Schilling Test Procedure, Definition, 4 Stages of Schilling Test, Interpretation and Risk

Schilling Test Definition

Schilling test can be defined as an investigation that is done to detect rate of Vitamin B12 (Cobalamin) absorption by use of radioactive Cobalamin; it also helps to know if the body is producing Intrinsic factor (a protein produced by the stomach that helps in absorption of vitamin B12. Intrinsic factor level is confirmed by Schilling test anti-intrinsic factor antibody or anti-parietal antibody.

What is Schilling Test?

The Schilling test helps to determine the cause of malabsorption of Vitamin B12 using a 4-stage process. The absorption of vitamin B12 is normally tested by giving radioactive vitamin B12 called (Cyano-Cobalamin) and then measuring its excretion in the urine. If the radioactivity excreted in the urine over a period of 24 hours is less than 8% of the amount administered, then there is Mal-absorption of Cyanocobalamin and the test is said to be positive. A negative Schilling test means there was excretion of greater than 8% in urine over 24 hours and therefore there was adequate absorption.

Disease conditions that require a Schilling test to be done

Disease Conditions that require Schilling Test

1. Deficiency of intrinsic factor that could be as a result of Pernicious anemia or gastric resection
2. Pancreatic insufficiency
3. Bacterial overgrowth in the intestine
4. Ileal resection or disease that affects the ileum

Any disease condition that causes malabsorption of vitamin B12 will require a Schilling Test. The use of the 4 stage Schilling test helps to differentiate these disease conditions mentioned above.

The 4-stage Schilling Test (How is Schilling Test Performed)

The 4 stage Schilling test has 4 phases that help to identify the underlying cause of Vitamin B12 deficiency.

1. Stage 1: Radioactive Cobalamine is given orally with non-labeled cobalamine this is given intramuscularly (to saturate body needs). Then 24 hours urine cobalamine excretion is determined . Normally >8% should be excreted, but if the excretion rate is < 8% , it may indicate malabsorption to Vitamin B12.
2. Stage 2: Labeled cobalamine bound to intrinsic factor is given orally; if Vitamin B12 deficiency was caused by pernicious anemia, Vitamin B12 absorption will be corrected i.e. the daily urinary excretion rate will be >8%. In patients with abnormal results (<8% excretion rate) such as in disease of the terminal ileum or pancreatic insufficiency, Vitamin B12 absorption will not be corrected.
3. Stage 3: Radioactive cobalamin repeated after 2 weeks of antibiotics. Vitamin B12 absorption is corrected in patients with bacterial over growth such as in blind loop syndrome.
4. Stage 4: A fourth stage is done to determine Malabsorption of Vitamin B12 caused by Chronic pancreatitis. In this stage: Radiolabeled Cobalamin is given after a 3 day course of pancreatic enzymes; if it is caused by chronic pancreatitis; the excretion rate is corrected.

Use of Schilling Test to differentiate Malabsorption caused by Ileal disease and malabsorption caused Pernicious Anemia

In order to differentiate malabsorption caused by Pernicious anemia and that caused by Ileal disease, the Schilling test is repeated but with the addition of intrinsic factor; if normal absorption occurs when intrinsic factor is added, then it was pernicious anemia due to intrinsic factor deficiency that caused the malabsorption of Vitamin B12; but if there is still abnormal result even after adding intrinsic factor then the malabsorption is caused by ileal disease.

Use of Schilling Test to differentiate bacterial overgrowth and Ileal disease

The Schilling test can also be used to differentiate if mal-absorption of Cobalamin was caused by disease of the ileum or it was due to bacterial overgrowth. This can be done by repeating the Schilling test with an antibiotic that destroys Anaerobes (anaerobicidal antibiotic) this reduces the bacterial overgrowth and enables commencement of Vitamin B12 absorption and normal absorption occurs giving a Negative Schilling Test following the antibiotic addition (This means the malabsorption was earlier caused by Bacterial overgrowth). If a Positive Schilling test still occurs following addition of Antibiotics, then it was caused disease of the Ileum.

Schilling Test Procedure and Interpretation

Schilling Test Procedure

1. Give 1microgram of ⁵⁴Co-labelled cobolamin orally and collect urine for 24hrs
2. Administer 1mg intramuscularly of ordinary cobolamin 1hr after the first radiolabelled dose in order to block hepatic cobolamin binding sites (flushing out dose)
3. Urine is collected over a 24 hour period, (the urine passed before giving the labelled B12 is discarded)
4. Radioactivity of urine collected and of a standard is measured.
5. Step 1: Radiolabeled Cobalamin plus intrinsic factor corrects for pernicious anemia
6. Step 2: Radiolabeled Cobalamin plus pancreatic enzymes corrects in chronic pancreatitis
7. Step 3: Repeat Radiolabeled Cobalamin after 5 days of oral antibiotics this normalizes in bacterial overgrowth

Calculation of the percentage of Vitamin B12 dose excreted in the urine:

Percentage = [(Total counts/min. in 24 hr urine sample) / (counts/min. in the standard known as the test dose)] X 100

When radiolabelled vitamin B12 is given orally and the amount of radioactivity absorbed into the blood and excreted in the urine is measured. If lack of intrinsic factor is a problem, then absorption will be low unless intrinsic factor is also given orally.

If absorption is low when vitamin B12 and intrinsic factor are given together, then the terminal ileum is likely to be damaged or there is something else blocking absorption of the B12/Intrinsic Factor complex.

Causes of Positive Schilling Test (Reasons for Malabsorption)

1. The absorption is decreased in ileal disease
2. Intrinsic factor deficiency such as in Pernicious anemia
3. Bacterial overgrowth in the Gastrointestinal tract

Types of Radioactive Cobalamin Isotopes used in Schilling Test

1. Co 60 or Co 58 (with half-life of 71 days)
2. Co 57 with half-life of 270 days

Schilling Test Interpretation

1. Normal Schilling test should give a value of > 30% excretion in 24hrs
2. Abnormal test is defined as < 10% excretion in 24hrs and is seen in Pernicious anemia, Chronic pancreatitis, Bacterial overgrowth and Ileal disease.

Note: False results may be obtained in patients with associated renal diseases.

Schilling Test Uses

1. Test used to determine absorption of vitamin B12 by measuring excretion of radioactive B12 in the urine.
2. Used to distinguish pernicious anemia from nutritional anemia.

Risks of Schilling Test (Side effects)

1. Inflammation at site of injection (Local skin reaction)
2. Nausea
3. Lightheadedness