Tag Archives: exocrine pancreatic testing

Measurement of Exocrine Pancreatic Insufficiency in IBD and the Real-World

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J Fernandez et al. JPGN 2023; 76: 475-479. Prevalence of Exocrine Pancreatic Dysfunction Based on Direct Function Testing in Pediatric Inflammatory Bowel Disease

Methods: Direct stimulated endoscopic pancreatic function test (ePFT) was performed in 74 children with IBD

Key findings:

  • 42 (56.7%) children had either generalized or partial exocrine pancreatic insufficiency (EPI). 
  • Weight z scores were significantly lower in those with abnormal ePFT (Crohn cases: P = 0.008; UC cases: P = 0.046). 

In their discussion, the authors assert: “We can confidently recommend ePFT in established or new IBD patients who have stricturing and/or penetrating CD, weight loss, low weight Z-score, or qualify for the diagnosis of malnutrition.”

My take: In my real-world experience (~30 years), I have yet to have one patient presenting with IBD who needed pancreatic enzyme supplementation to reverse growth failure/malnutrition. As a consequence, I have a difficult time accepting the premise that more than 50% have EPI. To me, this suggests that testing children when they are acutely-ill or malnourished is yielding unreliable results.

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Tumamoc Hill, Tucson AZ

Endoscopic Pancreatic Function Testing -NASPGHAN Position Paper

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N Patel et al. JPGN 2021; 72: 144-150. full text Endoscopic Pancreatic Function Testing (ePFT) in Children: A Position Paper From the NASPGHAN Pancreas Committee

This articles serves as a good review of exocrine pancreatic insufficiency (EPI).

Etiologies:

  • “Cystic fibrosis is the most common cause of EPI in children .” Other congenital causes include  aberrant embryonic development of the pancreas, “Shwachman-Diamond syndrome, Johanson-Blizzard syndrome, Pearson marrow pancreas syndrome, and Jeune syndrome”
  • “Acquired causes of EPI can be transient, such as in the aftermath of acute pancreatitis (which can persist weeks to months)”
  • Also, infants, compared to adults, have “physiological” EPI. Lipase output is 5–10% of adult values during the 1st 6 months of life.

Advantages/Disadvantages of Endoscopic Testing for EPI:

  • Advantages:
    • • Safe, technically easy, and quick procedure to perform in conjunction to routine investigative EGD
    • • Allows assessment of acinar and ductal function
    • • High sensitivity and specificity in detection of isolated and generalized enzyme deficiencies
    • • Can diagnose minor and more severe degrees of EPI and aid in early diagnosis of CP in patients with unremarkable radiological changes
  • Disadvantages:
    • • Can be done only in conjunction with EGD and the patient will likely require sedation• Prolongs routine EGD
    • • Assesses peak enzyme activity and bicarbonate concentrations rather than total secretory capacity
    • • No standardized pancreatic fluid collection frequency or duration in pediatrics
    • • Lack of age-specific standardized reference ranges in pediatrics

Endoscopic Testing Caveats:

  • Any sample with a pH less than 7 may be unreliable as it is below the pH optimum of the enzymes and may reflect contamination with gastric fluid; however, ” the inability to increase pH, or bicarbonate, upon secretin stimulation may be reflective of loss of cystic fibrosis transmembrane conductance regulator (CFTR) function”
  • Samples need to be frozen or placed on dry ice
  • “Commonly used laboratory (Kaleida Health Children’s Hospital Laboratory, Buffalo, NY) are: trypsin >55.4 nmol · mL−1 · minute−1, amylase >32 μmol · mL−1 · minute−1, lipase >146 μmol · mL−1 · minute−1, and chymotrypsin >2.5 μmol · mL−1 · minute−1“

My take: With careful clinical judgement, endoscopic EPI testing is rarely needed. First of all, fecal elastase measurements can detect most patients with EPI. In addition, a lot of patients with poor growth and suspected malabsorption are too young for reliable endoscopic EPI testing.

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How Helpful is Endoscopic Pancreatic Testing in Pediatrics?

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A recent study (P Hopson et al. JPGN 2019; 68: 854-60) reports a high rate of isolated amylase deficiency of 10.1% in their cohort. Is this really accurate? I am skeptical.

