What is the workup for pancreatic insufficiency?

Workup for Pancreatic Insufficiency

Begin with fecal elastase-1 (FE-1) testing as the initial diagnostic test when clinical suspicion exists, interpreting values <200 μg/g as abnormal and <100 μg/g as consistent with exocrine pancreatic insufficiency (EPI). 1

Clinical Recognition and Risk Stratification

Suspect EPI in patients presenting with:

• Steatorrhea, chronic diarrhea, bloating, abdominal pain, increased flatulence, or unexplained weight loss 1
• Malnutrition with reduced food intake and impaired digestion 1

High-Risk Conditions (Testing Strongly Indicated)

• Chronic pancreatitis (especially severe), cystic fibrosis, pancreatic cancer (particularly head lesions), total pancreatectomy, recurrent acute pancreatitis 1
• Patients with total pancreatectomy require no further testing—initiate pancreatic enzyme replacement therapy (PERT) immediately 1

Moderate-Risk Conditions

• Duodenal diseases, long-standing diabetes mellitus, hypersecretory states, bariatric GI surgery 1

Lower-Risk/Overlapping Conditions

• Celiac disease, inflammatory bowel disease, diabetes mellitus 1

Diagnostic Testing Algorithm

Primary Test: Fecal Elastase-1

• FE-1 is the most frequently used indirect pancreatic function test because it is simple, noninvasive, and relatively inexpensive 1
• Must be performed on semi-solid or solid stool samples for accuracy 1, 2
• Interpretation:
  • >200 μg/g: Normal pancreatic function 1, 2
  • <200 μg/g: Abnormal 1
  • <100 μg/g: Consistent with EPI 1, 2
  • <50 μg/g: Most reliable for severe EPI 1

Critical caveat: FE-1 values between 100-200 μg/g have lower specificity—consider repeat testing if initial result is in this range, particularly if FE-1 is >15 μg/g 3

• Patients with initial FE-1 <15 μg/g are unlikely to be reclassified on repeat testing and should proceed directly to treatment 3
• PERT use does not alter FE-1 results, so testing can be done while on therapy 1
• Repeat FE-1 measurements are NOT useful for assessing treatment response 1, 2

Imaging Studies for Underlying Pancreatic Disease

• Cross-sectional imaging (CT or MRI) should be performed to diagnose underlying pancreatic disease 1
• Pancreatic protocol CT is preferred for initial evaluation 1
• Endoscopic ultrasonography (EUS) can be used as an accurate alternative to screen for structural abnormalities 1
• Patients with abnormal pancreatic imaging are 10 times more likely to respond to PERT 3

Direct Pancreatic Function Tests (Specialized Centers Only)

• Direct measurements of pancreatic secretions are the most accurate but are invasive, time-consuming, and available only at limited specialized centers 1
• These involve stimulating the pancreas and aspirating pancreatic secretions for 30-60 minutes, analyzing for bicarbonate concentration and pancreatic digestive enzymes 1
• Used most commonly for diagnosing early-stage chronic pancreatitis rather than established EPI 1

Alternative Indirect Tests

• Serum pancreatic enzyme levels (e.g., trypsin) have the advantage of not being affected by PERT, but are unreliable if the patient has ongoing pancreatic inflammation 1

Fecal Fat Testing (Rarely Needed)

• Quantitative fecal fat testing is rarely needed and generally not practical for routine clinical use 1
• Requires a high-fat diet (known fat content) ingested over 5 days with stool collection over the final 3 days 1
• Steatorrhea is defined as coefficient of fat absorption <93% (>7% of ingested fat in stool) 1
• Consider only when clinical features are inconclusive or when assessing inadequate response to therapy 1
• Sudan stain and other stool fat measures are nonspecific for EPI 1

Additional Baseline Laboratory Studies

At admission or initial evaluation, obtain:

• Serum amylase or lipase level 1
• Triglyceride level 1
• Calcium level 1
• Liver chemistries (bilirubin, AST, ALT, alkaline phosphatase) 1
• Baseline micronutrient status and fat-soluble vitamins (A, D, E, K) 2
• Glucose and HbA1c for endocrine function assessment 1, 2

Common Pitfalls to Avoid

• Do not rely on a therapeutic trial with pancreatic enzymes as a diagnostic test—response to PERT is not reliable for diagnosing EPI 2
• Do not perform FE-1 testing on liquid or watery stool samples—results will be unreliable 1, 2
• Do not repeat FE-1 to monitor treatment response—it does not change with therapy 1, 2
• Do not assume all patients with FE-1 100-200 μg/g have EPI—47.5% may have normal repeat testing 3
• Consider alternative diagnoses if patients fail to respond to adequate PERT: celiac disease, small intestinal bacterial overgrowth, bile acid diarrhea, or infections like giardiasis 1

Establishing Etiology

The etiology should be established in at least three-fourths of patients 1

Focus history on:

• Previous symptoms or documentation of gallstones 1
• Alcohol use 1
• History of hypertriglyceridemia or hypercalcemia 1
• Family history of pancreatic disease 1
• Prescription and nonprescription drug history 1
• History of trauma 1
• Presence of concomitant autoimmune diseases 1