Exocrine Pancreatic Insufficiency

TL;DR. Exocrine pancreatic insufficiency (EPI) is a manageable condition where the pancreas fails to produce the enzymes needed to digest food, leading to severe weight loss and chronic diarrhea despite a ravenous appetite.

The pancreas plays a dual role in the body, producing both systemic hormones and essential digestive enzymes.

What is it?

To understand exocrine pancreatic insufficiency (EPI), it helps to look at the dual role of the pancreas. This small, V-shaped organ nestled alongside the stomach and small intestine has two primary functions. The endocrine pancreas produces hormones like insulin directly into the bloodstream to regulate blood sugar. The exocrine pancreas, on the other hand, produces vital digestive enzymes—specifically lipase, amylase, and proteases—and secretes them into the small intestine to break down fats, carbohydrates, and proteins.

When a pet has EPI, the exocrine portion of the pancreas is either destroyed or fails to develop properly. This leads to a severe deficiency in these essential digestive enzymes. Without them, your pet cannot break down macronutrients into absorbable particles. Even if your pet is eating large quantities of high-quality food, the nutrients pass through the gastrointestinal tract completely undigested.

This functional syndrome results in a state of progressive starvation at the cellular level. The undigested food remains in the intestines, drawing in water and fermenting, which leads to chronic diarrhea, gas, and severe weight loss. As a leading veterinary internal medicine reference notes:

"The pancreas is the only significant source of lipase, so fat maldigestion with fatty feces (steatorrhea) and weight loss are the predominant signs of EPI."

Causes & risk factors

There are two primary pathways that lead to the development of exocrine pancreatic insufficiency in dogs and cats:

• Pancreatic Acinar Atrophy (PAA): This is the most common cause of EPI in dogs. It is an immune-mediated process where the body's own immune system targets and destroys the enzyme-producing cells (acinar cells) of the pancreas. This destruction typically occurs early in life, and clinical signs only appear once more than 90% of the pancreatic secretory capacity has been lost.
• End-stage Chronic Pancreatitis: This is the primary cause of EPI in cats and is also a significant cause in some small-breed dogs. Repeated bouts of low-grade or severe pancreatic inflammation (pancreatitis) gradually destroy the healthy pancreatic tissue, replacing it with non-functional scar tissue over time.

While any dog or cat can develop EPI, certain breeds have a much higher risk. German Shepherd Dogs are highly predisposed to pancreatic acinar atrophy. Other breeds with documented predispositions include the Boxer, Chow Chow, Cavalier King Charles Spaniel, English Cocker Spaniel, Collie, Greyhound, and English Setter. In cats, EPI is less common overall but is increasingly recognized as a consequence of chronic pancreatitis or concurrent inflammatory bowel disease.

Signs to watch for

The signs of EPI are directly related to the body's inability to digest and absorb nutrients. Because the pet is starving despite eating, the clinical signs are often dramatic and highly characteristic.

• Weight loss (Cardinal): Pets will lose weight rapidly and progressively, even though they are eating normal or increased amounts of food.
• Fatty feces (steatorrhea) (Cardinal): Stools are typically pale, voluminous, greasy, clay-colored, or yellow, and they carry a distinct, foul odor due to undigested fat.
• Chronic diarrhea (Common): Stools are frequently soft, watery, or semi-formed, and pets may need to defecate much more often than usual.
• Emaciation (Common): In advanced cases, pets will lose muscle mass and appear visibly wasted, with prominent ribs and hip bones.
• Ravenous appetite (Common): Also known as polyphagia, affected pets are constantly hungry. They may beg aggressively, steal food, or eat non-food items (pica) and feces (coprophagia).
• Hypocobalaminemia (Common): A severe deficiency in Vitamin B12 (cobalamin) occurs because the pancreas produces a protein necessary for B12 absorption in the gut.
• Vomiting (Occasional): Some pets may experience intermittent vomiting.
• Chronic seborrheic skin disease (Occasional): Due to the lack of essential fatty acid absorption, the skin may become dry, flaky, and greasy, and the coat may lose its luster.
• Diabetes mellitus (Occasional): If the underlying cause is chronic pancreatitis, the inflammation can destroy both the exocrine and endocrine portions of the pancreas, leading to concurrent diabetes.
• Anorexia (Occasional): While a ravenous appetite is standard, some pets may lose their appetite if they are suffering from severe concurrent pancreatitis or extreme cobalamin deficiency.

Severe weight loss and a dull, greasy coat are common physical signs of advanced EPI.

How vets diagnose it

If your vet suspects EPI based on your pet's clinical signs and breed, they will recommend specific blood and fecal tests to confirm the diagnosis and rule out other gastrointestinal diseases.

• Serum Trypsin-Like Immunoreactivity (TLI) [GOLD STANDARD]: This is the definitive diagnostic test for EPI in both dogs and cats. It measures the level of trypsinogen (a precursor to digestive enzymes) in the blood. In healthy animals, small amounts of trypsinogen leak into the bloodstream. In pets with EPI, these levels are extremely low or undetectable. As a leading veterinary internal medicine reference explains:

  "Measurement of decreased TLI in the blood has a high sensitivity and specificity for the diagnosis of EPI in dogs and cats and is currently the single test of choice for diag nosis in small animals. It is important to measure it on a fasting sample because the release of pancreatic enzymes associated with feeding can raise the activity in the serum."

