What is Pancreatic Insufficiency?

The pancreas is a soft, delicate organ found behind the lining of the abdomen on the back wall of your belly. It carries out two main jobs – endocrine and exocrine. Basically, it’s necessary for the breakdown, absorption, and processing of things we eat like sugars, fats, and proteins. Exocrine Pancreatic Insufficiency (EPI) is a condition where the pancreas doesn’t produce enough enzymes (such as lipase) required for digestion. This deficiency can be linked to various causes like improper stimulation of enzyme production, low release of enzymes by the pancreas cells, blockage of the pancreas duct, or incorrect mixing of the enzymes with food.

People with EPI can display a variety of symptoms including fatty stools (steatorrhea), excessive gas (flatulence), weight loss, and belly pain, which can vary in intensity and location. This health problem can lower the quality of life, leading to a higher risk of health issues resulting from malnutrition and changes in bone density and increased risk of muscle movement problems. Even though problems with the pancreas could impact both of its functions (endocrine and exocrine), when we say ‘pancreatic insufficiency,’ we usually mean exocrine deficiency. In this context, the focus is all on exocrine pancreatic insufficiency.

What Causes Pancreatic Insufficiency?

Exocrine pancreatic insufficiency, or EPI, is a condition where your pancreas can’t make or send out enough digestive enzymes to break down the food you eat. The leading causes of EPI are chronic pancreatitis, which typically affects adults, and cystic fibrosis, mostly affecting kids. However, other reasons like acute pancreatitis, pancreatic tumors, diabetes, celiac disease (an autoimmune disorder that affects absorption of nutrients), inflammatory bowel disease (like Crohn’s disease and ulcerative colitis), after weight loss surgery, HIV/AIDS, and certain genetic and congenital conditions can also cause EPI.

The TIGAR-O system was developed to classify the causes and risk factors of chronic pancreatitis, a prolonged state of inflammation in the pancreas, and EPI based on the following six groupings:

Toxic-metabolic causes, which include exposure to alcohol, tobacco smoking, high levels of calcium in the blood (hypercalcemia), high levels of fat in the blood (hyperlipidemia) and chronic kidney disease.
Idiopathic causes, which refer to EPI cases where the cause is unknown, account for almost a quarter of all EPI. Recent studies suggest these may be due to genetic defects.
Genetic defects that can cause EPI include mutations in theCFTR and SPINK1 genes and hereditary pancreatitis, a rare form of pancreatitis that runs in families.
Autoimmune causes include pancreatitis that occurs along with autoimmune disorders like Sjogren syndrome, primary biliary cirrhosis, and inflammatory bowel disease.
Recurrent and severe acute pancreatitis category takes into account cases caused by recurring pancreatitis (inflammation of the pancreas), and post-necrotic (tissue death), vascular diseases (diseases of the blood vessels), and effects from radiation exposure.
Obstructive causes are when the ducts in the pancreas, which transport digestive enzymes, become blocked. This can occur due to abnormal development of these ducts, dysfunction of Oddi’s sphincter (a ring of muscle regulating flow of pancreatic fluid), blockage by tumors, or scarring after an injury.

Drinking excessive alcohol is a well-known cause of chronic pancreatitis. In the US, heavy drinkers are three times more likely to develop chronic pancreatitis, and the risk is even higher for heavy drinkers who also smoke. Similarly, cystic fibrosis heavily impacts the pancreas, causing EPI in around 85% of patients, often detected soon after birth. Therefore, all patients, irrespective of age, should be tested for EPI. EPI could also occur in a small number of patients with celiac disease, but typically gets better once the disease is under control with a gluten-free diet.

EPI isn’t rare in inflammatory bowel disease. It could be due to the disease itself or the medications used to treat it. Both acute and chronic pancreatitis occur more frequently in patients with inflammatory bowel disease. EPI is also a recognized complication following weight loss (bariatric) surgery, hard to distinguish due to overlapping symptoms. As this surgery involves bypassing or removing a part of the digestive tract, the extent of nutrient malabsorption depends on the portion bypassed. EPI has been associated with HIV and is a significant cause of chronic diarrhea in HIV patients; therefore, those presenting with chronic diarrhea should be screened for EPI.

Risk Factors and Frequency for Pancreatic Insufficiency

The number of people with exocrine pancreatic insufficiency (EPI) isn’t definitely known. EPI can be caused by many things and its prevalence varies. For those diagnosed with chronic pancreatitis, 60% to 90% of them will have EPI within 10 to 12 years. Chronic pancreatitis is the most common disorder that leads to pancreatic insufficiency and affects between 42 to 73 people out of every 100,000 in the United States. In places like Japan, China, and India, the numbers range from 36 to 125 per 100,000.

