Schilling test

The Schilling's test is a medical investigation used in patients with vitamin B₁₂ deficiency. The purpose of the test is to determine if the patient has pernicious anemia. There are a few variations on the exact procedure used.

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In the first part of the test, the patient is given radiolabeled vitamin B₁₂ to drink. The most commonly used radiolabels are ⁵⁷Co and ⁵⁸Co. An intramuscular injection of unlabeled vitamin B₁₂ is given at around the same time. The purpose of this injection is to saturate tissue stores with normal vitamin B₁₂ to prevent radioactive vitamin B₁₂ binding in body tissues, so that if absorbed, 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 radiolabelled vitamin B₁₂ in the urine over the first 24 hours. In patients with pernicious anemia or with deficiency due to impaired absorption, less than 5% of the radiolabeled vitamin B₁₂ is detected.

If an abnormality is found, 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, 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.

In some versions of the Shilling's 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 Shilling's 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 Shilling 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 full folate and B₁₂ replacement be normally performed before a Shilling's 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 intrinsic factor-related B₁₂ malabsorption.

Many labs have stopped performing the Shilling's test, due to lack of production of the cobalt radioisotopes and labeled-B₁₂ test substances.