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- Measurement of Thyroid Hormones
- Measurement of Pituitary Function
- Iodine Uptake
- Thyroid Scan
- Thyroid Ultrasound
- Thyroid Antibodies
- Thyroid Needle Biopsy
As we have seen
from our overview of normal thyroid physiology, the thyroid gland
produces T4 and T3. But this production is not possible without
stimulation from the pituitary gland (TSH) which in turn is also
regulated by the hypothalamus's TSH Releasing Hormone. Now, with
radioimmunoassay techniques it is possible to measure circulating
hormones in the blood. Knowledge of this thyroid physiology is
important in knowing what thyroid test or tests are needed to
diagnose different diseases.
No one single laboratory test is 100%
accurate in diagnosing all types of thyroid disease; however, a
combination of two or more tests can usually detect even the
slightest abnormality of thyroid function. For example, a low T4
level could mean a diseased thyroid gland or a non-functioning
pituitary gland not stimulating the thyroid function. Since the
pituitary gland would normally release TSH if the T4 is low, a
high TSH level is also present; this confirms that the thyroid
gland (not the pituitary gland) is responsible for the
hypothyroidism. If the T4 level is low and TSH is not elevated,
the pituitary gland is more likely to be the cause for the
hypothyroidism. Of course, this would drastically effect the
treatment since the pituitary gland also regulates the body's
other glands (adrenals, ovaries, and testicles) as well as
controlling growth in children and kidney function. Pituitary
gland failure means that the other glands may also be failing and
other treatment than just thyroid may be necessary. The most common
cause for the pituitary gland failure is a tumor of the pituitary
and this might also require surgery to remove.
The older tests of
thyroid function: Basal Metabolic Rate (BMR), basal body
temperature, Achilles Heel Reflex Time, and measurement of Protein
Bound Iodine (PBI) have been replaced by much more accurate
thyroid function tests. Modern measurement of thyroid hormones is
done by a new technique, radioimmunoassay (RIA), discovered by Dr.
Solomon A. Berson and Dr. Rosalyn S. Yallow. They were awarded the
1977 Nobel Prize in Medicine for this discovery which
revolutionized the study of thyroid disease as well as the entire
field of endocrinology.
The following tests of the thyroid are
those currently used today.
A. Measurement of Thyroid Hormones
T4 by
RIA (radioimmunoassay) is the most used thyroid test; it is
frequently referred to as a T7 which means that a resin T3 uptake
(RT3u) has been done to correct for certain medications such as
birth control pills, other hormones, seizure medication, cardiac
drugs, or even aspirin that may alter the routine T4 test. The T4
(or T7) reflects the amount of thyroxine in the blood. If the
patient does not take any type of thyroid medication, this test is
usually a good measure of thyroid function. As stated earlier,
thyroxine represents 80% of the thyroid hormone produced by the
normal gland and generally represents the overall function of the
gland. The other 20% is triiodothyronine measured as T3 by
RIA. Sometimes the diseased thyroid gland will start producing very
high levels of T3 but still produce normal levels of T4. Therefore
measurement of both hormones provides an even more accurate
evaluation of thyroid function.
Most of the thyroid hormones in the
blood are attached to a protein called thyroid binding globulin
(TBG). If there is an excess or deficiency of this protein it
alters the T4 or T3 measurement but does not affect the action of
the hormone. If a patient appears to have normal thyroid function,
but an unexplained high or low T4, or T3, it may be due to an
increase or decrease of TBG. Direct measurement of TBG can be done
and will explain the abnormal value.
Excess TBG or low levels of
TBG are found in some families as an hereditary trait. It causes
no problem except falsely elevating or lowering the T4 level.
These people are frequently misdiagnosed as being hyperthyroid or
hypothyroid, but they have no thyroid problem and need no
treatment.
