The Schilling test is a medical investigation used for patients with vitamin B12 (cobalamin) deficiency. The purpose of the test is to determine whether the patient has pernicious anemia. It is named for Robert F. Schilling.
The Schilling test has multiple stages. As noted below, it can be done at any time after vitamin B12 supplementation and body store replacement, and some clinicians recommend that in severe deficiency cases, at least several weeks of vitamin repletion be done before the test (more than one B12 shot, and also oral folic acid), in order to ensure that impaired absorption of B12 (with or without intrinsic factor) is not occurring, due to damage to the intestinal mucosa from the conditions of malabsorption arising from B12 and folate deficiency themselves.
Stage 1: oral vitamin B12 plus intramuscular vitamin B12
In the first part of the test, the patient is given radiolabeled vitamin B12 to drink or eat. The most commonly used radiolabels are 57Co and 58Co. An intramuscular injection of unlabeled vitamin B12 is given an hour later. This is not enough to replete or saturate body stores of B12 (this requires about 10 B12 injections over some length of time). The purpose of the single injection is to temporarily saturate B12 receptors in the liver with enough normal vitamin B12 to prevent radioactive vitamin B12 binding in body tissues (especially in the liver), so that if absorbed from the G.I. tract, it will pass into the urine. The patient's urine is then collected over the next 24 hours to assess the absorption.
Normally, the ingested radiolabeled vitamin B12 will be absorbed into the body. Since the body already has liver receptors for transcobalamin/vitamin B12 saturated by the injection, much of the ingested vitamin B12 will be excreted in the urine.
- A normal result shows at least 10% of the radiolabeled vitamin B12 in the urine over the first 24 hours.
- In patients with pernicious anemia or with deficiency due to impaired absorption, less than 10% of the radiolabeled vitamin B12 is detected.
The normal test will result in a higher amount of the radiolabeled cobalamin in the urine because it would have been absorbed by the intestinal epithelium, but passed into the urine because all hepatic B12 receptors were occupied. An abnormal result will cause less of the labeled cobalamin to appear in the urine because it will remain in the intestine and be passed into the feces.
Stage 2: vitamin B12 and intrinsic factor
If an abnormality is found, i.e. the B12 in the urine is only present in low levels, the test is repeated, this time with additional oral intrinsic factor.
- If this second urine collection is normal, this shows a lack of intrinsic factor production, or pernicious anemia.
- A low result on the second test implies abnormal intestinal absorption (malabsorption), which could be caused by coeliac disease, biliary disease, Whipple's disease, small bowel bacterial overgrowth syndrome, fish tapeworm infestation (Diphyllobothrium latum), or liver disease. Malabsorption of B12 can be caused by intestinal dysfunction from a low vitamin level in-and-of-itself (see below), causing test result confusion if repletion has not been done for some days previously.
Stage 3: vitamin B12 and antibiotics
This stage is useful for identifying patients with bacterial overgrowth syndrome.
Stage 4: vitamin B12 and pancreatic enzymes
Combined stage 1 and stage 2
In some versions of the Schilling test, B12 can be given both with and without intrinsic factor at the same time, using different cobalt radioisotopes 57Co and 58Co, which have different radiation signatures, in order to differentiate the two forms of B12. This allows for only a single radioactive urine collection.
Note that the B12 shot which begins the Schilling test is enough to go a considerable way toward treating B12 deficiency, so the test is also a partial treatment for B12 deficiency. Also, the classic Schilling test can be performed at any time, even after full B12 repletion and correction of the anemia, and it will still show if the cause of the B12 deficiency was intrinsic-factor related. In fact, some clinicians have suggested that folate and B12 replacement for several weeks be normally performed before a Schilling test is done, since folate and B12 deficiencies are both known to interfere with intestinal cell function, and thus cause malabsorption of B12 on their own, even if intrinsic factor is being made. This state would then tend to cause a false-positive test for both simple B12 and intrinsic factor-related B12 malabsorption. Several weeks of vitamin replacement are necessary, before epithelial damage to the G.I. tract from B12 deficiency is corrected.
Many labs have stopped performing the Schilling test, due to lack of production of the cobalt radioisotopes and labeled-B12 test substances. Also, injection replacement of B12 has become relatively inexpensive, and can be self-administered by patients, as well as megadose oral B12. Since these are the same treatments which would be administered for most causes of B12 malabsorption even if the exact cause were identified, the diagnostic test may be omitted without damage to the patient (so long as follow-up treatment and occasional serum B12 testing is not allowed to lapse).
It is possible for use of other radiopharmaceuticals to interfere with interpretation of the test.
|Part 1 test result||Part 2 test result||Diagnosis|
|Normal||-||Normal or vitamin B12 deficiency|
|Low||Normal||Problems with IF production e.g Pernicious anemia|
|Low||Low||Malabsorption (terminal ileum)|
- Zuckier LS, Chervu LR (September 1984). "Schilling evaluation of pernicious anemia: current status". Journal of Nuclear Medicine 25 (9): 1032–9. PMID 6470805.
- "Schilling+test - Definition from Merriam-Webster's Medical Dictionary". Retrieved 2008-10-05.
- "MedlinePlus Medical Encyclopedia: Schilling test". Retrieved 2009-05-02.
- Krynyckyi BR, Zuckier LS (September 1995). "Accuracy of measurement of dual-isotope Schilling test urine samples: a multicenter study [corrected]". J. Nucl. Med. 36 (9): 1659–65. PMID 7658228.
- Zuckier LS, Stabin M, Krynyckyi BR, Zanzonico P, Binkert B (December 1996). "Effect of prior radiopharmaceutical administration on Schilling test performance: analysis and recommendations". J. Nucl. Med. 37 (12): 1995–9. PMID 8970521.