  • This is a retrospective study and the authors undertook endoscopic pancreatic function testing (ePFT) in a large number of patients, 712 over a 6 year period.  The authors state “whenever there is clinical indication for esophagogastroduodenoscopy (EGD) we usually obtain” ePFT collections.
  • To determine the amylase levels, the authors relied upon their in-house laboratory.  Before accepting widespread deficiencies in amylase production, it would be useful to have specimens checked in more than one laboratory. At the same time, given the normalcy of the other pancreatic enzymes, it is likely that the specimens were of good quality.
  • 59 of the 72 (82%) patients with isolated amylase deficiency were younger than 2 years. It is notable that in the same issue, some of the same authors in a review article describe the technique for ePFT (JPGN 2019; 68: 768-76) and note that amylase activity is undetectable at 1 month of age and is normal at 2 years of age.  “Data are lacking as to when it is expected that most children have normal pancreatic amylase activity before 2 years of age.”
  • The authors note that 48 patients (67%) with isolated amylase deficiency had failure to thrive or poor growth.

Amylase Levels:

  • Looking at the authors’ Figure 1, they do provide their mean amylase levels; they considered a level below 10.3 micromol/min/mL to be deficient.  Is this the right cutoff? Is there evidence that levels below this result in a disease state?
  • Particularly in the first year of life, the amylase activities are much lower: approximately 2 micromol/min/mL for age 0-6 months and 12 micromol/min/mL for 6-12 months.
  • In their cohort of 72 with abnormal amylase levels, 35 (approximately half) are less than 1 year of age.  Thus, given how low the mean levels are, it is not surprising that nearly half of the patients (35/82) in this age group had abnormal ePFT.
  • Even in the 1-1.5 year olds, the mean amylase activity is lower than the older group (approximately 24 micromol/min/mL compared to more than 40 micromol/min/mL for patients older than 6 years).  The authors found 25% of the ePFT testing in this age group (1-15. yr olds) to have isolated amylase deficiency; again, this seems implausible.
  • It is notable that there is not a control population.  How often in healthy patients less than 2 years of age is the amylase level below their cutoff? In fact, the authors state that 10 of their patients with isolated amylase deficiency had constipation, and 5 had reflux which would be quite atypical presenting indications.

The technique for obtaining ePFT is detailed in the review (JPGN 2019; 68: 768-76) and includes the following:

  • Before endoscopic intubation, “a bolus of secretin (0.2 mcg/kg to max of 16 mcg) is administered” (or alternatively synthetic CCK octapeptide in a dose of 0.02 or 0.04 mcg/kg).
  • Initial fluid in stomach and duodenum is aspirated and discarded
  • Using an aspiration catheter (or thru biopsy channel if scope too small), collect 3 to 4 aliquots of fluid between 3-10 minutes after injection of secretin (should be completed within 10 minutes of secretin)
  • Place immediately on ice or dry ice
  • Samples with low pH may be contaminated
  • Avoid trauma to mucosa as bleeding can give erroneous results

I would suggest a more selective approach in utilizing endoscopy to check for both pancreatic function as well as disaccharidases.  The sensitivity, specificity, positive predictive value and negative predictive value of a test is highly dependent on the study population. In those at low risk, the results of the testing is highly suspect.

My take: The reference to the review article is worth keeping as it gives a clear description of endoscopic pancreatic function testing.  The study describing a 10% rate of amylase deficiency among a large cohort of pediatric patients requires careful interpretation, particularly as more than 80% of the deficiency group were less than 2 years of age. Clearly, a prospective study is needed.  In those with possible isolated amylase deficiency at a young age (<2 years), a double-blind randomized trial may be needed to determine if enzyme supplementation is beneficial.

Related blog posts: Transient Exocrine Pancreatic Insufficiency or Misleading Tests?

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

 

Camille Passaro, Rue Saint-Honore por la Tarde. Efecto de lluvia.  Thyssen-Bornemisza Museum; https://www.museothyssen.org/en/collection/artists/pissarro-camille/rue-saint-honore-afternoon-effect-rain