B. Measurement of Pituitary Function
TSH by IRMA (immunoradiometric assay) is produced by the
pituitary gland. Normally, low levels (less than 5 units) of TSH
are sufficient to keep the normal thyroid gland functioning
properly. When the thyroid gland becomes inefficient such as in
early hypothyroidism, the TSH becomes elevated even though the T4
and T3 may still be within the "normal" range. This rise in TSH
represents the pituitary gland's response to a drop in circulating
thyroid hormone; it is usually the first indication of thyroid
gland failure. Since TSH is normally low when the thyroid gland
functions properly, the failure of TSH to rise when circulating
thyroid hormones are low is an indication of impaired pituitary
function. The new "sensitive" TSH test will show very low levels
of TSH when the thyroid is overactive. Interpretations of the TSH
level depends upon the level of thyroid hormone; therefore, the
TSH is usually used in combination with other thyroid tests such
as the T4 RIA and T3 RIA.
TRH test: In normal people TSH can be
increased by giving TSH Releasing Hormone (TRH). A baseline TSH of
5 or less usually goes up to 10-20 after giving an injection of
TRH. Patients with too much thyroid hormone (thyroxine or
triiodothyronine) will not show a rise in TSH when given TRH. This
"TRH test" is presently the most sensitive test in detecting early
hyperthyroidism. Patients who show too much response to TRH (TSH
rises greater than 40) may be hypothyroid. This test is also used
in cancer patients who are taking thyroid replacement to see if
they are on sufficient medication. It is sometimes used to measure
if the pituitary gland is functioning. The new "sensitive" TSH test
has eliminated the necessity of performing a TRH test in most
clinical situations.
C. Iodine Uptake
A third parameter of
measuring thyroid function is to measure how much iodine is taken
up by the thyroid gland (RAI uptake). Hypothyroid patients usually
take up too little iodine and hyperthyroid patients take up too
much iodine.
The test is performed by giving a tracer dose of
radioactive iodine on an empty stomach. The iodine is concentrated
in the thyroid gland or excreted in the urine over the next few
hours. The amount of iodine that goes into the thyroid gland can
be measured by a "Thyroid Uptake". Of course, patients who are
taking thyroid medication will not take up iodine in their thyroid
gland because their own thyroid gland is turned off and is not
functioning. At other times the gland will concentrate iodine
normally but will be unable to convert the iodine into thyroid
hormone; therefore, interpretation of the iodine uptake is usually
done in conjunction with blood tests.
D. Thyroid Scan
Taking a
picture of the thyroid gland requires giving a radioisotope to the
patient and letting the thyroid gland concentrate the isotope.
Therefore, it is usually done at the same time that the iodine
uptake test is performed. Although other isotopes, such as
technetium, will be concentrated by the thyroid gland; these
isotopes will not measure iodine uptake. It has also been found
that thyroid nodules that concentrate iodine are never cancerous;
this is not true if the scan is done with technetium. Therefore,
all scans we do are now done with iodine. Pregnant women should
not have thyroid scans performed.
Two types of thyroid scans are
available:
A rectilinear scan draws a picture of the gland to scale
on paper. This is the only type of scan that can be used to
measure the size of the gland. It is also best for identifying the
location of nodules when needle biopsies are necessary. This type
of scan is obtained by the scanner moving back and forth over the
gland and takes approximately forty-five minutes to perform.
Rectiliniear Thyroid Scan
A
camera scan is done using a gamma camera. The same camera as is
used for scanning the liver, brain, etc. The camera operates in a
fixed position and views the entire thyroid gland at once. This
type of scan takes only five to ten minutes, but the image
produced is not related to the actual size of the thyroid gland,
and the gland looks distorted similar to a picture taken with a
camera using a fisheye lens.
Camera Thyroid Scan
A rectilinear scan is the preferred
method of scanning. In the 1990's, a new scanner called a
Computerized Rectilinear Thyroid (CRT) scanner was introduced. The
CRT scanner utilizes computer technology to improve the clarity of
thyroid scans and enhance thyroid nodules. It measures both
thyroid function and thyroid size. A lifesize 1:1 color scan of
the thyroid is obtained giving the size in square centimeters and
the weight in grams. The precise size and activity of nodules in
relation to the rest of the gland is also measured.
CTS of the normal thyroid gland
In addition to making
thyroid diagnosis more accurate, the CRT scanner improves the
results of thyroid biopsy. The accurate sizing of the thyroid
gland aids in the follow-up of nodules to see if they are growing
or getting smaller in size. Knowing the weight of the thyroid
gland allows more accurate radioactive treatment in patients who
have Graves' disease.
