Diagnosing and Managing Exocrine Pancreatic Insufficiency, With Andres Gelrud, MD

To diagnose exocrine pancreatic insufficiency, clinicians should combine careful "detective work" on symptoms and risk factors with imaging and fecal elastase testing, while recognizing the test's limitations, especially with watery stools, and not relying on it in isolation.

"So making the diagnosis of EPI at the beginning can be very challenging... it's super important to do the detective work, look for risk factors... you really have to take your time if you want to make this diagnosis early," said Andres Gelrud, MD, a gastroenterologist at Baptist Health Miami Cancer Institute, part of Baptist Health South Florida, in an interview with HCPLive.

A fecal elastase-1 result below 200 µg/g is considered abnormal, with values below 100 µg/g indicating a high likelihood of EPI and levels between 100 and 200 µg/g considered indeterminate, though false positives are common when stool is watery or diluted, underscoring the need to interpret results in clinical context.¹

Once the diagnosis is made, clinicians should promptly initiate adequately dosed pancreatic enzyme replacement therapy taken with meals and evaluate for fat-soluble vitamin deficiencies, bone disease, and diabetes. Per the 2023 AGA Clinical Practice Update, PERT should be initiated at a minimum of 40,000 USP units of lipase per main meal in adults, with half that dose for snacks, adjusted based on meal size and fat content and taken during the meal — not before or after. For patients on non-enteric-coated preparations, concurrent H2 blocker or PPI therapy is recommended.² This combination both relieves malabsorptive symptoms and addresses the broader metabolic consequences of EPI.

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. This gap is significant given that EPI develops in approximately 20% of patients after acute pancreatitis, rising to 30% after severe episodes, and in 47–76% of those with autoimmune pancreatitis.³ As a result, clinicians should remain alert to symptoms such as bloating, diarrhea, and unexplained weight loss.

Monitoring after treatment initiation should focus on clinical response rather than repeat fecal elastase testing, which is not a reliable indicator of treatment efficacy. Per the AGA's Best Practice Advice, markers of successful PERT include reduction in steatorrhea and gastrointestinal symptoms, weight gain, improved muscle mass and function, and normalization of fat-soluble vitamin levels (A, D, E, and K). Baseline measurements of BMI, quality of life, and fat-soluble vitamins should be obtained at diagnosis, along with a baseline DEXA scan repeated every one to two years given EPI's association with metabolic bone disease.²

"Once we start to supplement the patient with pancreatic enzymes, you see that the symptoms very, very quickly start to resolve... as soon as you start to take the enzymes, the symptoms very, very fast start to improve," said Gelrud.

References

1. Whitcomb DC, Buchner AM, Forsmark CE. AGA clinical practice update on the epidemiology, evaluation, and management of exocrine pancreatic insufficiency: expert review. Gastroenterology. 2023;165(5):1292-1301. doi:10.1053/j.gastro.2023.07.007

2. Whitcomb DC, Buchner AM, Forsmark CE. AGA clinical practice update on the epidemiology, evaluation, and management of exocrine pancreatic insufficiency: expert review. Gastroenterology. 2023;165(5):1292-1301. doi:10.1053/j.gastro.2023.07.007

3. Capurso G, Traini M, Piciucchi M, Signoretti M, Arcidiacono PG. Exocrine pancreatic insufficiency: prevalence, diagnosis, and management. Clin Exp Gastroenterol. 2019;12:129-139. doi:10.2147/CEG.S168266