• Serum Cobalamin (Vitamin B12) and Folate Concentrations: These vitamins are absorbed in specific parts of the small intestine. Because EPI severely alters the gut environment and prevents proper absorption, measuring these levels is crucial. A vast majority of dogs with EPI have low cobalamin levels, which must be addressed for treatment to succeed.

• Fecal Elastase: This test measures a specific pancreatic enzyme in a stool sample. While it can be useful, it is generally considered less reliable than the TLI blood test.

• Canine Pancreatic Lipase Immunoreactivity (cPLI): This test may be run to evaluate the pet for active or underlying pancreatitis, especially if the pet is a cat or a breed prone to chronic inflammation.

Treatment options

EPI cannot be cured, but it can be highly successfully managed. Treatment is lifelong and focuses on replacing the missing pancreatic enzymes and correcting any secondary nutritional deficiencies.

First-Line Therapies

• Pancreatic Enzyme Supplements: Your pet will require exogenous pancreatic enzymes with every single meal for the rest of their life. These are typically prescribed as a raw, dried porcine pancreatic powder that is mixed thoroughly into the food. Enteric-coated capsules are also available and have been shown to be highly effective.

  "All dogs and cats with clinical EPI require enzyme supplementation for the rest of their lives. In most cases, this is provided as a powder or in the form of a capsule, which is opened and then sprinkled on the food. A recent study confirmed that an enteric coating of a canine enzyme preparation improved its efficacy..."

• Cyanocobalamin (Vitamin B12) Supplementation: Because hypocobalaminemia is incredibly common and prevents the gut from healing, your vet will prescribe Vitamin B12. This is typically administered via regular subcutaneous injections, though oral supplementation may be used in some cases. Addressing this deficiency is critical, as a leading reference notes:

  "In one large study of dogs with EPI, 82% of dogs had low serum cobalamin concentrations... Cobalamin deficiency causes villous atrophy and reduced gastrointestinal function, weight..."

Dietary Management

Your vet will help you select a highly digestible, moderate-to-low-fat diet. It is best to feed your pet two or more smaller meals per day, with the prescribed enzymes mixed into each meal. Additionally, strict environmental control is necessary:

"It is best to feed two or more meals a day, each with enzymes added, and the dog should not be allowed to scavenge. This is often difficult because they are polyphagic, but scavenging, especially of fatt..."

Preventing your pet from scavenging is vital, as eating untreated food or garbage will trigger immediate diarrhea and digestive upset.

The serum TLI test is the gold standard for diagnosing EPI and must be performed on a fasted blood sample.

Prognosis

The long-term prognosis for pets with EPI is generally good, provided they respond well to enzyme and cobalamin therapy. Many dogs achieve a median survival time of more than five years on appropriate treatment, maintaining an excellent quality of life.

However, there is a significant hurdle during the initial phase of treatment. Up to 19% of dogs are euthanized within the first year of diagnosis. This is typically due to a poor response to therapy, the financial commitment of lifelong enzyme supplementation, or the challenges of managing a pet with severe, chronic diarrhea and a ravenous appetite. Once a pet successfully transitions past this initial stabilization phase, their outlook is highly positive.

Prevention

Because EPI is primarily an inherited genetic condition (such as pancreatic acinar atrophy in German Shepherds) or the result of unpredictable chronic pancreatitis, there are no known ways to prevent the disease from developing.

Responsible breeding practices are the most effective tool for reducing the prevalence of EPI. Dogs diagnosed with EPI, as well as their immediate relatives, should not be used for breeding. For pet owners, early detection through routine veterinary exams and prompt investigation of chronic weight loss or stool changes is the best way to ensure a successful treatment outcome.

When to call your vet

Managing a pet with EPI requires close observation. You should contact your veterinarian if you notice any of the following signs:

• A return of chronic diarrhea or greasy, foul-smelling stools.
• Continued weight loss despite consistent enzyme supplementation.
• Signs of skin irritation, hair loss, or a greasy coat.
• Severe, persistent vomiting.
• Complete loss of appetite (anorexia) or extreme lethargy.
• Signs of abdominal pain, such as a hunched posture or whining when touched.

For specific breeds

If you own a German Shepherd Dog, you should be particularly vigilant. This breed is highly predisposed to pancreatic acinar atrophy (PAA), which often manifests in young adulthood. While the exact genetic markers are still being studied, any German Shepherd showing unexplained weight loss or chronic diarrhea should be screened for EPI immediately.

Similarly, owners of Boxers, Chow Chows, Cavalier King Charles Spaniels, English Cocker Spaniels, Collies, Greyhounds, and English Setters should be aware of this predisposition. While the disease may present slightly differently in breeds prone to chronic pancreatitis (such as smaller spaniels), the diagnostic and treatment protocols remain highly effective across all breeds.

Sources

• Textbook of Veterinary Internal Medicine, 5th Edition, Pages 651, 653, 655.