Faecal Elastase

Pancreatic elastase-1 is a proteolytic enzyme secreted by pancreatic acinar cells that passes through the gut almost intact and is not broken down by intestinal bacteria. Its concentration in stool therefore mirrors pancreatic exocrine output. It is measured in a single stool sample by monoclonal ELISA, which is specific for human elastase and unaffected by pancreatic enzyme replacement, and reported in microg of elastase/g of stool (microg/g).

The test is a non-invasive screen for exocrine pancreatic insufficiency (EPI). It is used in patients with steatorrhoea, weight loss or unexplained chronic diarrhoea, and in those at risk, such as chronic pancreatitis, cystic fibrosis and after pancreatic surgery. It replaces the 72-hour faecal fat collection and invasive secretin tests in most practice.

Chronic pancreatitis has an incidence of about 5 to 12 per 100 000 people a year, and EPI develops in most patients within 10 to 20 years of onset. Exocrine failure occurs in over 85% of cystic fibrosis patients, in up to 30 to 50% of those with type 1 diabetes, and in a third or more of those with advanced coeliac disease and untreated pancreatic cancer.

Indications. Chronic diarrhoea with steatorrhoea (pale, bulky, offensive, floating stools), unexplained weight loss, deficiency of fat soluble vitamins, chronic pancreatitis, cystic fibrosis, pancreatic cancer, after pancreatic or gastric surgery, long standing diabetes with gut symptoms, and monitoring of pancreatic function in children.

Specimen. A single formed or semi-formed random stool, about 5 g, collected in a clean container. Watery stool dilutes the enzyme and gives falsely low results, so the test is repeated on formed stool when possible. The sample is stable for several days at room temperature and longer when frozen.

Reference values.

• Over 200 microg/g: normal exocrine function.
• 100 to 200 microg/g: mild to moderate insufficiency, or borderline and often a false positive.
• Under 100 microg/g: severe exocrine insufficiency.

Diagnostic accuracy. At a cut off of 200 microg/g, sensitivity is about 90 to 100% in severe EPI, 60 to 70% in moderate EPI and only 30 to 60% in mild disease. Specificity is 80 to 90%, lower in watery stool and in non-pancreatic diarrhoea. A value under 100 microg/g has a high positive predictive value for pancreatic disease.

Clinical use.

• Under 100 microg/g with steatorrhoea: EPI is likely, and enzyme replacement is started.
• 100 to 200 microg/g: repeat on formed stool, and weigh the symptoms. A short course of enzymes can be used.
• Over 200 microg/g with persistent steatorrhoea: look for other causes, such as coeliac disease, bile acid malabsorption, small bowel bacterial overgrowth and giardiasis.
• Values fall with disease progression in chronic pancreatitis, and track pancreatic reserve in cystic fibrosis.

Causes of low faecal elastase.

• Pancreatic: chronic pancreatitis (alcohol, genetic, autoimmune), cystic fibrosis, pancreatic cancer, severe acute pancreatitis, pancreatic resection, and haemochromatosis.
• Pancreatic duct obstruction: tumour, stricture, and ampullary disease.
• Extrapancreatic: advanced coeliac disease, Crohn disease, diabetes mellitus (types 1 and 2), Shwachman-Diamond syndrome, and Johanson-Blizzard syndrome.
• False low: watery diarrhoea (dilution), and delay or poor storage of the sample.

Pancreatic enzyme replacement. Does not interfere with the test, because porcine enzymes are not detected by the human specific assay. The test is not used to monitor dosing.

Critical values and findings needing immediate action.

• Faecal elastase under 100 microg/g with marked weight loss, fat soluble vitamin deficiency (night blindness, bleeding, bone pain) or hypoalbuminaemia: nutritional support and enzyme replacement.
• Low elastase with new jaundice, back pain and weight loss in an older adult: imaging for pancreatic cancer.
• A low value in an infant with failure to thrive and recurrent chest infection: sweat chloride testing and cystic fibrosis assessment.

Interferences and pitfalls.

• Watery stool is the main cause of a false low result. A repeat on formed stool is needed when the first sample is liquid.
• Mild EPI is easily missed, and a normal result does not exclude it.
• It does not diagnose the cause, and imaging is needed.
• The test does not measure fat digestion, and clinical response to enzymes matters.
• Elastase can be low in non-pancreatic conditions, which lowers specificity in a low prevalence population.
• Do not use the test within days of acute pancreatitis, since values may be transiently low.
• It does not detect isolated lipase deficiency.

Special groups.

• Newborns: low values on the first days of life normalise by 2 to 4 weeks, and a persistent low value suggests cystic fibrosis or a syndromic cause.
• Children with cystic fibrosis: a value under 200 microg/g marks pancreatic insufficiency, and it is checked yearly in those who are pancreatic sufficient.
• Older adults: values may fall modestly, and chronic diarrhoea has many causes.
• Pregnancy: no major change.
• Regions: untreated malabsorption from tropical sprue or severe malnutrition can lower the result, and the test is repeated after nutritional recovery.

Follow up tests. Repeat on formed stool, faecal fat estimation, serum fat soluble vitamins (A, D, E and the prothrombin time), CT or MRI pancreas with MRCP, endoscopic ultrasound, sweat chloride and CFTR genotyping, coeliac serology, HbA1c, IgG4 for autoimmune pancreatitis, a short course of pancreatic enzyme therapy, and genetic testing (PRSS1, SPINK1, CFTR, CTRC) in early onset pancreatitis.