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Thyroid Cancer

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Copyright 2006, 2013

NORD is very grateful to David S. Cooper, MD, Professor of Medicine and Radiology, The Johns Hopkins University School of Medicine, for assistance in the preparation of this report.

Synonyms of Thyroid Cancer

Disorder Subdivisions

General Discussion

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 that 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 cases, 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 cases. Although thyroid cancer is relatively uncommon, it 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.
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.

Symptoms

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 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, 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 cases arise from follicular cells (the cells that comprise most of the thyroid and make thyroid hormone), and 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. 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 cases. 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; all of them are extremely rare. Common subtypes include follicular, tall cell, and diffuse sclerosing variants.

The follicular variant of PTC, which is different from follicular thyroid carcinoma, is the most common subtype. 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 all cases. 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. HCC accounts for approximately 3 percent of cases 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 cases of thyroid cancer. MTC arises from "C cells" (also called parafollicular cells); this type of cell produces the hormone calcitonin, which helps to regulate calcium and sodium metabolism in animals, but has no known function in man. MTC is a more aggressive form of cancer 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 cases of MTC occur randomly for no known reason (sporadic cases). However, about 30% of cases may run in families (familial MTC or FMTC), affecting only the thyroid or as part of a rare disorder known as multiple endocrine neoplasia (MEN).

Anaplastic (Undifferentiated) Thyroid Carcinoma (ATC)
ATC accounts for approximately 5 percent of cases 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.

Thyroid Lymphoma
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.

Causes

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 within the nuclei of cells 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. Ionizing radiation from medical x-rays or atomic fallout 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, many cases of papillary thyroid carcinoma have been linked to 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 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 types I and II (MEN 1 and MEN 2). (For more information on these disorders, see the Related Disorders section of this report.)

Genetic diseases are determined by two genes, 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 1 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 1 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). Thyroid conditions such as hypothyroidism or hyperthyroidism are not associated with an increased risk of cancer.

Individuals with certain 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.)

Affected Populations

According to the American Cancer Society, approximately 56,000 new cases of thyroid cancer were diagnosed in the United States in 2012. Of those cases, more than 43,000 occurred in women. Thyroid cancer can affect individuals of any age and specific forms occur with greater frequency among different age groups. According to medical textbooks, the incidence of thyroid cancer in individuals under 20 years of age is 4.9 cases per million in the United States. Most cases occur in adolescent females. In general, for unclear reasons, the rates of thyroid cancer have been increasing rapidly over the past few decades. Some researchers believe that this increase in frequency is due to the greater use of imaging (CT scans, 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.

Related Disorders

Symptoms of the following disorders can be similar to those of thyroid cancer. Comparisons may be useful for a differential diagnosis.

Multiple endocrine neoplasia (MEN) type 2 is a rare genetic cancer syndrome in which tumors develop in the endocrine glands (e.g., thyroid, parathyroid, adrenal glands). Two main subtypes exist called MEN 2A and MEN 2B. Familial medullary thyroid carcinoma (FMTC) is considered a third subtype. Nearly all individuals with MEN 2 develop medullary thyroid carcinoma (MTC) at some point. (For more information on these disorders, choose "multiple endocrine neoplasia" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
The diagnosis of thyroid cancer is based upon a thorough clinical evaluation, characteristic symptoms and physical findings, a detailed patient history, and a variety of specialized tests. Such testing includes microscopic evaluation of tumor cells.

In rare cases 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 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 thyroid ultrasound, thyroid scans, blood tests, or fine-needle aspiration biopsy.

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.

Thyroid scans may also be used to aid in a diagnosis of thyroid cancer. During this procedure, radioactive material is injected into a vein or given orally, and then travels and concentrates inside the thyroid. If a nodule is present is will have more or less radioactivity than the surrounding tissue. A special camera that can detect the different levels of radioactivity is used to take a picture of the thyroid. While a thyroid scan can detect nodules, the procedure cannot distinguish between benign and malignant nodules.

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, especially among individuals diagnosed with thyroid cancer. 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.

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.

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.

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.

Treatment
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), physician 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 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, radioactive iodine therapy, external beam radiation and rarely, chemotherapy. Thyroid hormone replacement therapy is used in conjunction with these therapies.

Surgery
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 most cases of follicular and papillary thyroid carcinoma, surgical removal of as much of the thyroid as can be safely taken out (near-total thyroidectomy) is recommended. Near-total thyroidectomy reduces the chance of recurrence as opposed to surgery to remove only a portion of the thyroid (e.g., one lobe). If any lymph nodes are involved with cancer, they will be removed as well. In patients with very small cancers (1 centimeter or less), a lobectomy on the side of the cancer, sparing the other side, may suffice.

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.

Radioactive Iodine
Research has indicated that therapy with radioactive iodine may improve survival rates among individuals with more advanced follicular and papillary thyroid carcinoma. Iodine is a chemical element used by the thyroid gland to synthesize thyroid hormones. Nearly all of the iodine in a person's blood is absorbed by thyroid tissue. 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 thyroid tissue that remains after a near-total thyroidectomy, and also may destroy any residual microscopic thyroid cancer, a process sometimes referred to as radioactive iodine ablation. For radioactive iodine therapy to be most effective, blood TSH levels must be high. TSH stimulates 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 bothersome symptoms such as cold intolerance, weight gain, and constipation. To minimize the effects of hypothyroidism, physicians may prescribe Cytomel®, but this may not prevent symptoms from developing, since this medication also has to be stopped prior to the radioiodine treatment.

Researchers have developed a synthetic form of TSH made in a laboratory that can be injected into a patient’s arm or thigh muscle, thereby achieving high TSH levels without causing hypothyroidism. 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 not usually recommended for low-risk individuals, whose prognosis after surgery is excellent even without radioactive iodine.

