Thyroid Cancer

There are four major types of thyroid cancer.

The thyroid gland is a butterfly-shaped gland located in the front of the neck and is most well-known and responsible for producing thyroid hormone, the chemical in the body that is responsible for regulating the body's metabolism. It has two lobes, right and left, that are connected by a fibrous bridge called the isthmus.

Parafollicular cells in the thyroid produce the thyroid hormone. Too much thyroid production can cause hyperthyroidism (hyper=too much) where a person can experience rapid heartbeat and palpitations, sweating, heat intolerance, weight loss, and anxiety. Hypothyroidism (hypo=too little) may cause lethargy, weight gain, hair thinning, gravelly voice, and cold intolerance. The pituitary gland in the brain controls the amount of thyroid hormone that is produced by secreting thyroid stimulating hormone (TSH).

C cells in the thyroid produce a hormone called calcitonin that helps to regulate calcium levels in the body.

Other cells that are found in the thyroid include lymphocytes that are part of the body's immune system and stromal cells that help support the architecture of the thyroid gland itself.

Thyroid cancer about 44,000 people in the U.S. every year and about 2,170 cancer deaths. Thyroid cancer is the most common endocrine cancer.

DNA (mutations) that occur spontaneously or in response to an environmental exposure or a toxic substance can alter normal thyroid cells. The genetic changes cause the cells to multiply very rapidly without the normal controls found in the rest of the gland. Any of the cell types found in the thyroid gland can mutate into a specific type of cancer.

Cancer is different than goiter, an enlargement of the thyroid gland that may be associated with hyper or hypothyroidism. Worldwide, the most common cause of goiter is iodine deficiency. In countries where table salt is iodinated, the autoimmune disease Hashimoto's thyroiditis, is the most common cause. Graves' disease, another autoimmune disease, can also be associated with thyroid enlargement.

Research from the U.S. National Cancer Institute (NCI) has found that while the number of thyroid cancers being diagnosed has increased in the past 30 years, the death rate from thyroid cancer has remained the same. This suggests that there are not more cancers occurring but instead health care professionals and patients have become better at finding lumps in the thyroid gland and making the diagnosis.

The exact cause of thyroid cancer is not known, though there are factors that may be associated with an increased risk of developing the cancer. Even if the risk factors are present, there is not a way of knowing whether cancer might develop; patients without risk factors still may develop thyroid cancer.

What are the risk factors for thyroid cancer?

Most solitary thyroid nodules (lumps) are benign, but the risk of cancer increases if they occur in people younger than 30 or older than 60.

Women are three times more likely to develop thyroid cancer than men and at a slightly younger age (40 to 50 years old for women versus 60 to 70 for men). Thyroid cancer is often found at a younger age than most other cancers in adults, and the average age at diagnosis is 51.Thyroid cancer is about 40% to 50% less common in Black people than in other racial or ethnic groups.

A solitary nodule found in a male is more likely to be cancerous than a solitary nodule found in a female.

A rapidly growing nodule is more likely to be cancerous and is an ominous sign.

Radiation exposure is a known risk factor for thyroid cancer. Radiationn exposure may occur with certain medical treatments as well as radiation fallout from power plant accidents or nuclear weapons. Receiving head or neck radiation treatments in childhood is a risk factor for thyroid cancer. Studies have looked at children who were given radiation treatments 50-60 years ago when the risks of radiation where less well understood, and their rate of thyroid cancer is increased. Children and women survivors of nuclear reactor accidents (Chernobyl in 1986).

Diets low in iodine may increase the risk of thyroid cancer, but in developed countries, there is usually enough iodine used as food additives so that this is not a problem. Lower levels of iodine in the diet may enhance the risk of radiation induced thyroid cancer.

There may be a genetic predisposition to thyroid cancer, especially in certain rare types of thyroid cancer. Several inherited conditions have been linked to an increased risk of thyroid cancer. About 20% of thyroid cancers of the medullary thyroid carcinomas (MTCs) type result from inheriting an abnormal gene in a condition known as familial medullary thyroid carcinoma (FMTC). When FMTC occurs in combination with tumors of other endocrine glands, the condition is known as multiple endocrine neoplasia type 2 (MEN 2). MEN2 is caused by mutations in a gene called RET.

