What is pancreatic insufficiency?

Pancreatic Insufficiency: Definition, Diagnosis, and Management

Pancreatic insufficiency, formally known as exocrine pancreatic insufficiency (EPI), is a disorder caused by the failure of the pancreas to deliver sufficient digestive enzymes to the intestine, resulting in maldigestion of nutrients and macronutrients, leading to malnutrition and associated complications. 1

Definition and Pathophysiology

Pancreatic insufficiency occurs when:

• The pancreas fails to produce or secrete adequate amounts of digestive enzymes (lipase, amylase, protease)
• Pancreatic enzyme activity is reduced below the threshold needed for normal digestion
• The delivery of enzymes to the intestine is impaired

This results in:

• Maldigestion of fats, proteins, and carbohydrates
• Nutrient malabsorption
• Nutritional deficiencies

Causes

EPI can develop from various conditions:

• Pancreatic diseases:

  • Chronic pancreatitis (most common cause)
  • Acute necrotizing pancreatitis
  • Pancreatic cancer
  • Cystic fibrosis (present in >80% at diagnosis, increasing to >90% with age) 1

• Surgical causes:

  • Pancreatoduodenectomy (19-100% risk)
  • Distal pancreatectomy (0-82% risk)
  • Other gastrointestinal surgeries affecting the upper GI tract 2

• Other conditions:

  • Long-standing diabetes (may impact EPI risk)
  • Type 3c (pancreatogenic) diabetes 1
  • Obstruction of the main pancreatic duct
  • Decreased pancreatic stimulation

Clinical Manifestations

Common symptoms include:

• Steatorrhea (fatty, foul-smelling stools)
• Abdominal cramps and discomfort
• Weight loss
• Malnutrition
• Fat-soluble vitamin deficiencies (A, D, E, K)
• Deterioration in quality of life 2, 3

Diagnosis

The diagnosis of EPI should be based on:

1. Fecal elastase test - the most appropriate initial test:

   • <100 μg/g of stool: good evidence of EPI
   • 100-200 μg/g: indeterminate for EPI
   • Must be performed on semi-solid or solid stool specimen
   • Can be performed while on pancreatic enzyme replacement therapy 1

2. Assessment of nutritional status:

   • Weight loss
   • Micronutrient deficiencies
   • Fat-soluble vitamin levels

3. High-risk populations that should be screened:

   • Severe necrotizing pancreatitis
   • Post-gastrointestinal or pancreatic surgery
   • Pancreatic cancer (especially of the head)
   • Patients with pancreatic calcifications 4

Treatment

The cornerstone of EPI management is:

1. Pancreatic Enzyme Replacement Therapy (PERT):

   • Initial dosing: 500 units of lipase per kg per meal and 250 units of lipase per kg per snack
   • 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 1
   • Enzymes should be administered throughout food intake 2
   • Enteric-coated minimicrospheres are considered the most effective commercially available enzyme preparations 4

2. Nutritional support:

   • Nutritional counseling by an experienced dietitian is essential
   • High-calorie, high-protein diet
   • Normal fat content with enzyme supplementation (fat restriction is no longer recommended)
   • Fat-soluble vitamin supplementation if deficiencies are present 1, 4

Monitoring and Follow-up

Regular monitoring should include:

• Annual assessment of micronutrient status
• Endocrine function check
• DEXA scan every 2 years to monitor for osteoporosis
• Regular follow-up to assess nutritional status and treatment effectiveness 1

Clinical Significance

Proper diagnosis and treatment of EPI is crucial because:

• Untreated EPI leads to malnutrition, which is associated with increased morbidity and mortality
• Malnutrition increases risk of cardiovascular events and other complications 4
• PERT improves digestion, symptoms, nutritional status, and quality of life 5
• In pancreatic cancer patients, PERT is associated with longer survival 5

Common Pitfalls

• EPI is frequently underdiagnosed and undertreated 3, 5
• No single widely available test allows for perfectly accurate diagnosis 5
• Patients may not report classic symptoms like steatorrhea
• Treatment may be limited by cost issues with PERT 3
• Enzyme dosing needs to be individualized and adjusted based on response