A complete laboratory evaluation is required not only to diagnose exocrine pancreatic insufficiency (EPI) but also to determine the extent of the malabsorption and assess manifestations of the underlying disease, if present.

Blood tests

A complete blood count (CBC) may reveal microcytic anemia due to iron deficiency or macrocytic anemia due to vitamin B-12 or folate malabsorption. Serum iron, vitamin B-12, and folate concentrations may help establish the diagnosis of EPI. Prothrombin time (PT) may be prolonged because of malabsorption of vitamin K, a fat-soluble vitamin. A study by Lindkvist et al found that serum nutritional markers (eg, magnesium, albumin, prealbumin) can be used to determine the probability of EPI in patients with chronic pancreatitis. [26]

Malabsorption can involve electrolyte imbalances such as hypokalemia, hypocalcemia, hypomagnesemia, and metabolic acidosis. Protein malabsorption may cause hypoproteinemia and hypoalbuminemia. Fat malabsorption can lead to low serum levels of triglycerides, cholesterol, and alpha- and beta-carotene. The Westergren erythrocyte sedimentation rate (ESR) may provide a clue to an underlying autoimmune disease.

Serum levels of antigliadin and antiendomysial antibodies can be used to help diagnose celiac sprue. The serum immunoglobulin A (IgA) level can be assessed to rule out IgA deficiency.

Stool tests

Determination of fecal elastase and chymotrypsin (2 proteases produced by the pancreas) can be used to try to distinguish between pancreatic causes and intestinal causes of malabsorption.

Tests of malabsorption

A full malabsorption workup is required to differentiate EPI from other causes of malabsorption. Such a workup may include a number of tests, as follows.

Fat absorption tests

A fat absorption test is usually the first one ordered because there are many disease processes that can result in fat malabsorption. For quantitative measurement of fat absorption, a 72-hour fecal fat collection is often performed and is considered the standard. Qualitative tests include the acid steatocrit test and Sudan III stain of stool, but these tests are less reliable.

Patients are instructed to consume a normal amount (80-100 g/day) of fat before and during the collection. On the basis of this level of intake, fecal fat excretion in healthy individuals should be less than 7 g/day.

The current standard for measuring fat malabsorption is the coefficient of fat absorption (CFA), [12] which is the percentage of absorbed fat in the diet. Normally, the CFA is approximately 90%. The various diseases that can give rise to EPI will produce different degrees of pancreatic insufficiency and, hence, different CFAs. For example, cystic fibrosis often results in a CFA lower than 40%, which typically increases to more than 80% with therapy.

D-xylose test

If the 72-hour fecal fat collection results demonstrate fat malabsorption, the D-xylose test is used to document the integrity of the intestinal mucosa.

D-xylose is readily absorbed in the small intestine. Approximately half of the absorbed D-xylose is excreted in urine without being metabolized. If absorption of D-xylose is impaired by either a luminal factor (eg, bacterial overgrowth) or a reduced or damaged mucosal surface area (eg, from surgical resection or celiac disease), urinary excretion will be lower than normal. Cases of pancreatic insufficiency usually result in normal urinary excretion because absorption of D-xylose is still intact.

Carbohydrate absorption test

A simple sensitive test for carbohydrate malabsorption is the hydrogen breath test, in which patients are given an oral solution of lactose. [27, 28] In cases of lactase deficiency, colonic organisms digest the unabsorbed lactose, which results in an elevated hydrogen content in the expired air.

Bacterial overgrowth or rapid transit also can cause an early rise in breath hydrogen, in which case it is necessary to use glucose instead of lactose to make a diagnosis. However, 18% of patients are hydrogen nonexcretors, in whom the hydrogen breath test will yield false-negative test results.

Bile salt absorption test

The bile salt breath test can determine the integrity of bile salt metabolism. The patient is given an oral conjugated bile salt, such as glycine cholic acid with the glycine radiolabeled in the carbon position. The bile salt is deconjugated and subsequently metabolized by bacteria. If interrupted enterohepatic circulation (eg, from bacterial overgrowth, ileal resection, or disease), a radioactively labeled elevated breath carbon dioxide level will be noted.

Schilling test

Malabsorption of vitamin B-12 may occur as a consequence of an intrinsic factor deficiency (eg, from pernicious anemia or gastric resection), pancreatic insufficiency, bacterial overgrowth, ileal resection, or disease. The 3-stage Schilling test can often help differentiate these conditions.

13C-D-xylose breath test

A study by Hope et al suggested that small intestinal malabsorption in chronic alcoholism may be identified by means of a13 C-D-xylose breath test. [29] The investigators evaluated this test in 14 alcoholics, compared the results with those obtained from untreated celiac disease patients and healthy control subjects, and correlated the breath test findings with the morphologic findings from the duodenal mucosa.

In this study, absorption of13 C-D-xylose was significantly less in the alcoholic patients than in healthy control subjects, whereas the time curve of13 C-D-xylose absorption in the alcoholics was similar to that in the untreated celiac patients. [29] In addition, although few changes were observed on light microscopy in the alcoholics, morphologic pathology (primarily reduced surface area of microvilli) was observed on electron microscopy in the majority of the patients.