Schilling test

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Schilling test
Purposeinvestigation used for patients with vitamin B12 deficiency

The Schilling test was a medical investigation used for patients with vitamin B12 (cobalamin) deficiency. [1] The purpose of the test was to determine how well a patient is able to absorb B12 from their intestinal tract. The test is now considered obsolete and is rarely performed, and is no longer available at many medical centers. It is named for Robert F. Schilling. [2]

Contents

Process

The Schilling test has multiple stages. [3] 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 B12 and folate deficiency themselves.

Stage 1: oral vitamin B12 plus intramuscular vitamin B12 (without IF)

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[ clarification needed ] or saturate body stores of B12. 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.

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 is caused by 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.

Stage 3: vitamin B12 and antibiotics

This stage is useful for identifying patients with bacterial overgrowth syndrome. The physician will provide a course of 2 weeks of antibiotics to eliminate any possible bacterial overgrowth and repeat the test to check whether radio-labeled Vitamin B12 would be found in urine or not.

Stage 4: vitamin B12 and pancreatic enzymes

This stage, in which pancreatic enzymes are administered, can be useful in identifying patients with pancreatic insufficiency. The physician will give 3 days of pancreatic enzymes followed by repeating the test to check if radio-labeled Vitamin B12 would be detected in urine.

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 is performed with the 'Dicopac' kitset. This allows for only a single radioactive urine collection. [4]

Complications

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, [5] 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. [6]

Diagnoses

Part 1 test resultPart 2 test resultDiagnosis
Normal-Normal or dietary vitamin B12 deficiency
LowNormalProblems with intrinsic factor production, e.g. Pernicious anemia
LowLow Malabsorption (terminal ileum)

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<span class="mw-page-title-main">Intrinsic factor</span> Glycoprotein produced in the stomach which binds to vitamin B12

Intrinsic factor (IF), cobalamin binding intrinsic factor, also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells (in humans) or chief cells (in rodents) of the stomach. It is necessary for the absorption of vitamin B12 later on in the distal ileum of the small intestine. In humans, the gastric intrinsic factor protein is encoded by the CBLIF gene. Haptocorrin (transcobalamin I) is another glycoprotein secreted by the salivary glands which binds to vitamin B12. Vitamin B12 is acid-sensitive and in binding to haptocorrin it can safely pass through the acidic stomach to the duodenum.

<span class="mw-page-title-main">Pernicious anemia</span> Anemia caused by vitamin B12 deficiency

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Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety of anaemias.

<span class="mw-page-title-main">Achlorhydria</span> Medical condition

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<span class="mw-page-title-main">Folate deficiency</span> Abnormally low level of folate (vitamin B9) in the body

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<span class="mw-page-title-main">Hydroxocobalamin</span>

Hydroxocobalamin, also known as vitamin B12a and hydroxycobalamin, is a vitamin found in food and used as a dietary supplement. As a supplement it is used to treat vitamin B12 deficiency including pernicious anemia. Other uses include treatment for cyanide poisoning, Leber's optic atrophy, and toxic amblyopia. It is given by injection into a muscle or vein.

<span class="mw-page-title-main">Subacute combined degeneration of spinal cord</span> Medical condition

Subacute combined degeneration of spinal cord, also known as myelosis funiculus, or funicular myelosis, also Lichtheim's disease, and Putnam-Dana syndrome, refers to degeneration of the posterior and lateral columns of the spinal cord as a result of vitamin B12 deficiency (most common), vitamin E deficiency, and copper deficiency. It is usually associated with pernicious anemia.

Vitamin B<sub>12</sub> deficiency Disorder resulting from low blood levels of vitamin B12

Vitamin B12 deficiency, also known as cobalamin deficiency, is the medical condition in which the blood and tissue have a lower than normal level of vitamin B12. Symptoms can vary from none to severe. Mild deficiency may have few or absent symptoms. In moderate deficiency, feeling tired, anemia, soreness of the tongue, mouth ulcers, breathlessness, feeling faint, rapid heartbeat, low blood pressure, pallor, hair loss, decreased ability to think and severe joint pain and the beginning of neurological symptoms, including abnormal sensations such as pins and needles, numbness and tinnitus may occur. Severe deficiency may include symptoms of reduced heart function as well as more severe neurological symptoms, including changes in reflexes, poor muscle function, memory problems, blurred vision, irritability, ataxia, decreased smell and taste, decreased level of consciousness, depression, anxiety, guilt and psychosis. If left untreated, some of these changes can become permanent. Temporary infertility reversible with treatment, may occur. In exclusively breastfed infants of vegan mothers, undetected and untreated deficiency can lead to poor growth, poor development, and difficulties with movement.

Jejunoileal bypass (JIB) was a surgical weight-loss procedure performed for the relief of morbid obesity from the 1950s through the 1970s in which all but 30 cm (12 in) to 45 cm (18 in) of the small bowel were detached and set to the side.

Vitamin B<sub><small>12</small></sub> Vitamin used in animal cells metabolism

Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. It is important in the normal functioning of the nervous system via its role in the synthesis of myelin, and in the circulatory system in the maturation of red blood cells in the bone marrow. Plants do not need cobalamin and carry out the reactions with enzymes that are not dependent on it.

<span class="mw-page-title-main">Cyanocobalamin</span> Manufactured form of vitamin B-12

Cyanocobalamin is a form of vitamin B
12
used to treat vitamin B
12
deficiency
except in the presence of cyanide toxicity. The deficiency may occur in pernicious anemia, following surgical removal of the stomach, with fish tapeworm, or due to bowel cancer. It is less preferred than hydroxocobalamin for treating vitamin B
12
deficiency. It is used by mouth, by injection into a muscle, or as a nasal spray.

Robert Frederick Schilling, M.D. (1919– 30 September 2014) was a physician best known for his research on Vitamin B12. Schilling was a Professor Emeritus at the University of Wisconsin. He is the namesake of the Schilling test.

<span class="mw-page-title-main">Imerslund–Gräsbeck syndrome</span> Medical condition

Imerslund–Gräsbeck syndrome is a rare autosomal recessive, familial form of vitamin B12 deficiency caused by malfunction of the "Cubam" receptor located in the terminal ileum. This receptor is composed of two proteins, amnionless (AMN), and cubilin. A defect in either of these protein components can cause this syndrome. This is a rare disease, with a prevalence about 1 in 200,000, and is usually seen in patients of European ancestry.

Cubam, is the term used to refer to a multi-ligand receptor located in the terminal ileum, specializing in absorption of vitamin B12. Cubam is essentially composed of amnionless (AMN), and cubilin. Cubilin is essential as a cell receptor recognizing the "vitamin B12-intrinsic factor" complex, whereas amnionless is more involved in the receptor mediated endocytosis of the complex.

References

  1. Zuckier LS, Chervu LR (September 1984). "Schilling evaluation of pernicious anemia: current status". Journal of Nuclear Medicine. 25 (9): 1032–9. PMID   6470805.
  2. "Schilling+test - Definition from Merriam-Webster's Medical Dictionary". Archived from the original on 2013-01-28. Retrieved 2008-10-05.
  3. "MedlinePlus Medical Encyclopedia: Schilling test" . Retrieved 2009-05-02.
  4. 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.
  5. Nickoloff E (1988). "Schilling test: physiologic basis for and use as a diagnostic test". Crit Rev Clin Lab Sci. 26 (4): 263–76. doi:10.3109/10408368809105892. PMID   3077032.
  6. 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.