Exocrine Pancreatic Insufficiency (EPI)

Exocrine pancreatic insufficiency (EPI) is when the pancreas does not make enough digestive enzymes for the body to properly digest food. It can cause issues like not absorbing enough nutrients (malabsorption) from the foods you eat and weight loss. EPI commonly affects people with recurrent acute pancreatitis, chronic pancreatitis, and other disorders of the pancreas. Although there is no cure for EPI, symptoms can be managed with pancreatic enzymes and dietary changes.

What is exocrine pancreatic insufficiency (EPI)?

Exocrine pancreatic insufficiency (EPI) is a condition in which the pancreas does not make enough natural juices, called digestive enzymes. As a result, people with EPI cannot properly absorb nutrients (malabsorption) from the foods they eat, which can lead to other complications, such as malnutrition, vitamin deficiency, and other digestive symptoms.

Typically, exocrine pancreatic insufficiency develops slowly over years. However, for some patients, it may develop over weeks to months.

Listen to Dr. Steve Freedman of Harvard Medical School explain:

  • What exocrine pancreatic insufficiency (EPI) is
  • Who’s at risk of developing EPI
  • Symptoms of EPI
  • Treating EPI

Understanding EPI

The term “exocrine” in exocrine pancreatic insufficiency (EPI) refers to the exocrine function of the pancreas. In a healthy pancreas, the exocrine pancreas produces and releases juices made up of digestive enzymes (amylase, protease, and lipase) into small pancreatic ducts (tubes) once food enters your stomach. These ducts move the juices into the first part of the small intestine, called the duodenum, where they mix with bile (made by your liver and stored in the gallbladder) to break down food.

In exocrine pancreatic insufficiency, however, the pancreas is not producing and releasing enough digestive enzymes. As a result, people with EPI cannot properly break down nutrients from their food. This includes nutrients from:

  • Fat. Fat gives your body energy and helps it store and use vitamins from the food you eat. Foods with high dietary fat include nuts, dairy, and eggs.
  • Protein. Protein helps your body grow and repair tissue and keeps your muscles and bones healthy. Foods with high dietary protein include meat, fish, dairy, and lentils.
  • Carbohydrates. Carbs are the main source of energy for your body’s cells, tissues, and organs. Foods high in dietary carbohydrates include whole grains, fruits, and starchy vegetables.

Your body needs nutrients from these different sources to stay healthy. However, people with EPI face challenges in absorbing enough of these nutrients due to the exocrine function of the pancreas not working properly. As a result, EPI patients may become deficient in nutrients and may need PERT and nutritional supplements.

Learn more about the functions of the pancreas.

What causes exocrine pancreatic insufficiency (EPI)?

Exocrine pancreatic insufficiency is common in people with pancreatic disorders, the most common cause being chronic pancreatitis.

The causes of exocrine pancreatic insufficiency include:

  • Chronic Pancreatitis. EPI is observed in about 60% to 90% of chronic pancreatitis patients within 10 to 12 years of diagnosis.
  • Cystic Fibrosis. EPI is observed in about 85% of all cystic fibrosis patients, which usually develops within the first year of life.
  • Pancreatic Cancer. EPI is observed in about 66% to 92% of patients with advanced pancreatic cancer. About 20% to 30% of people with pancreatic cancer can go on to develop EPI.
  • Pancreatic Surgery. EPI can also be a complication following pancreatic surgery. The observable occurrence of EPI varies depending on the type of pancreatic surgery.
  • Diabetes. EPI is observed in about 30% of patients with diabetes (including both type 1 and type 2 diabetes).

Exocrine pancreatic insufficiency can also be observed in patients with acute pancreatitis, celiac disease, inflammatory bowel disease, bariatric surgery, HIV/AIDS, older age, infants up to 6 months of age, and certain genetic and congenital abnormalities.

Learn more about chronic pancreatitis.

What causes EPI in children?

Exocrine pancreatic insufficiency (EPI) in children is most commonly caused by cystic fibrosis. Cystic fibrosis is a genetic disease that leads to dysfunction in various organs due to the buildup of thick, sticky mucus. For the pancreas, this mucus prevents the release of digestive enzymes, causing EPI. Most cystic fibrosis patients develop EPI within the first year of life.

Chronic pancreatitis can also be a cause of EPI in children (pediatric pancreatitis). This is because, when the pancreas becomes damaged and scarred, the part of the pancreas that generates enzymes is destroyed.

Another potential cause of EPI in children is Shwachman-Diamond syndrome (SDS). Shwachman-Diamond syndrome is a rare, inherited condition that affects the body’s bone marrow, pancreas, and bones. Many infants with SDS do not produce enough digestive enzymes and develop EPI.

Symptoms of Exocrine Pancreatic Insufficiency (EPI)

Exocrine pancreatic insufficiency causes many challenging symptoms, often resulting from the body’s inability to absorb nutrients from food. The most common symptoms of exocrine pancreatic insufficiency include:

  • Steatorrhea (pale, oily, and sticky stools that are hard to flush)
  • Unexplained weight loss
  • Malnutrition
  • Fat-soluble vitamin deficiency
  • Bloating
  • Abdominal distension and gas
  • Cramping
  • Chronic fatigue
  • Muscle loss
  • Changes to skin and hair health

What are the signs of fat-soluble vitamin deficiency?

Fat-soluble vitamins (A, D, E, and K) are absorbed best into the body when they are consumed with some amount of dietary fat. People with EPI are at risk of becoming deficient in these vitamins because their bodies cannot digest the fat needed to absorb them.

