Serum Trypsin-Like Immunoreactivity (TLI)

Control Ranges

Turnaround: 1-2 business days after receipt of samples.

Interpretation

In dogs, values below 2.5 µg/L are diagnostic for EPI. Values between 3.5 and 5.7 µg/L are rarely if ever associated with signs of EPI but may reflect subclinical pancreatic disease such as subtotal pancreatic acinar cell destruction secondary to on-going immune-mediated lymphocytic pancreatitis. Progression of the disease in such patients may ultimately lead to EPI. Values between 2.5 and 3.5 µg/L are sometimes (but rarely) associated with clinical signs due to EPI. In these cases the TLI assay should be repeated after one month paying particular attention to ensuring that food is withheld for 12 to 15 hours before the blood sample is collected.

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

Serum TLI values above 50.0 µg/L (dogs) and 100.0 µg/L (cats) are consistent 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 in some malnourished patients (dogs usually) without evidence of pancreatitis, and in some cats with patchy pancreatic hypertrophy/atrophy (generally considered to be a benign age-related change). Serum TLI is increased in approximately 30-40% of cats and dogs with pancreatitis; it is important to recognize that normal test results do not rule out the possibility of pancreatic inflammation. We believe that in acute pancreatitis testing of samples obtained as soon as possible after the onset of clinical signs is most likely to yield an abnormal test result. If pancreatitis is suspected, a PLI test should be performed. In cats increased serum TLI is often also observed with small intestinal disease. In these cases serum concentrations of cobalamin and folate should be determined for evaluation of the small intestine.

Sample

• 0.5 ml fasting (12-18 hours) non-hemolyzed serum for canines
• 0.2 ml fasting (12-18 hours) non-hemolyzed serum for felines

Stability

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

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.