- Also Known As:
- Papillary thyroid cancer
- Follicular thyroid cancer
- Medullary thyroid cancer (MTC)
- Anaplastic thyroid cancer
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What is the thyroid and what is thyroid cancer?
The thyroid is a small, butterfly-shaped gland located at the base of the neck that produces thyroid hormones, primarily thyroxine (T4) and some triiodothyronine (T3). These hormones travel throughout the body and regulate metabolism by telling the cells in the body how fast to use energy and produce proteins. The thyroid gland also makes calcitonin, a hormone that helps to regulate calcium levels in the blood by preventing the…
The thyroid is a small, butterfly-shaped gland located at the base of the neck that produces thyroid hormones, primarily thyroxine (T4) and some triiodothyronine (T3). These hormones travel throughout the body and regulate metabolism by telling the cells in the body how fast to use energy and produce proteins. The thyroid gland also makes calcitonin, a hormone that helps to regulate calcium levels in the blood by preventing the breakdown (reabsorption) of bone and increasing calcium elimination from the kidneys.
The body has an elaborate feedback system to control the amount of T4 and T3 in the blood:
- When blood levels of the hormones decrease, the hypothalamus releases thyrotropin-releasing hormone, which in turn causes the pituitary gland to release thyroid-stimulating hormone (TSH), also called thyrotropin. TSH stimulates the thyroid gland to produce and release T4 (primarily) and T3.
- As thyroid hormone levels increase in the blood, the pituitary gland produces less TSH and the thyroid produces less T4 and T3.
Under normal circumstances, this feedback system regulates thyroid activity to maintain relatively stable levels of thyroid hormones in the blood.
Thyroid cancer is the unregulated growth of thyroid cells. Thyroid cancer is most commonly suspected when your healthcare practitioner notices a change in the size or shape of your thyroid gland, or you or your practitioner feels a lump or swelling in the neck during a physical exam.
Because many other conditions can cause changes in thyroid gland size, shape or texture, further evaluations such as blood tests for thyroid function, ultrasound imaging, or other tests are often required. An enlarged thyroid can be a sign of many conditions besides cancer. Those conditions range from low iodine levels to inflammation caused by Hashimoto disease.
Many times, further evaluation of the thyroid gland reveals the presence of thyroid nodules. About 90% of thyroid nodules, or tumors, are not harmful (benign).
Rates of thyroid cancer diagnosis have increased worldwide over the last decade, likely due to tests that are more sensitive in detecting the disease. Thyroid cancer is three times more common in women than in men. Each year, about 53,000 new cases of thyroid cancer are diagnosed and roughly 2,000 people die of the disease.
Most thyroid cancers are found early, when they are most treatable, and have a good outlook (prognosis). Often, they can be cured, especially if they have not spread to other areas of the body. This is particularly true of the most common types, papillary and follicular thyroid cancers (see below).
There are four main types of thyroid cancer. They develop from different areas of the thyroid, which impacts treatment options and prognosis. The main types of thyroid cancer include:
- Papillary thyroid cancer: this is the most common form of thyroid cancer—about 80% of cases are papillary. The cancer cells develop from cells that line the follicles in the thyroid, which are the cells that make T4 and T3. These cancers grow slowly and are rarely fatal.
- Follicular thyroid cancer: this is the second most common thyroid cancer—about 10% of cases. These cancer cells also develop from cells that line the follicles. It is most common in countries where diets lack iodine. Hürthle cell carcinoma is a form of follicular thyroid cancer and accounts for about 3% of all thyroid cancer cases. Follicular and papillary thyroid cancer are sometimes referred to as differentiated thyroid cancer.
- Medullary thyroid cancer: this accounts for up to 4% of all thyroid cancers. The cancer cells develop from other cells in the thyroid called C cells, which make the hormone calcitonin. It can be sporadic or be inherited. Inherited medullary thyroid cancer, called familial medullary thyroid cancer (FMTC), is caused by a variant (mutation) in the RET gene. This type may be associated with multiple endocrine neoplasia type 2 (MEN2), which is also caused by variants in the RET gene. Medullary thyroid cancer may require more than one type of treatment and is harder to cure than more common thyroid cancers.
