Chronic pancreatic insufficiency may occur as a result of pancreatitis or hemochromatosis in adults and in the disease known as cystic fibrosis of the pancreas in children. The diagnosis may be quite difficult, since the disease either represents an end-stage phenomenon with an acute process going on or else may take place slowly and subclinically over a long period. The classic case of chronic pancreatitis consists of diabetes, pancreatic calcification on x-ray study, and steatorrhea. The diagnosis of diabetes will be discussed in the next chapter. Either of these parameters may be normal or borderline in many patients. The sensitivity of this test, and that of other pancreatic function tests, depends on the amount and degree of pancreatic tissue destruction and whether it occurs acutely or in a low-grade fashion.

Tests useful in diagnosis of chronic pancreatitis

Serum amylase. The serum amylase level in chronic pancreatitis is important, although it is much less reliable than in acute disease. In about one half of the patients it is within normal range. Repeated determinations are necessary at intervals of perhaps 3 days. Moreover, the values may be borderline or only slightly elevated, leading to confusion with other causes of elevated amylase levels mentioned previously. In this situation, the urine amylase level or the A/CCR is the most helpful test.

Serum immunoreactive trypsin. Serum immunoreactive trypsin was discussed earlier as a test for acute pancreatitis. In chronic pancreatitis with pancreatic insufficiency there is variation in SIT data, depending on the severity of deficiency. In severely deficient cases 75% or more patients are reported to have decreased SIT values. In mild or moderate cases the values are more often within reference limits. One report indicated decreased values in nearly 40% of childhood diabetics on insulin therapy.

Bentiromide test. Bentiromide is a synthetic peptide linked to a p-aminobenzoic acid (PABA) molecule. The patient must fast overnight and remain fasting until the test is begun. A control urine specimen is collected just before starting the test. A 500-mg test dose of bentiromide is given orally with sufficient food to stimulate the pancreas. After the bentiromide passes into the duodenum, the pancreatic enzyme chymotrypsin splits off the PABA molecule. The PABA is then absorbed into the bloodstream, conjugated in the liver, and excreted by the kidneys as arylamines. The arylamines are assayed in a 6-hour urine collection beginning with the oral dose. Decreased excretion (<50% of the test dose) suggests decreased absorption from the duodenum, which, in turn, suggests deficient activity of pancreatic chymotrypsin due to decreased pancreatic function. Sensitivity of the test for chronic pancreatitis depends to some extent on the severity of the disease, with greater sensitivity correlating with greater severity. Overall sensitivity appears to be 75%-80% (range, 39%-100%), with specificity about 90% (range, 72%-100%).

One report obtained better results in children using a larger bentiromide dose (30 mg/kg) plus a liquid meal, and measurement of plasma PABA at 2 and 3 hours after bentiromide ingestion.

Various conditions such as severe liver disease (interfering with conjugation), poor renal function (impaired excretion), malabsorption, incomplete urine collection, diabetes mellitus, previous gastrectomy, and inflammatory bowel disease may produce falsely decreased excretion (false positive test result). Certain medications (acetaminophen, phenacetin, lidocaine, procainamide, sulfas, thiazide diuretics, sunscreens containing PABA, and pancreatic enzyme supplements) may produce false normal results. The baseline (pretest) urine specimen can be tested to exclude presence of exogenous PABA metabolites. If there is a question of differentiating pancreatic from primary small intestine malabsorption, a d-xylose test (which is not affected by pancreatic insufficiency) can be done.

Endoscopic retrograde cholangiopancreatography. Duodenal intubation using the ERCP technique with injection of x-ray contrast medium into the common bile duct and pancreatic ducts provides useful information about biliary tract stones or pancreatic disease in 61%-81% of cases and may be the only method that can obtain a diagnosis. However, as noted previously, ERCP requires considerable expertise and does not always succeed.

Pancreatic stimulation tests. A tube can be passed into the duodenum with direct assay of pancreatic fluid constituents collected by duodenal tube drainage before and after injection of secretin, the pancreatic stimulating hormone. This procedure used to be considered the best diagnostic test for chronic pancreatitis and still can be useful. However, with the advent of ERCP this test has lost much of its importance. The stimulation tests do not become abnormal until 75% of pancreatic exocrine function is lost.

Other tests. As noted previously, the D-xylose test may be useful if the patient has demonstrable steatorrhea. A normal D -xylose result is usually found in pancreatic insufficiency or in cystic fibrosis. Stool examination can be performed in a patient with steatorrhea, with differentiation of neutral fat and fatty acid. Theoretically, in pancreatic insufficiency there should be a large amount of neutral fat but very little fatty acid. Unfortunately, some of the colon bacteria apparently are able to convert neutral fat to fatty acid, so some fatty acids might be present in spite of pancreatic insufficiency in some patients. Presence of undigested meat fibers also suggests abnormal pancreatic function.