Karen Bailey
There has been a recent update to the interpretation guidelines for canine serum Trypsin-Like Immunoreactivity (TLI).
TLI is the test of choice for Exocrine Pancreatic Insufficiency (EPI) in dogs. EPI occurs when there is inadequate synthesis and secretion of digestive enzymes by pancreatic acinar tissue, though clinical signs (polyphagia, weight loss, voluminous pale faeces etc.) may not be seen until exocrine secretory capacity is less than about 15% of normal.
There are several causes of EPI, with pancreatic acinar atrophy the most common in German Shepherds and Rough Coated Collies, breeds particularly prone to this condition. In other dog breeds and also in cats, chronic pancreatitis is the most common cause. Heritability, likely polygenic, has been demonstrated in German Shepherds, with signs most commonly becoming apparent between the ages of 6 months and 6 years. Reduced serum TLI concentrations may precede the onset of clinical disease.
Trypsinogen is made exclusively by acinar cells in the pancreas. Measurement of this zymogen (inactive precursor of pancreatic protease, in this case trypsin) provides a good index of pancreatic function. The TLI test detects both trypsinogen and trypsin so “trypsin-like” is used in its name, but the active form, trypsin, is only found in serum when there is pancreatic inflammation.
Serum TLI is stable in serum, so samples do not need to be frozen/kept on ice for shipping. Oral pancreatic extract supplementation does not affect serum TLI so if supplementation has already started there is no need to stop this before testing.
Recent work at the Gastrointestinal Laboratory (GI Lab) at Texas A & M University identified that some dogs, with TLI results within the existing reference interval, had signs that could not be attributed to another cause and they responded clinically to enzyme supplementation. An assay shift was suspected. Testing of 100 healthy dogs supported this, resulting in a changed reference interval. It is not known exactly when this assay shift occurred. While further studies are underway to refine the clinical cut offs, provisional changes in diagnostic thresholds and recommendations have been instituted.
Results <2.5 ng/mL are still diagnostic for EPI. Results 2.6 – 10 ng/mL are equivocal. However, based on historical information from 500,000 dogs, EPI is considered likely in symptomatic patients if the result is <7.5 ng/mL, so a trial of supplementation could be considered. Results 10-50 ng/mL are considered normal. Results >50 ng/mL raise concern for pancreatitis unless a canine pancreatic lipase (cPL) test is normal.
The test used at GI Lab is the same as that used at Gribbles in New Zealand so, while we await the results of the prospective studies, we too have adopted these new provisional guidelines, which you may have noticed in recent reports since 24 October 2023 (see below*):
Old interpretation guidelines for canine TLI:
<2.5 ng/mL indicative of EPI
2.5 – 5.0 ng/mL suspicious result, · advise retesting in 4 weeks
5.0 – 35.0 ng/mL normal, not EPI
>35 ng/mL may occur with pancreatitis.
New interpretation guidelines for canine TLI:
<2.5 ng/mL diagnostic for EPI
2.6 – 7.5 ng/mL* subnormal cTLI concentration, highly suggestive of EPI. Assess response to pancreatic enzyme replacement therapy to confirm diagnosis
7.6 – 10.0 ng/mL* 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 – 50.0 ng/mL* result is within the reference interval
>50 ng/mL* 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.
Comments:
Elevations sometimes occur in postprandial samples. Food should be withdrawn for at least 12-15 hours before sampling. Concurrent active pancreatitis may also elevate TLI levels.
Please be aware of this change when comparing current and historical results.
Summary:
Using the updated guidelines, some dogs previously classified as having suspicious or low normal results (i.e. <10 ng/mL) may warrant re-evaluation, especially if clinical signs remain supportive of EPI.
Photo credit: Kinshik Bose, UnSplash