Exocrine Pancreatic Insufficiency: Symptoms and Testing

← Patient Education

Exocrine pancreatic insufficiency, often shortened to EPI, happens when the pancreas does not deliver enough of its digestive enzymes to the intestine, so food, especially fat, is not fully broken down and absorbed. The result can be greasy, oily, hard-to-flush stools, bloating and gas, weight loss, and low levels of certain vitamins. This page is for adults in Arlington, Annandale, and the rest of Northern Virginia who have one of the conditions that raise the risk of EPI, who have been told their stool test was low, or who are trying to make sense of stools that look and smell different than they used to. It explains what exocrine pancreatic insufficiency is, who gets it, how it is tested, and how it is treated, based on the American Gastroenterological Association's guidance.

This article is general education, not medical advice. It cannot tell you whether your own symptoms come from exocrine pancreatic insufficiency.

What exocrine pancreatic insufficiency is

The pancreas sits behind the stomach and has two separate jobs. Its "endocrine" job is making hormones such as insulin. Its "exocrine" job is making digestive enzymes: lipase to break down fat, proteases to break down protein, and amylase to break down starches. Those enzymes flow through the pancreatic duct into the duodenum, the first part of the small intestine, where they meet food.

In its 2023 Clinical Practice Update on exocrine pancreatic insufficiency, the American Gastroenterological Association (AGA) defines EPI as a failure of the pancreas to deliver a minimum level of specific digestive enzymes to the intestine. Without enough enzymes, nutrients are poorly digested, and over time that leads to shortfalls in fat, protein, and vitamins. The AGA also notes that EPI is frequently underdiagnosed, and that as a result many people are not treated appropriately.

EPI is different from pancreatitis, though the two are closely linked. Pancreatitis is inflammation of the pancreas. EPI is a loss of function, and long-standing inflammation is one of the main ways that function is lost. Our page on pancreatitis covers the inflammation itself.

Symptoms of exocrine pancreatic insufficiency

The AGA lists these clinical features of EPI:

• Steatorrhea, the medical word for fatty stool, with or without diarrhea. Stools may look pale, greasy, or oily, float, smell especially foul, or be hard to flush.
• Weight loss
• Bloating
• Excessive gas
• Low levels of fat-soluble vitamins, which are vitamins A, D, E, and K
• Protein-calorie malnutrition

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) describes the same picture in people with chronic pancreatitis: diarrhea, greasy, foul-smelling stools, and weight loss.

None of these symptoms is specific to EPI. Bloating and gas are far more often caused by other things, which our page on chronic bloating and gas covers. Fatty stools can also come from problems in the small intestine or with bile, not the pancreas. That overlap is why testing, not symptoms alone, is how the diagnosis is made.

Why weight loss and vitamin levels matter

Mild EPI can go unnoticed for a long time, because the body has some reserve and the stool changes come and go. The longer-term effects come from what is not being absorbed. NIDDK lists maldigestion, malnutrition, and thinning bones (osteopenia and osteoporosis) and fractures among the complications of chronic pancreatitis. The 2020 American College of Gastroenterology (ACG) guideline on chronic pancreatitis likewise names fat-soluble vitamin deficiency, malnutrition, and osteoporosis among the main outcomes of the disease. Unexplained weight loss always deserves a medical evaluation, whatever the cause; our page on unexplained weight loss explains how gastroenterologists approach it.

Who is at risk for exocrine pancreatic insufficiency

The AGA sorts the conditions linked to EPI into two groups.

High-risk conditions

The AGA says EPI should be suspected in people with:

• Chronic pancreatitis, where years of inflammation scar the gland. NIDDK names heavy alcohol use and inherited disorders of the pancreas as the most common causes of chronic pancreatitis.
• Relapsing acute pancreatitis, meaning repeated attacks. The ACG guideline notes that about 30% of people with recurrent acute pancreatitis go on to develop chronic pancreatitis.
• Pancreatic cancer (pancreatic ductal adenocarcinoma)
• Cystic fibrosis, an inherited condition that affects the pancreas from early life
• Previous pancreatic surgery, such as removal of part of the pancreas

Moderate-risk conditions

The AGA says EPI should be considered in people with:

• Diseases of the duodenum, including celiac disease and Crohn's disease
• Previous intestinal surgery
• Long-standing diabetes
• Conditions that cause the stomach to make too much acid, such as Zollinger-Ellison syndrome

Having one of these conditions does not mean a person has EPI. It means that if symptoms like fatty stools, weight loss, or low vitamin levels show up, EPI belongs on the list of possible causes.