In cases of acute pancreatitis, more than half (62%) of patients will have EPI, and this number goes down to 35% after some time.
EPI risk is higher if alcohol caused the pancreatitis, and double if the pancreatitis is severe.
Among diabetics, the prevalence of EPI is low and mostly mild to moderate. In studies, 13% of patients with diabetes had low FE-1, an indicator of EPI.
With Type 1 diabetes, 10% to 30% had severe EPI and 22% to 56% had moderate EPI.
In Type 2 diabetes, between 5% to 46% had EPI.
For 66% to 92% of people with advanced pancreatic cancer, EPI occurs.
EPI may affect between 14% and 74% of patients with irritable bowel disease.
Even after bariatric surgery and despite enzymatic and nutritional supplements, the risk of EPI remains high.
For patients with HIV/AIDS, the estimated percentage suffering from EPI is between 26% to 45%.

Signs and Symptoms of Pancreatic Insufficiency

Pancreatic insufficiency, a condition where the pancreas doesn’t generate enough digestive enzymes, can cause improper digestion and absorption of nutrients (a state known as steatorrhea). Combining this with low food intake, it puts people at a high risk of malnutrition. This condition can result in various noticeable symptoms which can badly affect a person’s quality of life and potentially lead to serious health complications. The signs of exocrine pancreatic insufficiency are not always specific, but include:

Steatorrhea (excessive fat in the stool)
Abdominal discomfort
Bloating
Weight loss

In addition to these symptoms, malnutrition, deficiencies in essential nutrients and vitamins, bone disease such as osteoporosis or osteomalacia, muscle spasms, lowered immune competence, and an increased risk of cardiovascular events may also occur.

Steatorrhea is one of the most common signs of pancreatic insufficiency. It’s defined as having more than 7 grams of fat per day in the stool, assuming a diet of 100 grams of fat per day. At least a 5% to 10% drop in levels of two digestive enzymes found in the pancreas (known as lipase and trypsin) indicate fat malabsorption. After bariatric surgery, some patients may show these symptoms combined with weight loss and difficulties with digestion and absorption of nutrients, making the diagnosis of exocrine pancreatic insufficiency more complex.

Testing for Pancreatic Insufficiency

Exocrine pancreatic insufficiency, or EPI, is a condition where the pancreas does not make enough enzymes to digest food properly. This condition can be mild, moderate, or severe. Mild EPI happens when there is less secretion of one or two enzymes, but the digestion process isn’t hugely affected. Moderate EPI is similar to the mild form but also includes impaired secretion of bicarbonate, which helps break down certain kinds of food. Severe EPI is when all of these signs are present along with steatorrhea, a condition where the body has trouble absorbing fat.

EPI can be suspected in patients based on their symptoms and medical history. However, the severity of the condition and its cause can also play a part. To confirm EPI, doctors would need to do lab tests and possibly medical imaging.

There are two kinds of tests: direct and indirect. Direct tests like the secretin-cholecystokinin stimulation test and endoscopic pancreatic function test are used to evaluate the pancreatic secretive function. They are very accurate, but are invasive, expensive, and take a long time that limit their use. Indirect tests involving stool, breath, and blood evaluate effects of EPI, are more feasible, less invasive and less expensive but less accurate.

The most reliable test for diagnosing EPI is the 72-hour fecal fat test, but is not commonly used due to the inconvenience for both patient and laboratory. Fecal elastase-1 (FE-1) is a preferred test as it’s reliable, less invasive and less time-consuming. However, it isn’t always accurate in patients with chronic pancreatitis or in patients who have had surgery on the pancreas.

Serum pancreatic enzymes are not considered a reliable tool to diagnose pancreatic insufficiency, but serum trypsinogen levels below 20 ng per milliliter could be a useful indicator for EPI. The endoscopic pancreatic function test (ePFT) measures the concentration of bicarbonate in the duodenum, it is a highly sensitive test and can be used to confirm EPI in borderline cases.

Breath tests are another possible method for diagnosing EPI. These measure the reaction of pancreatic lipase, an enzyme that helps digest fat. Tests for nutritional deficiencies like magnesium and vitamins A, E, D and K can also support the diagnosis and monitor the treatment. Finally, Secretin-stimulated magnetic resonance cholangiopancreatography (S-MRCP), a type of medical imaging of the pancreas, might be used as an indicator of pancreatic function, but its accuracy and supporting evidence in diagnosing EPI are still limited.

Treatment Options for Pancreatic Insufficiency

If you have exocrine pancreatic insufficiency (EPI), a condition where your pancreas can’t make enough digestive enzymes, the main goal of your treatment plan is to avoid complications from malnutrition and to improve your quality of life. This generally involves regularly checking your weight, body mass index, and various nutritional indicators like vitamin levels and measurements of body composition.