Symptoms of fat-soluble vitamin deficiency include:

  • Rash and night blindness (vitamin A deficiency)
  • Metabolic bone disease (vitamin D deficiency)
  • Anemia, nerve issues (vitamin E deficiency)
  • Easy bruising or bleeding (vitamin K deficiency)

How is exocrine pancreatic insufficiency (EPI) diagnosed?

If you have a pancreatic disorder or are experiencing the classic symptoms of exocrine pancreatic insufficiency, your doctor may want to test you for EPI. Currently, the fecal elastase test is the most common and accurate test used to diagnose EPI.

To diagnose exocrine pancreatic insufficiency, your doctor may use one of the following tests:

  • Fecal elastase test (FE-1)
  • 72-hour fecal fat test
  • Breath tests*
  • Blood tests (to check vitamin and mineral levels)

If your doctor suspects you have EPI, they may begin treating you with Pancreatic Enzyme Replacement Therapy (PERT) without a diagnostic test. If you respond well to PERT, it may help your doctor diagnose you with EPI.

*Breath tests are not commonly used in the United States.

Listen to Dr. Steve Freedman of Harvard Medical School explain:

  • What tests are used to diagnose EPI
  • What EPI diagnostic tests involve
  • Requirements for EPI diagnostic tests
  • And more

What’s involved in the fecal elastase test?

The fecal elastase test looks at how much elastase (a pancreatic enzyme) is in your stool to diagnose EPI. Specifically, doctors are looking at the micrograms (MCG) of elastase per gram of stool. The fecal elastase test must be conducted on a formed (solid) stool to be accurate, meaning it cannot be performed on diarrhea, steatorrhea, or loose stool. If little or no elastase is found in the formed stool (less than 200 mcg/g), your pancreas may not be producing enough digestive enzymes. In this case, your doctor may diagnose you with EPI.

Exocrine Pancreatic Insufficiency (EPI) Treatment

Exocrine pancreatic insufficiency is treated with Pancreatic Enzyme Replacement Therapy (PERT). PERT involves taking medication to replace the enzymes your pancreas would normally make so you can better digest food. This medication (pancreatin/pancrelipase) contains a mixture of enzymes extracted from pig pancreas and is given in the form of capsules or tablets.

The goal of pancreatic enzyme replacement therapy is to mimic the function of the pancreas during the digestive process. While PERT isn’t as effective as the enzymes your pancreas would naturally produce, it can improve carbohydrate, fat, and protein absorption in patients. This can reduce the digestive symptoms of those with EPI, such as diarrhea, abdominal pain, and malabsorption, which leads to nutritional deficiency.

Some patients may also need assistance from their doctor or a dietitian to develop a plan aimed at getting enough nutrients from the foods they eat. This plan may involve a specialized diet and nutritional supplements, including vitamins and minerals.

Learn more about pancreatic enzyme replacement therapy (PERT).

Frequently Asked Questions

Other conditions can mimic the symptoms of exocrine pancreatic insufficiency (EPI), causing a misdiagnosis or delayed diagnosis of EPI. Conditions that can cause similar symptoms to EPI include small intestinal bacterial overgrowth (SIBO), Crohn’s disease, irritable bowel syndrome (IBS), giardiasis, and bile acid (salt) malabsorption. If you’ve had your gallbladder removed, it can also cause symptoms similar to EPI. It’s important for your doctor to determine if your symptoms are from one of these conditions or EPI. If your doctor is unsure, a fecal elastase test can help diagnose EPI and rule out these other conditions.

If you continue to have or have re-developed symptoms of exocrine pancreatic insufficiency (EPI) despite being on pancreatic enzyme replacement therapy (PERT), you may need to talk to your doctor about adjusting your dosage or check that you are taking them correctly. Symptoms may also get worse or reappear if you have developed another condition, such as small intestinal bacterial overgrowth (SIBO) or giardiasis, in addition to EPI. Talk to your doctor if you believe that is the case.

Exocrine pancreatic insufficiency (EPI) can lead to early death in severe, untreated cases; but, with the right treatment, it can be managed and your condition can improve. If you’re experiencing symptoms of EPI, talk to your doctor about a fecal elastase test and pancreatic enzyme replacement therapy.

Exocrine pancreatic insufficiency (EPI) cannot be reversed, but pancreatic enzyme replacement therapy (PERT) can help reduce symptoms, manage your condition, and prevent further complications.

Causes of exocrine pancreatic insufficiency (EPI) can be hereditary, but EPI itself is not believed to be hereditary. Hereditary causes of EPI can include chronic pancreatitis, cystic fibrosis, and Shwachman-Diamond syndrome.

The ICD-10 code for exocrine pancreatic insufficiency is K86.81.

Key Takeaways

  • Exocrine pancreatic insufficiency (EPI) is a condition in which the pancreas does not make enough digestive enzymes to properly digest and absorb nutrients from food.
  • Causes of EPI include recurrent acute pancreatitis, chronic pancreatitis, cystic fibrosis, pancreatic cancer, pancreatic surgery, and diabetes.
  • EPI in children is most commonly caused by cystic fibrosis. Other causes can include chronic pancreatitis and Shwachman-Diamond syndrome.
  • Symptoms of EPI include steatorrhea, weight loss, malnutrition, vitamin and mineral deficiency, abdominal symptoms, fatigue, muscle loss, and changes to skin and hair health.
  • EPI is most commonly and accurately diagnosed with a fecal elastase test. Other tests used for diagnosing EPI include the 72-hour fecal fat test, breath tests, and blood tests (to check for vitamin deficiencies).
  • EPI is treated with Pancreatic Enzyme Replacement Therapy (PERT). PERT replaces the enzymes the pancreas would normally make, allowing patients to better absorb nutrients from food.

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