Symptoms and Diagnosis

It is essential to diagnose exocrine pancreatic insufficiency (EPI) early and initiate treatment as soon as the diagnosis is made, to reduce the long-term consequences of untreated EPI.¹

For patients suspected to have EPI:^1-4

Obtain medical and surgical history

Examine patient’s body weight and pay close attention to unexplained weight loss. Ask about previous use of digestive enzymes. Assess underlying conditions and any past surgeries/procedures suggestive of EPI, some of which may include:^2-4

Acute pancreatitis
Celiac disease
Chronic pancreatitis
Crohn’s disease
Cystic fibrosis
Gastric surgery
Gastric resection
Pancreatic resection
Pancreatic cancer
Type 1 diabetes
Type 2 diabetes

Ask about diet and lifestyle factors

Each of the following factors independently increases the risk of EPI:

Alcohol use
Smoking
Certain medications

Perform symptom assessment

Patients with EPI may experience some or all of the following signs and symptoms:

Abdominal pain/discomfort
Osmotic diarrhea
Unexplained weight loss
Steatorrhea
Bloating
Flatulence

Assess the onset, frequency, and severity of presenting symptoms. Be mindful that symptoms may vary depending on the degree and etiology of EPI, and might be masked by low fat intake.

Perform laboratory testing

Perform fecal testing to confirm fat malabsorption
Perform blood testing to assess manifestations of the underlying disease (e.g., malabsorption of fat soluble vitamins, microcytic or macrocytic anemia, electrolyte imbalance, etc.)

Unlock the Secrets of EPI Diagnosis:
Expert Physician Shares Actionable Steps for Accurate and Efficient Diagnosis

Diagnosing EPI

While EPI is largely a clinical diagnosis, there are multiple tests to evaluate the exocrine function and help confirm diagnosis but there is no gold standard.^5,6

Fecal Test

Test	Description	Limitations
Fecal Elastase-1^1,7,8	Measures the amount of elastase-1 in the stool Simple, noninvasive, and relatively inexpensive Most appropriate initial test for EPI Can be performed while on pancreatic enzyme replacement therapy Cutoff suggestive of EPI: <200 µg/g stool	Poor accuracy in mild/moderate EPI, and nonpancreatic causes of EPI False positives with watery stool Does not determine efficacy of enzyme replacement therapy
Quantitative fecal fat^1,8	Measures the amount of fat in the stool Coefficient of fat absorption is determined using absorbed fat and excreted fat Diagnostic for steatorrhea Cutoff suggestive of EPI: >7 g/100 g of fat ingested	Not practical for routine clinical use Not specific for EPI Must be performed on a high-fat diet
Endoscopic pancreatic function^1,8-11	Measures bicarbonate or pancreatic enzyme output after stimulation with secretin or CCK Most accurate Cutoff suggestive of EPI: <80 mEq/L over 60 min	Expensive, invasive, and technically challenging Not broadly available or standardized

Blood Test

There is no standard blood test for diagnosing EPI. Malnutrition-related complications can be preceded by deficiencies of macro- or micronutrients detectable by blood tests.

Manifestations/complications of EPI

Low serum levels of triglycerides, cholesterol, and alpha- and beta-carotene due to fat malabsorption
Low serum levels of vitamin A, D, E, and K due to fat malabsorption
Prolonged prothrombin time (PT) due to malabsorption of vitamin K
Low serum protein, albumin, or prealbumin levels due to protein malabsorption
Low levels of serum magnesium, calcium, potassium, or bicarbonate due to nutrient malabosorption
Serum immunoglobulin A (IgA) level can be assessed to rule out IgA deficiency

What Are the Diagnostic Challenges in EPI?

EPI is often under-recognized¹²

66% of patients have never heard of EPI

78% of patients are not aware of EPI signs and symptoms

34% of GI physicians report EPI is not top of their differential diagnosis for patients with complaint of diarrhea

24% of GI physicians said that they don’t see patients with EPI-related symptoms

This data is based on the EPI Uncovered survey was conducted online by Harris Poll on behalf of the American Gastroenterological Association (AGA) and was sponsored by AbbVie. It included 1,001 adults who have experienced at least two GI issues three or more times in the past three months (“patients”) and 500 HCPs, including 250 primary care physicians and 250 gastroenterologists.

Despite bothersome symptoms, patients delay HCP visits¹²

Patients hesitate to
address GI symptoms

Patients wait nearly 4 years to see a doctor about their GI symptoms on average.