How exocrine pancreatic insufficiency is diagnosed

Diagnosis usually starts with a conversation about symptoms and risk factors, then a stool test. The AGA's guidance on testing is specific, and it explains a few results that often confuse patients.

The fecal elastase test

Elastase is an enzyme the pancreas makes that passes through the gut largely intact, so the amount in a stool sample reflects how much the pancreas is producing. The AGA calls the fecal elastase test the most appropriate first test for EPI. It reads the results this way:

• Below 100 micrograms per gram of stool: good evidence of EPI
• 100 to 200 micrograms per gram: indeterminate, meaning the result does not settle the question

The AGA also states that the test can be done while a person is already taking pancreatic enzyme replacement, so there is no need to stop enzymes before the test. The test measures the body's own elastase, not the enzymes in the capsules.

Why watery stool can give a falsely low fecal elastase

The AGA states that the fecal elastase test must be done on a semi-solid or solid stool sample. A loose or watery sample can make the level look low when the pancreas is working normally. A 2024 commentary on the AGA update in Hepatobiliary Surgery and Nutrition makes the same point from practice: when the test is ordered for people whose history does not suggest a pancreas problem and whose pancreas imaging is normal, especially people with diarrhea, it produces many false positives. The authors describe patients with on-and-off diarrhea, no weight loss, and normal imaging whose elastase came back low and who did not have a pancreatic disorder.

This matters for anyone being evaluated for chronic diarrhea, and for people with diarrhea after gallbladder removal, where bile acids rather than the pancreas are often the cause. A single low elastase result from a loose sample is a reason to look at the whole picture, not proof of EPI. The same commentary also cautions in the other direction: in people very likely to have EPI, such as after major pancreatic surgery, a normal result can be a false negative.

Fecal fat testing

Fecal fat testing measures how much fat is lost in the stool. MedlinePlus describes the full version: collecting all stool for 24 hours, or sometimes 3 days, while eating a set amount of fat each day. The AGA says this test is rarely needed, must be done on a high-fat diet, and that the quantitative version is generally not practical for routine care.

Tests that cannot diagnose EPI on their own

• A trial of enzymes. The AGA states that whether symptoms improve on a trial of pancreatic enzymes is an unreliable way to diagnose EPI.
• Imaging. The AGA states that CT scans, MRI, and endoscopic ultrasound cannot identify EPI, although they play an important role in finding diseases of the pancreas such as chronic pancreatitis and cancer. The ACG guideline recommends CT or MRI as the first test to diagnose chronic pancreatitis itself. Our page on pancreatic cysts covers what imaging of the pancreas can show.
• Breath tests and direct pancreatic function tests. The AGA says these hold promise but are not widely available in the United States.

Other causes to rule out

Fatty stools and weight loss have other causes, and some overlap with EPI. Celiac disease can cause malabsorption on its own and also raises the chance of EPI. The 2024 commentary notes that small intestinal bacterial overgrowth (SIBO) is common in people with chronic pancreatitis and after pancreatic surgery, and should be looked for when symptoms do not improve on enzymes; our page on the SIBO breath test explains that test. Lactose intolerance and microscopic colitis cause diarrhea without the pancreas being involved.

How exocrine pancreatic insufficiency is treated

The AGA states that once EPI is diagnosed, treatment with pancreatic enzyme replacement therapy, called PERT, is required. Left untreated, it says, EPI leads to complications from fat malabsorption and malnutrition and harms quality of life. The ACG chronic pancreatitis guideline also suggests enzyme replacement for people with chronic pancreatitis and EPI to improve the complications of malnutrition.

What pancreatic enzyme replacement is

PERT is a prescription medicine, usually a capsule, that contains the same three kinds of enzymes the pancreas makes: lipase, protease, and amylase. The AGA notes that all of the products are made from pig (porcine) pancreas and that they work equally well at equivalent doses. Some products are not enteric-coated, meaning they lack the coating that protects them from stomach acid, and the AGA says those need to be taken with an acid-reducing medicine. People who avoid pork for religious or other reasons, or who have had a reaction to pork proteins, should raise it with their doctor before starting.

Enzyme replacement is not the same as the digestive enzyme supplements sold over the counter. Talk with your doctor before substituting one for the other.

How enzyme replacement is taken

• With food, every time. The AGA says PERT should be taken during the meal, with a smaller dose for snacks. Enzymes taken on an empty stomach have no food to work on.
• Dose is set by your doctor. The AGA gives a starting dose based on lipase units and says it can then be adjusted to meal size and fat content. Your gastroenterologist will set and adjust your own dose. Do not change it on your own.
• Swallowed whole. The prescribing information for one widely used product, Creon on DailyMed, says not to crush or chew the capsules or hold them in the mouth, which can irritate the mouth and change how the medicine works. For people who have trouble swallowing capsules, the label describes opening them and sprinkling the contents on a small amount of acidic soft food such as applesauce.

