NORD gratefully acknowledges David S. Cooper, MD, Professor of Medicine and Radiology, The Johns Hopkins University School of Medicine, for assistance in the preparation of this report.
Thyroid cancer (carcinoma) is cancer affecting the thyroid gland, a butterfly-shaped structure located at the base of the neck. The thyroid is part of the endocrine system, the network of glands that secrete hormones. Thyroid hormones regulate the chemical processes (metabolism) that influence the body’s activities as well as regulating the heart rate, body temperature, and blood pressure. Hormones are secreted directly into the bloodstream where they travel to various areas of the body.
In many people, there are no symptoms (asymptomatic) associated with thyroid cancer. Pain in the neck, hoarseness and swollen lymph nodes especially in the neck may be present in some people. Thyroid cancer is the most common form of cancer affecting the endocrine system. Most forms rarely cause pain or disability and are easily treated with surgery and follow-up therapy. However, some forms are aggressive and more difficult to treat.
The term “cancer” refers to a group of diseases characterized by abnormal, uncontrolled cellular growth that invades surrounding tissues and may spread (metastasize) to distant bodily tissues or organs via the bloodstream, the lymphatic system, or other means. Different forms of cancer, including thyroid cancer, may be classified based upon the cell type involved, the specific nature of the malignancy, and the disease’s clinical course. The four main types of thyroid cancer are papillary, follicular, medullary and anaplastic. Rare forms of thyroid cancer include thyroid teratoma, lymphoma, and squamous cell carcinoma. Papillary cancer is by far the most common, comprising about 80% of all thyroid cancer.
Malignant cells pass their abnormal changes on to all their “daughter” cells and typically grow and divide at an unusually rapid, uncontrolled rate that cannot be contained by the body’s natural immune defenses. Eventually, such proliferation of abnormal cells may result in formation of a mass known as a tumor (neoplasm). Disease progression may be characterized by invasion of surrounding tissues, infiltration of regional lymph nodes, and spread of the malignancy via the bloodstream, the lymphatic circulation, or other means to other bodily tissues and organs.
The vast majority individuals with thyroid cancer have no symptoms (asymptomatic). In most cases, a small growth or lump (nodule), discovered by the patient, health care provider, or incidentally on an imaging study (e.g., a CT scan, MRI, or carotid artery ultrasound), is the first sign of thyroid cancer. Thyroid “nodules” or lumps in the thyroid may be caused by a variety of conditions and do not necessarily mean that an individual has cancer. In fact, more than 90 percent of thyroid nodules are not cancerous (benign).
Symptoms that may be associated with thyroid cancer include hoarseness, difficulty breathing or swallowing, swollen lymph nodes especially in the neck, and pain in the throat or neck.
Cancer can arise from any of the types of cells found in the thyroid gland. Approximately 90 percent of thyroid cancers arise from follicular cells (the cells that comprise most of the thyroid and make thyroid hormone). Most of the remaining cases arise from C cells (parafollicular cells). Cancer arising from white blood cells (lymphocytes), known as lymphoma, may also occur. Extremely rare forms of thyroid cancer include squamous cell carcinoma and teratomas.
Thyroid cancer may also be classified as well-differentiated or poorly differentiated. Differentiation refers to how abnormal the cells look under a microscope, how rapidly they grow, and whether they retain the features of normal thyroid cells, such as the ability to trap iodine. Well-differentiated cancers are made of cells that retain the look of the cells from which they arose (e.g., thyroid follicular cells). More “poorly differentiated” or “undifferentiated” cancers are made of cells that have undergone transformation and revert to a less specialized, more primitive form. Therefore, they are no longer capable of performing their “intended”, specialized functions within the tissue in question.
Well-differentiated thyroid cancer usually refers to papillary or follicular forms of thyroid cancer. These forms of thyroid cancer are sometimes simply referred to as differentiated thyroid cancer or DTC. Insular thyroid carcinoma is referred to as poorly differentiated thyroid cancer. Anaplastic thyroid cancer is also known as undifferentiated thyroid cancer. Naturally, well-differentiated carcinomas have a better prognosis.
Papillary Thyroid Carcinoma (PTC)
PTC is the most common form of thyroid cancer, accounting for approximately 80 percent of patients. PTC arises from the thyroid follicular cells. This form of thyroid cancer usually presents as a single lump in the thyroid and often progresses slowly. PTC has a propensity to spread (metastasize) via the lymph nodes and the lymphatic system, especially to local lymph nodes in the neck.
