Exocrine Pancreatic Insufficiency: What It Is and Who’s at Risk

You may know this about the relationship between the pancreas and diabetes: The pancreas makes insulin, the hormone that helps your body control its glucose levels. But this organ does more than that.

In addition to creating insulin, “the second important role for the pancreas has to do with digestion,” explains Darshan Kothari, MD, a gastroenterologist at Duke Health in Raleigh, North Carolina. “The pancreas assists digestion by secreting enzymes or chemicals that help you digest food.”

What is EPI?

Exocrine glands make substances that are released through tubes or ducts in your body, such as sweat, saliva, and tears, as well as the enzymes from your pancreas that help you digest your food. So, if you’ve been diagnosed with exocrine pancreatic insufficiency (EPI), your pancreas isn’t producing enough of these enzymes, and you can’t digest your food properly.

“It’s a relatively rare disorder,” Kothari says. “Over the last several years, there has been an increasing incidence of the disease. People are more inclined to test for, and therefore, diagnose and treat it. So, the incidence is rising, but it’s probably more likely diagnosis of people who have been living with vague symptoms for years.”

What Causes Exocrine Pancreatic Insufficiency?

Most often, EPI is caused by damage to the pancreas or by pancreatic disease.

“Pancreatic insufficiency generally presents in one of two ways," Kothari says. "The first way is patients who have known pancreatic disease, meaning that they’ve had a history of pancreatitis or a family history of pancreatitis, or [they] have a personal history or diagnosis of pancreatic cancer.” Other patients don’t have any diagnosis, but have EPI symptoms.

According to the National Institute of Diabetes and Digestive and Kidney Diseases, 30%-90% of people with chronic pancreatitis and 80%-90% of people with cystic fibrosis have problems with producing pancreatic enzymes.

Chronic pancreatitis happens when your pancreas has been inflamed for a long time. This can damage the organ and its ability to produce enzymes. Heavy alcohol use and smoking can cause chronic pancreatitis, but some types of it also run in families.

Cystic fibrosis is a genetic disorder. It causes your body to make a thick, sticky mucus that can block your organs, including the pancreas, keeping it from releasing enzymes. If you have cystic fibrosis, your doctor might want to test you for EPI. It’s especially important to get pancreas problems diagnosed in children because they need the right amount of nutrients and vitamins to grow.

Although diabetes is often listed as an EPI risk, Kothari says it depends on the type of diabetes you have:

Type 1 diabetes affects the pancreas directly. Studies have shown that pancreas in people with type 1 diabetes can become damaged and even shrink, making it harder for them to produce the digestive enzymes they need. This increases the risk of EPI.

Type 2 diabetes is more about your body not being able to use insulin properly, so it’s not really a pancreas problem. That said, people with type 2 diabetes still have a higher risk of EPI than someone who doesn’t have it, just not as high as those with type 1 diabetes.

Other health conditions that could cause problems with the enzymes and lead to EPI include:

Surgery on your stomach, pancreas, or gallbladder
Other disorders that affects your pancreas, such as Sjögren's syndrome or Shwachman-Diamond syndrome
Stomach ulcers
Untreated celiac disease
Inflammatory bowel disease

You’re also at risk if you smoke or drink alcohol.

If you’re on a low-fat diet for a pancreas-related condition, you might have EPI but no symptoms.

What Are the Symptoms of Exocrine Pancreatic Insufficiency?

Your pancreas makes enzymes that break down the fats, proteins, and starches you eat so your body can use them. If the organ can’t do its job, you can have digestive and other problems. You may not notice any symptoms at first. They may only become obvious once your pancreas gets so damaged that it stops working properly. Symptoms include:

Loss of appetite
Oily, greasy, watery, pale, or gray diarrhea, called steatorrhea (it can also be frothy or extremely foul smelling)
Weight loss
Fatigue
Stomach pain and cramps
Gas and bloating
Bone pain
Muscle loss
Muscle cramps
Brittle nails
Hair loss
Swelling in your lower legs
Skin that is pale, bruises easily, or gets rashes

Without treatment, EPI can make you malnourished — you won’t get enough important vitamins and nutrients from your diet. This can lead to other serious conditions, such as thinning bones (osteoporosis) or anemia (which means you don’t have enough red blood cells to carry oxygen).

You could have problems with walking and balance, as well as weakness or numbness in your hands and feet.

How Is EPI Diagnosed?

First, your doctor will ask about your medical history and the symptoms you have. They may ask you questions such as:

Do you have pain in your upper belly?
Have you had bad-smelling bowel movements that are oily and hard to flush down the toilet?
Do you have gas or diarrhea?
Have you lost weight?
Do you drink a lot of alcohol?
Do you smoke?
Do you have a family history of any of the conditions that can cause EPI, including pancreatitis?

The physical exam might include:

Looking for signs of weight loss or malnutrition
Checking to see if your belly is swollen
Listening to your abdominal sounds
Tapping on your belly to see if there’s any tenderness or pain

It can be hard to diagnose EPI because most of the symptoms could be caused by other health issues. Your doctor might test you for other diseases before diagnosing EPI.