Being overweight or obese also increases the risk of thyroid cancer.

While smoking is associated with thyroid disease, worsening hypothyroidism and being a risk factor for Graves' disease, smoking does not appear to increase the risk of thyroid cancer.

Most often, a thyroid cancer is found when the patient or the patient's health care professional feels (palpates) a lump or nodule in the lower front of the neck where the thyroid is located. It is most often painless and found incidentally, by chance. Occasionally, an enlarged lymph node may be palpated by itself in the more lateral neck or in addition to a thyroid nodule.

Most patients have normal thyroid function at the time the nodule is discovered and have no symptoms related to hyper or hypothyroidism.

If the tumor grows large enough, it can affect nearby structures. There may be difficulty swallowing food (dysphagia) if the tumor compresses the esophagus, but this is rare. If the recurrent laryngeal nerve, which controls the vocal cords, is involved, hoarseness may develop due to vocal cord paralysis.

In children, lumps in the neck are found frequently. Most often they are not in the thyroid gland itself. Aside from swollen lymph nodes associated with infections like pharyngitis, strep throat, or an ear infection (otitis media), lumps should not be ignored. In pediatric patients, thyroid cancer is the third most common solid tumor malignancy and the most common endocrine malignancy. The first sign might be a lump that is felt in the thyroid gland.

A thyroid nodule is an abnormal growth found within the thyroid gland. It may be solid, fluid filled (cystic) -- usually with a jelly like substance called colloid -- or a combination of both.

Most often nodules are found incidentally when the patient or health care professional feels the neck. Whether the nodule is benign or cancerous cannot necessarily be determined just by feeling it and further tests may be warranted.

Thyroid malignancies are classified based upon which cell type is involved.

Well differentiated cancers (in which thyroid cells are less abnormal looking) include:

• Papillary thyroid carcinoma: This is the most common type of thyroid cancer. Papillary thyroid cancer accounts for 80% of cases.
• Hürthle cell carcinoma: This is a rare variant of papillary cancer (also known as oncocytic carcinoma).
• Follicular thyroid carcinoma: Follicular cancer is the second most common type of thyroid cancer. The follicular variety accounts for 10% of cases.
• Medullary thyroid carcinoma: This thyroid cancer type arises from the C cells in the thyroid that produce calcitonin. Medullary thyroid cancers (MTC) comprise 5% of all cases.
  • There may be a genetic predisposition to MTC, known as familial medullary thyroid cancer (FMTC).
  • FMTC may just appear with MTC alone.
  • FMTC may be seen as part of a syndrome called multiple endocrine neoplasia (MEN), either type 2A or 2B, in which other organs also develop cancers.
• Anaplastic thyroid cancer: This rare cancer involves thyroid cells are very abnormal looking, accounting for 1% of all cases.
• Lymphoma: This rare cancer is most often non-Hodgkin's B cell type.
• Sarcoma: This type of thyroid cancer is very rare.

The diagnosis of thyroid cancer often occurs before symptoms develop, when a lump is discovered in the thyroid gland. This may occur on routine physical exam of the neck by a health care provider, or it may be found by the patient.

Once a lump in the thyroid is discovered, it is important to know whether it is benign or malignant (cancerous).

An ultrasound usually is performed to assess whether there is a single nodule or whether multiple nodules are present. Ultrasound can determine whether the nodule is fluid filled or solid. Ultrasound also can determine the general appearance of thyroid looking for inflammation or irregularities and the presence of nearby enlarged lymph nodes that may represent metastatic cancer.

Fine needle aspiration biopsy (FNAB) is usually the next step. It is a procedure performed to obtain a sample of cells from the nodule to determine if it is cancerous. Using ultrasound, a thin needle is placed into the nodule and cells from the nodule are obtained. These cells can be examined under a microscope by a pathologist to determine whether a cancer is present and if so, what type of cancer it is.