Why do they wait?

3 out of 5 patients who found it difficult to discuss symptoms with their HCP said it was due to embarrassment.

What do they do instead?

Patients try to self-manage their GI symptoms by eating healthier (60%) and/or researching symptoms or self‑diagnosing their condition (50%).

EPI can be challenging to diagnose¹

There is no specific test of pancreatic exocrine function and fat malabsorption

EPI shares overlapping symptoms with other gastrointestinal diseases

Patients have a median of 4 HCP visits until EPI diagnosis¹

Steatorrhea—the hallmark symptom of EPI—does not manifest clinically until >90% of the pancreas’s enzyme production is lost

EPI shares overlapping symptoms with other gastrointestinal diseases making clinical diagnosis challenging

EPI symptoms mimic those of other GI conditions.

Symptoms	EPI²	IBS-D^13,14	SIBO¹⁵	IBD^16-19	Celiac Disease²⁰
Diarrhea
Abdominal Pain
Bloating
Flatulence

Subtle differences in clinical features can be seen.

Clinical Features	EPI^18,21,22	IBS-D^13,18,23	SIBO^15,18	IBD^16-18	Celiac Disease^18,20
Stool Quality	Fatty Stool may not be very loose	Watery	Fatty	Bloody/Purulent	Watery/Fatty
Symptom Onset Related to Food Intake			Particularly foods high in sugar and fiber	Symptoms may occur despite fasting (ileitis)	Triggered by gluten, improves with fasting
Nocturnal Symptoms		Symptoms improve at night		Ileitis
Urgency
Fecal Incontinence
Unexplained Weight Loss			Only in extreme cases

Learn how to differentiate between EPI and IBS-D with these 8 questions.

BACK TO EPI Fundamentals

CONTINUE TO EPI Management

CCK=cholecystokinin; GI=gastrointestinal; HCP=healthcare professional; IBS=irritable bowel syndrome; IBS-D=irritable bowel syndrome with diarrhea; SIBO=small intestine bacterial overgrowth.

References: 1. Whitcomb DC et al. Gastroenterology. 2023;165(5):1292-1301. 2. Alkaade S et al. Am J Manag Care. 2017;23(12)(suppl):S203-S209. 3. Fieker A et al. Clin Exp Gastroenterol. 2011;4:55-73. 4. Durie P et al. Curr Med Res Opin. 2018;34(1):25-33. 5. Fieker A et al. Clin Exp Gastroenterol. 2011;4:55-73. 6. Durie P et al. Curr Med Res Opin. 2018;34(1):25-33. 7. Leeds JS et al. Nat Rev Gastroenterol Hepatol. 2011;8(7):405-415. 8. Hart PA et al. Curr Treat Options Gastroenterol. 2015;13(3):347-353. 9. Capurso G et al. Clin Exp Gastroenterol. 2019;12:129-139. 10. Patel N et al. J Pediatr Gastroenterol Nutr. 2021;72(1):144-150. 11. Issaka RB et al. Gastroenterology. 2023;165(5):1280-1291. 12. EPI Uncovered. American Gastroenterological Association website. Updated October 24, 2016. Accessed February 12, 2024. https://s3.amazonaws.com/agaemailassets/images/EPI_Uncovered_AGA_Survey_Infographic.pdf 13. Lacy BE et al. J Gastroenterol. 2021;116(1):17-44. 14. Owyang C. Harrison’s Principles of Internal Medicine. 20th ed. McGraw Hill; 2018:2496-2502. 15. Pimentel M et al. Am J Gastroenterol. 2020;115(2):165-178. 16. Gu P et al. Inflamm Bowel Dis. 2018;24(6):1280-1290. 17. Rubin DT et al. Am J Gastroenterol. 2019;114(3):384-413. 18. Burgers K et al. Am Fam Physician. 2020;101(8):472-480. 19. Farrell D et al. J Crohns Colitis. 2016;10(3):315-322. 20. Rubio-Tapia A et al. Am J Gastroenterol. 2013;108(5):656-676. 21. Phillips ME et al. BMJ Open Gastroenterol. 2021;8(1):e000643.1. 22. Johnson CD et al. Pancreatology. 2019;19(1):182-190. 23. Simrén M et al. Neurogastroenterol Motil. 2017;29(2):10.1111/nmo.12919.