Gut: first published as 10.1136/gut.4.1.32 on 1 March 1963. Downloaded from Gut, 1963, 4, 32 The reliability and reproducibility of the Schilling test in primary malabsorptive disease and after partial gastrectomy J. F. ADAMS AND E. JUNE CARTWRIGHT From the Western Infirmary, Glasgow EDITORIAL SYNOPSIS A study of the reproducibility and reliability of the Schilling test in patients with primary malabsorptive disease and after partial gastrectomy is reported. The value of the test was assessed by repeated tests in each patient. Consistently normal or abnormal results were obtained in only one of the seven patients with primary malabsorptive disease and in only two of the eight patients who had undergone partial gastrectomy. From these results it is concluded that the result of a single test may be of little clinical value. Assessment of the results suggests that the mean value for a series of Schilling tests may give some indication of value clinically about the capacity to absorb radioactive vitamin B12 at the time of the tests at least in patients who have undergone partial gastrectomy. The significance of the findings is discussed, particularly in relation to the aetiology of post-gastrectomy megaloblastic anaemia. http://gut.bmj.com/ Absorption tests using radioactive vitamin B12 may ml. water; two hours later 1,000 ptg. vitamin B12 was given be of considerable value in establishing a precise intramuscularly and urine was collected for the subsequent diagnosis in conditions in which anaemia results 24 hours. The radioactivity in a 450 ml. aliquot was from malabsorption. It is obviously important to measured as described by Adams and Seaton (1961) and the total urinary radioactivity expressed as a percentage appreciate the limitations of such tests. Of the of the oral dose was calculated. The normal value was various tests, the urinary excretion test introduced taken as > 7 5% dose excreted. The 68Co vitamin B,2 on September 26, 2021 by guest. Protected copyright. by Schilling (1953) is the most convenient for general solutions used were assayed microbiologically each week use and has gained wide acceptance but its reliability to detect any deterioration in vitro. and reproducibility in various conditions has not The amount of fat in three-day collections of faeces been fully established. ofthe patients on a ward diet was estimated by the method In this paper we report the results of an investi- of Harrison (1947), the normal value being less than 5 g. gation into the reliability and reproducibility of the fat excreted per day. The amount of d-xylose in a five- Schilling test in patients with primary malabsorptive hour collection of urine after an oral dose of 25 g. in disease and in patients who had evidence of mal- 500 ml. water was estimated by the method of Roe and Rice (1948) the normal value being taken as more than absorption after partial gastrectomy. 5 g. 'Blood sugar' concentrations before and after an oral dose of 50 g. glucose in 500 ml. water were estimated by the method of Somogyi (1952), the normal fasting PATIENTS, MATERIALS, AND METHODS value being taken as 65-100 mg./100 ml. and the upper limit of normal as 160 mg./100 ml. Serum vitamin B12 All patients with primary malabsorptive disease had come levels were estimated by a modification of the method of under observation with a megaloblastic anaemia and the Hutner, Bach, and Ross (1956) using Euglena gracilis 3 Schilling tests were done as part of the diagnostic strain as the test organism: the normal value was taken as investigations. The post-gastrectomy patients had come > 140 pug./ml. The presence or absence of gastric acid under observation with anaemia or because of symptoms was established by the augmented histamine test (Kay, such as diarrhoea. 1953). Samples of gastric or intestinal mucosa were Schilling tests were performed at intervals of from three obtained by a biopsy tube (Shiner, 1956) or capsule days to six months, the usual interval between the tests (Crosby and Kugler, 1957), the position of the instrument being one week. After an overnight fast the oral dose of being checked fluoroscopically. Other procedures were by 0 5 ug. 0 5 tic. 58Co vitamin B12 was given in 200 to 400 standard laboratory methods. 