PTC can affect individuals of any age including children, but most often affects people between 30 and 50 years of age. Women are affected more often than men.
Variants of Papillary Thyroid Carcinoma
There are several subtypes or variants of PTC; common subtypes include follicular, tall cell, and diffuse sclerosing variants. These names refer to what the thyroid cancers look like under the microscope.
The follicular variant of PTC, which is different from follicular thyroid carcinoma, is the most common subtype in the United States. The follicular variant is a slow growing form of cancer. The clinical behavior of this subtype is similar to PTC in general.
The tall cell variant (TCV) of PTC is a relatively rare form of thyroid cancer. TCV can be more aggressive than PTC in general, and has higher rates of recurrence than PTC. Most cases tend to occur in older individuals. TCV gets its name because the height of the characteristic cells is two to three times greater than the width. More than 70% of cancer cells for this tumor must be “tall” cells for a diagnosis of tall cell variant thyroid cancer. Tumor size is generally larger than the tumor size generally associated with PTC. Some researchers believe that TCV is underdiagnosed.
The diffuse sclerosing variant is more common in younger individuals, especially younger women. It often develops between the ages of 15-30. The first sign is often an enlarged thyroid (goiter). This subtype of PTC can spread to the lymph nodes or lungs. Recurrence is more likely with the diffuse sclerosing variant than with PTC.
Follicular Thyroid Carcinoma (FTC)
Although FTC is the second most common form of thyroid cancer, it accounts for only approximately 10 percent of patients. As with papillary thyroid carcinoma, FTC also arises from thyroid follicular cells, but is far less likely to spread to the lymph nodes. It may spread to the lungs, brain, or bone. FTC is often classified as minimally invasive or widely invasive. FTC usually presents as a painless thyroid lump (nodule).
Most individuals with FTC are more than 50 years of age. Women are affected more often than men by greater than a 2-1 ratio.
Poorly differentiated (insular) thyroid carcinoma is a rare subtype of follicular thyroid carcinoma. It is extremely rare, but is aggressive and often spreads to the surrounding lymph nodes and other areas of the body, especially the lungs, bone or brain where it may cause life-threatening complications. This form of thyroid cancer also usually presents as a mass in the neck.
Poorly differentiated thyroid carcinoma usually affects individuals 55 years old or older and affects women twice as often as men. While most of the medical literature classifies poorly differentiated thyroid carcinoma as a form of follicular thyroid carcinoma, its cellular makeup may also be related to papillary thyroid carcinoma.
Hürthle Cell Carcinoma
The World Health Organization (WHO) classifies this form of thyroid cancer as a subtype of FTC, although recent research suggests that it is a distinct form of thyroid cancer. HCC accounts for approximately 3 percent of thyroid cancer. This form of thyroid cancer may affect any age group and usually occurs in individuals between 40-50 years of age. HCC affects women more often than men and is considered to have a worse prognosis than regular FTC. This form of thyroid cancer is also known as oncocytic thyroid carcinoma.
The first sign of Hürthle cell carcinoma is usually a painless lump in the neck. Hürthle cell carcinoma may spread to affect the bone, liver, or lung. Rare cases have been described that have spread to the adrenal glands and brain.
Medullary Thyroid Carcinoma (MTC)
This type of thyroid cancer accounts for approximately 2-3 percent of thyroid cancer. MTC arises from “C cells” (also called parafollicular cells); this type of cell produces the hormone calcitonin (which is why they are called “C cells”). Calcitonin helps to regulate calcium and sodium metabolism in animals, and may have effects to protect the skeleton from calcium loss in man. MTC is a more aggressive form of cancer than DTC, and may spread via the lymph nodes or bloodstream to affect other organs. The first sign of MTC is often a firm mass in the thyroid or abnormal enlargement of nearby lymph nodes (lymphadenopathy). In some cases, MTC may already have spread (metastasized) to other organs before a mass is detected.
Most people with MTC develop it randomly for no known reason (sporadic cases). However, about 30% of patients may have a type that runs in families (familial MTC or FMTC), affecting only the thyroid or as part of a rare disorder known as multiple endocrine neoplasia (MEN Type 2).
