(Tg) and Tg Antibody (TgAb) Testing for Patients Treated for Thyroid
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 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
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
October 23, 2006