Side effects and safety

The same label lists the warnings for this class of medicine. Fibrosing colonopathy, a rare and serious narrowing of the colon, has been reported with high doses, usually over long periods and most often in children with cystic fibrosis. High doses have also been linked to raised uric acid, so people with gout or kidney disease may need monitoring. Because the enzymes come from pig pancreas, the label notes that the presence of pig viruses that could infect people cannot be completely ruled out. These are reasons to take enzymes as prescribed and keep follow-up visits, not reasons to avoid a needed treatment.

Diet and vitamins with exocrine pancreatic insufficiency

Many people assume they should cut fat to the bone. The AGA advises against that. It recommends a low-to-moderate fat diet with frequent, smaller meals, and specifically says to avoid very-low-fat diets, which make it harder to get enough calories and fat-soluble vitamins. It also says routine supplementation and monitoring of fat-soluble vitamin levels are appropriate. A registered dietitian can help with meal planning; ask your doctor for a referral if you want one.

For people whose EPI comes from chronic pancreatitis, the ACG guideline recommends stopping alcohol and stopping smoking. NIDDK notes that some people with chronic pancreatitis also need vitamin B12 shots, and that chronic pancreatitis can cause diabetes, which needs its own care plan.

Monitoring exocrine pancreatic insufficiency over time

The AGA describes how to tell whether treatment is working: less fatty stool and fewer digestive symptoms, gain in weight, muscle mass, and muscle strength, and improving vitamin levels. Because fecal elastase reflects the body's own enzymes, it does not change with treatment and is not used to adjust the dose.

For ongoing care, the AGA recommends baseline measures of nutrition, including body mass index, a quality-of-life measure, and fat-soluble vitamin levels. It also recommends a baseline bone density scan (a DEXA scan), repeated every 1 to 2 years, because poor fat and vitamin D absorption puts bones at risk.

If symptoms do not improve on enzymes, that is worth raising at your next visit rather than simply living with. The reasons can include the dose, how and when the capsules are taken, acid in the stomach, or a second condition such as SIBO.

When to seek care

EPI itself develops slowly and is not an emergency. Some of the conditions behind it are. Based on NIDDK's guidance on pancreatitis, seek care right away for:

• Severe belly pain, or belly pain that keeps getting worse
• Nausea and vomiting with belly pain
• Fever or chills, a fast heartbeat, or shortness of breath
• Yellowing of the skin or the whites of the eyes

Call 911 for severe symptoms. Make a prompt appointment, rather than waiting, for weight loss you cannot explain, stools that have changed for more than a few weeks, or new diabetes alongside digestive symptoms. Our guide to when to see a gastroenterologist covers other symptoms worth a visit.

Preparing for a visit about exocrine pancreatic insufficiency

The visit goes further when you bring:

• Any earlier stool test results, including fecal elastase, and whether the sample was formed or loose
• Imaging reports of the pancreas, and records of any pancreatic or intestinal surgery
• A history of pancreatitis attacks, cystic fibrosis, celiac disease, Crohn's disease, or diabetes
• A list of every medicine and supplement you take, including any enzymes, acid reducers, and vitamins
• A short record of your stools, weight changes, and how symptoms relate to meals
• Your alcohol and tobacco use, described plainly; it helps your doctor and is not a judgment

Our page on what to expect at your first gastroenterologist visit covers the rest.

Care for exocrine pancreatic insufficiency at GC of NoVA

Gastroenterology Center of Northern Virginia sees adults across Arlington, Annandale, and the surrounding communities who have symptoms of exocrine pancreatic insufficiency, a low stool elastase result, or a condition such as chronic pancreatitis that raises the risk. Our five gastroenterologists review earlier tests, look at whether a stool result fits the rest of the picture, consider other causes of malabsorption, and, when EPI is confirmed, work with you on enzyme treatment, nutrition, and follow-up.

We see patients at our Arlington office at 1715 N George Mason Drive, adjacent to VHC Health, and our Annandale office at 3299 Woodburn Road in the Woodburn Medical complex. To schedule a visit, call Arlington at (703) 522-7476 or Annandale at (703) 560-6106, or learn more at gcofnova.com.

This article is for general education and is not medical advice. Talk with a qualified gastroenterologist about your symptoms, diagnosis, and treatment options.