Serum Trypsin-Like Immunoreactivity (TLI)

Reference Intervals

Canine 10.1 – >50 µg/L
Feline 12.0 – 82.0 µg/L

Turnaround: 2-3 business days after receipt of samples.


  • 0.5 ml fasting (8-12 hours) non-hemolyzed serum for canines
  • 0.2 ml fasting (8-12 hours) non-hemolyzed serum for felines


Canine trypsin-like immunoreactivity assay

IMPROTANT: new reference interval and decision thresholds 

The cTLI assay we use is a commercial assay made by Siemens that is widely used by veterinary laboratories world-wide. We recently became aware that there are dogs with a cTLI that is higher than the current cut-off value of ≤2.5 µg/L that appear to have exocrine pancreatic insufficiency (EPI). We gathered serum samples from more than 100 healthy dogs to determine whether maybe there has been an assay shift, which there does appear to be. Thus, we have adjusted our reference interval to 10.1 to >50.0 µg/L. Of course the more important question is what the cut-off value for diagnosing EPI in dogs should be. We have started a prospective observational study to determine the best cut-off value for the shifted assay. Until this study is completed, we have instituted provisional diagnostic thresholds and recommendations (see below). Values ≤2.5 µg/L are still considered to be diagnostic for EPI. Our recommendation for dogs with equivocal cTLI concentrations in the lower range (2.6 to 7.5 µg/L) is to initiate a trial with pancreatic enzyme replacement therapy and to closely monitor their response. Based on epidemiological data from more than 500,000 dogs we feel confident that these dogs likely have EPI. For dogs with equivocal cTLI concentrations in the higher range (7.6 to 10.0 µg/L), incorporate how well the dog’s clinical signs fit with EPI, whether other causes of these signs have been eliminated, and possibly the patient’s response to pancreatic enzyme replacement therapy.

Additionally, some healthy dogs have cTLI concentrations >50 µg/L but cTLI concentrations may also be increased in dogs with pancreatitis or renal insufficiency. Therefore, the clinical significance of a cTLI concentration >50.0 µg/L is uncertain. If you are concerned about pancreatitis consider running a cPLI test as this is more reliable for diagnosing this condition. In dogs without clinical signs of pancreatitis or with normal cPLI concentrations, a cTLI >50 µg/L is unlikely to be clinically important.

We will update you as soon as we have gathered enough prospective data to make more definitive recommendations. As always, we are available to consult on complex cases.

New cTLI interpretations:

0 to 2.5 µg/L Diagnostic for EPI
2.6 to 7.5 µg/L Subnormal cTLI concentration, highly suggestive of EPI. Assess response to pancreatic enzyme replacement therapy to confirm diagnosis.
7.6 to 10.0 µg/L Subnormal cTLI concentration, EPI cannot be excluded. If signs are consistent with EPI, consider assessing response to pancreatic enzyme replacement therapy to confirm diagnosis.
10.1 to 50.0 µg/L Result is within the reference interval.
>50.0 µg/L The clinical significance of a cTLI concentration >50.0 µg/L is uncertain. If you have also run a cPLI and this is within the reference interval pancreatitis is unlikely.

Feline trypsin-like immunoreactivity assay

In cats, values equal to or below 8.0 µg/L are diagnostic for EPI, with values between 8.0 and 12.0 µg/L being equivocal. For equivocal results, repeating the assay one month later should be considered.

Serum fTLI values above 100.0 µg/L may be associated with either acute or chronic pancreatitis or decreased renal excretion due to severe renal insufficiency, although our experience suggests that serum TLI is often minimally increased even in severe renal failure. Elevated serum TLI concentrations are also seen without any apparent reason in or in some cats with intestinal disease without apparent pancreatitis.

Because increased serum TLI concentrations are not specific for pancreatitis it is important to perform a PLI test before concluding a patient has pancreatitis. Serum TLI is increased in only approximately 30 to 40% of cats (and dogs) with pancreatitis. Therefore, normal test results do not rule out the possibility of pancreatic inflammation. If pancreatitis is suspected, a PLI test should be performed.

