Refer to: Goff JS: Pancreatic exocrine function testing (Medical Medical Progress Progress). West J Med 135:368-374, Nov 1981 Pancreatic Exocrine Function Testing JOHN S. GOFF, MD, Denver It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measure- ment of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of a/l these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weak- nesses of each. EXOCRINE FUNCTION of the pancreas is required initiated. If pancreatic insufficiency is suspected, for digestion of fat, protein and carbohydrates. it is important to confirm the diagnosis by ob- For efficient digestion the pancreas must secrete jective testing. Many tests have been designed to bicarbonate as well as enzymes. Because the major assess pancreatic exocrine secretion; unfortu- enzymes secreted by the pancreas (amylase, tryp- nately, some of the traditional tests are difficult to sin, chymotrypsin and lipase) are denatured by carry out and the results often are misleading.'-3 acid or the combination of acid and pepsin, Therefore, any clinician who deals with malab- maldigestion can occur if bicarbonate secretion is sorptive disorders should understand which pan- diminished, even though the enzymes are present creatic function tests are available and how to in adequate concentrations. Impaired secretion of best interpret the results. This review attempts to pancreatic enzymes, bicarbonate, or both, results place into perspective the traditional pancreatic either from diffuse destruction of the gland (usu- exocrine function tests and explore newer tests. ally the result of chronic relapsing pancreatitis) The pancreatic function tests described below or from obstruction of the main duct in the head are classified as direct or indirect. The direct tests of the pancreas by carcinoma or stricture. measure pancreatic secretion in response to phar- It is often difficult to determine the cause of macological or physiological stimulants, whereas a patient's malabsorption by history or physical the indirect tests assess pancreatic secretion by examination, but it is desirable to make a specific measuring its effect on ingested nutrients. diagnosis so that appropriate therapy can be From the Division of Gastroenterology, Department of Medi- Direct Tests of Pancreatic Exocrine Function cine, University of Colorado School of Medicine, Denver. Reprint requests to: John S. Goff, MD, Division of Gastro- The secretin stimulation and Lundh tests are enterology, Department of Medicine, University of Colorado Health Sciences Center, 4200 East 9th Ave., Denver, CO 80262. the oldest and most studied of the pancreatic 368 NOVEMBER 1981 * 135 * 5 PANCREATIC EXOCRINE FUNCTION TESTING a nonabsorbable marker, such as polyethylene ABBREVIATIONS USED IN TEXT glycol or bromsulphalein'0; the opening of this BT-PABA = N-benzoyl-N-tyrosyl para-amino- tube must be proximal enough to the collection benzoic acid port of the first tube so there will be adequate CCK = cholecystokinin mixing of the marker substance with the pan- C02 = carbon dioxide IF = intrinsic factor creatic secretions before aspiration. The marker substance is introduced at a known concentration and rate. The concentrations of the marker, bi- exocrine function tests. In these tests one measures carbonate and enzymes in the collected duodenal the volume of fluid, enzymes and bicarbonate juice are then determined, and from simple mathe- secreted into the duodenum after a pancreatic matical equations the output of pancreatic enzymes stimulus. Another direct test of pancreatic secre- and bicarbonate can be calculated.10'11 Before the tion is the measurement of stool enzyme concen- nonabsorbable marker technique (which does not trations. The measurement of trypsin or isoam- require the complete collection of duodenal juice) ylase activity in serum also has been used to was used, incomplete collection was a major cause assess pancreatic function more or less directly. of erroneous results. After a control period of infusion of the marker Secretin Test and aspiration of duodenal content (usually half The stimulants of the pancreas used in the an hour), the hormone is administered. If volume secretin test are intravenously injected gastro- and bicarbonate production are to be measured, intestinal hormones.4 Formerly, crude prepara- pure secretin from the Karolinska Institute in tions of secretin were used for this purpose, but Sweden should be used (usual dose is 0.5 to 1.0 it was discovered that these contained cholecys- CU per kg of body weight per hour). The syn- tokinin (CCK) as well as secretin. Secretin stimu- thetic octapeptide of CCK sincalide (Kinevac), the lates bicarbonate and water secretion by the active portion of the CCK molecule, is the most