Chronic pancreatitis includes a number of progressive inflammatory diseases, such as calcifying, chronic obstructive, and steroid-responsive or autoimmune chronic pancreatitis, which lead to pancreatic damage. At its later stages, chronic pancreatitis can result in pancreatic exocrine and endocrine insufficiency and diabetes. Treatment does not stop disease progression; it serves only to relieve pain and address complications. The pathogenesis of chronic pancreatitis is not fully understood, but episodes of acute pancreatitis are associated with the development of chronic pancreatitis. Alcohol use, smoking, and genetic factors also influence risk. Although late-stage chronic pancreatitis may be obvious, early-stage chronic pancreatitis presents a diagnostic challenge because pancreatic function may not yet be compromised, and the pancreas might appear normal on imaging. Definitive diagnosis requires a combination of diagnostic tools, such as clinical examination, imaging, endoscopic procedures, and laboratory tests of pancreatic function.
Quick Answers for Clinicians
Patients with chronic pancreatitis commonly report episodes of acute pancreatitis or epigastric pain that spreads to the back. At later stages, they may present with abdominal pain, exocrine insufficiency (often manifesting as steatorrhea), and diabetes (due to endocrine insufficiency). Pain is observed in up to 85% of patients. It may be years before exocrine insufficiency and diabetes develop in patients with chronic pancreatitis.
Indirect pancreatic function tests are typically used as part of chronic pancreatitis assessment. The fecal elastase-1 test is one of the primary tests used. Diarrheal specimens (watery stool) should be avoided for use in fecal elastase-1 testing because the enzyme in the sample will be diluted, potentially causing a false-positive test result. The 72-hour fecal fat, serum trypsin, lipase, and amylase tests may also be useful. In addition to indirect function tests, there are direct pancreatic function tests, but these are invasive tests that are neither widely available nor widely used. See Laboratory Testing. Imaging and/or endoscopic procedures are also important in the evaluation of suspected chronic pancreatitis and should be performed in conjunction with laboratory tests and clinical examination.
It was once thought that all patients with chronic pancreatitis were heavy alcohol users, but alcohol consumption is now understood as one risk factor among others, and accounts for only 44-65% of chronic pancreatitis cases. Smoking and alcohol use are both dose-dependent risk factors for chronic pancreatitis, but also work synergistically and together increase the risk of disease progression. Other risk factors for chronic pancreatitis include recurrent episodes of acute pancreatitis, severe necrotizing acute pancreatitis, obesity, diabetes, and long-term ductal obstruction. However, many patients have idiopathic chronic pancreatitis with no clear cause.
A number of genetic variants are associated with chronic pancreatitis, including variants in CFTR, CTRC, PRSS1, SPINK1, CASR, PRSS2, and CLDN2. Specific genetic variants can also increase the risk of secondary pancreatic cancer in patients with chronic pancreatitis. Genetic testing is indicated when the goal is to identify the etiology of chronic pancreatitis and to determine familial risk of the disease. See Genetic Testing.
Indications for Testing
Laboratory testing for chronic pancreatitis can be used to evaluate pancreatic function in patients with suspected chronic pancreatitis, uncover the genetic cause of hereditary or idiopathic pancreatitis, and monitor patients with an established diagnosis of chronic pancreatitis to guide treatment and assess treatment response.
Diagnosis of chronic pancreatitis is difficult early in the disease course, and the laboratory tests used for chronic pancreatitis have limited sensitivity for early-stage disease. No single test can be used for diagnosis. Instead, a combination of clinical examination, functional testing, and imaging is typically needed to make a diagnosis. Risk factor classification systems for chronic pancreatitis, which account for laboratory and nonlaboratory factors, may help clinicians determine when to proceed with testing. The American Pancreatic Association (APA) recommends that indirect pancreatic function tests be used along with imaging to rule out cancer.
Pancreatic Function Tests
Indirect Pancreatic Function Tests
Indirect tests of pancreatic function are used to detect steatorrhea, to assess the extent of exocrine and endocrine insufficiency, and to assist in the diagnosis of chronic pancreatitis. The tests are discussed in more detail below.
The fecal elastase-1 test is a primary test for chronic pancreatitis and measures fecal elastase-1, a pancreatic-specific enzyme and a marker of pancreatic exocrine function. Concentrations <200 µg/g suggest exocrine insufficiency, although levels can be falsely low in patients with diarrhea because the enzyme will be diluted in specimens. For that reason, watery stool samples should be avoided. The monoclonal assay is considered to be better standardized than the polyclonal assay.