0 to 8 µg/L Diagnostic for exocrine pancreatic insufficiency (EPI).
8.1 to 12 µg/L Result is equivocal for exocrine pancreatic insufficiency.  TLI should be repeated in 1-2 months.  Ensure animal is fasted 12-18 hours before sample is taken.
12.1 to 81.9 µg/L Result is within the reference interval.
82 to 99.9 µg/L Mildly increased serum fTLI concentration. Consider measurement of serum fPLI concentration.
>100.0 µg/L Values of higher than 100 ug/L can be seen in cats with gastrointestinal disease, pancreatitis, and other conditions. A fPLI will allow for more specific assessment of your patient for pancreatitis. Also consider checking serum cobalamin and folate to assess small intestinal absorption.


Serum TLI is extremely stable and serum can be shipped at ambient temperatures.

Please see other assays’ stability and shipping recommendations if requesting additional testing in addition to TLI.

Background Information

Exocrine pancreatic insufficiency (EPI) occurs as a consequence of insufficient synthesis and secretion of digestive enzymes by the pancreatic acinar tissue. The functional reserve of the pancreas is considerable, however, and EPI only develops when the exocrine secretory capacity is reduced to less than 10 – 15% of normal. At this point residual pancreatic function together with extra-pancreatic mechanisms of digestion cannot support adequate nutrient digestion and so weight loss, diarrhea, and other clinical signs ensue.

Assay Principle

Small quantities of zymogens (inactive precursor molecules) of pancreatic proteases are present in the blood of normal animals. Trypsinogen is synthesized exclusively by the acinar cells of the pancreas, and measurement of this zymogen by assay of TLI provides an excellent indirect index of pancreatic function. This assay detects both trypsinogen and trypsin (hence the use of the term TLI to describe the total concentration of these two immunoreactive species), but the active enzyme (trypsin) is only present in the serum when there is pancreatic inflammation.

Special Considerations

Administration of oral pancreatic extracts does not affect serum TLI concentrations in either normal dogs or cats with EPI, so withdrawal of enzyme supplementation prior to testing of dogs and cats that are already receiving supplementation is unnecessary.

Additionally, assays of serum cobalamin (vitamin B12) and folate are strongly recommended whenever serum TLI is assayed. Serum vitamin abnormalities are common in dogs and especially cats with EPI. Therapeutic supplementation may be essential before an optimal response to enzyme supplementation is obtained.

Additional Reading

  1. Williams DA. The Pancreas. In: Strombeck DR, Guilford WG, Center SA, Williams DA, Meyer DJ, eds. Small Animal Gastroenterology. Philadelphia: W.B. Saunders 1996:381-410.
  2. Williams DA, Batt RM. Sensitivity and specificity of radioimmunoassay of serum trypsin-like immunoreactivity for the diagnosis of canine exocrine pancreatic insufficiency. J.Am.Vet.Med.Assoc. 1988;192:195-201.
  3. Steiner JM, Williams DA. Feline exocrine pancreatic disorders. The Veterinary Clinics of North America 1999;29:551-75.
  4. Steiner JM, Williams DA, Moeller EM, Melgarejo TL. Development and validation of an enzyme-linked immuno sorbent assay (ELISA) for feline trypsin-like immunoreactivity (fTLI). Am.J.Vet.Res. 2000;61:620-3.
  5. Bruner JM, Steiner JM, Williams DA, Van Alstine WG, Blevins W. High feline trypsin-like immunoreactivity in a cat with pancreatitis and hepatic lipidosis. J Am.Vet.Med.Assoc. 1997;210:1757-60.
  6. Parent C, Washabau RJ, Williams DA et al. Serum trypsin-like immunoreactivity, amylase and lipase in the diagnosis of feline acute pancreatitis. J.Vet.Int.Med. 1995;9:194 (abstr).
  7. Swift NC, Marks SL, MacLachlan NJ, Norris CR. Evaluation of serum feline trypsin-like immunoreactivity for the diagnosis of pancreatitis in cats. Journal of American Veterinary Medical Association 2000;217:37-42.
  8. Steiner JM, Williams DA. Disagrees with criteria for diagnosing pancreatitis in cats. J.Am.Vet.Med.Assoc. 2000;217:816-7.
  9. Steiner JM, Williams DA. Serum feline trypsin-like immunoreactivity in cats with exocrine pancreatic insufficiency. J.Vet.Intern.Med. 2000;14:627-9.