First, you may need some blood tests to see if you’re getting enough vitamins and check your pancreatic health.

Stool tests

The 72-hour fecal fat test (also called a quantitative fecal fat test). You follow a specific diet that contains a lot of fat, and your stool is collected over the three days for testing.

Stool elastase test, also called fecal elastase-1 (FE-1) test. A common stool test that checks for levels of FE-1 in your stool. If you they are low, it could be a sign of EPI.

You may also need to get some tests that check to see if your pancreas is inflamed, including:

CT scan. This uses a powerful X-ray to make detailed pictures inside your body.

MRI. It uses strong magnets and radio waves to make pictures of organs and structures inside your body.

Endoscopic ultrasound. This test uses sound waves to take pictures inside your digestive system. The sound waves are sent out by a thin tube that your doctor places through your mouth into your digestive system.

Questions for Your Doctor

If you find out you’ve got EPI, you’ll probably have a lot of questions. You may want to start by asking your doctor:

What might have caused this?
What treatments do you recommend?
Do I need to follow a special diet?
Are there vitamins I should take?
Can I drink alcohol?
What can I do if I’m losing weight?

How Is Exocrine Pancreatic Insufficiency Treated?

Your doctor may recommend the following treatments for EPI:

Diet

Eating a healthy diet is the first place to start. While you might think you have to cut fat out of your diet, that’s not necessarily the case. As you start the enzyme therapy, you might want to eat a low-fat diet as you and your doctor adjust your medication to find the right doses. But once your correct dose is found, you should be able to eat what you like. Be careful though — spread the fats throughout the day, and don’t have them in just one big snack or meal. That would be harder for your body. A well-rounded diet would normally include grains, vegetables, fruits, proteins, and dairy.

Enzyme replacements

The main treatment for EPI is pancreatic enzyme replacement therapy (PERT). You take prescription pills that replace the enzymes your pancreas isn’t making.

“They’re formulated to supplement the body when the pancreas is not able to provide the amount of digestive support it needs,” Kothari says. “All of these formulations have the three major enzymes: lipase, amylase, and protease. There are different brands that are on the market, all of which are, for the most part, equally effective.”

You take these medications with meals, and the enzymes break down your food so you can more easily digest and absorb it. If you take them before you eat, the replacement enzymes may move through your stomach before your food gets there. If you take the pills after you eat, you may have the opposite problem. So, it’s important to take them at the right time.

There are five FDA-approved pancreatic enzyme products that are only available by prescription:

Creon
Pancreaze
Pertzye
Viokace
Zenpep

Don’t dissolve the pill in a liquid such as milk or take it with any over-the-counter stomach acid medicine that has calcium or magnesium. These products can break down the coating and enzymes in your pills.

The amount you take depends on your body weight. You’ll start with the lowest possible dosage and take more if you need it.

Acid reducers

You may also take drugs to lower stomach acid along with your PERT. Your doctor can prescribe these, and they’re also available over the counter. According to Kothari, these and antacids aren’t an EPI treatment but might be necessary if the enzymes you take don’t have a protective coating against your stomach acid. The antacids protect the medication from dissolving too soon. Other medicines that help with this include:

Proton pump inhibitors such as esomeprazole or omeprazole
H2 blockers such as cimetidine, famotidine, or ranitidine

Other medications

You may also need medicine to treat pain. If your doctor says it’s okay, you may take over-the-counter pain medicines such as acetaminophen (Tylenol) or ibuprofen (Advil, Motrin) on occasion.

If those don’t bring you relief, your doctor may prescribe stronger pain drugs, such as hydrocodone and oxycodone. Keep in mind that ibuprofen may lead to internal bleeding in the digestive tract, and drugs such as hydrocodone and oxycodone should be used with caution because of addiction potential.

Emotional stress can also trigger pancreas inflammation for some people. Tricyclic antidepressants such as amitriptyline or nortriptyline may help ease pain. Gabapentin (Gralise, Neurontin), a drug that helps control seizures, can also help fight EPI pain. Pregabalin (Lyrica), which is used to treat seizures and nerve pain, also shows promise.

Treating the Root Cause

While treating EPI, you’ll need treatment for the health problem that caused it.

Cystic fibrosis

Treatments include enzyme replacement therapy, but there are many other medications and therapies, too. These are just a few:

Bronchodilators, which open the bronchial tubes so you can breathe more easily
Aantibiotics to prevent or treat infections
Stool softeners, as constipation and blocked bowels are a strong risk
Acid-reducing medications if needed
Airway clearing therapy (techniques that make you cough up and clear the mucus in your lungs)

If you have cystic fibrosis and EPI, you may also get a specific type of diabetes called cystic fibrosis-related diabetes, or CFRD. Speak with your doctor about how best to keep your blood sugar levels under control, and take insulin or other medications if your doctor prescribes them.