32 Gut: first published as 10.1136/gut.4.1.32 on 1 March 1963. Downloaded from The reliability and reprodtcibility of the Schilling test in primary malabsorptive disease 33 RESULTS TABLE II RESULTS OF REPEATED SCHILLING TESTS IN CASE PG. 81 The results of the Schilling tests are shown in Tables Test No. Schilling Test Results I and II and the results of other investigations in (% dose excreted) Tables III and IV. There was no evidence of a con- 0 stant trend to an increase or decrease in the values 2 5-6 for Schilling tests in any patient over the period of 3 9.7 4 7-8 the investigation. 5 7-4 Deterioration of the 8Co vitamin B12 solutions 6 14-7 7 4-6 in vitro was not observed. 8 9.7 9 9.9 10 7-4 DISCUSSION 11 3-4 12 3-6 The striking feature of the 13 6-7 results is that con- 14 12-6 sistently normal or subnormal values for the 15 8-8 Schilling tests were obtained in only one of the 16 17-0 17 7-4 seven patients with primary malabsorptive disease 18 5.9 (case M.2) and in only two of the eight patients who 19 9-1 had undergone partial gastrectomy (cases PG.1 and 20 11-7 7). It is clear therefore that the test cannot be Mean S. D. regarded as reliable or reproducible for practical clinical purposes. It may be the case that the result of All Tests 8-15 3.97 each test does accurately reflect the capacity to Excluding tests 2, 3, and 4 8-18 4-36 absorb radioactive vitamin B12 at the time of the test 'The results are shown in chronological order extending over a and that the capacity to absorb radioactive vitamin period of two and a half years. Tests 2 and 3 were done with intrinsic factor and test 4 after four days' treatment with tetracycline, 0-25 g. B12 varics from day to day. Even if this were so it is q.i.d. orally. still obvious from the results that a single test is valueless clinically. It may also be the case that a http://gut.bmj.com/ different technique might give different results: It is logical to consider whether the mean value of modifications of the test described by Schilling (1953) a series of tests, as opposed to the result of a single have been introduced by several workers, notably test, is of any value in clinical practice. The most in respect of the mass of radioactive vitamin B12 satisfactory approach to this problem is to consider orally and the mass and timing of the intramuscular the mean value of a series of Schilling tests in relation dose, and it must be stressed that the results reported to unequivocal evidence of vitamin B12 deficiency in this study were obtained using one of these modi- and also, if possible, to unequivocal evidence of fications. Again this does not alter the fact that by failure to develop vitamin B12 deficiency. Failure on September 26, 2021 by guest. Protected copyright. the technique employed, which is in wide use, the to develop vitamin B12 deficiency can only be result of a single test is of little value clinically. determined by necessarily long-term follow-up BLE I RESULTS OF SCHILLING TESTS IN CHRONOLOGICAL ORDER IN SEVEN PATIENTS WITH PRIMARY MALABSORPTIVE DISEASE (CASES M.1-7) AND IN SEVEN PATIENTS AFTER PARTIAL GASTRECTOMY (CASES PG.1-7) Case Schilling Test Results (% Dose Excreted) Mean S.D. 1 2 3 4 5 6 7 8 M.l 10-7 22-0 13-1 2-7 14-0 9-4 14-9 15-3 12-7 5-53 M.2 21-8 14-4 8-6 17-7 19-6 13-8 15-9 4-72 M.3 11-5 3-0 18-2 27-7 24-1 14-8 16-5 8-90 M.4 14-8 6-2 11-2 7-3 8-9 0 8-0 3-06 M.5 13-7 4-5 7.7 8-6 M.6 7-4 9-4 8-9 2-7 2-1 0-9 5-2 2-74 M.7 6-5 25-0 31-8 20-4 11-0 18-9 10-27 PG.1 21-2 22-9 20-7 12-9 14-1 8-0 16-6 5-85 PG.2 6-9 4-8 3-4 9-5 8-1 8-1 6-8 2-28 PG.3 3-9 7-6 5-5. 10-9 11-2 0 6-5 4-30 PG.4 1-6 10-5 18-8 26-6 13-9 5-7 12-8 9-04 PG.5 14-1' 0 0 0 0 4-1 3-0 PG.6 1-8 16-5 7-3 5-5 0 0 5-1 5-74 PG.7 0 0 0 1-3 0 4-1 0-9 Gut: first published as 10.1136/gut.4.1.32 on 1 March 1963. Downloaded from 34 J. F. Adams and E. June Cartwright TABLE III RESULTS OF VARIOUS INVESTIGATIONS IN PATIENTS WITH PRIMARY MALABSORPTIVE DISEASE Case Age Sex Megaloblastic Anaemia Faecal Xylose Glucose Intestinal Gastric Intestinal Biopsy (yr.) Fat Test Tolerance Radiology Acid Hb Serum Therapeutic Response (g.ldav) (g.5 hours) (mg.