- Anaplastic thyroid cancer: also called undifferentiated carcinoma; makes up only 2% of thyroid cancers. It spreads quickly and is hard to treat.
About Thyroid Cancer
Causes and Risk Factors
The exact causes of thyroid cancer are not known. However, it is known that certain changes (mutations) in genes that make up DNA can cause thyroid cells to become cancerous. Although some of these genetic changes may be inherited, most of the changes that cause cancer are acquired during a person’s lifetime. They may happen spontaneously or may be due to something in the environment, such as radiation exposure. Examples of genes that are associated with thyroid cancer include BRAF, KRAS, NRAS, and fusion genes such as RET/PTC, Pax8/PPARG.
There are a number of factors that increase the risk of developing thyroid cancer. Some examples include:
- Gender – women are three times more likely than men to develop thyroid cancer.
- Age – two-thirds of thyroid cancers are diagnosed in people between the ages of 20 and 55.
- Exposure to radiation – x-rays received during the course of routine medical care are not a risk for thyroid cancer. Examples of radiation exposures that may increase risk include:
- Genetics – about 2 out 10 cases of medullary thyroid cancer are caused by an inherited variant in the RET gene. As mentioned above, these cases are called familial medullary thyroid cancer (FMTC) and may be associated with MEN2. Besides FMTC, other types of thyroid cancer can be inherited. Most of these cases are part of familial cancer syndromes such as:
- Familial adenomatous polyposis
- Cowden syndrome
- Carney complex
- Pendred syndrome
- Werner syndromePeople who have one of these syndromes are at increased risk of developing thyroid cancer, especially papillary thyroid cancer. There are typically other medical features or family history clues that would make your healthcare provider suspect one of these syndromes.
- Family history – having a close relative, such as a parent, sibling or child with thyroid cancer can increase your risk of developing thyroid cancer, even if it is not associated with a known familial cancer syndrome. In these cases, the genetic basis of the cancer is not clear.
Signs and Symptoms
A number of conditions can cause symptoms similar to thyroid cancer. For example, thyroid nodules are abnormal growths of thyroid tissue that form a swelling or lumps within the thyroid gland. These are common and usually not cancerous.
Detection of thyroid cancer relies on you or your healthcare practitioner recognizing the signs and symptoms, since screening tests for thyroid cancer are not recommended in the general population. Palpation of the thyroid is a routine part of a physical exam and may detect abnormalities in the thyroid gland. Talk to your healthcare provider right away if you have any of the following signs and/or symptoms:
- A lump that you can feel on your neck, sometimes with no other symptoms
- Neck swelling
- Voice changes, including increasing hoarseness
- Trouble breathing
- Trouble swallowing
- Swollen neck lymph nodes without an upper respiratory infection
The goals of thyroid cancer testing are to help diagnose and stage the cancer, weigh treatment options, and monitor treatment.
Screening tests are not recommended if you have no symptoms of thyroid cancer and have an average risk for developing thyroid cancer. However, if you have very high risk because you have a family history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia type 2 (MEN 2), it may be recommended that you are regularly screened with thyroid ultrasounds. In addition, you may receive genetic counseling and genetic testing for RET gene variants associated with MTC.
Diagnosis and Staging
If you have signs or symptoms of thyroid cancer, a healthcare practitioner will feel for changes in your thyroid and lymph nodes and ask about your medical and family history.
Thyroid cancer is ultimately diagnosed by biopsy. However, before a healthcare practitioner decides to perform a biopsy or surgery, you will receive imaging scans and blood tests. These tests help your healthcare provider diagnose your signs and symptoms, assess thyroid function, and, if present, determine the type of thyroid cancer.
Initial testing may include:
- Thyroid-stimulating hormone (TSH)—this is a blood test that evaluates thyroid function. It measures TSH levels released by the pituitary gland. TSH is used to evaluate other conditions that may cause signs and symptoms similar to thyroid cancer. If TSH levels are high, the thyroid may not be making enough hormones, a sign of hypothyroidism. If they are low, it may be a sign of hyperthyroidism. TSH levels are usually normal or high with thyroid cancer.
- Total or free T3 and free T4 (thyroid hormones)—these blood tests measure hormones made by the thyroid gland. These hormones are sometimes measured along with TSH to evaluate thyroid function. Levels are usually normal with thyroid cancer.