Shwachman-Diamond syndrome

Along with the enzymes, someone with this syndrome may have:

Blood transfusions
Platelet transfusions
Granulocyte-colony stimulation factor (G-CSF) to boost the neutrophils, a type of white blood cell that fights infections
Stem cell transplant

Chronic pancreatitis

There are lifestyle changes you can make if you have chronic pancreatitis:

If you have alcoholic pancreatitis, it’s important to stop drinking. You may need to enter a treatment program or work with a counselor to stop.
If you smoke, stop it.
If there are stones blocking your ducts, your doctor can remove them.
If you have a systemic illness such as lupus or cystic fibrosis, treatment for the underlying condition may help the chronic pancreatitis.

Can Surgery Treat EPI?

Surgery might be an option to help manage EPI, but it’s not a cure, and it’s not for everyone.

“Surgery really is designed for two reasons,” Kothari says. “It’s either to remove [cancerous] tissue or [precancerous] tissue or to help promote adequate drainage of the pancreas.”

The surgery can open ducts that are clogged or blocked by gallstones, and decompression can widen a main pancreatic duct that’s too narrow.

“If you imagine that the pancreas looks like an ear of corn lying on its side in the middle of your abdomen, each of those kernels are sacks of enzymes,” Kothari says. “Each kernel is producing an enzyme and drains it into the middle stalk, and that stalk then connects to the small intestines. Sometimes, when you have pancreatitis, there can be inflammation that causes scarring of the stalk, and as a result, those enzymes are not able to get to the small intestines.”

Another option is to remove your pancreas and give you an autologous islet cell transplant. These are cells from your own body that make insulin. The doctor will get them into your body through a vein in your liver.

This surgery can ease severe chronic pancreatitis pain or prevent or ease diabetes caused by chronic pancreatitis. But it’s only used if other treatments haven’t worked.

If other treatments fail, the doctor might remove a portion of your pancreas, but this is usually a last resort.

Living With EPI

Living with EPI will take some lifestyle adjustments, but they’re important to help your body digest your food properly. Here are a few tips:

Eat small, frequent meals instead of the traditional three. A big meal might not be appealing if you have digestive troubles from EPI.
Speak with a dietitian who can help you choose the foods you enjoy that keep your energy level up and give you the nutrition you need.
Don’t drink or smoke. Alcohol can make it even harder for your body to absorb fat and may damage your pancreas over time. Alcoholism is one possible cause of EPI. Smoking can lead to calcium buildup in your pancreas.
Take vitamins as prescribed by your doctor. You may need to take vitamins A, D, E, and K to replace ones that you aren’t absorbing from your diet. EPI makes it hard for you to get the right nutrients because your body can’t break down your foods.
Be as physically active as you can. Physical activity can be gym exercise or sports, but it also can be dancing, walking, gardening — or anything that gets you moving.

What to expect

You can manage the symptoms of EPI by taking enzyme replacements and following an eating plan that gives you the right nutrition. Make sure you get the advice of a dietitian or nutritionist. One of your big challenges is to make sure you don’t lose weight.

Also, talk with your family and friends to get the support you need while you’re getting treatment. Ask your doctor about support groups, which let you talk to others who are going through the same things you are.

Getting support

You can find more information about pancreas problems by visiting the web site of the National Pancreas Foundation website. Kothari says, “It’s a great resource. They’ve got cookbooks. They’ve got animated patients. They’ve got videos. They’ve got patient registries, and they’ve got support.”

Depending on what disease you have that caused the EPI, you can visit their related associations or patient advocacy sites, such as the Cystic Fibrosis Foundation and the Shwachman-Diamond Syndrome Foundation.

Takeaways

Exocrine pancreatic insufficiency, or EPI, is a rare condition. But if you have it, you know it causes uncomfortable and sometimes painful symptoms. Your doctor might do tests to rule out other gastrointestinal conditions before diagnosing EPI, to make sure there isn’t another reason for your symptoms. If you do have EPI, it’s important to follow your treatment plan so you’re able to digest your food properly and get the vitamins and nutrients your body needs to stay healthy.

Exocrine Pancreatic Insufficiency FAQs

What foods should I avoid with EPI?

The most important thing to avoid if you have EPI is alcohol. If you’re having diarrhea or stomach pain, it’s a good idea to avoid eating foods that are very high in fat, such as sausages and pastries. But once your enzyme doses are regulated, you won’t need to avoid those all the time.

Can EPI affect the kidneys?

EPI itself doesn’t affect the kidneys, but the disease that caused the EPI might. That said, a recent study did find that people with EPI may be more at risk for developing kidney stones.

Can you live a long life with EPI?

How long someone with EPI lives depends on many things, including the disease that caused it. But if it’s just EPI, the answer depends on when and if it’s diagnosed, how much damage has been done (malnutrition, for example), and if you follow your treatment plan and take the medications as prescribed.

What Is Exocrine Pancreatic Insufficiency?