Radioactive iodine therapy is often effective when thyroid cancer has spread to nearby lymph nodes or other organs of the body (metastases).

External Beam Radiation
Another form of radiation therapy sometimes used to treat individuals with thyroid cancer is called external beam radiation. 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 do not respond to radioactive therapy and have spread beyond the thyroid. External beam radiation therapy may be also be used for medullary thyroid carcinoma and anaplastic 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. If the cancer has spread, then 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 vandetanib (Caprelsa®) was approved by the U.S. Food and Drug Administration (FDA) in 2011 as a treatment for 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. Caprelsa is manufactured developed by AstraZeneca.

In individuals with anaplastic thyroid carcinoma, total or near-total thyroidectomy is often performed. However, in some cases, the primary tumor may be inoperable. 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.

Hürthle cell and poorly differentiated insular carcinoma are both treated with total or near-total thyroidectomy. Chemotherapy and radiation therapy have generally proven ineffective in treating these forms of thyroid cancer.

Follow-up
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 a variety of tests including blood tests to detect elevated levels of thyroglobulin, a thyroid protein. Thyroglobulin is only produced by thyroid tissue, so that after surgery 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.

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, a synthetic form of TSH, achieves the necessary TSH levels without requiring individuals to stop hormone replacement therapy.

In individuals with MTC, physicians may conduct blood tests to determine the levels of calcitonin and carcinoembryonic antigen. Elevated levels of these substances may indicate a return of thyroid cancer, and physicians will often conduct imaging scans to check for residual cancer. Before a blood test, physicians may inject the drug pentagastrin into affected individuals. Pentagastrin stimulates C cells to release calcitonin. Absence or very low levels of calcitonin in the blood after pentagastrin injection is a good indicator that MTC is gone. Although used in other countries, pentagastrin is not available in the United States.

Investigational 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.

In addition to 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 sunitinib, sorafenib, motesanib, axitinib, 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. Redifferentiation agents that have been studied to treat thyroid cancer include retinoids (synthetic forms of vitamin A), thiazolidenediones, drugs that inhibit histone deacetylases such as vorinostat or romidespin, and 5-azacytidine. Researchers are conducting studies to determine whether these drugs can increase the absorption of iodine by thyroid tissue, thereby improving the effectiveness of radioactive iodine therapy.

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:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Information on cancer Clinical Trials is available through the Internet on www.cancer.gov or by calling (800) 4 CANCER.

Organizations related to Thyroid Cancer

References

TEXTBOOKS
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Carling T, Udelsman R. Thyroid Tumors. In: Cancer: Principles & Practice of Oncology, DeVita VT, Lawrence TS, Rosenberg SA, editors. 2008 Lippincott, Williams & Wilkins. Philadelphia, PA. pp. 1663-1682.

Larsen PR, Kronenberg HM, Melmed S, Polonsky KS, eds. Williams Textbook of Endocrinology. 10th ed. Elsevier Saunders. Philadelphia, PA. 2003:464-90.

JOURNAL ARTICLES
Giuffrida D, Prestifilippo A, Scarfia A, Martino D, Marchisotta S. New treatment in advanced thyroid cancer. J Oncol. 2012;2012:391629. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485527/

Liebner DA, Shah MH. Thyroid cancer: pathogenesis and targeted therapy. Ther Adv Endocrinol Metab. 2011;2:173-195. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474640/#bibr1-2042018811419889

Lloyd RV, Buehler D, Khanafshar E. Papillary thyroid carcinoma variants. Head Neck Pathol. 2011;5:51-56. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037461/

Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19:1167-1274. http://www.ncbi.nlm.nih.gov/pubmed/19860577

Ghossein R, Livolsi VA. Papillary thyroid carcinoma tall cell variant. Thyroid. 2008;18:1179-1181. http://www.ncbi.nlm.nih.gov/pubmed/18925842

Elaraj DM, Clark OH. Changing management in patients with papillary thyroid cancer. Curr Treat Options Oncol. 2007;8:305-313. http://www.ncbi.nlm.nih.gov/pubmed/18040607

Ain KB, Lee C, Williams KD. Phase II trial of thalidomide for therapy of radioiodine-unresponsive and rapidly progressive thyroid carcinomas. Thyroid. 2007;17:663-670. http://www.ncbi.nlm.nih.gov/pubmed/17696837

Mvouni S, Tombu S, Meurisse M, Moreau P. Management of an insular thyroid carcinoma invading the larynx and trachea. B-ENT. 2006;2:17-20. http://www.ncbi.nlm.nih.gov/pubmed/16676842

Di Cataldo A, Sgroi AV, Occhipinti R, et al. Rare malignant tumors of the thyroid. G Chir. 2004;25:420-3. http://www.ncbi.nlm.nih.gov/pubmed/15803821


INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:155240; Last Update:05/25/2012. Available at: http://omim.org/entry/155240 Accessed on: November 10, 2012.

Mayo Foundation for Medical Education and Research. Thyroid Cancer. April 2, 2011. Available at: http://www.mayoclinic.com/health/thyroid-cancer/DS00492 Accessed On: November 10, 2012.

National Cancer Institute. Thyroid Cancer. Available at: http://www.cancer.gov/cancertopics/types/thyroid Accessed On: November 10, 2012.

American Cancer Society. Detailed Guide: Thyroid Cancer. January 24, 2012. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?rnav=cridg&dt=43 Accessed On: November 10, 2012.

American Thyroid Association. Cancer of the Thyroid. 2012. Available at: http://www.thyroid.org/patients/brochures/ThyroidCancer_brochure.pdf Accessed On: November 10, 2012.

Report last updated: 2013/01/25 00:00:00 GMT+0