Anaplastic (Undifferentiated) Thyroid Carcinoma (ATC)
ATC accounts for approximately 5 percent of thyroid cancer and mostly affects individuals 70 years and older. ATC is highly aggressive and often spreads quickly to surrounding lymph nodes and organs especially the windpipe (trachea), lungs or bone. ATC may quickly result in life-threatening complications such as obstruction of the trachea or massive hemorrhaging. ATC often develops from an existing follicular or papillary cancer.
Primary lymphoma of the thyroid does not arise from follicular or C cells, but instead arises from the immune system cells known as lymphocytes. Most lymphomas develop in the lymph nodes, but can occur in other organs such as the thyroid. Thyroid lymphoma is extremely rare accounting for less than 2 percent of thyroid cancers.
Thyroid lymphoma spreads rapidly and quickly replaces thyroid tissue. Thyroid lymphoma usually affects individuals more than 70 years old and affects women three times more often than men. It occurs most commonly in women who have a history of hypothyroidism due to autoimmune (Hashimoto’s) thyroiditis.
The cause(s) of thyroid cancer are unknown. Researchers speculate that genetic and immunologic abnormalities, environmental factors (e.g., certain chemicals, ionizing radiation), diet, and/or other factors may play contributing roles in causing specific types of cancer. Rarely, thyroid cancer can be hereditary, especially medullary thyroid cancer, as noted above. Investigators are conducting ongoing basic research to learn more about the many factors that may result in cancer.
Current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body’s genetic code, are the underlying basis of cellular malignant transformation. In individuals with cancer, including thyroid cancer, malignancies most often develop due to abnormalities in the structure of specific genes known as “oncogenes” or “tumor suppressor genes”. Oncogenes control cell growth; tumor suppressor genes control cell division and ensure that cells die at the proper time. These abnormal genetic changes may occur spontaneously for unknown reasons or, more rarely, may be inherited. Exposure to ionizing radiation from medical treatments or atomic fallout during childhood is the most well-established environmental factor.
DNA mutations that cause papillary or follicular thyroid carcinoma have been found in several different genes located on various chromosomes. For example, some people with papillary thyroid carcinoma have mutations of the RET gene on chromosome 10. Mutations in the BRAF gene and the RAS family of genes are also commonly associated with papillary thyroid carcinoma. These genes normally regulate a cell’s growth and differentiation, and mutations can lead to unrestricted growth and de-differentiation. Most of these genetic mutations are acquired during life, are found only in the cancer cells and are not passed on to an affected individual’s children.
In thyroid cancer, damage to DNA may occur from external radiation. Individuals who have undergone radiation therapy of the head and neck region, especially children, have a greater chance of developing thyroid cancer than the general population. Individuals who have been exposed as children or adolescents to radioactive particles such as those from atomic weapons tests or nuclear power plant accidents (e.g., Chernobyl) also have a higher risk of developing thyroid cancer. Diagnostic x-rays, such as chest x-rays, dental x-rays, and the like are not known to cause cancer.
Medullary thyroid cancer may occur spontaneously for no known reason (sporadically), as part of an isolated inherited syndrome (i.e., familial medullary thyroid carcinoma [FMTC]), or as part of a more complex disorder called multiple endocrine neoplasia type II (MEN 2). (For more information on these disorders, see the Related Disorders section of this report.)
DNA is the code that allows the body’s cells to make proteins. DNA forms genes, that are translated by the body’s cells into proteins that are needed for the body to function. Cells have two genes for each protein, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. FMTC and MEN 2 are inherited as autosomal dominant traits. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child. FMTC and MEN 2 have been linked to mutations of the RET gene on chromosome 10.
Individuals who have benign thyroid disease or have a family history of benign thyroid disease are at a greater risk of develop thyroid cancer than the general population. Benign thyroid disease includes goiter, thyroid nodules, or inflammation of the thyroid (thyroiditis).
Individuals with certain genetic disorders are also at a greater risk of developing thyroid cancer. These disorders include familial adenomatous polyposis (FAP), Gardner syndrome, PTEN hamartoma tumor syndrome and Carney complex. (For more information on these disorders, choose the specific disorders name as your search term in the Rare Disease Database.)
