Exocrine Pancreatic Insufficiency (EPI)
Exocrine pancreatic insufficiency (EPI) is a disorder caused by the failure of the pancreas to deliver a minimum threshold level of specific pancreatic digestive enzymes to the intestine, leading to maldigestion of nutrients and macronutrients, resulting in their variable deficiencies. 1
Definition and Pathophysiology
EPI occurs when normal digestion cannot be sustained due to insufficient pancreatic digestive enzyme activity. This insufficiency can result from:
- Progressive destruction of pancreatic tissue (replacing normal tissue with fibrous tissue)
- Obstruction of the pancreatic duct
- Decreased pancreatic stimulation
- Acid-mediated inactivation of pancreatic enzymes
- Failure in the synchronization of secretions to mix with ingested food
High-Risk Conditions for EPI
Definite Risk (High-Risk Conditions)
- Chronic pancreatitis
- Relapsing acute pancreatitis
- Pancreatic ductal adenocarcinoma
- Cystic fibrosis
- Previous pancreatic surgery (especially pancreatoduodenectomy with 19-100% risk) 2
Possible Risk (Moderate-Risk Conditions)
- Duodenal diseases (including celiac disease and Crohn's disease)
- Previous intestinal surgery
- Long-standing diabetes mellitus
- Hypersecretory states (e.g., Zollinger-Ellison syndrome)
Clinical Manifestations
Primary Symptoms
- Steatorrhea (pale, bulky, foul-smelling fatty stools that are difficult to flush)
- Weight loss
- Abdominal bloating
- Excessive flatulence
Other Symptoms
- Abdominal pain and cramping
- Diarrhea
- Undigested food in stools
- Fat-soluble vitamin deficiencies (A, D, E, K)
- Protein-calorie malnutrition
Diagnostic Approach
Primary Diagnostic Test
- Fecal elastase test: Most appropriate initial test, must be performed on semi-solid or solid stool specimen 1
- <100 μg/g of stool: Good evidence of EPI
- 100-200 μg/g: Indeterminate for EPI
- Can be performed while on pancreatic enzyme replacement therapy
Other Diagnostic Considerations
- Fecal fat testing (rarely needed, must be performed on high-fat diet)
- Cross-sectional imaging (CT, MRI, endoscopic ultrasound) to diagnose underlying pancreatic disease
- Direct pancreatic function tests (not widely available)
Treatment
Pancreatic Enzyme Replacement Therapy (PERT)
- Once EPI is diagnosed, treatment with pancreatic enzyme replacement therapy is required 1
- Initial dosing:
- 500 units of lipase per kg per meal (e.g., 40,000 units for an 80 kg patient)
- 250 units of lipase per kg per snack (e.g., 20,000 units for an 80 kg patient)
- Titrate up to reduce steatorrhea or GI symptoms
- Maximum dose: 2,500 units of lipase per kg per meal or 10,000 units per kg per day
Dietary Management
- Nutritional counseling by an experienced dietitian is essential
- High-calorie, high-protein diet
- Normal fat content (30% of total energy intake) with enzyme supplementation
- Medium-chain triglycerides (MCT) may be used if steatorrhea persists
- Low-fiber diet (fiber can absorb enzymes and reduce nutrient intake)
- Fat-soluble vitamin supplementation (A, D, E, K) if deficiencies are present
Lifestyle Modifications
- Abstinence from alcohol
- Smoking cessation
- Frequent small meals to achieve adequate intake
Monitoring and Follow-up
- Annual assessment of micronutrient status
- Endocrine function check (glucose, HbA1c)
- DEXA scan every 2 years to monitor for osteoporosis
- Regular follow-up to assess nutritional status and treatment effectiveness
Complications if Untreated
- Malnutrition and weight loss
- Fat-soluble vitamin deficiencies
- Osteoporosis
- Sarcopenia
- Reduced quality of life
- Higher rates of surgical complications
- Increased mortality
Special Considerations
Cystic Fibrosis
- Pancreatic insufficiency is present at diagnosis in >80% of persons with CF
- Increases with age to >90%
- Associated with specific CFTR gene mutations 1
Diabetes and EPI
- Long-standing diabetes may impact risk of developing EPI
- Type 3c (pancreatogenic) diabetes can occur with pancreatic insufficiency
- Characterized by insulin deficiency, concurrent glucagon deficiency, and reduced pancreatic polypeptide levels 3
- Can lead to "brittle" diabetes with hypoglycemic episodes
EPI remains frequently underdiagnosed and undertreated, leading to significant morbidity and reduced quality of life. Early diagnosis and appropriate treatment with enzyme replacement therapy are essential for improving outcomes.