Development of a dual label Schilling test for pancreatic exocrine function based on the differential absorption of cobalamin bound to intrinsic factor and R protein

Abstract

Cobalamin is bound by R protein in gastric juice and is not transferred to intrinsic factor until R protein is partially degraded by pancreatic enzymes. Using this phenomenon, we devised a new dual label Schilling test for pancreatic exocrine function which is based on the relative absorption of R protein-cobalamin and intrinsic factor-cobalamin. The following were given together orally in Schilling tests: (a) 0.2 nmol human intrinsic factor-[57Co]cobalamin; (b) 0.2 nmol hog R protein-[58Co]cobalamin; (c) 0.4 nmol free human intrinsic factor; and (d) 200 nmol cobinamide (a cobalamin analogue that binds only to R protein and prevents endogenous R protein from removing [57Co]cobalamin from intrinsic factor). Values for the ratio R protein-cobalamin/intrinsic factor-cobalamin in 24-hr urines ranged as follows: 26 normals, 0.52–1.00; 15 patients with pancreatic disease and symptoms of pancreatic exocrine insufficiency, 0.02–0.15; and 11 patients with other gastrointestinal diseases, 0.45–0.86. All patients with pancreatic disease and symptoms of pancreatic exocrine insufficiency malabsorbed R protein-cobalamin and had low values for the ratio R protein-cobalamin/intrinsic factor-cobalamin which did not overlap with values obtained with normals or patients with other gastrointestinal diseases. In 18 patients with pancreatic disease without symptoms of pancreatic exocrine insufficiency values ranged from 0.26 to 0.89. Direct comparisons indicated that the test was comparable to the trypsin output test and at least comparable to the fecal fat test in terms of its sensitivity in detecting decreased pancreatic exocrine function. The simultaneous measurement of R protein-cobalamin and intrinsic factor-cobalamin and the use of their ratio obviate the necessity for quantitative urine collections and make the test applicable to patients with decreased renal function and to patients with combined pancreatic and intestinal diseases. The dual label pancreatic Schilling test is superior to the fecal fat test in specificity, speed, and convenience, and to the trypsin output test in cost, convenience, and potential availability. We believe that it will be clinically useful as a diagnostic test for pancreatic exocrine function.