According to the American Cancer Society, approximately 53,000 new cases of thyroid cancer will be diagnosed in the United States in 2020. Of those cases, more than 41,000 will occur in women. In fact, thyroid cancer is now the 5th most common cancer in women. Thyroid cancer can affect individuals of any age and specific forms occur with greater frequency among different age groups. In general, thyroid nodules in children and adolescents are more likely may be malignant than those that occur in adults. In general, for unclear reasons, the rate of thyroid cancer incidence has been increasing rapidly over the past few decades. Some researchers believe that this increase in frequency is due to the greater use of imaging (e.g., chest CT scans, cervical spine MRI), with the result being an increase in the rate of detection of small thyroid cancers that may not ever have been detected while the individual was alive. However, there may also be an increase in the frequency of larger thyroid cancers, possibly the result of environmental factors.
The diagnosis of thyroid cancer is based upon a thorough clinical evaluation, including a detailed patient history and physical exam, and a variety of specialized blood tests and imaging tests. Such testing often includes microscopic evaluation of tumor cells obtained by fine needle aspiration biopsy.
Rarely, affected individuals may notice a hard, fixed mass or lump (nodule) usually to the lower left or right of the Adam’s apple. Sometimes a physician or other health care provider may discover such a nodule upon a routine medical exam. Often, the nodule is found accidentally on radiology study performed for another purpose. Thyroid nodules are a common finding, and as people get older, the frequency increases; in some reports, up to 50-75% of older persons have a thyroid nodule that can be detected on a thyroid sonogram (ultrasound). Fortunately, more than 90 percent of them are non-cancerous (benign).
Clinical Testing and Work-up
To confirm a diagnosis of thyroid cancer a variety of tests may be performed including blood tests, thyroid ultrasound, and fine-needle aspiration biopsy.
Blood tests can reveal the overall function of the thyroid by determining thyroid-stimulating hormone (TSH) levels. TSH is hormone produced by the pituitary gland that promotes the growth of the thyroid and most likely stimulates thyroid cancer cells to grow. Most patients with thyroid cancer have normal thyroid function, however.
During a thyroid ultrasound reflected sound waves create an image of the thyroid. A machine known as a transducer creates these sound waves and then records the pattern when they bounce back from the thyroid (echo pattern). Normal thyroid tissue and thyroid nodules have different echo patterns, so the physician can see whether the nodule has a suspicious appearance that may require further evaluation, typically with FNA biopsy. In addition, ultrasound examination of lymph nodes in the neck can be performed, and suspicious lymph nodes can be biopsied prior to surgery.
Additional specialized imaging techniques may be used to help evaluate the size, placement, and extension of the tumor and to serve as an aid for future surgical procedures. Such imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. Laboratory tests and specialized imaging tests may also be conducted to determine possible infiltration of regional lymph nodes and the presence of distant metastases.
Fine-need aspiration biopsy (FNA) is the most accurate diagnostic test. FNA involves passing a thin, hollow needle through the skin and inserted into the nodule under ultrasound guidance to withdraw small samples of tissue from the nodule. This procedure may be repeated a few times to gather tissue samples from different sections of the nodule. If multiple nodules are present, the procedure may be performed on each one. The collected tissue is then smeared on to glass slides, stained with colored dye, and studied under a microscope. This is similar to what is done in a PAP test for cervical cancer. Newly developed genetic tests can also be performed on samples obtained by biopsy. These tests can help to clarify whether a nodule is more likely to be benign or malignant when the biopsy sample is “indeterminate”, i.e., neither clearly benign or malignant. Indeterminate biopsy results occur in about 25% of nodules.
In cases where MTC is suspected, blood tests to determine the levels of calcitonin may be performed. Such individuals may undergo genetic testing to detect the presence of a RET gene mutation to confirm a diagnosis of familial MTC. Family members of individuals who have this mutation should also be evaluated for the presence of the RET mutation. Nearly 100% of individuals who have this mutation gene will eventually develop MTC. Consequently, many researchers recommend that individuals who have this specific genetic change undergo preventive (prophylactic) surgery as children to remove the thyroid. Removing the thyroid before cancer has a chance to develop has a very high probability of being curative.
The therapeutic management of individuals with thyroid cancer may require the coordinated efforts of a team of medical professionals, such as specialists in the diagnosis and treatment of hormone-related disorders (endocrinologists), thyroid surgeons, specialists in the use of radioactive iodine (nuclear medicine physicians), physicians who use radiation to treat cancer (radiation oncologists), and other healthcare specialists. Physicians who specialize in the diagnosis and treatment of cancer (medical oncologists) are usually not involved in the care of thyroid cancer, except for rare advanced cases.
Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as primary tumor size and location, extent of the primary tumor (stage), and degree of malignancy (grade); whether the tumor has spread to lymph nodes or distant sites; individual’s age and general health; and/or other elements. Decisions concerning the use of particular interventions should be made by physicians and other members of the health care team in careful consultation with the patient, based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks; patient preference; and other appropriate factors.
The various techniques used to treat thyroid cancer include surgery first, sometimes followed by radioactive iodine therapy, external beam radiation and rarely, chemotherapy. Thyroid hormone replacement therapy is used in conjunction with these therapies in patients who have undergone removal of all or part of their thyroid gland.
In virtually all individuals with thyroid cancer, standard initial therapy involves surgical removal of the malignancy and affected tissue, including the entire thyroid (thyroidectomy). In many cases of follicular and papillary thyroid carcinoma, especially larger and more invasive tumors, surgical removal of as much of the thyroid as can be safely taken out (near-total thyroidectomy) is recommended. In such cases, near-total thyroidectomy reduces the chance of recurrence as opposed to surgery to remove only a portion of the thyroid (e.g., one lobe). On the other hand, removal of one lobe of the thyroid is sufficient in patients with uncomplicated tumors, e.g., tumors <4 cm. If any suspicious or cancerous lymph nodes are found preoperatively or intraoperatively, they will be removed as well. Hormone Replacement Therapy
After a thyroidectomy, individuals must take levothyroxine, to replace the hormones that the thyroid normally produces, so that individuals do not develop hypothyroidism. Levothyroxine also suppresses the activity of thyroid stimulating hormone (TSH), a hormone made by the pituitary gland that stimulates the growth of normal thyroid tissue as well as any remaining thyroid cancer cells. Many patients who have undergone a lobectomy will not require thyroid hormone therapy, as the remaining lobe can make enough thyroid hormone to maintain normal thyroid hormone levels.
Research has indicated that therapy with radioactive iodine may improve survival rates among individuals with more advanced follicular and papillary thyroid carcinoma. However, radioactive iodine therapy is not usually recommended for low-risk individuals, who comprise the majority of patients, whose prognosis after surgery is excellent even without radioactive iodine. Iodine is a chemical element used by the thyroid gland to synthesize thyroid hormones. Since iodine is also absorbed by differentiated thyroid cancer cells, radioactive iodine can be used to target thyroid cancer tissue while sparing the rest of the body.
Radioactive iodine therapy destroys any normal thyroid tissue that remains after a near-total thyroidectomy, a process sometimes referred to as radioactive iodine ablation. It may also destroy any residual microscopic thyroid cancer, a process called “adjuvant therapy”. For radioactive iodine therapy to be most effective, blood TSH levels must be high. TSH stimulates both thyroid tissue and thyroid cancer cells to absorb iodine. Elevating the blood TSH levels can be accomplished by stopping hormone replacement therapy (which leads to low levels of thyroid hormone [hypothyroidism] and a large increase in TSH levels). However, many individuals made hypothyroid in this way feel sluggish, and have other symptoms such as cold intolerance, weight gain, and constipation. To minimize the effects of hypothyroidism, physicians may prescribe a synthetic form of T3 called Cytomel (liothyronine), but this may not prevent symptoms from developing, since this medication also has to be stopped prior to the radioiodine treatment.
A synthetic form of TSH, Thyrogen (thyrotropin alfa), made in a laboratory is also available. This is injected into a patient’s arm or thigh muscle, thereby achieving high TSH levels without the patient needing to stop hormone replacement treatment. Prior to radioiodine therapy, patients are typically placed on a low iodine diet for 1-2 weeks prior to radioiodine administration. After raising TSH levels, prior to the actual treatment, patients may undergo a whole body radioiodine scan using a small amount of radioactive iodine, in order to see how much of the normal thyroid is still present in the neck. If the scan shows that there is a large thyroid remnant a larger treatment dose of radioactive iodine may be administered.
Radioactive iodine therapy is often effective when thyroid cancer has spread to nearby lymph nodes or other organs of the body (metastases).
Hürthle cell and poorly differentiated insular carcinoma are both treated with total or near-total thyroidectomy. These kinds of cancer often do not take up radioactive iodine, so it usually cannot be used to treat these forms of thyroid cancer.
