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Contents of this Page
Thyroid Nodules and Cancer
Thyroid Nodules: Evaluation
Fine Needle Aspiration of the Thyroid
Blood Tests for People Treated for Thyroid Cancer
Thyroid Stimulating Hormone and TSH Suppression
Thyroglobulin (Tg) and Tg Antibody (TgAb) Testing for Patients Treated for Thyroid Cancers
Background About the Thyroid Gland
For More Information
By Leonard Wartofsky, M.D. Reprinted, with permission, from page 17 of Chapter 3 of the reference book “Thyroid Cancer: A Guide for Patients,” (Douglas Van Nostrand, M.D., Gary Bloom, and Leonard Wartofsky, M.D., editors. See http://www.thyca.org/about/TCGuide/
Are All Thyroid Nodules Cancer?
Most thyroid nodules are in fact benign (non-cancerous), and just the fact that you have a thyroid nodule should not create undue concern that it may be a cancer.
Most nodules rather than being cancer (carcinomas) are actually tumorous collections of benign cells variously called adenomas or adenomatoid nodules.
Whether nodules are "cold" or "hot" on thyroid nuclear scanning relates to their ability to trap and collect radioactive substances such as radioactive iodine or other radioactive elements used in nuclear medicine. These isotopes are either swallowed or injected intravenously and their extraction from the blood and concentration within the nodules causes the areas corresponding to the nodules to show up as black "hot" spots on the scan image.
Hot nodules are rarely cancer and most often represent benign follicular adenomas. In addition, such hot nodules may in fact be overproducing thyroid hormone and may cause hyperthyroidism. The larger the "hot" nodule the more likely it will be associated with hyperthyroidism. These nodules may produce either T4 or T3 or a combination of both.
Approximately 10 to 15 percent of patients with thyroid nodules that can be detected by physical examination will have cancerous nodules.
Most commonly, these cancerous nodules will be a specific type of thyroid cancer derived from the thyroid gland itself; hence they are referred to as primary thyroid tumors.
Less frequently, a nodule may represent spread of cancer from elsewhere in the body (metastatic or "secondary" cancer).
Steps in evaluating a thyroid nodule may include:
- Physical examination. This should include a laryngeal exam (checking the vocal cords).
- Neck ultrasound
- Fine needle aspiration (FNA) biopsy, often under ultrasound guidance. The fine needle aspiration (FNA) is the most reliable way to determine whether a nodule is benign, definitely cancerous, or possibly cancerous. The FNA cannot always determine whether cancer is definitely present. In this situation, the tissue analysis after thyroid surgery is used to determine the diagnosis.
- Thyroid function lab tests—blood tests
- Chest X-ray
- CT (computerized tomography) without iodine contrast—or other imaging techniques
- Thyroid scan with low-dose radioactive iodine or technetium
- Other blood testing involving molecular markers, for patients with indeterminate thyroid nodules
by Yolanda C. Oertel, M.D. Director, Fine Needle Aspiration Service Cancer Institute, Washington Hospital Center, Washington DC
This material plus many additional questions and answers were published as part of a chapter in the new book The Patient’s Guide to Thyroid Cancer, edited by Douglas Van Nostrand, M.D., Leonard Wartofsky, M.D., and Gary Bloom. This information is provided as an educational service to people being tested for possible thyroid cancer. It is not a substitute for a physician’s care, and you should consult with your physician about any medical condition. Special thanks to the physicians involved in thyroid cancer care at the Washington Hospital Center and the volunteers of ThyCa: Thyroid Cancer Survivors’ Association, Inc., for their assistance in developing this publication.
(c) Copyright 2010 by Yolanda C. Oertel, M.D. All rights reserved. You may print this out for your own use.
Your physician has just told you that you have a “lump” (or nodule) in your thyroid gland. Or you have felt a lump in your neck and have made an appointment to see your primary physician. If you are a woman from about 20 to 50 years old, you should understand that this is a common finding. Nevertheless, you may be concerned about the possibility of cancer. In fact, most nodules or “lumps” in the thyroid are NOT cancerous.
The challenge for the physician is to determine which nodules are benign and which nodules are cancerous. The following qualities may provide useful information, but they will NOT determine whether the nodule is benign or malignant:
- How long the nodule has been present
- Whether it is tender or not
- Whether it feels soft, rubbery, or firm to the touch
- The blood tests of thyroid function
- The response to thyroid hormone suppressive therapy
- Ultrasound findings
- Thyroid scans and uptake
The only test, prior to surgery, that is proven to differentiate a benign from a malignant nodule is the fine needle aspiration (FNA). Hence, your doctor will tell you that you need a fine needle aspiration of the nodule. What follows is some information about this procedure that will help you understand why and how it will be done.
What is a fine needle aspiration?
It is a simple procedure, similar to drawing blood from your arm. The needle used is thinner than the one for drawing blood and is attached to a syringe in a syringe holder that allows the operator to apply suction easily. Cells from your thyroid lesion will be extracted through this thin needle. If there is fluid in the “lump,” we will drain it. These cells are smeared (spread) on glass slides, stained, and made ready to be examined under the microscope. After examining all the slides, the pathologist will make a cytologic diagnosis and issue a written report.
