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Is Exocrine Pancreatic Insufficiency Overlooked?

Is Exocrine Pancreatic Insufficiency Overlooked?
By Rita Baron-Faust, MPH
Reviewed by Sanjai Sinha, MD, FACP, Chief, Primary Care - Internal Medicine, US Department of Veterans Affairs, Montrose, NY

Published: 04/25/2012

Take Note
• Between 25% and 50% of patients with type 1 diabetes and as many as 35% of patients with type 2 diabetes may have EPI.
• As many as 20% of people with inflammatory bowel disease (IBD) also have pancreatic insufficiency.

Exocrine pancreatic insufficiency (EPI) is a common finding in cystic fibrosis (CF)—about 95% of CF patients have EPI—so CF specialists test for it and treat it.1 However, EPI is also comorbid to other diseases and is often overlooked, sometimes because the symptoms of EPI may be attributed to those diseases.

It is estimated that between 25% and 50% of patients with type 1 diabetes, and as many as 35% of patients with type 2 diabetes, may have EPI.2,3
Though EPI awareness has existed for decades, its links to diabetes have been overlooked in recent years and patients with diabetes are rarely tested for EPI. "The close relationship between diabetes and changes of the exocrine pancreas became less interesting and was more or less forgotten," remarks Philip D. Hardt, MD, professor of medicine and medical head of the interdisciplinary endoscopy unit at Giessen University Hospital in Germany, who has done extensive research into the links between diabetes and EPI.4

In addition to diabetes, it is estimated that as many as 20% of people with inflammatory bowel disease (IBD) as well as several other autoimmune diseases also have pancreatic insufficiency.5,6Many of the signs and symptoms of EPI—weight loss, nausea, loss of appetite, gas, bloating, steatorrhea, and even bone loss—can also occur in these other conditions, making it more difficult to diagnose EPI.6,7 "Pancreatic insufficiency and intestinal diseases may [share] similar symptoms," says Tyler Stevens, MD, assistant professor of medicine at The Cleveland Clinic.8Indeed, symptoms of EPI and IBD often overlap.9

Fat in the stool is often the first sign of EPI, and there are several fecal tests that can be done to detect this abnormality. These include testing for fecal fat, serum trypsin, and fecal elastase. High levels of fecal fat and low levels of trypsin and elastase are indicative of EPI.7

A trypsin/chymotrypsin fecal test is typically used in newborns and infants with cystic fibrosis and symptoms of EPI (such as steatorrhea, failure to thrive, and malnutrition), as well as in children or adults with diabetes or IBD, to determine if further testing is needed for pancreatic insufficiency.7Trypsinogen and chymotrypsinogen are secreted by the pancreas and sent to the small intestine, where mucosal enzymes convert them to their active forms to break down protein into peptides for digestion. If a patient's pancreas is normal, trypsin and chymotrypsin will be detectable in the small intestine and in the stool. If not, amounts will be low or nondetectable.

A separate blood test that looks for low levels of serum trypsinogen (immunoreactive trypsin) can also detect pancreatic insufficiency.7
If the diagnosis is still in question, further testing may include endoscopic ultrasound, hormone-stimulated pancreatic function tests, endoscopy, computed tomography, endoscopic retrograde cholangiopancreatography, or magnetic resonance cholangiopancreatography.8,10

For some patients with diabetes whose disease is caused by autoimmune pancreatitis, EPI may be controlled by steroids, notes Hardt.4 However, for most people, "If EPI is diagnosed, it should be treated using pancreatic enzyme supplementation," says Stevens.8

Published: 04/25/2012

1. MedLine Plus: Questions and Answers: Delayed-Release Pancreatic Enzyme Product Receives FDA Approval. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm149337.htm. Accessed January 15, 2012.
2. Hardt PD, et al. and the S2453112/S2453113 Study Group. High Prevalence of Exocrine Pancreatic Insufficiency in Diabetes Mellitus. A Multicenter Study Screening Fecal Elastase 1 Concentrations in 1,021 Diabetic Patients. Pancreatology. 2003;3:395-402.
3. Hardt PD, et al. Is Pancreatic Diabetes (Type 3c Diabetes) Underdiagnosed and Misdiagnosed? Diabetes Care. 2008;31(suppl 2):S165-S169.
4. E-mail interview with Philip D. Hardt, MD, January 27, 2012.
5. Barthet M, et al. Frequency and Characteristics of Pancreatitis in Patients With Inflammatory Bowel Disease.Pancreatology. 2006;6:464-471.
6. Watts RA, et al. Pancreatic Disease in the Autoimmune Rheumatic Disorders. Semin Arthritis Rheum. 1989;19:158-165.
7. American Association for Clinical Chemistry. Pancreatic Insufficiency. http://labtestsonline.org/understanding/conditions/pancreatic-insuf/. Accessed April 16, 2012.
8. E-mail interview with Tyler Stevens, MD, January 27, 2012.
9. Leeds JS, et al. Is Exocrine Pancreatic Insufficiency in Adult Coeliac Disease a Cause of Persisting Symptoms? Aliment Pharmacol Ther. 2007;25:265-271.
10. Stevens T, et al. Evaluation of Duct-Cell and Acinar-Cell Function and Endosonographic Abnormalities in Patients With Suspected Chronic Pancreatitis. Clin Gastroenterol Hepatol. 2009;7:114-119.

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