Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. Cancer can also occur in the thyroid after spread from other locations, in which case it is not classified as thyroid cancer.
Risk factors include radiation exposure at a young age, having an enlarged thyroid, and family history. The four main types are papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, and anaplastic thyroid cancer. Diagnosis is often based on ultrasound and fine needle aspiration. Screening people without symptoms and at normal risk for the disease is not recommended as of 2017.
Treatment options may include surgery, radiation therapy including radioactive iodine, chemotherapy, thyroid hormone, targeted therapy, and watchful waiting. Surgery may involve removing part or all of the thyroid. Five-year survival rates are 98% in the United States.
Globally as of 2015, 3.2 million people have thyroid cancer. In 2012, 298,000 new cases occurred. It most commonly occurs between the ages of 35 and 65. Women are affected more often than men. Those of Asian descent are more commonly affected. Rates have increased in the last few decades, which is believed to be due to better detection. In 2015, it resulted in 31,900 deaths.
|Micrograph of a papillary thyroid carcinoma demonstrating diagnostic features (nuclear clearing and overlapping nuclei).|
|Symptoms||Swelling or lump in the neck|
|Risk factors||Radiation exposure, enlarged thyroid, family history|
|Diagnostic method||Ultrasound, fine needle aspiration|
|Differential diagnosis||Thyroid nodule, metastatic disease|
|Treatment||Surgery, radiation therapy, chemotherapy, thyroid hormone, targeted therapy, watchful waiting|
|Prognosis||Five year survival rates 98% (US)|
|Frequency||3.2 million (2015)|
Most often, the first symptom of thyroid cancer is a nodule in the thyroid region of the neck. However, up to 65% of adults have small nodules in their thyroids, but typically under 10% of these nodules are found to be cancerous. Sometimes, the first sign is an enlarged lymph node. Later symptoms that can be present are pain in the anterior region of the neck and changes in voice due to an involvement of the recurrent laryngeal nerve.
Thyroid nodules are of particular concern when they are found in those under the age of 20. The presentation of benign nodules at this age is less likely, thus the potential for malignancy is far greater.
Thyroid cancers are thought to be related to a number of environmental and genetic predisposing factors, but significant uncertainty remains regarding their causes.
Environmental exposure to ionizing radiation from both natural background sources and artificial sources is suspected to play a significant role, and significantly increased rates of thyroid cancer occur in those exposed to mantlefield radiation for lymphoma, and those exposed to iodine-131 following the Chernobyl, Fukushima, Kyshtym, and Windscale nuclear disasters. Thyroiditis and other thyroid diseases also predispose to thyroid cancer.
After a thyroid nodule is found during a physical examination, a referral to an endocrinologist or a thyroidologist may occur. Most commonly, an ultrasound is performed to confirm the presence of a nodule and assess the status of the whole gland. Measurement of thyroid stimulating hormone and antithyroid antibodies will help decide if a functional thyroid disease such as Hashimoto's thyroiditis is present, a known cause of a benign nodular goiter. Measurement of calcitonin is necessary to exclude the presence of medullary thyroid cancer. Finally, to achieve a definitive diagnosis before deciding on treatment, a fine needle aspiration cytology test is usually performed and reported according to the Bethesda system.
In adults without symptoms, screening for thyroid cancer is not recommended.
Thyroid cancer can spread directly, via lymphatics or blood. Direct spread occurs through infiltration of the surrounding tissues. The tumor infiltrates into infrahyoid muscles, trachea, oesophagus, recurrent laryngeal nerve, carotid sheath, etc. The tumor then becomes fixed. Anaplastic carcinoma spreads mostly by direct spread, while papillary carcinoma spreads so the least. Lymphatic spread is most common in papillary carcinoma. Cervical lymph nodes become palpable in papillary carcinoma even when the primary tumor is unpalpable. Deep cervical nodes, pretracheal, prelaryngeal, and paratracheal groups of lymph nodes are often affected. The lymph node affected is usually the same side as that of the location of the tumor. Blood spread is also possible in thyroid cancers, especially in follicular and anaplastic carcinoma. The tumor emboli do angioinvasion of lungs; end of long bones, skull, and vertebrae are affected. Pulsating metastases occur because of their increased vascularity.