Do I really need an aspiration?
An FNA is the only non-surgical method of determining whether your thyroid nodule is benign or malignant.
The “tumor is large and has to be removed.” In this instance, do I really need an aspiration (FNA)?
Yes, to avoid surprises for the surgeon. On rare occasions, a patient may have a medullary carcinoma or anaplastic carcinoma of the thyroid. Knowing this in advance will help the surgeon plan accordingly. Additional tests will be needed to exclude the possibility of other tumorssuch as pheochromocytoma. This is important because pheochromocytomas occur with high frequency in patients with medullary thyroid cancer, and they need to be managed prior to undertaking thyroid surgery.
Should I have an ultrasound prior to an FNA?
Most of the time it is not necessary. If your physician discovers a nodule and he or she (or the pathologist he or she works with) can perform an aspiration immediately, there is no need to wait for an ultrasound. You may have a diagnosis in 24 hours, and if the nodule is malignant, your appointment with a sorgeon can be scheduled within a few days.
What are the possible cytologic results of the FNA?
Usually the results will fall into one of four categories: benign (70-75% of cases), malignant (4-7%), inconclusive (10-15%), and unsatisfactory (1-10%). We will explain the meaning of each of these.
What is a benign diagnosis?
This implies that your nodule or lump is not a malignant tumor. It could be due to inflammation (thyroiditis), accumulated secretion from your gland (colloid nodule), irregular growth of your gland (hyperplastic nodule), or a cyst (fluid-filled nodule).
What is a malignant diagnosis?
This implies that your nodule is cancerous. There are several types of thyroidal cancers. The most common and the easiest to treat successfully is papillary carcinoma.
What is an inconclusive diagnosis?
An inconclusive diagnosis is one for which there is no certainty about the nature of your nodule; it could be either benign or malignant. This means that it is not possible to determine the nature of your lump. Either the FNA has to be repeated or the possibility of surgery should be discussed with your doctor.
What is an unsatisfactory diagnosis?
Whoever performed the FNA was not successful in obtaining enough cells from your thyroid to allow the pathologist to make a diagnosis. Most likely the doctor just obtained blood. It is as if no procedure had been done. The FNA has to be repeated (preferably by a more experienced aspirator). Please make sure that this is not confused with a benign diagnosis.
What are the recommended steps for someone whose results are reported as inconclusive?
The patient should discuss this interpretation with an endocrinologist. If the physician who ordered the FNA is an internist or family practitioner, I suggest that the patient consult an endocrinologist. If the FNA report is inconclusive because the nodule is cellular but not suspicious of malignancy, then the FNA should be repeated. Some endocrinologists believe that a trial of thyroid hormone therapy with subsequent repeat FNA in six to eight months might be appropriate. It might help to have the smears reviewed by another pathologist (second opinion) with a special interest or training in thyroid diseases who might be able to render a more definite diagnosis. If the diagnosis is “follicular neoplasm,” then surgery is indicated.
Could I have cancer that is not detected on FNA?
Yes, because no technique is 100% accurate. If your lump is large and there is a small focus of cancer (next to it or in it), the cancer may not be detected.
What is the accuracy rate of FNA?
The rate of accurate results depends on the skill and experience of the physician obtaining the samples and interpreting the smears under the microscope. The resuts reported in the medical literature vary considerably and may be difficult to interpret accurately.
Who may perform FNAs?
Any physician who is interested in learning how to perform the procedure properly and who has adequate physical facilities (examining table, sink, counter space, slides, slide-holders, etc.). These include endocrinologists and internists, surgeons, pathologists, and radiologists.
Free Booklet Available:
To receive a free copy of the 14-page booklet from which this article was taken, send a stamped (66 cents postage for 2 ounces mailed to address in USA), self-addressed #10 envelope or 6 x 9 envelope to:
FNA Patient’s Guide
PO Box 1102
Olney, MD 20830-1102
Note: The booklet fits folded in a #10 (business size) envelope or flat in a 6 x 9 envelope.
Last updated: March 13, 2023
Differentiated Thyroid Cancer (Papillary, Follicular, and their Variants)
There are three main blood tests:
- Thyroid Stimulating Hormone (TSH). See the section on Thyroid Stimulating Hormone and TSH Suppression
- Thyroglobulin (Tg): Thyroglobulin is a protein produced by thyroid cells (both normal and cancerous cells). After removal of the thyroid gland, Thyroglobulin can be used as a "cancer marker." Its number should be as low as possible. Sometimes this is termed "undetectable.” After your surgery and RAI, it may take months or years for the Tg number to come down to zero or undetectable.
A positive Tg test indicates that thyroid cells, either normal or cancerous, are still present in your body. Depending on the level of Tg in your blood, your doctor may want to monitor you more closely with other tests or scans and/or prescribe additional treatment.
If you did not receive RAI, your Tg level will probably be detectable. This is because some remnant thyroid tissue nearly always remains in your neck after surgery. If you had a lobectomy rather than a thyroidectomy, your remaining lobe will almost certainly produce Tg. However, it is still helpful to follow your Tg levels over time. If Tg levels increase, your doctor may recommend further imaging studies to locate the source.