- Ultrasound of the thyroid gland—this is also one of the first tests used to evaluate your thyroid. Results of the ultrasound may show suspicious areas or that a nodule is present. It will also show a nodule’s location, size, shape and other characteristics and whether more than one nodule is present. The American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) guidelines recommend ultrasound evaluation of thyroid nodules, along with testing TSH levels, to determine if a biopsy is needed.
- Biopsy—a biopsy may be done to examine a small amount of tissue and/or fluid from a thyroid nodule. Often, a fine-needle aspiration (FNA) biopsy is done. This is a procedure that involves inserting a very thin needle into the thyroid nodule and withdrawing cells. An ultrasound may be used to guide the needle into the correct position. A pathologist will examine the cells using a microscope. (For in-depth information, see the article on Anatomic Pathology.)
- Calcitonin—this is a hormone produced by special cells in the thyroid called C-cells. It plays a role in how the body uses calcium. The cells that make calcitonin can also develop into medullary thyroid cancer. This test may be used during diagnosis to check for MTC. Elevated levels indicate that MTC is likely present.
- Carcinoembryonic antigen (CEA)—this is a protein that may be elevated with certain types of cancer. Blood tests for this protein are sometimes used to look for MTC. The protein is often elevated in people with MTC.
- Molecular testing of biopsied tissue—up to 30% of thyroid biopsy results are “indeterminate,” meaning it is not clear if they are cancerous. Diagnosing those cases often requires removing all or part of the thyroid during surgery. To avoid unnecessary surgeries, molecular tests may be used to help determine if nodules are cancerous or benign. Testing may include:
- Molecular testing of the biopsy material to detect cancer-causing variants (mutations) in certain genes (e.g., BRAF, KRAS, NRAS, and fusion genes such as RET/PTC, Pax8/PPARG).
- miRNA analysis—miRNAs are small RNA fragments that affect the behavior of certain genes. Since certain miRNAs are linked to cancer development, their presence in biopsied thyroid tissue can help determine if a nodule is malignant. Since miRNAs circulate in the bloodstream, they also offer promise for diagnostic blood tests.
Tests to Guide and Monitor Treatment
- Thyroglobulin (Tg)—this is a blood test for a protein made by the follicular cells of the thyroid. Thyroglobulin levels may be tested once the thyroid has been removed; if no thyroid tissue is left, and there is no remaining thyroid cancer, then thyroglobulin levels should be undetectable. If the level is high, or rises after surgery, it could be a sign that there are still thyroid cancer cells in the body or that the cancer is returning.
- Thyroglobulin antibody (TgAb)—these are proteins produced by the immune system that target thyroglobulin. Depending on the test method used, these antibodies can interfere with the results of the thyroglobulin test if they are present in your blood. If the antibodies are present, either the thyroglobulin test cannot be used to monitor levels or a method that is not affected by thyroglobulin antibodies must be used to monitor levels.
- Calcitonin—in addition to aiding diagnosis of MTC, the blood test for this hormone may be used for monitoring treatment and recurrence of MTC. With successful treatment, calcitonin levels will usually fall to very low levels. If, after successful treatment, calcitonin levels begin to rise, then it is likely that there is a recurrence of medullary thyroid cancer.
- Molecular markers—individuals who may benefit from targeted therapy will receive tests to look for the genetic mutations and proteins that those treatments target. Examples include BRAF mutations or fusion genes such as NTRK or RET/PTC.
- Radioactive iodine uptake—this test can assist in the evaluation of a thyroid nodule in patients with low TSH, because it can detect nodules that are producing too much thyroid hormone (which contains iodine). It is also used to look for persistence or recurrence of cancer in patients who have had previous surgery for papillary or follicular thyroid cancer and have an elevated thyroglobulin level. During the test, a small amount of radioactive iodine is swallowed or injected and pictures are taken at timed intervals to track the radioactive iodine’s location. For additional details on this test, visit RadiologyInfo.org. After surgery, areas of increased iodine uptake may represent thyroid cancer, and higher doses of radioactive iodine can be used to treat the cancer.