Thyroidectomy and dissection of central neck compartment is initial step in treatment of thyroid cancer in the majority of cases. Thyroid-preserving operations may be applied in cases, when thyroid cancer exhibits low biological aggressiveness (e.g. well-differentiated cancer, no evidence of lymph-node metastases, low MIB-1 index, no major genetic alterations like BRAF mutations, RET/PTC rearrangements, p53 mutations etc.) in patients younger than 45 years. If the diagnosis of well-differentiated thyroid cancer (e.g. papillary thyroid cancer) is established or suspected by FNA, then surgery is indicated, whereas watchful waiting strategy is not recommended in any evidence-based guidelines. Watchful waiting reduces overdiagnosis and overtreatment of thyroid cancer among old patients.
Radioactive iodine-131 is used in people with papillary or follicular thyroid cancer for ablation of residual thyroid tissue after surgery and for the treatment of thyroid cancer. Patients with medullary, anaplastic, and most Hurthle-cell cancers do not benefit from this therapy.
The prognosis of thyroid cancer is related to the type of cancer and the stage at the time of diagnosis. For the most common form of thyroid cancer, papillary, the overall prognosis is excellent. Indeed, the increased incidence of papillary thyroid carcinoma in recent years is likely related to increased and earlier diagnosis. One can look at the trend to earlier diagnosis in two ways. The first is that many of these cancers are small and not likely to develop into aggressive malignancies. A second perspective is that earlier diagnosis removes these cancers at a time when they are not likely to have spread beyond the thyroid gland, thereby improving the long-term outcome for the patient. No consensus exists at present on whether this trend toward earlier diagnosis is beneficial or unnecessary.
The argument against early diagnosis and treatment is based on the logic that many small thyroid cancers (mostly papillary) will not grow or metastasize. This view holds the overwhelming majority of thyroid cancers are overdiagnosed that is, will never cause any symptoms, illness, or death for the patient, even if nothing is ever done about the cancer. Including these overdiagnosed cases skews the statistics by lumping clinically significant cases in with apparently harmless cancers. Thyroid cancer is incredibly common, with autopsy studies of people dying from other causes showing that more than one-third of older adults technically have thyroid cancer, which is causing them no harm. Detecting nodules that might be cancerous is easy, simply by feeling the throat, which contributes to the level of overdiagnosis. Benign (noncancerous) nodules frequently co-exist with thyroid cancer; sometimes, a benign nodule is discovered, but surgery uncovers an incidental small thyroid cancer. Increasingly, small thyroid nodules are discovered as incidental findings on imaging (CT scan, MRI, ultrasound) performed for another purpose ; very few of these people with accidentally discovered, symptom-free thyroid cancers will ever have any symptoms, and treatment in such patients has the potential to cause harm to them, not to help them.
Thyroid cancer is three times more common in women than in men, but according to European statistics, the overall relative 5-year survival rate for thyroid cancer is 85% for females and 74% for males.
The table below highlights some of the challenges with decision making and prognostication in thyroid cancer. While general agreement exists that stage I or II papillary, follicular, or medullary cancer have good prognoses, when evaluating a small thyroid cancer to determine which ones will grow and metastasize and which will not is not possible. As a result, once a diagnosis of thyroid cancer has been established (most commonly by a fine needle aspiration), a total thyroidectomy likely will be performed.
This drive to earlier diagnosis has also manifested itself on the European continent by the use of serum calcitonin measurements in patients with goiter to identify patients with early abnormalities of the parafollicular or calcitonin-producing cells within the thyroid gland. As multiple studies have demonstrated, the finding of an elevated serum calcitonin is associated with the finding of a medullary thyroid carcinoma in as high as 20% of cases.