From time to time, your doctor may recommend what is called a “stimulated Tg” measurement. This means that your TSH is elevated, by withdrawal from thyroid hormone or by receiving injections of the drug Thyrogen, and then your Tg is measured. Thyroglobulin testing can be more accurate when your TSH level is elevated.
- Anti-thyroglobulin anti-bodies (TgAb): Some people produce anti-thyrogloblin antibodies. These are not harmful. However, they mask the reliability of the Tg value. If you have TgAb, imaging studies may be used to monitor for persistent or recurrent disease. Sometimes the antibodies disappear over time, although not always.
In addition to these tests described above, some doctors will also recommend the measurement of Free T4. If so, discuss this with your doctor.
Medullary Thyroid Cancer
For people with medullary thyroid cancer, regular blood tests will measure calcitonin and CEA levels and any changes over time.
Anaplastic Thyroid Cancer
For people with anaplastic thyroid cancer who have had their thyroid gland removed, the blood testing for TSH is to monitor that the TSH is in the normal range.
If your thyroid was removed surgically, you will receive thyroid hormone replacement therapy (levothyroxine) for the rest of your life.
- If you have medullary or anaplastic thyroid cancer, you will receive a dose to keep your thyroid stimulating hormone (TSH) within the normal range.
- If you have papillary, follicular, or one of their variants, your dose of thyroid hormone replacement will be set for a target TSH level tailored to your individual risk of persistent or recurrent disease. Your doctor will order blood tests periodically to ensure that you are on the proper dose of thyroid hormone replacement.
- In low-risk patients, the goal for your TSH level may be 0.1 to 0.5 mU/L, which is just below or near the low end of the normal range. The goal may change to a level within the normal range, rather than below it, as time goes on.
- In people who are medium or high risk, the dose will be high enough to suppress the thyroid stimulating hormone (TSH) below the range that is normal for someone not diagnosed with thyroid cancer. The goal is to prevent the growth of cancer cells while providing essential thyroid hormone to the body. At first, your TSH will probably be suppressed to below 0.1 mU/L. The level may change, depending on your body’s response to the treatment.
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 (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
Why is the thyroid gland important?
The thyroid gland affects how we feel and how our body functions.
The thyroid gland is an endocrine gland. It produces hormones that circulate in your blood to the rest of your body.
Where is the thyroid gland and how big is it?
The thyroid gland is located in the front of your neck, just below the voice box or Adam’s apple. You usually cannot feel your healthy thyroid gland through your skin.
This gland is small. In an adult, it usually weighs one half to three fourths of an ounce (14 to 20 grams). It is about an inch wide (2.5 centimeters). It is shaped like a butterfly, with one “wing”(lobe) on each side of the windpipe (trachea). The two lobes are connected by a thin piece of tissue called the isthmus.
The thyroid gland contains 2 important types of cells. These are thyroid follicular cells and C cells (also referred to as parafollicular cells). C cells produce calcitonin, a specific hormone that helps to regulate the body’s use of calcium.
Differentiated thyroid cancer and anaplastic cancer are cancers of the follicular cells. Medullary thyroid cancer is cancer of C cells.
Parathyroids. Also important are four small glands behind the thyroid gland—the parathyroids. They produce parathyroid hormone, important in regulating your body’s calcium levels.
What does the thyroid gland do?
The thyroid hormones affect each body tissue, depending on the nature of the tissue. Your bloodstream carries thyroid hormones to all parts of your body.
A main effect of thyroid hormones is to regulate your body’s metabolism. Thyroid hormone regulates the rates of metabolism of carbohydrate, protein, and fat; growth and development; and physical and mental development and function. In the heart, thyroid hormone affects the heart rate.
People with thyroid nodules that are possibly cancer usually have normal levels of thyroid hormone. Also, most people with low or high levels of thyroid hormone do not have cancer.
Thyroid disorders involving low or high thyroid hormone levels are much more common than thyroid cancer. Too little thyroid hormone in the bloodstream can result in a condition known as hypothyroidism, which causes metabolism to slow down, and may leave the person feeling tired. Too much thyroid hormone in the bloodstream can result in a condition known as hyperthyroidism, which causes metabolism to speed up, and can result in an increased heart rate, among other things.
Hypothyroidism and hyperthyroidism are not usually related to thyroid cancer. However, anyone who has them should discuss treatment with their doctor, because each can have a serious negative impact on a person’s overall health.
- How Your Thyroid Works
- Common Tests to Examine Thyroid Gland Function
- Thyroid Nodules and Their Evaluation in Children and Adolescents
- Webinar: Afirma Gene Expression Classifier in Testing Thyroid Nodules
- Afirma Thyroid FNA Analysis: The Afirma Thyroid FNA Analysis from Veracyte combines cytopathology and the Afirma Gene Expression Classifier, for determining whether a thyroid nodule is benign or cancerous if the FNA is inconclusive.
- Physician Guidelines on Nodules and their Management
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Last updated: May 12, 2022