External Beam Radiation
External beam radiation is another form of radiation therapy sometimes used to treat individuals with thyroid cancer. During this procedure a machine is used to deliver a beam of radiation that destroys cancer cells. External beam radiation therapy is typically used in patients with thyroid cancer who have residual disease after surgery, and who do not respond to radioactive therapy, or whose disease has spread beyond the thyroid. External beam radiation therapy may be also be used for medullary thyroid carcinoma and anaplastic thyroid carcinoma.
Targeted drug therapies
Targeted therapies are being studied for the treatment of individuals with advanced thyroid cancer. Targeted therapies are drugs and other substances that prevent the growth and spread of cancer by blocking or inhibiting certain specific molecules (often proteins) that are involved in the growth and spread of specific cancers. Generally, targeted therapies are less toxic than other treatments for cancer. Targeted therapies being investigated for thyroid cancer include protein kinase inhibitors and angiogenesis inhibitors. Lenvima (lenvatinib) and Nexavar (sorafenib) are two protein kinase inhibitors approved by the U.S. Food and Drug Administration (FDA) for use in advanced DTC.
Medullary Thyroid Carcinoma
Individuals with medullary thyroid carcinoma are also treated by the surgical removal of the entire thyroid. If the cancer has not spread beyond the thyroid, the prognosis is excellent. However, the cancer has usually spread to the local lymph nodes by the time medullary cancer is diagnosed. The prognosis depends upon several factors, including the size of the tumor, its rate of growth, and how far and to what organs the cancer has spread. Radioactive iodine therapy is not used in people with MTC because the tumors (which consist of C cells and not follicular cells) do not take up iodine. In some cases, external beam radiation therapy or chemotherapy is used to treat individuals with MTC.
A drug called Caprelsa (vandetanib) is approved by the FDA as a treatment for advanced medullary thyroid cancer. Vandetanib is a kinase inhibitor indicated for the treatment of symptomatic or progressive medullary thyroid cancer in individuals with unresectable (non-operable) locally advanced or metastatic disease. A kinase inhibitor is a type of drug that specifically blocks or stops the activity of certain proteins known as kinases.
Another kinase inhibitor called Retevmo (selpercatinib) was approved by the FDA in May 2020 to treat MTC and other types of thyroid cancer in patients whose tumors have an alteration in the RET gene. Retevmo is the first therapy approved specifically for patients with RET gene alterations.
Anaplastic Thyroid Carcinoma
In individuals with anaplastic thyroid carcinoma, total or near-total thyroidectomy is often performed. However, in some cases, the primary tumor may be inoperable because it involves structures in the neck such as the windpipe or large blood vessels. Radioactive iodine therapy is ineffective because the undifferentiated cells do not absorb the iodine. External beam radiation therapy has been used to treat individuals with ATC and may shrink tumors. For some affected individuals therapy with certain anticancer drugs (chemotherapy) may also be used, possibly in combination with surgical procedures and/or radiation; physicians may recommend combination therapy with multiple chemotherapeutic drugs that have different modes of action in destroying tumor cells and/or preventing them from multiplying. In most cases, however, chemotherapy and external beam radiation therapy have had only limited success in slowing or stopping progression of ATC and cannot eliminate advanced disease.
In 2018, the combination of Taflinar (dabrafenib) and Mekinist (trametinib) administered together was approved by the FDA to treat anaplastic thyroid cancer that cannot be removed by surgery or has spread to other parts of the body and has a V600E mutation in the BRAF gene.
Individuals with thyroid cancer receive periodic evaluations to determine whether the cancer has returned. These evaluations include a thorough clinical evaluation, including a detailed patient history, physical examination of the neck and the rest of the body, and a variety of tests including blood tests to detect elevated levels of thyroglobulin, a thyroid protein. Thyroglobulin is only produced by thyroid tissue and DTC, so that after removal of the thyroid or radioactive iodine therapy, thyroglobulin should be absent from the bloodstream. Detection of thyroglobulin in the blood may indicate the return of thyroid cancer. Thyroglobulin is often abbreviated as Tg. Neck ultrasound to examine the central and lateral (the sides) of the neck is another cornerstone of thyroid cancer surveillance.
