Do concurrent diseases affect pancreatitis testing results?

Two studies investigating risk factors for pancreatitis have documented an association between the presence of hyperadrenocorticism and the development of pancreatitis. One study was a retrospective case series of 101 dogs with the diagnosis of pancreatitis (37 of these were confirmed via laparotomy or necropsy) based on clinical signs and supporting laboratory findings (elevated amylase and lipase activities).1

This study showed that many dogs had coexisting diseases. Hyperadreno­corticism was also diagnosed in 12 of the dogs. The study population was composed mainly of older dogs, as the median age was 9 years. This would, of course, make hyperadrenocorticism more common, as it is mainly seen in geriatric patients. Since this study did not have a control group for disease, it is difficult to interpret this result, though it would suggest that hyperadrenocorticism was prevalent more than one would expect.

A necropsy study looked at risk factors for fatal pancreatitis in dogs.2 This study also included a control group of dogs that had suffered trauma. Risk factors for developing pancreatitis included obesity, diabetes mellitus, hyperadrenocorticism, hypothyroidism, prior gastrointestinal disease and epilepsy.

New research brings new insight

A research abstract presented at the 2012 ACVIM Forum in New Orleans further suggests a link between pancreatic disease and hyperadreno­corticism.3 Researchers from the University of Tennessee and Texas A&M University compared healthy dogs (n=20, Group 1), dogs with signs of hyperadrenocorticism but normal ACTH stimulation test results (n=12, Group 2) and dogs with hyperadrenocorticism (n=20, Group 3). Dogs were excluded from the study if they had signs that would suggest pancreatitis. The concentration of canine pancreatic lipase immunoreactivity (cPLI) in these dogs was determined by using the Spec cPL Test (IDEXX) and SNAP cPL Test (IDEXX) assay.

In healthy dogs, only one out of 20 had a positive SNAP cPL test result (high positive result). In Group 2, three of the 12 dogs had positive test results (one low positive, two high positive), and in dogs with hyperadrenocorticism, 11 of 20 had positive results, with nine having a high positive result.

Results were similar with the SPEC cPL Test. The one healthy dog had a cPLI concentration of 200 to 400 µg/L. From Group 2, one dog had a cPLI concentration of 200 to 400 µg/L, and one had a cPLI concentration of 400 µg/L. In the dogs with hyperadrenocorticism, five had results 200 to 400 µg/L, and seven had a cPLI concentration of 400 µg/L (the abstract lists the measurement unit as mg/L, but the concentration is µg/L for this assay). These differences were statistically significant.

Deciphering the results

The results of this study would suggest that these dogs had pancreatitis, as concentrations of 400 µg/L are considered diagnostic for pancreatitis. But all the dogs that had positive results in this study did not have clinical signs of pancreatitis, of course, since this was an exclusionary criterion for the study.

This study results suggest that in dogs with hyperadrenocorticism, it would be difficult to diagnose clinically overt pancreatitis by using cPLI testing since many dogs without clinical signs have positive results as well. It is not known if the dogs with hyperadreno­corticism that had positive results had pancreatic disease since it would require biopsies of the pancreas to be certain. Also, inflammation with pancreatitis can be quite localized, so a single biopsy would not be adequate to rule out pancreatitis. Doing so would require sectioning of the entire pancreas to definitively exclude pancreatitis.

Previous studies using necropsy have suggested that there are few false positive cPLI results when using the cutoff of 400 µg/L. Specificity of 90 to 100 percent has been documented.4-6 In some of these studies, though, the 95 percent confidence intervals were quite wide, so the true specificity may be lower. Wide confidence intervals are commonly seen in studies in which few cases were evaluated.

There are other scenarios in which cPLI concentration can be elevated without convincing clinical evidence of pancreatitis. Hypertriglyceridemia in miniature schnauzers has been associated with elevated cPLI concentrations.7

Unfortunately no clinical information was available to determine if the dogs had consistent clinical signs. In another study in healthy dogs (25 overweight, 10 obese), animals that had markedly elevated postprandial triglyceride concentrations (> 442 mg/L) were 16.7 percent more likely than other dogs to have a cPLI concentration > 400 µg/L.8 None of these dogs had signs of pancreatitis, and over a four-year followup, none developed signs of pancreatitis.

The takeaway

There has always been a quest to develop a great pancreatitis test. In a way, cPLI assays do offer this in that specificity does appear to be very high. Necropsy studies have shown that when an elevated cPLI concentration is found, the patient probably does have pancreatitis.

However, what I am after clinically is not whether a dog has pancreatitis. What I want is a test that, when positive, tells me that the clinical signs I am seeing in that dog are attributable to pancreatitis. The cPLI test cannot make this cause-and-effect determination. This is evidenced by both some dogs with hyperadrenocorticism and some dogs with elevated postprandial triglyceride concentrations being shown to have marked cPLI concentration elevations without any clinical signs of pancreatitis.

This means, in my opinion, that if you have a patient with appropriate clinical signs and an elevated cPLI concentration, you cannot get complacent and assume that pancreatitis is the main clinical problem—another issue, such as hyperadrenocorticism, may be the real culprit behind the elevated cPLI concentration.

References

1. Cook AK, Breitschwerdt EB, Levine JF, et al. Risk factors associated with acute pancreatitis in dogs: 101 cases (1985-1990). J Am Vet Med Assoc 1993;203:673-679. 2. Hess RS, Kass PH, Shofer FS, et al. Evaluation of risk factors for fatal pancreatitis in dogs. J Am Vet Med Assoc 1999;214:46-51.3. Mawby DL, Whittemore JC, Fecteau K, et al. Naturally-occurring hyperadrenocorticism is associated with increased pancreatic lipase immunoreactivity concentrations in dogs (abst). J Vet Intern Med 2012;26:770.4. Trivedi S, Marks SL, Kass PH, et al. Sensitivity and specificity of canine pancreas-specific lipase (cPL) and other markers for pancreatitis in 70 dogs with and without histopathologic evidence of pancreatitis. J Vet Intern Med 2011;25:1241-1247.5. Mansfield CS, Anderson GA, O’Hara AJ. Association between canine pancreatic-specific lipase and histologic exocrine pancreatic inflammation in dogs: assessing specificity. J Vet Diag Invest 2012;24:312-318.6. Neilson-Carly SC, Robertson JE, Newman SJ, et al. Specificity of a canine pancreas-specific lipase assay for diagnosing pancreatitis in dogs without clinical or histologic evidence of the disease. Am J Vet Res 2011;72:302-307. 7. Xenoulis PG, Suchodolski JS, Ruaux CG, et al. Association between serum triglyceride and pancreatic lipase immunoreactivity concentrations in miniature schnauzers. J Am Anim Hosp Assoc 2010;46:229-234. 8. Verkest KR, Fleeman LM, Morton JM, et al. Association of postprandial serum triglyceride concentration and serum canine pancreatic lipase immunoreactivity in overweight and obese dogs. J Vet Intern Med 2012;26:46-53.