From the Guidelines
For suspected exocrine pancreatic insufficiency, fecal elastase-1 is the recommended first-line test due to its non-invasive nature and good sensitivity, as indicated by the most recent guidelines 1.
Evaluation of Pancreatic Function
The choice of test for evaluating pancreatic function depends on the specific concern, whether it be exocrine or endocrine pancreatic insufficiency.
- For exocrine pancreatic insufficiency, the focus is on the pancreas's ability to produce digestive enzymes.
- For endocrine pancreatic insufficiency, the focus is on the pancreas's ability to produce hormones like insulin and glucagon.
Exocrine Pancreatic Insufficiency (EPI) Evaluation
For EPI, the fecal elastase-1 (FE-1) test is recommended as the initial diagnostic test 1. This test is non-invasive, relatively inexpensive, and can distinguish between normal, moderate, and severe EPI.
- An FE-1 value of <200 mg/g of stool is considered abnormal, with levels <100 mg/g of stool more consistent with EPI.
- Some studies suggest that an FE-1 value of <50 mg/g is most reliable for severe EPI 1.
Other Diagnostic Tests
Other tests for evaluating pancreatic function include:
- The 72-hour fecal fat test, which remains the gold standard for diagnosing malabsorption, where fat excretion exceeding 7g/day confirms malabsorption.
- Serum tests like trypsinogen for diagnosing chronic pancreatitis, and amylase and lipase for acute pancreatitis.
- Imaging studies including CT, MRI, endoscopic ultrasound, and MRCP, which provide structural information that complements functional tests.
- The secretin stimulation test, which offers direct measurement of pancreatic secretory capacity but is invasive and not widely available.
Clinical Presentation Guidance
Test selection should be guided by clinical presentation, with consideration of the specific pancreatic function (exocrine vs. endocrine) being evaluated.
- For patients with high-risk clinical conditions such as chronic pancreatitis, relapsing acute pancreatitis, pancreatic ductal adenocarcinoma, cystic fibrosis, and previous pancreatic surgery, EPI should be suspected 1.
- For patients with moderate-risk clinical conditions, such as duodenal diseases, previous intestinal surgery, longstanding diabetes mellitus, and hyper-secretory states, EPI should be considered 1.
From the FDA Drug Label
The coefficient of nitrogen absorption (CNA) was determined by a 72-hour stool collection during both treatments, when nitrogen excretion was measured and nitrogen ingestion from a controlled diet was estimated The mean change in CFA from the run-in period to the end of the double-blind period in the CREON and placebo groups is shown in Table 3 Table 3: Change in Coefficient of Fat Absorption in Adults with Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis and Pancreatectomy (Study 4) CREON N = 24Placebo N = 28 CFA [%] Run-in Period (Mean, SD) 54 (19) 57 (21) End of Double-Blind Period (Mean, SD) 86 (6) 66 (20) Change in CFA * [%] Run-in Period to End of Double-Blind Period (Mean, SD) 32 (18) 9 (13) Treatment Difference (95% CI) 21 (14,28)
The pancreatic function evaluation can be assessed through the measurement of Coefficient of Nitrogen Absorption (CNA) and Coefficient of Fat Absorption (CFA).
- The CNA values were 86% with CREON treatment compared to 49% with placebo treatment in Study 1, and 80% with CREON treatment compared to 45% with placebo treatment in Study 2.
- The CFA values showed a mean change of 32% in the CREON group compared to 9% in the placebo group in Study 4. The treatment with pancrelipase (CREON) resulted in a significant improvement in CNA and CFA values compared to placebo, indicating an improvement in pancreatic function 2. Key points:
- CNA and CFA are used to evaluate pancreatic function
- CREON treatment improves CNA and CFA values
- Significant improvement in pancreatic function with CREON treatment compared to placebo 2
From the Research
Pancreatic Function Evaluation Methods
- Direct pancreatic function tests, such as the secretin-pancreozymin test and the Lundh test, are considered the best way to assess exocrine pancreatic function 3
- Indirect pancreatic function tests, including measurement of fecal elastase-1, the pancreolauryl test, and the BT-PABA test, are available for the assessment of pancreatic function 4
- Non-invasive pancreatic function tests, such as fecal chymotrypsin, NBT-PABA test, pancreolauryl test, and fecal elastase-1, have limited sensitivity in diagnosing mild to moderate exocrine pancreatic insufficiency 5
Diagnostic Validity of Non-Invasive Tests
- A meta-analysis of non-invasive pancreatic function tests found that none of the tests are sensitive enough to diagnose reliably a slight to moderate exocrine pancreatic insufficiency 5
- The sensitivity and specificity of non-invasive tests vary, with fecal elastase-1 showing a sensitivity of 54% and specificity of 79% in diagnosing exocrine pancreatic insufficiency 5
Role of Serum Pancreatic Enzymes
- Serum pancreatic enzyme determination is not useful in identifying patients with chronic pancreatitis or revealing the presence of exocrine pancreatic insufficiency 6
- Serum trypsinogen appears to be a useful marker in the diagnostic work-up of chronic pancreatitis, with a sensitivity of 28% and specificity of 100% 6
Clinical Practice
- No non-invasive test is routinely used in clinical practice to diagnose chronic pancreatitis due to their poor sensitivity in diagnosing mild pancreatic insufficiency 7
- The mixed triglyceride breath test may be useful in finding the correct dosage of enzyme substitutive therapy to prevent malnutrition in patients with known pancreatic insufficiency 7