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Exocrine Pancreatic Insufficiency

Understanding Exocrine Pancreatic Insufficiency

By Rita Baron-Faust, MPH, CHES
Reviewed by Sanjai Sinha, M.D., F.A.C.P., Chief, Primary Care - Internal Medicine, U.S. Department of Veterans Affairs, Montrose, NY

Published: 03/01/2012

Take Note
• EPI may be a complication of pancreatitis, IBD, diabetes, autoimmune disease, or even surgical procedures.
• Activation of digestive enzymes within the pancreas itself may lead to autodigestion, tissue inflammation, and necrosis.

Exocrine pancreatic insufficiency (EPI), also referred to as pancreatic insufficiency, affects hundreds of thousands of people with associated diseases, such as cystic fibrosis (CF) and inflammatory bowel disease. Apart from its most frequent occurrence among children with CF, the disorder often goes unrecognized.

EPI is the inability of exocrine cells in the pancreas to produce enough digestive enzymes to allow for the proper digestion and absorption of nutrients in the intestines. It can lead to vitamin deficiency, growth retardation, bone loss, and non-specific GI symptoms such as weight loss, nausea, loss of appetite, steatorrhea (loose stools with unabsorbed fat), gas, or bloating.1

Those symptoms not only occur in children with CF and Shwachman-Diamond Syndrome (SDS) — the second most common cause of inherited EPI after CF1 — but EPI may also arise from chronic or acute pancreatitis, inflammatory bowel disease (IBD),2 diabetes,3 celiac disease or other autoimmune diseases,4,5 surgical procedures involving the pancreas, and, in rare cases, pancreatic cancer.1

"Diseases affecting either the pancreas or the small intestine can result in pancreatic insufficiency. This is because the intestine releases hormones that stimulate the pancreas in response to food, and activate proenzymes released by the pancreas," explains Tyler Stevens, MD, an assistant professor of medicine at the Cleveland Clinic Foundation. "Therefore, if there is a disorder affecting the proximal small intestine, such as celiac disease or Crohn's disease, and the disease is not controlled by medication or diet, it may not only affect intestinal absorption but also pancreatic secretion of digestive enzymes."

EPI may occur due to a physical blockage of pancreatic ducts, such as by mucus plugs in CF, exocrine cells that do not produce enough of the digestive enzyme trypsinogen for proper food breakdown due to pancreatitis, or generalized tissue damage from chronic immune attacks in type 1 diabetes.3 In some cases, the exact mechanisms are not well understood. The majority of cases of acute pancreatitis are due to alcoholism or gall bladder disease.1 Some studies also suggest that EPI may underlie diabetes.6

The end result is that key digestive enzymes and chemicals are either blocked or inhibited from reaching the duodenum (where they become activated for digestion) and instead become activated in the pancreas, possibly autodigesting and destroying the gland itself. The pancreatic enzyme trypsin "turns on the other pancreatic enzymes in the acinar cell and results in auto digestion of the gland, leakage of potent destructive enzymes into the surrounding tissue, severe inflammation, and necrosis," says Dr. Stevens.

If EPI is suspected, especially in people with longstanding type 1 diabetes, it can be diagnosed through noninvasive tests, which typically include testing stool for fecal elastase-1.1 Serum testing can also be done to measure reduced levels of trypsin. "The possibility of EPI should be considered in a patient with steatorrhea and weight loss. It should be especially considered in patients with a history of pancreatic problems like chronic pancreatitis, or risk factors for those diseases," Stevens adds.

However, outside of CF and SDS, tests for EPI are often done only when the disease becomes severe enough to generate symptoms.

Published: 03/01/2012

1. What is pancreatic insufficiency? Medline Plus. Accessed on 1/15/12 at: http://vsearch.nlm.nih.gov/vivisimo/cgi-bin/query-meta?v%3Aproject=medlineplus&;query=exocrine+pancreatic+insufficiency+&x=22&y=22
2. Navaneethan U, Shen B, Hepatopancreatobiliary Manifestations and Complications Associated with Inflammatory Bowel Disease. Inflamm Bowel Dis. 2010;16:1598-1619.
3. Hardt PD, Hauenschild A, Nalop J, et. al. High Prevalence of Exocrine Pancreatic Insufficiency in Diabetes mellitus. Pancreatology. 2003;3:395-402.
4. Leeds JS, Hopper AD, Hurlstone DP, et al. Is exocrine pancreatic insufficiency in adult coeliac disease a cause of persisting symptoms? Alimentary Pharmacology & Therapeutics. 2007;25:265-271.
5. Watts RA, Isenberg DA. Pancreatic disease in the autoimmune rheumatic disorders. Semin Arthritis Rheum. 1989;19:158-65.
6. Hardt PD, Ewald N, Exocrine pancreatic insufficiency in diabetes mellitus: a complication of diabetic neuropathy or a different type of diabetes? Exp Diabetes Res. 2011;2011:761950. Epub head of print.

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