A 72-hour fecal fat test, although difficult to perform and not widely available, can be useful in conjunction with other findings when performed appropriately and when small bowel bacterial overgrowth, celiac disease, and inflammatory bowel disease have been ruled out. Values of ≥7 g fecal fat over 24 hours suggest pancreatic exocrine insufficiency.
Serum trypsin levels can also be used to assess pancreatic function; levels <20 ng/mL suggest steatorrhea with a pancreatic etiology.
Serum Lipase and Amylase
Serum lipase and amylase are used to assess pancreatic inflammation in episodes of acute pancreatitis and will be markedly elevated in that context. Serum lipase increases within 4-8 hours of acute pancreatitis onset and remains elevated for 8-14 days; amylase is initially elevated but returns to normal in 48-72 hours. Lipase and amylase also have potential as markers of pancreatic function, and low levels may indicate pancreatic exocrine insufficiency associated with chronic pancreatitis.
Direct Pancreatic Function Tests
Direct pancreatic function tests are invasive tests that involve the use of hormones (secretin or cholecystokinin) to stimulate the pancreas; duodenal contents are then aspirated for measurement of pancreatic enzyme levels and bicarbonate concentrations. However, these tests are not widely available. Like indirect tests, direct pancreatic function tests have lower sensitivity for early chronic pancreatitis than for later-stage disease.
A number of genetic aberrations are associated with chronic pancreatitis, including variants in CFTR, CTRC, PRSS1, and SPINK1. Additional variants (eg, in CASR, PRSS2, and CLDN2), have also been linked to chronic pancreatitis. CFTR variants are causal for cystic fibrosis, a disease associated with chronic pancreatitis, and coinheritance of SPINK1 and CFTR increases the risk of chronic pancreatitis. The CLDN2 gene variant is associated with an increased risk for alcohol-related pancreatitis, whereas other variants (eg, in PRSS1) increase the risk of secondary pancreatic cancer. Genetic testing can be used to determine a genetic cause of chronic pancreatitis. Familial testing may be appropriate in the case of a known familial mutation. Panel tests have been developed for multiple pancreatitis-associated genetic variants. Refer to the Pancreatitis Panel Test Fact Sheet for additional information.
Maldigestion in chronic pancreatitis can interfere with nutrient absorption, so in patients with an established diagnosis of chronic pancreatitis, baseline concentrations of fat-soluble vitamins (A, D, E, and K) should be determined, and bone density should be assessed. Continued monitoring of fat-soluble vitamin levels (along with vitamin supplementation) is recommended in patients with pancreatic exocrine insufficiency who are undergoing treatment with pancreatic enzyme replacement therapy (PERT).
Fecal chymotrypsin and 72-hour fecal fat tests can be useful for therapeutic monitoring of patients receiving PERT. Some fecal elastase-1 tests use a monoclonal antibody that is specific for human elastase and will not cross-react with porcine enzymatic supplements used for PERT. For that reason, the fecal chymotrypsin test is preferred for therapeutic monitoring. Fasting hemoglobin A1c or glucose tolerance tests should be performed annually in patients with chronic pancreatitis to monitor for diabetes, which can result from pancreatic endocrine insufficiency.
Patients with chronic pancreatitis are at greater risk for pancreatic cancer. Weight loss, lingering abdominal pain, and functional decline should prompt further assessment for malignancy using imaging and cancer antigen (CA) 19-9 testing, for example. Patients with groove pancreatitis (pancreatitis that encompasses the pancreatic head, duodenum, and pancreaticoduodenal groove) may have increased CA 19-9 concentrations as a result of acute inflammation or biliary blockage. These patients may require further procedures, such as surgical resection, to rule out pancreatic adenocarcinoma.
ARUP Laboratory Tests
Use to test for exocrine pancreatic insufficiency
Quantitative Chemiluminescent Immunoassay (CLIA)
May be useful for establishing a diagnosis of pancreatic disease
Nuclear Magnetic Resonance Spectroscopy
May be useful to assess pancreatic function; lipase and amylase likely elevated in acute pancreatitis
May be useful to monitor pancreatic enzyme therapy
Preferred test for individuals with history of idiopathic pancreatitis
For additional test information, refer to the Pancreatitis Panel Test Fact Sheet.
Massively Parallel Sequencing/Sequencing
May be used to test for variants causative for mild cystic fibrosis in individuals with chronic pancreatitis
Massively Parallel Sequencing/Sequencing
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