In some cases, physicians may choose to repeat a whole body iodine scan to determine whether any thyroid cancer cells have returned. In the past, in order to achieve the elevated levels of TSH necessary to perform a whole body iodine scan, affected individuals have needed to stop hormone replacement therapy, which results in hypothyroidism. Thyrogen (thyrotropin alfa), a synthetic form of TSH, achieves the necessary TSH levels without requiring individuals to stop hormone replacement therapy.
In individuals with MTC, physicians may order blood tests to determine the levels of calcitonin and carcinoembryonic antigen (CEA). Elevated levels of these substances may indicate a return of thyroid cancer, and physicians will often conduct imaging scans to check for residual cancer.
In addition to lenvatinib, sorafenib, and vandetanib discussed above, other kinase inhibitors are being studied to determine whether they can be effective in the treatment of thyroid cancer. Such drugs include motesanib, axitinib, cabozantinib, and pazopanib.
Researchers are also studying the effectiveness of angiogenesis inhibitors, which are drugs that prevent the formation of new blood vessels (angiogenesis) needed to supply blood to tumors. Researchers believe targeting certain growth factors can disrupt tumor angiogenesis and prevent tumors from growing or spreading. Thalidomide, lenalidomide, and combrestatin A4 phosphate are examples of angiogenesis inhibitors that have been studied as potential therapies for individuals with thyroid cancer who have not responded to other therapies.
Redifferentiation agents are drugs or other substances that are used to attempt to “reprogram” undifferentiated cells to behave like the cells from which they originally developed (i.e. they help cells function like normal thyroid cells). For example, this might enable undifferentiated cells to take up radioiodine more effectively for radioactive treatment. Recently, a promising research study has shown that drugs called selumetinib and dabrafenib can often restore radioiodine uptake to thyroid cancer metastases in the lungs that had failed to concentrate radioactive iodine prior to drug treatment. Researchers are conducting additional studies to determine whether these drugs can increase the effectiveness of radioactive iodine therapy by enhancing the absorption of iodine by tumor tissue.
Researchers are studying various types of chemotherapy for advanced cases of thyroid cancer and those resistant to conventional therapies. No standard chemotherapy regimen currently exists for the treatment of thyroid cancer. Further clinical studies are necessary to determine the long-term safety and effectiveness (efficacy) of different chemotherapeutic agents, and combinations of agents, for treating advanced thyroid cancer to control metastatic or locally recurrent disease.
Many of the abovementioned therapies are undergoing clinical trials. Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Wartofsky L, Van Nostrand D. A Comprehensive Guide to Clinical Management 3rd edition. Springer, New York. 2016.
Werner & Ingbar’s The Thyroid, 10th edition. A Fundamental and Clinical Text. Wolters Kluwer 2013.
Differentiated thyroid cancer
Haugen B, Alexander E, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan; 26(1):1-133.
Cabanillas ME, Schlumberger M, Jarzab B, et al. A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: A clinical outcomes and biomarker assessment. Cancer. 2015 Aug 15;121(16):2749-56.
Francis G, Waguespack S, et al. Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer The American Thyroid Association Guidelines Task Force on Pediatric Thyroid Cancer. Thyroid. 2015;25(7):716–759.
Brito JP, Hay ID, Morris JC. Low risk papillary thyroid cancer. BMJ. 2014 Jun 16;348:g3045.
McLeod DS, Sawka AM, Cooper DS. Controversies in primary treatment of low-risk papillary thyroid cancer. Lancet. 2013 Mar 23;381(9871):1046-57.
Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet. 2013 Mar 23;381(9871):1058-69.
Medullary thyroid cancer
Wells S, Asa S, et al. Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma prepared by the American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma. Thyroid. 2015;25(6):567–610.
Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B, Vasselli JR, Read J, Langmuir P, Ryan AJ, Schlumberger MJ. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012 Jan 10;30(2):134-41.
Anaplastic thyroid cancer
Smallridge R, Ain K, et al. American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. Thyroid. 2012; 22(11):1104-1139.
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:155240; Last Update: 04/09/2014. Available at: http://omim.org/entry/155240 Accessed March 30, 2020.
Mayo Foundation for Medical Education and Research. Thyroid Cancer. Jan 21, 2020. Available at: http://www.mayoclinic.com/health/thyroid-cancer/DS00492 Accessed March 30, 2020.
National Cancer Institute. Thyroid Cancer. Available at: http://www.cancer.gov/cancertopics/types/thyroid Accessed March 30, 2020.
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