In Europe where the threshold for thyroid surgery is lower than in the United States, an elaborate strategy that incorporates serum calcitonin measurements and stimulatory tests for calcitonin has been incorporated into the decision to perform a thyroidectomy; thyroid experts in the United States, looking at the same data, have for the most part not incorporated calcitonin testing as a routine part of their evaluations, thereby eliminating a large number of thyroidectomies and the consequent morbidity. The European thyroid community has focused on prevention of metastasis from small medullary thyroid carcinomas; the North American thyroid community has focused more on prevention of complications associated with thyroidectomy (see American Thyroid Association guidelines below). As demonstrated in the table below, individuals with stage III and IV disease have a significant risk of dying from thyroid cancer. While many present with widely metastatic disease, an equal number evolve over years and decades from stage I or II disease. Physicians who manage thyroid cancer of any stage recognize that a small percentage of patients with low-risk thyroid cancer will progress to metastatic disease.
Improvements have been made in thyroid cancer treatment during recent years. The identification of some of the molecular or DNA abnormalities has led to the development of therapies that target these molecular defects. The first of these agents to negotiate the approval process is vandetanib, a tyrosine kinase inhibitor that targets the RET proto-oncogene, two subtypes of the vascular endothelial growth factor receptor, and the epidermal growth factor receptor. More of these compounds are under investigation and are likely to make it through the approval process. For differentiated thyroid carcinoma, strategies are evolving to use selected types of targeted therapy to increase radioactive iodine uptake in papillary thyroid carcinomas that have lost the ability to concentrate iodide. This strategy would make possible the use of radioactive iodine therapy to treat "resistant" thyroid cancers. Other targeted therapies are being evaluated, making life extension possible over the next 5–10 years for those with stage III and IV thyroid cancer.
Prognosis is better in younger people than older ones.
Prognosis depends mainly on the type of cancer and cancer stage.
Thyroid cancer type
|5-year survival||10-year survival|
|Stage I||Stage II||Stage III||Stage IV||Overall||Overall|
|Papillary||100%||100%||93%||51%||96% or 97%||93%|
|Medullary||100%||98%||81%||28%||80%, 83% or 86%||75%|
|Anaplastic||(always stage IV)||7%||7% or 14%||(no data)|
Thyroid cancer, in 2010, resulted in 36,000 deaths globally up from 24,000 in 1990. Obesity may be associated with a higher incidence of thyroid cancer, but this relationship remains the subject of much debate.
Thyroid cancer accounts for less than 1% of cancer cases and deaths in the UK. Around 2,700 people were diagnosed with thyroid cancer in the UK in 2011, and around 370 people died from the disease in 2012.
Anaplastic thyroid cancer is a form of thyroid cancer which has a very poor prognosis due to its aggressive behavior and resistance to cancer treatments. Its anaplastic cells have poor differentiation, including dedifferentiation.Cabozantinib
Cabozantinib, sold under the brand-name Cabometyx and Cometriq, is a medication used to treat medullary thyroid cancer and a second line treatment for renal cell carcinoma among others. It is a small molecule inhibitor of the tyrosine kinases c-Met and VEGFR2, and also inhibits AXL and RET. It was discovered and developed by Exelixis Inc.
In 2012 cabozantinib in its capsule formulation was approved by the U.S. FDA under the name Cometriq for treating patients with medullary thyroid cancer. The capsule form was approved in Europe for the same purpose in 2014.In April 2016 the US FDA granted approval for marketing the tablet formulation as a second line treatment for kidney cancer and the same was approved in Europe in October of that year.Effects of the Chernobyl disaster
The 1986 Chernobyl disaster triggered the release of substantial amounts of radioactivity into the atmosphere in the form of both particulate and gaseous radioisotopes. It is one of the most significant unintentional releases of radioactivity into the environment to present day.
The work of the Scientific Committee on Problems of the Environment (SCOPE), suggests that the Chernobyl incident cannot be directly compared to atmospheric tests of nuclear weapons through a single number, with one being simply j times larger than the other. This is partly due to the fact that the isotopes released at Chernobyl tended to be longer-lived than those released by the detonation of atomic bombs.Eli Marrero
Elieser Marrero (born November 17, 1973), is a former Major League Baseball player. Marrero started his career as a catcher, but spent time at first base, third base and in the outfield.Endocrine gland neoplasm
An endocrine gland neoplasm is a neoplasm affecting one or more glands of the endocrine system.
Pituitary adenomaThe most common form is thyroid cancer.Condition such as pancreatic cancer or ovarian cancer can be considered endocrine tumors, or classified under other systems.