pancreas, whereas CCK stimulates enzyme (protein) satisfactory and least expensive preparation avail- secretion. Now that essentially pure enzyme prep- able for the stimulation of pancreatic enzyme arations are available, one can test separately for secretion. The usual dose of CCK is 50 jg per kg water and bicarbonate secretion, on the one hand, of body weight per hour administered by con- or enzyme secretion, on the other hand, depend- tinuous infusion. Duodenal juice is collected by ing on which hormone is used.6 7 By simulta- gravity drainage in iced tubes at 15-minute inter- neously administering secretin and CCK, both kinds vals for 11/2 hours after the stimulants are given. of secretory response can be measured. Different The secretin test has several drawbacks: (1) the amounts of the hormones have been used alone length of the procedure, (2) the necessity for or in various combinations, either as bolus injec- nasogastric intubation, which frequently is poorly tions or as continuous infusions, to determine the tolerated by the patient and (3) radiation exposure optimal dose for distinguishing normal from ab- during placement of the tube. Nevertheless, when normal pancreatic function.8'9 The best results careful attention is given to all procedural details, have been reported with the use of submaximal 90 percent accuracy in differentiating normal from doses of the hormones given by continuous infu- abnormal pancreatic function can be attained.4 3 sion.3 Lundh Test The secretin test requires the passage of a triple lumen tube by mouth or nose into the In the Lundh test the stimulus to pancreatic stomach and duodenum, or a double lumen tube secretion is a standardized liquid meal ingested by into the duodenum and a separate single lumen the patient after a tube has been passed into the tube into the antrum of the stomach. The gastric duodenum.'2-'4 The constituents of this meal tube is necessary for the removal of gastric acid cause the duodenum to secrete the hormones CCK and pepsin so that enzymes secreted into the and secretin, which in turn stimulate pancreatic duodenum will not be denatured. The first of the secretion. The meal also distends the stomach, duodenal tubes is used for collecting duodenal producing pancreatic secretion via nervous system content; its distal opening usually is placed near reflexes. Even though this test sometimes is re- the angle of Treitz by fluoroscopic guidance. The ferred to as an indirect method of pancreatic second duodenal tube is used for the infusion of stimulation, it is in fact the physiological way in THE WESTERN JOURNAL OF MEDICINE 369 PANCREATIC EXOCRINE FUNCTION TESTING which the, pancreas is stimulated. The effect of The Lundh meal test is simpler and cheaper to the stimulant (food) on enzyme and bicarbonate do than is the secretin test, but it still requires secretion is measured directly in the aspirated nasogastric intubation, prolonged careful monitor- duodenal juice. ing and the need for expert handling of the col- The Lundh test also requires duodenal intuba- lected specimens. Because data produced by the tion. Traditionally, a single lumen tube is placed Lundh test may be less accurate or more difficult so that its distal opening is near the angle of to interpret, the secretin test is recommended as Treitz. The patient then drinks a 300-ml liquid the best available direct test of pancreatic exocrine meal (5 percent protein, 6 percent fat and 15 function. percent carbohydrate), and duodenal contents are aspirated at 15-minute intervals for two hours. Fecal Enzyme Assays The duodenal juice is assayed for bicarbonate Because feces are relatively easy to obtain from and enzyme concentrations. The test can distin- patients, many workers have attempted to corre- guish between normal and abnormal pancreatic late pancreatic exocrine function with the con- function found in pancreatic cancer or pancreatic centration of enzymes present in stool speci- insufficiency with an accuracy of 75 percent to mens.'7 8 Measurement of chymotrypsin is the 90 percent, depending on the type of disease least variable, but the range of values obtained is present (patients with pancreatic cancer may have so great that the test is not a reliable measure of normal or decreased outputs of enzymes and pancreatic secretion and is no longer used in bicarbonate, depending on the location of the adults. tumor) .14 In the standard Lundh meal technique, because Serum Enzyme Assays of uncertainty about completeness of duodenal Serum amylase and lipase concentrations can aspiration and because a marker is not used, only be measured easily, but values do not correspond enzyme concentrations rather than enzyme output with the amount of pancreatic exocrine function.