The Schilling test was a medical investigation used for patients with
vitamin B
B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism and synthesis of red blood cells. Though these vitamins share similar names (B1, B2, B3, etc.), they are chemically distinct compounds that often coexist ...
(cobalamin) deficiency.
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.
Process
The Schilling test has multiple stages.
As noted below, it can be done at any time after vitamin B 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 B shot, and also oral folic acid), in order to ensure that impaired absorption of B (with or without intrinsic factor) is not occurring due to damage to the intestinal mucosa from the B and folate deficiency themselves.
Stage 1: oral vitamin B plus intramuscular vitamin B12 (without IF)
In the first part of the test, the patient is given
radiolabeled
A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tr ...
vitamin B to drink or eat. The most commonly used radiolabels are
57Co and 58Co. An
intramuscular
Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have l ...
injection of unlabeled vitamin B is given an hour later. This is not enough to replete or saturate body stores of B. The purpose of the single injection is to temporarily saturate B receptors in the liver with enough normal vitamin B to prevent radioactive vitamin B 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 B will be absorbed into the body. Since the body already has liver receptors for
transcobalamin
Transcobalamins are carrier proteins which bind cobalamin (B12).
Types
* Transcobalamin I (TCN1), also known as haptocorrin, R-factor, and R-protein, is a glycoprotein produced by the salivary glands of the mouth. It primarily serves to protect ...
/vitamin B saturated by the injection, much of the ingested vitamin B will be
excreted
Excretion is a process in which metabolic waste
is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...
in the urine.
* A normal result shows at least 10% of the radiolabeled vitamin B 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 B 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 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 B 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
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 o ...
.
* If this second urine collection is normal, this shows a lack of intrinsic factor production. This is by definition
pernicious anemia
Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic fa ...
.
* A low result on the second test implies abnormal
intestinal
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...
absorption (
malabsorption
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 ...
), which could be caused by
coeliac disease
Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...
,
biliary
A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates.
Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...
disease,
Whipple's disease
Whipple's disease is a rare systemic infectious disease caused by the bacterium '' Tropheryma whipplei''. First described by George Hoyt Whipple in 1907 and commonly considered as a gastrointestinal disorder, Whipple's disease primarily causes m ...
, small bowel
bacterial overgrowth syndrome
Small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth, or small bowel bacterial overgrowth syndrome (SBBOS), is a disorder of excessive bacterial growth in the small intestine. Unlike the colon (or large bowel), which is ...
, fish tapeworm infestation (
Diphyllobothrium
''Diphyllobothrium'' is a genus of tapeworms which can cause diphyllobothriasis in humans through consumption of raw or undercooked fish. The principal species causing diphyllobothriasis is ''D. latum'', known as the broad or fish tapeworm, or b ...
latum), or
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
disease. Malabsorption of B 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 B and antibiotics
This stage is useful for identifying patients with
bacterial overgrowth syndrome
Small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth, or small bowel bacterial overgrowth syndrome (SBBOS), is a disorder of excessive bacterial growth in the small intestine. Unlike the colon (or large bowel), which is ...
. 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 B and pancreatic enzymes
This stage, in which
pancreatic enzymes
Digestive enzymes are a group of enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption into the cells of the body. Digestive enzymes are found in the digestive tracts of anima ...
are administered, can be useful in identifying patients with
pancreatic insufficiency
Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack of digestive enzymes made by the pancreas. EPI is found in humans afflicted with cystic fibrosis and Shwachman–Diamond syndrome, and is common in d ...
. 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, B 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 B. This is performed with the 'Dicopac' kitset. This allows for only a single radioactive urine collection.
Complications
Note that the B shot which begins the Schilling test is enough to go a considerable way toward treating B deficiency, so the test is also a partial ''treatment'' for B deficiency. Also, the classic Schilling test can be performed at any time, even after full B repletion and correction of the anemia, and it will still show if the cause of the B deficiency was intrinsic-factor related. In fact, some clinicians have suggested that folate and B replacement for several weeks be normally performed ''before'' a Schilling test is done, since folate and B deficiencies are both known to interfere with intestinal cell function, and thus cause malabsorption of B on their own, even if intrinsic factor is being made. This state would then tend to cause a false-positive test for both simple B and intrinsic factor-related B malabsorption. Several weeks of vitamin replacement are necessary, before epithelial damage to the G.I. tract from B deficiency is corrected.
Many labs have stopped performing the Schilling test,
due to lack of production of the cobalt radioisotopes and labeled-B test substances. Also, injection replacement of B has become relatively inexpensive, and can be self-administered by patients, as well as megadose oral B. Since these are the same treatments which would be administered for most causes of B 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 B testing is not allowed to lapse).
It is possible for use of other radiopharmaceuticals to interfere with interpretation of the test.
Diagnoses
References
External links
*
{{Digestive system procedures
Chemical pathology