A key part of treatment for EPI is known as pancreatic enzyme replacement therapy. This involves taking supplements that contain lipase, amylase, and protease — the enzymes your pancreas isn’t producing enough of. These supplements help prevent malabsorption — when your body has trouble absorbing nutrients — and they help restore your normal digestive process.

The supplements are commonly given an ‘enteric coating’. This is a special coating that protects the enzymes from the acidic environment in your stomach, allowing them to dissolve more effectively in your duodenum (the first part of your small intestine) where it’s more alkaline (or less acidic). However, if you have reduced bicarbonate secretion — a condition where your body isn’t making enough alkaline substances — you may also need treatment to reduce the acidity in your stomach so that the enteric coating can dissolve.

How much of these supplements you need will depend on how severe your enzyme deficiency is and your individual needs. It’s important to note that taking higher doses of these supplements is not without its risks, so the lowest effective dose is typically used.

Beyond enzyme replacement therapy, you may also be advised to make certain lifestyle changes such as quitting smoking and avoiding alcohol. Dietary changes, such as eating small meals frequently and avoiding hard-to-digest foods can also be helpful in managing EPI. Plus, if required, your doctor might recommend supplements of vitamins that are soluble in fat.

You might also be advised to try to follow a normal diet as much as possible without restricting fat or very high-fiber foods. Referral to a dietitian may be recommended for reviewing your dietary history as well as educating and supporting you in managing your condition.

For patients with EPI due to cystic fibrosis (a genetic disorder that affects the lungs and digestive system), pancreatic enzyme replacement can be helpful, with the dose carefully increased based on energy needs.

There is also some evidence to suggest that enzyme replacement therapy can improve survival rates among pancreatic cancer patients. In addition, stem cell technology, which involves using pluripotent (developing into many types) stem cells to produce pancreatic exocrine cells (cells that release enzymes into the digestive system), is a promising area of research that’s currently being explored.

Exocrine pancreatic insufficiency, or EPI, can often fly under the radar due to its wide-ranging and non-specific symptoms. It’s easy to mistake these symptoms for other, more common stomach and digestive issues. To make an accurate diagnosis, medical professionals need to thoroughly review a patient’s medical history and perform specific tests.

Some diseases and conditions that might cause confusion when diagnosing EPI include:

Celiac disease, which also causes the body to improperly absorb nutrients
Inflammatory bowel disease and irritable bowel syndrome, both causing digestion problems
Microscopic colitis, a condition which causes episodes of watery diarrhea
Intestinal bacterial overgrowth, a condition where harmful bacteria grow out of control in the small intestine
Giardiasis, a small intestine infection that’s common in areas with poor sanitation

Besides the above-mentioned diseases, EPI symptoms could also mimic conditions like Biliary obstruction and Zollinger-Ellison syndrome, hence adding to the complexity of the diagnosis process.

What to expect with Pancreatic Insufficiency

The long-term outlook for patients with pancreatic insufficiency greatly depends on the correct care and regular monitoring. If not treated properly, there’s a risk of possibly serious complications. However, with appropriate treatment, patients can likely see a reduction in symptoms and experience a better quality of life.

Possible Complications When Diagnosed with Pancreatic Insufficiency

Patients with untreated exocrine pancreatic insufficiency are at risk for several complications. These are mainly related to improper fat absorption and malnutrition which can lower the patient’s quality of life. In fact, about 65% of patients diagnosed with chronic pancreatitis may experience weakened bones, known as osteoporosis or osteopenia. Persistent symptoms can lead to decreased work productivity and financial difficulties. Lastly, untreated cases can also potentially lead to more serious health problems and even life-threatening conditions such as malnutrition and heart complications.

Common Complications:

Improper fat absorption (malabsorption)
Malnutrition, leading to lowered quality of life
Osteoporosis or osteopenia in chronic pancreatitis patients
Persistent symptoms causing reduced work productivity and financial strain
Serious health problems due to untreated conditions
Potential life-threatening heart complications

Preventing Pancreatic Insufficiency

The best way to prevent problems from arising is to deal with the things that cause them, like treating pancreatitis (an inflammation of the pancreas) as soon as it appears, and intervening early on to treat any complications. It’s also crucial to teach people about how important it is to make some changes in their lifestyle. This includes eating healthily, avoiding alcohol, and quitting smoking.

Patients should also be made aware of the treatment options available to them and the need to keep an eye on their symptoms. Sometimes, the amount of medication someone needs may need to be adjusted based on how they are responding to the treatment, so it’s vital to keep track of any changes in symptoms.