An Overview of Exocrine Pancreatic Insufficiency

A malabsorption condition caused by lack of digestive enzymes

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Exocrine pancreatic insufficiency (EPI) is a malabsorptive condition that occurs when the pancreas fails to produce important digestive enzymes. Without these enzymes, the body cannot properly digest food and absorb nutrients, particularly fat. EPI most often occurs in people who have conditions affecting the pancreas, though they often don't have symptoms until the condition has become advanced.

Exocrine pancreatic symptoms
Verywell / JR Bee 


The initial symptoms of EPI can be vague, mild, and similar to other gastrointestinal illnesses.

Common gastrointestinal symptoms of EPI include:

Other symptoms of EPI depend on the underlying cause of the condition. For example, a person with cystic fibrosis may also have respiratory symptoms.

Many symptoms a person with EPI experiences later in the course of the condition are related to malnutrition and specific nutritional deficiencies. A few of the nutritional deficiencies commonly seen in people with EPI include:

  • Vitamin K, which may cause abnormal bleeding or bruising
  • Vitamin D, leading to low bone density (osteopenia and osteoporosis)
  • Fat-soluble vitamins and electrolyte deficiencies can manifest with changes in vision (night blindness) neurological symptoms, (depression, memory), muscular or joint-related (pain and fatigue), and/or skin (rashes or swelling)

In more severe, prolonged, cases of malnutrition, more serious conditions can result. Untreated deficiencies and electrolyte disturbances can lead to kidney failure, neuropathy, severe anemia, seizures, fluid in the abdomen (ascites), infections and slow healing, and potentially fatal heart arrhythmias.


The pancreas is an organ located in the abdomen under the stomach. The role of the pancreas can be divided into exocrine and endocrine functions. The exocrine functions help the body digest food by producing special enzymes while the endocrine functions help regulate hormones.

In EPI, it's the exocrine function that becomes compromised. This can happen because of physical damage to the pancreas or disruption of the signals to the organ. Reduced production of three key digestive enzymes—amylase, protease, and lipase—leads to the maldigestion of food, malabsorption of nutrients, and eventually signs and symptoms of malnutrition.

Chronic pancreatitis is the most common cause of EPI. Inflammation causes the pancreas to become damaged over time, reducing its ability to produce enzymes.

Other conditions disrupt pancreatic function in other ways, such as by blocking ducts that carry enzymes. Surgery on the pancreas can also lead to reduced function.

Conditions commonly associated with EPI include:

  • Chronic pancreatitis
  • Cystic fibrosis
  • Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
  • Celiac disease
  • Pancreatic cancer
  • Shwachman-Diamond syndrome (a rare, inherited condition marked by bone marrow dysfunction in children and can lead to pancreatic insufficiency.)
  • Hemochromatosis
  • Diabetes mellitus
  • Zollinger-Ellison syndrome (a rare condition marked by tumors called gastrinomas that form in the pancreas or the upper part of the small intestine. The tumors secrete the hormone gastrin, which causes an increase in gastric acid, leading to the formation of ulcers in the stomach and upper small intestine.)

People who have had gastrointestinal surgery, particularly weight-loss surgery that removes part of the stomach or intestine, may also be more likely to develop EPI.

It's not clear why some people with these conditions develop EPI and others do not. It's likely that there are many reasons a person develops EPI, including genetic and lifestyle factors. For example, excessive alcohol use can lead to inflammation of the pancreas, which in turn may make the pancreas less effective at producing enzymes, eventually leading to EPI.

The severity of EPI also depends on the underlying cause. Some people will only have mild EPI and may have few (if any) symptoms. Progression, severe symptoms, and consequences (such as nutritional deficiencies and weight loss) are more likely to occur when EPI is complicated by conditions like cystic fibrosis, inflammatory bowel disease, or cancer.


The exact number of people with EPI is not known. The condition is considered rare in the general population, but it may be under-diagnosed. People with mild symptoms may not seek medical treatment. Among those who do seek treatment, they may not be correctly diagnosed with EPI until the condition has become more advanced.

Particularly in the early stages, EPI may be misdiagnosed as a functional gastrointestinal disorder such as irritable bowel syndrome (IBS).

In people who already have a diagnosis of another condition of the gastrointestinal system, such as Crohn's, the symptoms may initially be attributed to that condition and treated accordingly. It may take many years for the symptoms of EPI to be correctly diagnosed, as it can take a long time for the pancreatic function to become so compromised that the body can no longer overcompensate.

A diagnosis of EPI is made after other more common causes of gastrointestinal symptoms have been ruled out. If your healthcare provider suspects you could have EPI, she will ask you questions and may order some tests to confirm the diagnosis.

Your practitioner will likely ask you questions about:

  • Your symptoms, including how long you've had them, and if there is anything that makes them better or worse (such as eating a meal or having a bowel movement)
  • Changes in your bowel habits, such as how often you have a bowel movement and the consistency, color, or odor of your stool
  • Lifestyle habits, such as how often you drink alcohol and whether you smoke or use tobacco products
  • Other medical conditions you have, the surgeries you've had, and your family's medical history
  • Medications you take, including those prescribed by a healthcare provider, purchased over-the-counter, or any supplements or herbal remedies
  • Your diet, including the types of food you eat and fluids you drink, when you usually eat meals, and any food intolerances, sensitivities, or allergies
  • Other topics such as exercise, social and work history, and mental health

After carefully reviewing your history, your healthcare provider may want to order tests. While there is no specific test for EPI, your practitioner can use different tests to rule out other conditions that could cause your symptoms.