Pinealoma is often grouped with brain tumors because of its location.Follicular thyroid cancer
Follicular thyroid cancer accounts for 15% of thyroid cancer and occurs more commonly in women over 50 years of age. Thyroglobulin (Tg) can be used as a tumor marker for well-differentiated follicular thyroid cancer. Follicular cells are the thyroid cells responsible for the production and secretion of thyroid hormones.Hürthle cell
A Hürthle cell is a cell in the thyroid that is often associated with Hashimoto's thyroiditis as well as benign and malignant tumors (Hürthle cell adenoma and Hürthle cell carcinoma, formerly considered a subtype of follicular thyroid cancer). This version is a relatively rare form of differentiated thyroid cancer, accounting for only 3-10% of all differentiated thyroid cancers. Oncocytes in the thyroid are often called Hürthle cells. Although the terms oncocyte, oxyphilic cell, and Hürthle cell are used interchangeably, Hürthle cell is used only to indicate cells of thyroid follicular origin.Iodine-131
Iodine-131 (131I) is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with nuclear energy, medical diagnostic and treatment procedures, and natural gas production. It also plays a major role as a radioactive isotope present in nuclear fission products, and was a significant contributor to the health hazards from open-air atomic bomb testing in the 1950s, and from the Chernobyl disaster, as well as being a large fraction of the contamination hazard in the first weeks in the Fukushima nuclear crisis. This is because I-131 is a major fission product of uranium and plutonium, comprising nearly 3% of the total products of fission (by weight). See fission product yield for a comparison with other radioactive fission products. I-131 is also a major fission product of uranium-233, produced from thorium.
Due to its mode of beta decay, iodine-131 is notable for causing mutation and death in cells that it penetrates, and other cells up to several millimeters away. For this reason, high doses of the isotope are sometimes less dangerous than low doses, since they tend to kill thyroid tissues that would otherwise become cancerous as a result of the radiation. For example, children treated with moderate dose of I-131 for thyroid adenomas had a detectable increase in thyroid cancer, but children treated with a much higher dose did not. Likewise, most studies of very-high-dose I-131 for treatment of Graves disease have failed to find any increase in thyroid cancer, even though there is linear increase in thyroid cancer risk with I-131 absorption at moderate doses. Thus, iodine-131 is increasingly less employed in small doses in medical use (especially in children), but increasingly is used only in large and maximal treatment doses, as a way of killing targeted tissues. This is known as "therapeutic use".
Iodine-131 can be "seen" by nuclear medicine imaging techniques (i.e., gamma cameras) whenever it is given for therapeutic use, since about 10% of its energy and radiation dose is via gamma radiation. However, since the other 90% of radiation (beta radiation) causes tissue damage without contributing to any ability to see or "image" the isotope, other less-damaging radioisotopes of iodine such as iodine-123 (see isotopes of iodine) are preferred in situations when only nuclear imaging is required. The isotope I-131 is still occasionally used for purely diagnostic (i.e., imaging) work, due to its low expense compared to other iodine radioisotopes. Very small medical imaging doses of I-131 have not shown any increase in thyroid cancer. The low-cost availability of I-131, in turn, is due to the relative ease of creating I-131 by neutron bombardment of natural tellurium in a nuclear reactor, then separating I-131 out by various simple methods (i.e., heating to drive off the volatile iodine). By contrast, other iodine radioisotopes are usually created by far more expensive techniques, starting with reactor radiation of expensive capsules of pressurized xenon gas.
