Exocrine Pancreatic Insufficiency (EPI)
In DVM STAT’s recent CE webinar on EPI, Bryan Welch, DVM, MVSc, DACVIM (SAIM) shared practical, evidence-based guidance on recognizing, diagnosing, and managing EPI in both dogs and cats, including emerging concepts such as lipase-specific EPI and subclinical disease.
Missed the live CE? You can still take the free course on-demand and receive 1 hour of RACE-approved CE once it is available in the DVM STAT CE portal. Visit the CE library here.
Top Takeaways from the Webinar
EPI Is a Syndrome of Maldigestion
EPI is caused by insufficient synthesis and secretion of pancreatic digestive enzymes. The pancreas has a large functional reserve, so clinical signs typically do not appear until approximately 90 percent of exocrine function is lost.
The most common pathophysiologic mechanism is loss of pancreatic acinar cells, which explains why disease can progress silently before becoming clinically obvious.
Most Cases Have One of Two Underlying Causes
In dogs, Exocrine Pancreatic Insufficiency is most commonly associated with two primary underlying disease processes: chronic pancreatitis and pancreatic acinar atrophy (PAA). Together, these account for the majority of cases seen in clinical practice.
Chronic pancreatitis
This is more commonly identified in older patients and is estimated to account for approximately half of EPI cases. Progressive pancreatic inflammation and fibrosis lead to loss of functional exocrine tissue over time.
Pancreatic acinar atrophy (PAA)
PAA is most often diagnosed in young to middle-aged dogs and is responsible for a large proportion of cases. Certain breeds are at increased risk, including German Shepherd Dogs, Rough Collies, and Eurasians. A hereditary, autosomal recessive pattern of inheritance has been identified in some predisposed breeds.
Less common causes of EPI
Rare etiologies include suspected congenital pancreatic aplasia or hypoplasia, which have been proposed but not definitively confirmed in most cases, as well as pancreatic duct obstruction, which is considered an uncommon cause of clinical EPI.
EPI Has Downstream Gastrointestinal Consequences
Maldigestion leads to altered intestinal mucosal enzymes, impaired intestinal function, small intestinal bacterial overgrowth (SIBO/dysbiosis), and impaired cobalamin (vitamin B12) absorption.
More than 80 percent of dogs with EPI are hypocobalaminemic. The pancreas is the primary source of intrinsic factor required for vitamin B12 absorption. Concurrent ileal disease further worsens absorption.
Clinical Presentation of EPI in Practice
Typical clinical signs include:
Weight loss despite a good or ravenous appetite
Poor haircoat
Chronic loose, voluminous, or pulpy stools
Borborygmus and excessive flatulence
While certain breeds are predisposed, EPI can occur in any breed. Some patients present early with minimal diarrhea or vague gastrointestinal signs.
TLI Is the Diagnostic Test of Choice, With Important Caveats
Routine Diagnostics
Complete blood count and serum biochemistry are often unremarkable.
Imaging
Abdominal ultrasound is the preferred imaging modality when evaluating for EPI. The pancreas may appear small in some cases, but a normal pancreatic size does not rule out EPI. Concurrent small intestinal changes consistent with chronic enteropathy are commonly identified and may contribute to incomplete clinical response.
Test of choice: Serum TLI
Serum trypsin-like immunoreactivity (TLI) remains the diagnostic test of choice for EPI in both dogs and cats due to its high sensitivity and specificity.
Diagnostic Cut Offs:
Dogs less than 2.5 µg/L
Cats less than 8 µg/L
Important diagnostic exceptions
Clinicians should be aware of scenarios in which TLI may be misleading. Patients with lipase-specific EPI can have a normal TLI with an undetectably low pancreatic lipase immunoreactivity (PLI). Developing or subclinical EPI may present with low-normal or mildly decreased TLI values. Pancreatic duct obstruction can also result in a normal TLI despite clinically significant maldigestion.
Tests with limited clinical value
Several commonly available tests do not reliably diagnose EPI and should not be used as screening tools. These include serum amylase and lipase activities, Spec PLI except for identifying lipase-specific EPI, fecal microscopy, bentiromide absorption testing, and pancreatic histopathology, which is rarely pursued in practice.
A Hidden Diagnosis: Lipase-Specific EPI
Lipase-specific EPI was previously thought to be rare but is now increasingly recognized in clinical practice. Hallmarks of this presentation include a normal TLI with an undetectably low PLI, along with steatorrhea and failure to thrive. Increased suspicion is warranted in Arctic breeds.
In these cases, gastrointestinal panels may be otherwise normal except for hypocobalaminemia, which can be an important diagnostic clue. Empiric treatment is reasonable in suggestive cases, even when traditional diagnostics do not definitively confirm EPI.
Subclinical EPI Exists and Often Progresses
Some patients have persistently low TLI values with normal stool quality, coat condition, and body condition.
These patients often progress to clinical EPI. Recommended monitoring includes repeating TLI every three to six months and initiating treatment earlier if hypocobalaminemia or weight loss develops.
Pancreatic Enzyme Replacement Is the Foundation of Therapy
First-Line Therapy
Pancreatic enzyme replacement is the first-line therapy for Exocrine Pancreatic Insufficiency. The most commonly used formulation is dried pancreatic extract (porcine-derived).
Stool improvement is often seen within 3 to 7 days, while full gastrointestinal improvement may take 2 to 4 weeks. Improvement in weight and haircoat can take months.
Administration tips
Soaking the powder in moistened food for approximately 20 minutes may reduce oral bleeding, which is rare. If high doses are required to achieve clinical response, clinicians should evaluate for concurrent chronic enteropathy.
