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Value of 48- Or 72-Hr Urine Collections in Performing the Schilling Test

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Value of 48- Or 72-Hr Urine Collections in Performing the Schilling Test VALUE OF 48- OR 72-HR URINE COLLECTIONS IN PERFORMING THE SCHILLING TEST Edward B. Silberstein Radioisotope Laboratory, Cincinnati General Hospital, Cincinnati, Ohio In 21 % of 71 consecutive, normal Schilling serum vitamin B,2 levels less than 50 pg/mI, and tests evaluated in the Radioisotope Laboratory patients with abnormal vitamin B12 absorption as of the Cincinnati General Hospital, normal 57Co measured by a whole-body counter (6—10). cyanocobalamin excretion (greater than 8% of The test was performed, as previously described a test dose of 0.5 @g)was not achieved until 48— (5), with 0.5 @gof 57Co-cyanocobalamin, 1 @@Ci/ 72 hr. it is recommended that the vitamin B,2 @Lg;however, instead of a single day's collection, adsorption test, as described by Schilling, be serial 24-hr urines were collected for 48—72 hr with altered to routinely include at least a 48-hr additional “flushing―doses of 1 mg of cyanoco urine collection. balamin given intramuscularly at the beginning of the second and third days of the test. Each individual in this study produced at least 500 ml of urine per The Schilling test remains an important diagnos 24 hr with creatinine content exceeding 15 mg/kg tic procedure in the study of patients with megalo body weight if volume was under 500 ml to prove blastic anemia and/or peripheral neuropathy. In the that a full day's collection was made (1 1) . The 72-hr original description of the vitamin B,2 absorption collection was made if there was azotemia (BUN test by Schilling ( 1) , a 24-hr urine collection was exceeding 25 mg% ) or in any patient older than obtained after the oral administration of radioactive 65 years. A final diagnosis was made in each pa cyanocobalamin. Even very recent investigative work tient to establish the presence or absence of a vita (2,3) continues to use the single-day urine collec mm B12 malabsorption state. tion, despite a recommendation in 1956 (4) to collect urine for a longer period. The purpose of this RESULTS communication is to emphasize the necessity for One hundred seven sequential Schilling tests per 2—24-hrurine collections after oral administration formed in the Radioisotope Laboratory of the Cm of 57Co-cyanocobalamin to avoid making an incor cinnati General Hospital were examined. Table 1 rect diagnosis of vitamin B,, malabsorption. Received Oct. 27, 1972; revision received April 12, 1973. MATERIALS AND METHODS For reprints contact: Edward B. Silberstein, Radioisotope Laboratory, Cincinnati General Hospital, Cincinnati, Ohio The results of 107 patients studied sequentially 45229. with the Schilling test (Stage 1) performed in this laboratory were reviewed (5) . Of this total, 36 individuals were found to have vitamin B,2 mal TABLE 1. SCHILLING TEST RESULTS(STAGE 1) absorption, documented by not only an abnormal IN PATIENTS WITH DOCUMENTED Schilling test (Stage 1), corrected by intrinsic factor, VITAMIN B12MALABSORPTION but also by other data. These data included : patients Number of Duration of Percent of oral dose with vitamin B12 responsive megaloblastic anemia cases collection(hr) recoveredin urine who had relapsed when they discontinued vitamin Mean Range B1,injections,patientswithvitaminB12responsive, 20 48 2.6 0.7—6.0 peripheral neuropathy accompanying megaloblastic 16 72 2.8 1.0—6.4 anemia, individuals with megaloblastic anemia and 692 JOURNAL OF NUCLEAR MEDICINE indicates the mean and range of 36 first stage Schil ling tests (oral vitamin B12 given to the fasting pa TABLE 2. PERCENTOF ORALLY ADMINISTERED tient with flushing dose of 1 mg B122 hr later given 57Co-VITAMIN B12 ACTIVITY RECOVERED IN URINE DAILY FOR 48—72HR IN 15 PATIENTS intramuscularly) in patients with vitamin B12 mal WITHOUT VITAMIN B12 MALABSORPTION absorption. Table 2 indicates that the amount of radioactive B12recovered in urine in the first 24 hr Total%Name from 15 of the 7 1 normal patients tested in this Age Sex Day 1 Day 2 Day 3 recovery series (21 % ) did not exceed 8% of the adminis EC 75 F 53 7.4 1J 14.8 tered dose (normal in this .laboratory) . Thus, in LH' 73 M 33 3.2 2.7 9.6 15 of 71 sequential, normal Schilling tests, a 24-hr HC 46 F 1 32 — 33 urine collection alone would have given a result wJ* 61 M 4 2 6 12 JD 76 M 6 11 — 17 suggesting vitamin B12 malabsorption which, in fact, HE' 88 F 4.4 2.3 1.1 7.8 did not exist. MM 79 F 6.7 9.9 — 16.6 The mean and standard deviation for age and GB 35 F 1J 7.4 — 9.1 RC 57 F 6.2 2.9 — 9.1 blood-urea nitrogen level of the 15 normal