Tests your healthcare provider might order to help diagnose EPI include:

  • Blood tests: If your practioner suspects EPI, she will want to test to see if you have any nutritional deficiencies. Blood tests can also be used to look for inflammation, blood sugar, pancreatic enzymes, or specific markers of conditions that are associated with EPI.
  • Stool tests: People with EPI often experience bowel symptoms that indicate their intestines cannot properly absorb certain nutrients, especially fat. Your healthcare provider may need you to collect samples of your stool which will be tested for the presence of unabsorbed fat, an enzyme called elastase, as well as blood or mucus. If you experience persistent diarrhea, your stool can also be tested for microorganisms that can cause infections.
  • Imaging tests: CT scans, ultrasounds, and MRIs can be used to help your practitioner see inside your abdomen and assess whether your pancreas is visibly damaged, obstructed, or inflamed. While there are a few highly specialized diagnostic imaging tests that can assess pancreatic function, these tests are mostly used to rule out other conditions that could explain a person's symptoms rather than specifically diagnose EPI.
  • Breath tests: Some people with EPI will also be found to have a condition called small intestine bacterial overgrowth (SIBO). Your healthcare provider may want to use a hydrogen breath test to detect SIBO; while the condition has a number of causes, it can also be an indicator of malabsorption. Other breath tests can also be used, such as those to assess bile salt and carbohydrate metabolism.

Your healthcare provider will also want to see how well your pancreas is working. There are two different types of pancreatic function tests that can be used: direct and indirect. Many of the tests indicated above, particularly those that examine stool, are examples of indirect testing of pancreatic function.

The most direct way to test pancreatic function and potentially detect exocrine dysfunction is through a special type of endoscopy.

For the test, the pancreas is stimulated with the hormones that signal it to produce digestive enzymes. Then, a tube will be placed in the small intestine to collect digestive secretions, which are then analyzed under a microscope to look for enzymes.

While the procedure can be very helpful, it is generally only performed at specialized hospitals or clinics. As it is not widely available and can be costly, it may not be accessible to all patients with suspected EPI.


If a healthcare provider suspects EPI, they may prescribe treatment with pancreatic enzyme replacement therapy (PERT) and nutritional supplements such as vitamin B12 even before the diagnosis is confirmed. In fact, a good indicator a person has EPI is if their symptoms get better after they start taking oral enzymes, such as lipase, with meals.

Approved Medications

The Food and Drug Administration (FDA) has approved six medications for treating EPI. Each individual patient will need to work with a practitioner to establish a dosing schedule that takes into consideration any other medical problems they have, the extent of pancreatic function loss, and the severity of their symptoms.

While there are several different pancreatic enzyme replacement products (PERPs) they are not the same; each patient with EPI will need to find the PERP that works best for them.

Determining Dosing

Most patients begin PERT in divided doses at the beginning and in the middle of their meals. This dosing schedule helps recreate the normal secretion of digestive enzymes. People with EPI will need to be closely monitored by their healthcare provider and the dose of PERT they require may change over time.

Most patients taking PERT do no experience any serious side effects. Occasionally patients report some bloating and gas when they first begin taking the enzymes as their digestive system gets accustomed to them, though these side effects are usually mild.

When paired with lifestyle and dietary changes, as well as other nutritional supplementation to address deficiencies, many patients are able to effectively manage the symptoms of EPI.

Monitoring Changes

Immediate treatment for patients who have reduced pancreatic function is usually focused on restoring nutritional status and weight. Usually, patients are able to do this with the oversight of their healthcare provider and do not require hospitalization. However, if they are severely malnourished or unable to take food by mouth, they may need to be hospitalized for enteral nutrition (feeding tube) and intravenous (IV) hydration.

If you are diagnosed with EPI, your practitioner may also recommend dietary and lifestyle modifications, such as cutting back or quitting smoking or drinking alcohol, as these lifestyle choices can promote inflammation.

Long-term treatment goals for patients with EPI will be dependent on properly diagnosing and appropriately treating the underlying cause. Your healthcare provider may want to periodically test your pancreatic function. They will also continue to monitor your weight and nutritional status to ensure you are well-nourished and do not have any nutritional deficiencies.

Many patients with EPI are referred to the care of a nutritionist who can help them maintain a healthy weight and make dietary choices that won't exacerbate their symptoms.

Patients with underlying conditions such as celiac disease and diabetes may need to adhere to special diets.

In rare cases, people who have EPI and other medical conditions or complications may require surgery. Removal of part of the pancreas, for example, may be required in cases of pancreatic cancer or severe damage from chronic inflammation. However, this would be evaluated by a person's healthcare provider on a case-by-case basis.

A Word From Verywell

People with EPI often experience a range of symptoms related to specific nutritional deficiencies. When properly diagnosed, EPI can be treated with oral supplementation of the enzymes needed for digestion that the pancreas is no longer making. It's also important that any underlying or associated conditions are also diagnosed and appropriately treated. With pancreatic enzyme replacement therapy, dietary and lifestyle modifications, as well as ongoing monitoring for nutritional deficiencies and any need for supplementation, most people with EPI are able to effectively manage the condition.

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Additional Reading

By Abby Norman
Abby Norman is a freelance science writer and medical editor. She is also the author of "Ask Me About My Uterus: A Quest to Make Doctors Believe in Women's Pain."