- Other imaging tests may include chest x-ray, computed tomography (CT) scans, positron emission tomography (PET) scans, or magnetic resonance imaging (MRI). These may be used in certain cases to evaluate the thyroid and/or determine the tumor’s spread to other parts of the body. They may also be used when surgery is planned as part of treatment to remove all or part of the thyroid and in follow up to a surgical procedure.
Thyroid cancer is divided into stages that describe the tumor’s size and how far the tumor has spread through the body. Generally, a higher stage means the tumor is larger and/or the cancer has spread further in the body. Your healthcare practitioner will determine the cancer’s stage primarily through biopsy and imaging tests. Staging is important for determining treatment and prognosis. For more detail, see the section on “Biopsies and examination of tissues” in the Anatomic Pathology feature article.
For thyroid cancer, different staging criteria are used depending on your age and the type of thyroid cancer you have.
Papillary and Follicular thyroid cancer:
Younger people are less likely to die from papillary or follicular thyroid cancer, so the stages for these cancers take this into account.
If you are younger than age 55:
Stage I: The tumor is any size; cancer may be in the thyroid, or may have spread to nearby tissues and lymph nodes. It has not spread to other parts of the body.
Stage II: The tumor is any size; cancer has spread from the thyroid to other parts of the body and may have spread to the lymph nodes.
If you are older than age 55:
Stage I: The tumor is 2 centimeters or smaller; cancer is limited to the thyroid.
Stage II: The tumor is 2-4 centimeters; cancer is limited to the thyroid.
Stage III: The tumor is larger than 4 centimeters and cancer is limited to the thyroid, or the tumor is any size and cancer has spread to just outside the thyroid or has spread to lymph nodes near the trachea or larynx.
Stage IV: The tumor is any size; cancer has spread outside of the thyroid to neck tissues and possibly the lymph nodes, or has spread to distant parts of the body such as lungs and bones.
Medullary thyroid cancer for any age:
Stage I: Tumor is 2 centimeters or smaller; cancer is limited to the thyroid.
Stage II: Tumor is larger than 2 centimeters and cancer is limited to the thyroid or the tumor is any size and cancer has spread just outside the thyroid, but not to lymph nodes.
Stage III: Tumor is any size and cancer has spread to the lymph nodes near the trachea and larynx and may have spread to other neck tissues.
Stage IV: The tumor is any size; cancer has spread beyond the thyroid to other areas such as the trachea, esophagus, and voice box, may have spread to lymph nodes or distant parts of the body such as lungs and bones.
Anaplastic thyroid cancer:
All anaplastic thyroid cancers are considered stage IV because they grow rapidly and are usually not found until they have progressed and spread to other areas of the neck. The cancer may have spread to lymph nodes or to distant parts of the body, such as the lungs and bones.
Prevention and Treatment
Since most risk factors for thyroid cancer like age and gender are outside of your control, there is little that can be done to prevent it. However, for individuals who test positive for specific RET variants that increase the risk for developing aggressive MTC, the American Thyroid Association does recommend preventive thyroid removal, even in children.
Most thyroid cancers, especially papillary and follicular cancers, are highly treatable. Thyroid cancer treatment depends on the type of thyroid cancer, how far it has progressed, and your individual health and preferences.
Most thyroid cancers are treated with surgery to remove all or part of the thyroid, followed by one or more therapies to kill or control remaining cancer cells, if needed. Individuals treated with surgery that removes all of the thyroid will also require hormone therapy to replace those normally made by the thyroid.
Besides surgery, treatment options for thyroid cancer include:
- Radioactive iodine therapy (for papillary or follicular cancers)
- External beam radiation therapy (EBRT)
- Targeted therapy
Though surgery and EBRT are still used for some medullary thyroid cancers (MTC), radioactive iodine therapy is not effective against MTC. Researchers have been looking for new drugs that specifically target cancer genes and proteins while avoiding damage to healthy cells. These targeted therapies include the drugs cabozantinib, vandetanib, and sorafenib. These may be used to treat people with large tumors or advanced metastatic cancer.
The targeted therapies sorafenib and lenvatinib have also been used to treat papillary and follicular thyroid cancers that are too advanced for treatment with surgical removal or have become resistant to radioactive iodine therapy.
For additional details on treatment, see the links in the Related Content section.
Sources Used in Current Review
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