involve stimulating the pancreas and aspirating secretions for 30-60 minutes 1
• Analyze bicarbonate concentration and pancreatic enzymes 1
• Used mainly for diagnosing early-stage chronic pancreatitis, not routine EPI diagnosis 1
• Not widely available in the United States 1

Breath tests:

• Hold promise but are not widely available in the United States 1

What NOT to Do

Do not use therapeutic trial of pancreatic enzymes for diagnosis:

• Response to PERT is unreliable for EPI diagnosis 1
• Nonspecific symptoms (bloating, gas, foul-smelling stools) may improve with PERT due to placebo effect 1
• This approach can mask other disorders like celiac disease and delay correct diagnosis 1
• Always perform fecal elastase testing before initiating PERT 1

Do not rely on serum pancreatic enzyme levels:

• Serum trypsin levels are unreliable if the patient has ongoing pancreatic inflammation 1

Treatment Initiation

Once EPI is diagnosed, treatment with PERT is required to prevent complications related to fat malabsorption and malnutrition, which negatively impact quality of life. 1

Initial PERT dosing:

• 40,000 USP units of lipase during each meal in adults 1, 4
• Half that dose (20,000 units) with snacks 1, 4
• Take PERT during meals, not before or after 4
• All PERT formulations are derived from porcine sources and equally effective at equivalent doses 1
• Non-enteric-coated preparations require H2 blocker or proton pump inhibitor co-therapy 1

Monitoring treatment success:

• Reduction in steatorrhea and GI symptoms 1
• Weight gain, muscle mass improvement, and muscle function 1
• Improvement in fat-soluble vitamin levels 1
• Obtain baseline nutritional status (BMI, quality-of-life measure, fat-soluble vitamins) 1
• Baseline DEXA scan, repeated every 1-2 years 1

Dietary modifications:

• Low-moderate fat diet with frequent smaller meals 1
• Avoid very-low-fat diets 1
• Routine supplementation and monitoring of fat-soluble vitamin levels 1