Case Author(s): David A. Hillier, M.D., Ph.D. and Jerold Wallis, M.D. , . Rating: #D3, #Q3

Diagnosis: Pernicious anemia

Brief history:

40 year-old man with anemia.


Schilling test

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Full history/Diagnosis is available below

Diagnosis: Pernicious anemia

Full history:

40 year-old man with anemia and low serum B-12 levels.


Schilling test, 4.0 uCi Co-58 cyanocobalamin, po; 0.5 uCi Co-57 cyanocobalamin-intrinsic factor complex, po; Separate 1 mg intramuscular injections of cyanocobalamin following tracer adminstration on day 1, and again the following morining.


Poor absorption of free B12 (C0-58 labeled), with only 0.82% of the dose excreted in the urine (normal > 10%).

Good absorption of B12 when bound to intrinsic factor (Co-57-IF), with 16.3% of the dose excreted into the urine.

The ratio between these values is 19.9. If intrisic factor had not made a difference, this ratio would be close to 1.


Megaloblastic anemia may be due to folic acid or B12 deficiency. There are three types of B12 deficiency (1st two of which are tested by Schilling tests):

- Lack of intrinsic factor (Pernicious anemia, gastrectomy)

- Intestinal factors (malabsorption syndrome, blind loop syndrome, tapeworm)

- Impaired conversion of vitamin B12 to an active coenzyme

In the Schilling test (part 1), radiolabeled B12 is given orally. Rather than counting the patient to assess absorption, injections of non-radioactive B12 are given to flush the absorbed radioactive B12 into the urine. The urine is collected for 24 to 48 hours and then counted in a well counter, serving as a measure of the patient's absorption of B12. If part 1 is abnormal, we know that absorption is impaired, but not whether the cause is a deficiency of intrinsic factor.

In the Schillings test (part 2), intrinsic factor is given orally, along with the tracer dose, to see if absorption is improved.

In the dual-isotope test (used here), Shillings part 1 and part 2 are done simultaneously -- tracers bound to B12 and B12-IF complex are given orally using two different radioisotopes (so that we can distinguish them when counting the urine sample). At 1 hour, IM injection of B12 is given to block peripheral sites. The urine is collected for 24 hours. IM B12 is readministered. An additional 24 hour urine collection is obtained.

In this patient, the marked improved with intrinsic factor is diagnostic of intrinsic factor deficiency (Pernicious Anemia).

If the Schillings test is normal in a patient with low serum B12 levels, the most likely explanation is that the patient absorbs B12 when in pill form, but has difficulty absorbing B12 when bound to food (e.g., due to impaired digestion from atrophic gastritis). B12 suppliments in pill form will be effective in these patients.


Babior, B and Bunn HF. Megaloblastic anemias, in ..., 1726-.

Toh B, et al. Pernicious anemia. NEJM. 337, 1441-1448. 1997.

Differential Diagnosis List

Megaloblastic anemia may be due to cobalamin deficiency, folic acid deficiency and other rare miscellanious disorders. Coboloamin deficiency may be due to inadequate intake (e.g., vegetarians), malabsorption (intrinsic factor deficiency, terminal ileum disorders, bacterial overgrowth), some medications. The results in this patient indicate intrinsic factor deficiency,

ACR Codes and Keywords:

References and General Discussion of Schilling Test (Anatomic field:Gasterointestinal System, Category:Misc)

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Case number: st002

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