individ HS 62 M 5.0 7.0 — 12 imis who required 48—72hr to attain urine excretion WR 87 M 5.6 2.3 0.5 8.4 exceeding 8% of the administered dose appear in BM 76 F 4.0 4.8 1.3 10.1 VO. 59 F 4.4 3.3 1.7 9.4 Table 3. MZ 63 F 6.5 1.9 0.4 8.8 RK 75 M 3.0 5.1 3.5 11.6 DISCUSSION * 72-hr collection required to reach 8°!. urinary excretion. No 48—72-hrurine collection from a patient with documented vitamin B12 malabsorption contained more than 6.4% of the orally administered activity found in the urine. One reported case of pernicious TABLE 3. PATiENTSB12MALABSORPT1ON8%WITHOUTVITAMIN anemia where the 48-hr urine activity reached 7% of the oral dose was found (4) . In our laboratory, the excretionattainedexcretion8°!. urine radioactivity must exceed 8% of the adminis 48—72hrNumber5615Age59±1767±15BUN(mg%)19±in 24 hrattained in tered dose at 48—72hr to be considered normal. No patient with normal vitamin B12 absorption whom 7'‘Significant 5@28± we have studied has had a 72-hr urinary level of activity under 8 % . We have seen two patients post difference, p < 0.001. gastrectomy whose 48-hr Schilling test results fell in the “gray―zone between 7% and 8% . (One year seen a significant number of patients with 24-hr later both had less than 7% excretion at the time of Schilling test results below our previous normal of repeat Schilling tests.) 7% who did not have pernicious anemia or other In 71 patients in whom normal vitamin B12 ab cause of vitamin B12 malabsorption by clinical or sorption was demonstrated, 15 (2 1% ) required at laboratory criteria. Several of these patients received least a 2-day urine collection to excrete more than unnecessary second stage Schilling tests (with in 8% of oral 57Co-cyanocobalamin. Five of the 71 trinsic factor) which, if normal in a 24-hr collection, patients required a 72-hr urine collection for the led to the incorrect diagnosis of pernicious anemia. amount excreted to exceed 8% . This delayed pattern One individual had received a total of five Schilling of cyanocobalamin excretion has been described pre tests before it became apparent that there was no viously as characteristic of aged patients (5) or those abnormality on vitamin B12 absorption, but rather with renal disease (12,13) and may also be caused a pattern of delayed 57Co-vitamin B12 excretion. In by delayed intestinal transit. None of these patients fact, urine collection provides the greatest source for had chronic obstipation. The mean age of 67 ± 15 error in performing Schilling tests in this laboratory years for the 15 patients represented in Table 2 is (5) . When urine collection is impossible because not significantly different from the mean age of the of lack of patient cooperation or contamination of other 56 patients, aged 59 ± 17 years (p > 0.1) urine by feces, we use whole-body counting to deter who also had normal Schilling tests in this series. mine the percent of 57Co-cyanocobalamin absorption However, the blood-urea nitrogen levels in the group (6—10). requiring 2—3days to exceed 8% excretion was significantly higher (p < 0.001 ) than the group REFERENCES which reached normality within 24 hr (Table 3). 1. SCHILLINGRF: Intrinsic factor studies: H. The effect Before this change in collecting technique we had of gastric juice on the urinary excretion of radioactivity Volume 14, Number 9 693 SILBERSTEIN after the oral administration of radioactive vitamin Ba,. ‘7Co-labeledvitamin B@ in a double tracer test of absorp I Lab Clin Med 42: 860—866,1953 tion using a whole body monitor. Phys Med Biol 14: 455— 2. OLIVER RAM, BAKER GP: Juvenile pernicious anemia 462, 1969 and hypothyroidism. A family study. Br Med I 2 : 27—29, 9. IRVINEWJ, CULLERDR. [email protected], et al: Total 1969 body counting in the assessmentof vitamin B12absorption 3. GOLDBERGL, HICKEL Y, FUDENBERGH : Immunologic in patients with pernicious anemia, achlorhydnia without approaches to malabsorption of vitamin B@. Arch intern pernicious anemia, and in acid secretors. Blood 36: 20—27, Med 123:397—400,1969 1970 4. MILLERA, Coitaus H, SULLIVANJFA: Modified un 10. COTrRALL MF, WELLS DG, Thorn NG, et a!: Ra @ nary excretion test for measuring oral “Co-labeledvitamin dioactive vitamin absorption studies: comparison of the B@,absorption and its application in certain disease states. whole body retention, urinary excretion, and 8 hour plasma Blood 12:347—354,1957 levels of radioactive vitamin B12.Blood 38: 604—613,1971 5. SILBERSTEINEB: The Schilling test. JAMA 208: 2325— 11. CASTLEMAN B, MCNEELY B : Normal laboratory 2326, 1969 values.New Eng I Med 283: 1276—1285,1970 6. HEYSSELRM : Absorption and excretion of vitamin B@measured by whole-body counting.
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