Alternative formulations
Alternatives include enteric-coated pancrealipase (e.g., Creon), PancreaPlus tablets (the least expensive tablet option), and Cotazym. Tablets are significantly more expensive than powders.
Fresh raw pancreas
Fresh raw pancreas can be used as an alternative to commercial enzyme products. Raw pancreas can be frozen without loss of enzyme activity; however, there are risks of bacterial contamination and infectious disease exposure.
Emerging therapies
Plant- or microbial-derived enzymes are currently under investigation but are not commercially available.
Cobalamin Should Always Be Tested and Supplemented
There are two primary causes of hypocobalaminemia in patients with EPI, including lack of intrinsic factor (EPI) and chronic ileal disease. Because of this, all EPI patients should be tested, and supplementation is recommended if serum cobalamin is less than 400 ng/L. Cobalamin supplementation is safe and benign.
Supplementation protocols
Oral supplementation can be administered daily for 12 weeks, followed by a recheck 1 month later.
Subcutaneous injectable supplementation can be given weekly for 6 weeks, followed by a recheck 1 month later. Dosing should follow the chart available on the TAMU website.
If rechecks are declined, long-term oral supplementation is acceptable.
Consequences of untreated hypocobalaminemia
Untreated hypocobalaminemia leads to increased GI permeability and malabsorption, anemia (which can be regenerative in dogs), neurologic disease, and cardiovascular disease. It is also associated with worse outcomes in EPI, chronic enteropathy, and lymphoma.
Nutrition Matters and Low-Fat Diets Are Contraindicated
Low-fat diets are contraindicated in patients with Exocrine Pancreatic Insufficiency. High-fiber diets should also be avoided. Even with enzyme supplementation, fat digestion remains incomplete, and fat restriction increases the risk of deficiencies in essential fatty acids and fat-soluble vitamins.
While deficiencies in vitamins A, D, and E are documented in patients with EPI, evidence supporting routine supplementation is lacking.
When Treatment Fails, Look for Concurrent Disease
When patients fail to respond as expected to pancreatic enzyme replacement, the most common causes include inconsistent or improper enzyme administration and concurrent disease, including chronic enteropathy or IBD, dysbiosis, and diabetes mellitus.
Prognosis Is Typically Good With Lifelong Therapy
Exocrine Pancreatic Insufficiency requires lifelong therapy, but quality of life and life expectancy are typically normal when patients are appropriately managed.
In dogs, reported response rates include complete response in 60 percent, partial response in 17 percent, and poor response in 23 percent of cases. Severe hypocobalaminemia reduces median survival time by approximately 50 percent, reinforcing the importance of early recognition and appropriate supplementation.
Chronic diarrhea is the most common sign of incomplete response to therapy and should prompt evaluation for concurrent disease.
EPI, Chronic Enteropathy, and Dysbiosis
EPI frequently occurs alongside chronic enteropathy and dysbiosis. Up to 85 percent of dogs with EPI show chronic enteropathy changes on ultrasound, and 20 to 50 percent of cats have concurrent EPI and chronic enteropathy.
Dysbiosis is common in patients with EPI. Pre- and probiotics are often ineffective, while tylosin or fecal microbiota transplantation may be beneficial in select cases. Fecal microbiota capsules are commercially available, and there is data showing good efficacy in refractory dysbiosis.
Feline EPI: Key Differences
Feline EPI has several important distinctions compared to dogs. There is no age or sex predilection, and weight loss is the most common presenting sign, occurring in approximately 90 percent of cases. Between 70 and 100 percent of cats with EPI are hypocobalaminemic.
Concurrent disease is common and frequently includes chronic enteropathy, pancreatitis, and diabetes mellitus.
Treatment typically includes pancreatic enzyme powder. Lower fTLI and cobalamin supplementation are associated with improved response.
Prognosis for feline EPI is generally good with lifelong therapy. Reported response rates include complete response in 40 to 60 percent of cats and partial response in 27 to 60 percent. Up to 50 percent of cats develop concurrent chronic enteropathy or dysbiosis, which may impact long-term management.
Download the EPI Quick Reference (Free)
Want a concise, clinic-friendly summary you can save or share with your team?
Download the EPI Top Takeaways Quick Reference PDF, which includes the key diagnostic cutoffs, treatment protocols, nutrition pearls, and troubleshooting tips from this webinar in an easy, printable format.
About The Author & Webinar Presenter
Bryan Welch, DVM, MVSc, DACVIM (SAIM) is a board-certified small animal internal medicine specialist with a clinical focus on complex gastrointestinal, pancreatic, hepatic, and multisystem disease. Dr. Welch is known for his practical, case-based teaching style and emphasis on evidence driven medicine that can be implemented in real world clinical practice.
Need Help Co-Managing EPI Cases?
EPI is rarely an isolated diagnosis. Many patients have concurrent chronic enteropathy, dysbiosis, diabetes mellitus, pancreatitis, or nutrient deficiencies that complicate management and delay clinical response.
Through DVM STAT’s Internal Medicine teleconsultations, primary care teams gain access to board certified internal medicine specialists who provide:
Case specific diagnostic guidance
Step by step treatment plans
Support for interpreting complex or conflicting test results
Help managing refractory diarrhea, weight loss, and poor response to enzyme therapy
Guidance for complicated cases involving concurrent IBD, pancreatitis, endocrine disease, or dysbiosis
Follow up support to adjust treatment plans over time
Consults are available on demand and designed to support the veterinarian client patient relationship while improving patient outcomes.