Busting Some Popular Myths About Exocrine Pancreatic Insufficiency

David A. Johnson, MD


August 19, 2019

When it comes to exocrine pancreatic insufficiency (EPI), we could be doing a lot better. In many cases, EPI is not readily apparent, and diagnostic tests can be misapplied. This leads to invariable delays in its appropriate treatment, to say nothing of the many instances where patients never receive such care.

A good first step toward addressing these limitations would be taking what we think we know about EPI—more often grounded in myth than fact—and throwing it out the window. Therefore, in the interest of better serving our patients, let's bust some of the most popular myths about EPI.

Myth: All Patients With EPI Are Symptomatic and Always Have Abnormal Bowel Movements

Although most patients with EPI will have symptoms, some with mild EPI may be asymptomatic (or perhaps experience only mild bloating) and have normal bowel movements. It is claimed that classic recognizable steatorrhea does not occur until more than 90% of exocrine function is lost, yet a recent expert opinion[1] suggests a more graded response.

Myth: EPI Is Associated Only With Diseases or Surgeries Causing Direct Injury to the Pancreas

EPI is classically associated with such diseases as chronic pancreatitis and cystic fibrosis, or surgeries like pancreatic resection, yet other diseases and surgeries that alter pancreatic secretion can also cause it.[2] For example, proximal small-bowel mucosal disease (eg, untreated celiac sprue) reduces pancreatic secretion via an associated reduction in cholecystokinin release, resulting in EPI. Resolution should occur with avoidance of gluten and normalization of small-bowel mucosa. Gastric and small-intestinal resection can also lead to EPI by accelerating transits that reduce the surface area mucosal contact-mediated release of secretin or cholecystokinin-pancreozymin synthesis, with decreased mixing of chyme with pancreatic enzymes.

Myth: Diabetes Is a Result, Not a Cause, of EPI

Diminished pancreatic endocrine function is associated with loss of exocrine function, but diabetes can predispose someone to EPI.[3] Reduced levels of insulin, glucagon, and somatostatin (all with trophic effects on pancreatic acinar cells), as well as autoimmune pancreatic acinar destruction, may be causal.

Myth: Steatorrhea Is Typified by Foamy Stools That Float

Steatorrhea is actually best typified by loose, malodorous, "greasy" stools that stick to the toilet, similar to what is seen with melena.[4]

Myth: Fecal Pancreatic Elastase Testing Is Highly Sensitive but Variably Specific for Mild, Moderate, and Severe EPI

It's true that fecal elastase is the most sensitive indirect testing for EPI. However, for mild EPI, that sensitivity may be as low as 30%, compared with 100% for moderate or severe EPI.[1] Despite this, specificity remains high overall (93%).

Myth: Fecal Pancreatic Elastase Testing Should Not Be Performed on Solid Stool

Just the opposite is the case. Water from diarrhea or other malabsorptive or secretory conditions can dilute the enzyme. Although this can be potentially overcome with lypholization of a watery specimen,[5] it is recommended that this test be performed on solid, formed stool. Pancreatic enzymes do not have to be stopped when this test is done, because the porcine enzymes do not cross-react with the human fecal elastase antibody.[1]

Myth: EPI-Associated Vitamin Deficiency Only Relates to Fat-Soluble Vitamins

The fat-soluble vitamins (A, D, E, K) are subject to malabsorption.[6] More rarely though, vitamin B12 may be associated with deficient absorption due to an adverse associated change (lowered luminal pH caused by decreased pancreatic bicarbonate secretion), which can reduce the transfer of B12 from R protein to intrinsic factor.[7]

Myth: Fecal Chymotrypsin Testing Is a Reasonable Alternative to Fecal Elastase to Diagnose EPI

Low levels of fecal chymotrypsin, which is related to reduced pancreatic mass and secretion, have been used as a diagnostic test for EPI. But although this testing approach has good sensitivity for severe EPI, it is more variable for lesser degrees of this condition.[8] Fecal chymotrypsin testing is also not specific, because levels rise with acute pancreatitis and some other nonpancreatic diseases.

Myth: Once EPI Is Established, No Further Testing Is Warranted

Patients with causality from a clear disease history (eg, cystic fibrosis, chronic relapsing pancreatitis) may not need further imaging. However, most patients need to be evaluated for structural/neoplastic disease with imaging studies, including magnetic resonance cholangiopancreatography, pancreatic CT, and endoscopic ultrasound. Such evaluation is particularly important for patients with new-onset diabetes, steatorrhea, abdominal pain, anorexia, weight loss, or paraneoplastic manifestations of cancer (eg, hypercoagulable, altered sensory function).

Myth: Pancreatic Enzyme Replacements Should Be Taken Just Before Meals or Snacks

Among experts, there is very little consensus on meal-related timing. Although recent recommendations suggest that pancreatic enzyme replacements be taken at the onset of a meal, extending their ingestion throughout meals of longer duration is advisable to more physiologically mimic normal pancreatic secretion.[1] The recommended starting dose of lipase supplementation in adults is 50,000 units per meal and 25,000 units per snack.[1]

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