Thyroid scans are used for:
- Identifying
nodules and telling if they show increased function ("hot") which
rules out malignancy or show decreased function ("cold").
- Measuring the size of the goiter prior to treatment.
- Follow-up of thyroid cancer patients after surgery.
- Locating thyroid tissue outside the neck, i.e. base of the tongue or in the
chest.
E. Thyroid Ultrasound
Thyroid ultrasound refers to the use of
high frequency sound waves to obtain an image of the thyroid gland
and identify nodules. It tells if a nodule is "solid" or a
fluid-filled cyst, but it will not tell if a nodule is benign or
malignant. Ultrasound allows accurate measurement of a
nodule's size and can determine if a nodule is
getting smaller or is growing larger during treatment.
Ultrasound measurement
Ultrasound aids in performing thyroid needle biopsy by improving accuracy.
More recently, ultrasound has become a primary way to follow patients who have
been operated on for thyroid cancer to detect early recurrence.
F. Thyroid Antibodies
The body normally produces antibodies to foreign
substances such as bacteria; however, some people are found to
have antibodies against their own thyroid tissue. A condition
known as Hashimoto's Thyroiditis is associated with a high level
of these thyroid antibodies in the blood. Whether the antibodies
cause the disease or whether the disease causes the antibodies is
not known; however, the finding of a high level of thyroid
antibodies is strong evidence of this disease. Occasionally, low
levels of thyroid antibodies are found with other types of thyroid
disease. The presence of thyroid antibodies has recently been
associated with an increase frequency of miscarriage. When
Hashimoto's thyroiditis presents as a thyroid nodule rather than a
diffuse goiter, the thyroid antibodies may not be present.
G. Thyroid Needle Biopsy
This has become the most reliable test to differentiate
the "cold" nodule that is cancer from the "cold" nodule
that is benign ("hot" nodules are never cancerous). It
provides information that no other thyroid test will
provide. While not perfect, it will provide valuable
information in 75% of the nodules biopsied. The needle
biopsy has reduced the number of patients who are
operated on for benign nodules and also permitted earlier
diagnosis in those patients who have cancer. In the past,
when thyroid surgery was performed on a thyroid nodule,
only one lobe of the thyroid was removed. If the nodule turned
out to be cancerous, the patient was then re-operated
upon to remove the rest of the thyroid gland.
Today, if the thyroid biopsy shows cancer, the entire
thyroid gland is removed with the first operation,
therefore avoiding a second unnecessary operation.
Thyroid needle biopsy is an office procedure and
requires no anesthesia. Except for minor bleeding, no
complications have occurred. The purpose of the biopsy is
to rule out or confirm malignancy. About 20% of such
biopsies are inconclusive and the thyroid pathologist
cannot be certain if the tumor is benign or malignant. In
such cases, a decision to operate is made upon other
criteria. About 5% of biopsies do not yield enough cells to
make a diagnosis.
In checking a person's thyroid gland, most tests need
to be done while not taking thyroid medication. Thyroid
antibodies, thyroid ultrasound, and thyroid needle biopsy
are not affected by such medicine. The other thyroid tests
measure both the thyroid we make and the thyroid we take.
These tests will determine if there is too much or too little
thyroid in the blood, but do not determine how much comes from the
thyroid gland and how much comes from
the thyroid pills.
Thyroid Needle Biopsy
Occasionally, it is important to measure a person's thyroid status who is
on medications such as doing a thyroid scan on a patient who had surgery for
thyroid cancer, or a person who was put on thyroid without adequate testing
before being started on medication. Since Euthyrox or Synthroid, and most
other thyroid pills behave exactly as normal human thyroid hormone, they are
not rapidly cleared from the body as other medications are. Most thyroid
pills have a half life of 6.7 days which means they must be stopped
for five weeks (five half lives) before accurate thyroid testing is possible.
An exception to the long half life of thyroid medication
is Cytomel - a thyroid pill with a half life of only forty-eight hours.
Therefore it is possible to change a person's thyroid replacement
to Cytomel for one month to allow time for his
regular pills to clear the body. Cytomel is then stopped for ten
days (five half lives) and the appropriate test can then be done.
Usually patients, even those who have no remaining thyroid
function, tolerate being off thyroid replacement only ten days
quite well.
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