Thyroglobulin (Tg) and Tg Antibody (TgAb) Testing for Patients Treated for Thyroid Cancers

The measurement of the protein Thyroglobulin (abbreviated Tg) in blood, is an important laboratory test for checking whether a patient still has some thyroid present. The power of a serum Tg measurement lies in the fact that Tg can only be made by the thyroid gland (either the remaining normal part or the tumorous part). This means that when a patient has had their thyroid completely removed, the measurement of Tg in a blood sample can be used to check whether there is any tumor left behind.

• Detectable Tg Levels: When patients have had cancerous growths that make Tg, the absence of Tg in a blood sample is usually good news for a patient who has had thyroid surgery to remove their thyroid gland containing a cancerous growth. However, many patients still have measurable levels of Tg in their blood after surgery. Often this Tg is coming from a small amount of normal thyroid left behind. This means that a measurable level of Tg does not necessarily indicate the presence of tumor. Often physicians will give a small dose of radioiodine to get rid of the last remaining part of the normal thyroid gland in order to make later Tg measurements a better marker for any tumor left behind.

• TSH & Tg: Thyroid Stimulating Hormone (TSH) is the pituitary (master gland at the base of the brain) hormone that drives the thyroid gland to produce thyroid hormones and as a by-product, release Tg into the blood. TSH is believed to cause the growth of most thyroid tumors. This is why it is important to take thyroxine medicine (e.g.: synthroid, levoxyl, unithroid) to keep TSH levels low. When TSH is high (before scanning) Tg is increased about ten times. You should not compare the Tg level measured while taking thyroxine medicine (when TSH is low) with the Tg level measured when TSH is high.

• Tg Measurements before Surgery: Many physicians still do not recognize the value of a pre-operative Tg measurement. A high Tg level before surgery does not indicate that a tumor is present. However, when a biopsy suggests that the growth is cancerous, the finding of a high Tg level before surgery is a good sign, because it suggests that the tumor makes Tg, and that after surgery Tg can be used as a sensitive tumor marker test. In fact, Tg will be a more sensitive post-operative tumor marker test when the cancerous growth is small and the pre-operative Tg is high!

When a patient has a low Tg pre-operatively, the cancerous growth might be unable to efficiently make Tg. In such patients, an undetectable Tg level after surgery is less reassuring than if the patient had had a high pre-operative Tg value. Conversely, when Tg is detected post-operatively in such patients despite ablation of all normal thyroid, this could indicate that a large amount of tumor is still present.

• Tg Measurements after Surgery: Changes in the Tg level over time (six months or yearly intervals) are more important than any one Tg result. After surgery, blood samples are usually taken for Tg measurement while the patient is taking their daily dose of thyroxine medication (TSH low).

• Tg Method-to Method Differences: Unfortunately, Tg measurement is technically difficult and different Tg methods produce different results. Tg measurements made by different laboratories on the same blood specimen from a patient can vary as much as two-times! It is important to compare Tg measurements made by the same method, if possible performed by the same laboratory. This is because method-to-method differences makes it impossible to tell whether a change in the Tg level means there is a change in the amount of tumor, or is just a problem with the way the test is done.

• Concurrent Tg Re-measurement: Some laboratories save all the unused blood left after a Tg test has been completed, so that the spare blood can be re-measured side-by-side with a future blood sample. This "concurrent remeasurement" approach is the best way to tell whether a change in the Tg level means that there has been a change in the amount of tumor, or is just due to the way the test was done. The concurrent remeasurement approach helps the physician check for tumor re-growth at an earlier stage. Additionally, laboratories that bank patient specimens will have them available for any new tumor-marker tests that may be developed in the future.

• Tg Antibodies (TgAb): Approximately 15 to 20 percent of thyroid cancer patients have antibodies to Tg that circulate in their blood. These antibodies are abbreviated as TgAb on laboratory reports. Unfortunately, TgAb interferes with the measurement of Tg by most methods. Whether these antibodies cause incorrectly high or low values depends on the type of Tg method used by the laboratory. Most clinical labs use the more modern type of Tg method (called immunometric assays (IMAs) or "sandwich" methods).

These methods typically report falsely low Tg values when TgAb is present in a patient's blood. Falsely low values may lead to a delay in necessary treatment. Alternatively, an inappropriately high Tg level, which can be a problem with some of the older type of Tg method (called radioimmunoassays, RIAs) can cause patient anxiety and lead to unnecessary scans or treatment. There is currently disagreement between professionals regarding the best type of method to use (IMA or RIA) for patients with antibodies.

Some laboratories in the United States believe that RIA methods have less TgAb interference and provide more clinically reliable values than IMA methods. In fact, these laboratories believe that IMA methods should not be used at all when TgAb is present, because an falsely low Tg value is more of a problem than a falsely high Tg one.

For example, an inappropriately low Tg value reported because of TgAb interference can lead to a delay in treatment. In contrast, an inappropriately high Tg value reported because of TgAb interference usually increases vigilance on the part of the physician. Some laboratories now restrict the use of the IMA methods to patients without antibodies and continue to use the older RIA-type methods for patients with antibodies, although the RIA test result takes longer to report.

• TgAb Methods: Since interference by Tg Antibodies has serious effects on the reliability of the Tg value reported, it is important to use a precise and sensitive Tg antibody test method to detect TgAb. Unfortunately, TgAb methods differ even more than Tg methods! Some patients are judged to be antibody-positive by some methods and antibody-negative by others. It is therefore important to compare TgAb measurements made by the same method, if possible performed by the same laboratory.

It is also important for the laboratory to use a modern sensitive immunoassay test to check for TgAb. You can tell if your TgAb was measured by one of these tests by the units that are reported. If the antibody result is followed by U/mL or IU/mL it is a modern immunoassay test. If the antibody is reported in titers (1:100, 1:400, 1:1600 etc) this is an insensitive old-style agglutination test.

• Serial TgAb Measurements: It is important for the laboratory to measure TgAb in every specimen sent for Tg measurement. This is both because a patient's TgAb status may change from positive to negative or vice versa, and also because the trend in TgAb values over time (i.e. 6 to 12 months) gives additional information on how well the tumor is responding to treatment.

A trend down in TgAb levels overtime (years) is a good sign that treatment is effective. In contrast, an increase over time may be an early sign of a recurrence. When a patient has TgAb detected, it is not unusual to see a temporary rise in the TgAb level during the first six months following radioiodine therapy. This may even be a sign of the effectiveness of the treatment. Usually, TgAb values return to the original value or below after six months.

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