Rapid Review: Exocrine Pancreatic Insufficiency (EPI)

Medscape

17-07-2025

While historically underdiagnosed, increased awareness and improved diagnostic strategies for exocrine pancreatic insufficiency (EPI) have helped identify patients earlier, thus facilitating more effective management. However, despite advances in treatment modalities, patient outcomes vary considerably due to differences in individual physiology, adherence to treatment regimens, and concurrent health issues. Efforts to address these disparities focus increasingly on personalized medicine, emphasizing the integration of tailored nutritional strategies, patient education, and multidisciplinary care teams to improve patient outcomes comprehensively.
Recent guidelines advocate for the prompt initiation of PERT as soon as EPI is diagnosed. Additionally, a multidisciplinary evaluation to assess further nutritional needs and coordination with endocrinologists for the evaluation and treatment of diabetes is also warranted.
Untreated EPI can impair growth in pediatric patients, and is associated with a number of clinical symptoms including gastrointestinal effects, osteoporosis, sarcopenia, coagulopathy, neuropathy, and other sequelae related to nutrient deficiency.
Although other tests can help in certain cases, EPI can be sufficiently diagnosed with a validated pancreatic function test, and awaiting further confirmatory information such as severe clinical symptoms, positive imaging findings, or documented nutritional deficiencies is not necessary.
Learn more about management approaches for EPI.
Digestion of fat is a central function of the pancreas, with dysfunction causing deficiency in fat soluble essential vitamins. Although the American Gastroenterological Association (AGA) guidelines recommend a low-to-moderate-fat diet for patients with EPI, they specifically recommend against a very-low fat diet as this can exacerbate deficiencies. Further, meals should be more frequent and smaller, and vitamin and mineral deficiencies should be screened for at diagnosis and annually thereafter.
Learn more about diet in EPI.
Although fecal fat testing is considered the gold-standard for assessing fecal fat malabsorption, which is a measure of pancreatic dysfunction, it has low specificity for EPI since other diseases can present with steatorrhea. The AGA notes that fecal fat testing is 'rarely needed', it is burdensome (requires a 72 hour stool collection), and can only be done when the patient is on a high-fat diet. Additionally, fecal fat tests are known to be susceptible to false positive results in patients with diarrhea, which is a common symptom of EPI. The AGA recommends fecal elastase as the best test for initial screening, although fecal fat may be useful in cases with inconclusive clinical features and imaging.
Learn more about pancreatic function tests.
The AGA Clinical Practice Update emphasizes that while cross-sectional imaging — such as CT, MRI, and endoscopic ultrasound — cannot directly diagnose EPI, it plays an essential role in identifying benign and malignant pancreatic diseases that may underlie or contribute to exocrine insufficiency. Imaging can reveal features like advanced calcific chronic pancreatitis, ductal changes, or significant pancreatic atrophy, which correlate with the presence of EPI. However, moderate changes in imaging do not reliably correlate with EPI, and normal imaging is associated with its absence. Although advanced tools like secretin-enhanced MRCP or elastography show promise, current imaging lacks sufficient accuracy to predict EPI on its own. Therefore, imaging should be viewed as a complementary tool in the diagnostic process, providing context about pancreatic structure rather than functional status.
For dosing of PERT, the AGA has specific recommendations dependent on fat content of meals and current symptom profile, not imaging findings.
Learn more about the multidisciplinary workup for patients with EPI.
The latest AGA guidelines emphasize the importance of regular and comprehensive monitoring of nutritional status in all patients with EPI, including regular DEXA scans every 1-2 years. Additionally, baseline and periodic assessment of anthropometric indicators, biochemical markers, and clinical evaluation should be established.
DEXA scanning can help to detect sarcopenia, which is possible even in patients with obesity. It can be caused by the nutritional deficits seen in patients with EPI and is associated with increased adverse outcomes and physical disability. The AGA also notes that other muscle mass and function tests can be considered as well.
Learn more about the management of patients with EPI.