A 63-year-old male with a history of hypertension, well-controlled on amlodipine, presents with chronic diarrhea, bloating, and unintentional weight loss of 15 pounds over six months. He reports greasy, foul-smelling stools that are difficult to flush. He has a longstanding history of alcohol use (> 6 beers per day). He denies recent travel or antibiotic exposure. He notes fatigue and occasional crampy abdominal pain, worse after large meals.
Physical exam is notable for mild temporal wasting and dry mucous membranes. No abdominal tenderness, masses, or hepatosplenomegaly is appreciated.
Initial labs:
- Hemoglobin: 12.1 g/dL
- WBC: 6.3 x10^9/L
- Platelets: 245 x10^9/L
- Total bilirubin: 0.8 mg/dL
- AST: 24 U/L
- ALT: 26 U/L
- ALP: 72 U/L
- Albumin: 3.1 g/dL
- Fecal elastase: 83 mcg/g stool (normal >200)
Abdominal CT scan showed diffuse pancreatic calcifications without evidence of peripancreatic edema or fluid collections (Figure 1).
Figure 1: CT Scan showing diffuse pancreatic calcifications
Image from personal library of Sarah Enslin
What is the most appropriate next step in management?
A. Colonoscopy
B. Repeat fecal elastase in one month
C. Start pancreatic enzyme replacement therapy
D. Tissue transglutaminase IgA and total IgA
The correct answer is C, start pancreatic enzyme replacement therapy.
This patient’s symptoms, imaging, and low fecal elastase level are consistent with exocrine pancreatic insufficiency (EPI), most likely due to chronic pancreatitis. EPI results in malabsorption of fats, leading to steatorrhea, weight loss, and fat-soluble vitamin deficiencies.
Practice Pearls
Normal Pancreatic Physiology
- The pancreas secretes approximately 1.5 liters of pancreatic fluid per day, composed of water, electrolytes (notably bicarbonate), and digestive enzymes.1
- Regulation of secretion is primarily governed by hormonal and neuronal mechanisms:1,2
- Secretin, released by duodenal S cells in response to acidic chyme, stimulates bicarbonate-rich fluid secretion from ductal cells.1,2
- Cholecystokinin (CCK), secreted by I cells in the duodenum in response to fats and proteins, stimulates the acinar cells to release digestive enzymes (lipase, amylase, proteases).1,2
- The vagus nerve also plays a role via parasympathetic stimulation (cephalic and gastric phases of digestion).1,2
- Following a meal, pancreatic stimulation leads to an increase in the volume and bicarbonate concentration of pancreatic juice. This results in the delivery of a large volume of alkaline, enzyme-rich fluid into the duodenum, which serves to neutralize gastric acid and initiate digestion of carbohydrates, proteins, and fats.1,2
Etiology of Exocrine Pancreatic Insufficiency (EPI)
EPI occurs when pancreatic enzyme output is insufficient to maintain normal digestion and nutrient absorption, particularly of fats.1,2,4
- Chronic pancreatitis (most common cause in adults) – progressive inflammation and fibrosis lead to destruction of acinar tissue.1
- Cystic fibrosis – autosomal recessive disorder causing thick secretions and ductal obstruction, leading to acinar atrophy (common cause in children).1
- Pancreatic resection or pancreatic duct obstruction – including malignancy or strictures.1
- Zollinger-Ellison syndrome – excessive gastric acid may inactivate pancreatic enzymes.1
- Celiac disease and Crohn’s disease – may impair hormonal signaling or damage mucosal surfaces involved in enzyme activation.1
- Diabetes mellitus – associated with pancreatic fibrosis and impaired neural/hormonal signaling.1
Clinical Manifestations of EPI
Symptoms vary by severity and duration of enzyme deficiency:
- Mild EPI:1,2,4
- Often asymptomatic or presents with nonspecific symptoms such as abdominal discomfort, bloating, and postprandial fullness.
- Moderate to severe EPI:1,2,4
- Steatorrhea (bulky, greasy, foul-smelling stools)
- Bloating, cramping, and increased flatulence
- Weight loss due to malabsorption of fats and fat-soluble vitamins (A, D, E, K)
- In long-standing cases: signs of nutritional deficiencies, including osteoporosis, anemia, or night blindness
Diagnosis of EPI
- Fecal elastase-1:2,4
- Most widely used noninvasive, indirect marker of pancreatic exocrine function.
- Low fecal elastase (<200 mcg/g stool) suggests EPI; <100 mcg/g indicates severe insufficiency.
- Must be measured in a solid or semi-solid stool sample; liquid stool may result in falsely low values.
- Additional tests (less commonly used due to limited availability or invasiveness):2,4
- 72-hour fecal fat collection (gold standard for fat malabsorption)
- Direct pancreatic function tests (secretin stimulation test)
- Imaging (CT, MRI/MRCP, EUS) to evaluate structural causes
Management of EPI
- Pancreatic Enzyme Replacement Therapy (PERT):
- Mainstay of treatment.1,2,3,4
- Enzymes are typically porcine-derived and contain lipase, amylase, and protease.3
- Standard starting dose: 40,000–50,000 units of lipase per meal; half the dose with snacks.3
- Enzymes should be taken with the first bite of food and may be divided during the meal.3
- Titration based on symptom response; some patients require up to 75,000–100,000 units per meal.3
- Proton pump inhibitors may be added if response to PERT is suboptimal, particularly in patients with gastric acid hypersecretion. 2,4
- Nutritional support:
- Supplement fat-soluble vitamins and monitor for deficiencies.3
- Dietitian referral for high-calorie, nutrient-rich dietary planning may be beneficial.
References
- Gastroenterology, Volume 165, Issue 5, 1292 – 1301
- Dig Dis Sci 2024 Feb;69(2):615-633
- American Journal of Gastroenterology 2020; 115(3): 322-339
Author
Sarah Enslin, PA-C is a Physician Assistant at the University of Rochester Medical Center in Rochester, NY with over 10 years of experience as a practicing PA in GI. Sarah serves on several national GI committees and is a former member of the Ã÷ÐÇÂãÕÕPractice Operations Committee and current member of the Ã÷ÐÇÂãÕÕAPP Committee. Sarah serves on several national GI committees, is Section Editor for Advanced Practice Providers for iGIE.