Why Exocrine Pancreatic Insufficiency Is Frequently Underdiagnosed, With Andres Gelrud, MD

Exocrine pancreatic insufficiency (EPI) remains underdiagnosed and undertreated, but improving awareness could help address persistent gaps in clinical care.

Many clinicians and patients remain unaware of EPI’s strong association with diabetes and other pancreatic diseases, contributing to delays in diagnosis.

“Exocrine pancreatic insufficiency is a condition that is caused by multiple reasons, but mainly inadequate production of pancreatic enzymes,” said Andres Gelrud, MD, a gastroenterologist at Baptist Health Miami Cancer Institute, part of Baptist Health South Florida, in an interview with HCPLive. “It’s also defined as inadequate delivery or activity of the pancreatic enzymes needed for normal digestion, and here we’re talking about lipase, protease, and amylase.”

EPI results from inadequate secretion and/or delivery of pancreatic enzymes and bicarbonate into the duodenum, impairing normal digestion. Disruption of acinar cell function, reduced enzyme output, or ductal obstruction limits the availability of key digestive enzymes, including lipase, protease, and amylase. Lipase activity is typically affected earliest, leading to impaired fat digestion before carbohydrate and protein malabsorption. This progressive enzyme deficiency underlies the characteristic features of maldigestion and nutrient malabsorption seen in EPI.

The likelihood of developing EPI is increased in high-risk populations. Among patients with chronic pancreatitis, approximately 60%–90% develop EPI. Prevalence is also high in cystic fibrosis (~85%) and pancreatic cancer (66%–92%), with additional risk observed following pancreatic or bariatric surgery.

Symptoms of EPI are often nonspecific and overlap with other gastrointestinal conditions, including irritable bowel syndrome, inflammatory bowel disease, celiac disease, and small intestinal bacterial overgrowth. Despite this, fewer than 7% of patients with chronic pancreatitis or pancreatic cancer are tested for EPI. As a result, clinicians should remain alert to symptoms such as bloating, diarrhea, and unexplained weight loss.

“If the patient tells you that they have gas, bloating, soft bowel movements, but they’re losing weight, that weight loss should be a major red flag that something is going on,” Gelrud said.

Ruling out EPI in these cases is critical, particularly among patients who report planning meals around anticipated bowel movements. By the time classic symptoms such as steatorrhea emerge, severe pancreatic dysfunction, often reflecting up to 90% loss of exocrine function, may already be present.

To learn more about diagnostic tools for EPI, follow part 2 of this interview.

Editor’s Note: Gelrud reports no relevant disclosures.

References

1. de Rijk FEM, van Veldhuisen CL, Besselink MG, et al. Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: An international expert survey and case vignette study. Pancreatology. 2022;22(4):457-465. doi:https://doi.org/10.1016/j.pan.2022.03.013
2. Ghodeif AO, Azer SA. Pancreatic Insufficiency. PubMed. Published 2023. https://www.ncbi.nlm.nih.gov/books/NBK555926/

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