Iodine-131 is also one of the most commonly used gamma-emitting radioactive industrial tracer. Radioactive tracer isotopes are injected with hydraulic fracturing fluid to determine the injection profile and location of fractures created by hydraulic fracturing.Much smaller incidental doses of iodine-131 than those used in medical therapeutic procedures, are supposed by some studies to be the major cause of increased thyroid cancers after accidental nuclear contamination. These studies suppose that cancers happen from residual tissue radiation damage caused by the I-131, and should appear mostly years after exposure, long after the I-131 has decayed. Other studies can't find a correlation.Jennifer Grey
Jennifer Grey (born March 26, 1960) is an American actress. She is known for her roles in the 1980s films Ferris Bueller's Day Off (1986) and Dirty Dancing (1987), for which Grey earned a Golden Globe Award nomination. Her television work includes her 2010 victory in season eleven of Dancing with the Stars, and starring in the Amazon Studios comedy series Red Oaks.Jerry Dipoto
Gerard Peter Dipoto (born May 24, 1968) is an American baseball executive and former professional player. He is currently the general manager of the Seattle Mariners of Major League Baseball and previously worked in front office positions for the Arizona Diamondbacks, Los Angeles Angels, and Boston Red Sox. Dipoto played in the MLB for the Cleveland Indians, New York Mets, and Colorado Rockies from 1993 through 2000.Liraglutide
Liraglutide, sold under the brand name Victoza among others, is a medication used to treat diabetes mellitus type 2 and obesity. In diabetes it is a less preferred agent. Its effect on long term health outcomes like heart disease and life expectancy are unclear. In obesity if after 12 weeks less than 5% of body weight is lost it is recommended the medication be stopped. It is given by injection under the skin.Common side effects include low blood sugar, nausea, dizziness, abdominal pain, and pain at the site of injection. Other serious side effects may include medullary thyroid cancer, angioedema, pancreatitis, gallbladder disease, and kidney problems. Use in pregnancy and breastfeeding is of unclear safety. Liraglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 receptor agonist) also known as incretin mimetics. It works by increasing insulin release from the pancreas and decreases excessive glucagon release.Liraglutide was approved for medical use in Europe in 2009 and in the United States in 2010. A month supply in the United Kingdom costs the NHS about 78.50 £ as of 2019. In the United States the wholesale cost of this amount is about 98.30 USD. In 2016, it was the 188th most prescribed medication in the United States with more than 3 million prescriptions.Medullary thyroid cancer
Medullary thyroid cancer is a form of thyroid carcinoma which originates from the parafollicular cells (C cells), which produce the hormone calcitonin.
Medullary tumors are the third most common of all thyroid cancers and together make up about 3% of all thyroid cancer cases. MTC was first characterized in 1959.Approximately 25% of medullary thyroid cancer cases are genetic in nature, caused by a mutation in the RET proto-oncogene. This form is identified as familial medullary thyroid cancer (FMTC). When MTC occurs by itself it is termed sporadic medullary thyroid cancer (SMTC). When it coexists with tumors of the parathyroid gland and medullary component of the adrenal glands (pheochromocytoma) it is called multiple endocrine neoplasia type 2 (MEN2).Papillary thyroid cancer
Papillary thyroid cancer or papillary thyroid carcinoma is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases. It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck. It is often well-differentiated, slow-growing, and localized, although it can metastasize.Red Callender
George Sylvester "Red" Callender (March 6, 1916 – March 8, 1992) was an American string bass and tuba player. He is perhaps best known as a jazz musician, but worked with an array of pop, rock and vocal acts as a member of The Wrecking Crew, a group of first-call session musicians in Los Angeles.Selumetinib
Selumetinib (AZD6244) is a drug that was discovered by Array BioPharma and was licensed to AstraZeneca. It is being investigated for the treatment of various types of cancer, such as non-small cell lung cancer (NSCLC) and thyroid cancer.Squamous-cell thyroid carcinoma
Squamous-cell thyroid carcinoma is rare malignant neoplasm of thyroid gland which shows tumor cells with distinct squamous differentiation. The incidence of SCTC is less than 1% out of thyroid malignancies.Thyroid adenoma
A thyroid adenoma is a benign tumor of the thyroid gland, that may be inactive or active (functioning autonomously) as a toxic adenoma.Thyroid lymphoma
Thyroid lymphoma is a rare malignant tumor constituting 1% to 2% of all thyroid malignancies and less than 2% of lymphomas. Thyroid lymphomas are classified as non–Hodgkin's B-cell lymphomas in a majority of cases, although Hodgkin's lymphoma of the thyroid has also been identified.Thyroid neoplasm
Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm (thyroid cancer), such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected than men. The estimated number of new cases of thyroid cancer in the United States in 2010 is 44,670 compared to only 1,690 deaths. Of all thyroid nodules discovered, only about 5 percent are cancerous, and under 3 percent of those result in fatalities.