Thyroglobulin (TG) and TG Antibody (Tgab) Testing For Patients Treated For Thyroid Cancers

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

By Carole Spencer, Ph.D., F.A.C.B President, 2001-2002, American Thyroid Association

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 byproduct, 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 preoperative 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 preoperative 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.
Last updated: October 23, 2006

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