Sometimes, the results of the aspiration are unclear or indeterminate, and the aspiration may need to be repeated to get a better sample and more cells to study.

Guidelines developed by the American Thyroid Association help the provider interpret the results of the ultrasound and fine needle aspiration biopsy. When evaluated together, the test results give direction as to whether the nodule is benign or malignant (cancerous), and help inform the choice of treatment options.

Radio-iodine testing may be considered if the results of the FNAB don't provide a definite answer as to whether a nodule is benign or malignant. The patient swallows some radioactive iodine which is taken up by the thyroid gland. The gland is scanned by a Geiger counter-type apparatus that determines how much radioactive iodine has been taken up by the thyroid gland and any thyroid nodules. If the nodule picks up much of the iodine, it is referred to as a "hot nodule." Hot nodules are rarely cancerous. Nodules that take up little to no iodine are referred to as "cold nodules." Although the overwhelming majority of cold nodules are benign, 5% turn out to be malignant.

Although thyroid scans may be helpful, it is not a first-line test and fine needle aspiration of the gland is a much more useful test. There is an exception. In the patient with a thyroid nodule whose TSH (thyroid stimulating hormone) level is low, the next step may be a radio-iodine test. The risk for cancer in a patient who is hyperthyroid (low TSH) and who has a "hot nodule" is very low and biopsy may not be required.

Blood tests may be ordered to determine the function of the thyroid gland. Measuring blood levels of thyroid-stimulating hormone (TSH) secreted by the pituitary gland turns out to be very effective in determining thyroid function, including whether the patient is hyperthyroid or hypothyroid.

Calcitonin levels may be increased in medullary thyroid cancer (MTC), but because MTC is very rare, this test is not recommended to screen for cancer.

MTC, FMTC, and MEN are hereditary cancers. Genetic testing may be done in family members of people with these types of cancers. As well, other blood tests may be ordered, including CEA, RET proto-oncogene, calcium, and calcitonin. Screening for other associated diseases might include tests looking for a tumor known as pheochromocytoma.

Molecular genetic testing may be done to look for genetic changes that either suggest the diagnosis of thyroid cancer or to determine if the cancer cells have genetic changes (such as alterations in the BRAF, RET/PTC, or NTRK genes) that could mean that certain targeted therapy drugs might be effective in treating the cancer.

Thyroid cancer treatment usually requires surgery to remove the tumor. Two options are available, and decisions as to which option to pursue depend upon the clinical situation. Guidelines from the American Thyroid Association and the National Comprehensive Cancer Network can help the surgeon and patient decide on the best type of surgery for the situation.

• Lobectomy: The thyroid has two lobes joined in the middle with a fibrous tissue bridge called the isthmus. If the tumor is confined to only a small area, the surgeon may just remove the affected lobe.
• Total thyroidectomy: This is the most common surgery for thyroid cancer and the goal is to completely remove the thyroid gland and hopefully ensure that the cancer will not recur.
• Lymph node resection: Thyroid cancer can spread to local lymph nodes, and these nodes often are removed. Affected lymph nodes may only be recognized at the time of surgery.
• Open biopsy: Sometimes, the cancerous nature of a thyroid nodule is unclear, even after fine needle aspiration. A surgeon may operate to remove the nodule and send all the tissue for evaluation by a pathologist to make the diagnosis of cancer.

Thyroid hormone

If the thyroid gland has been removed, the body will no longer be able to make thyroid hormone, and daily thyroid hormone replacement will be necessary. Routine thyroid hormone blood tests will need to be performed to ensure there is an adequate amount of thyroid hormone to allow the body to function properly. Thyroid hormone replacement will be lifelong in total thyroidectomy patients.

Radioactive iodine (radioiodine, I-131)

Iodine is routinely absorbed by thyroid tissue. Radioiodine may be administered after surgery to destroy any remnant thyroid tissue remaining after thyroidectomy. The decision to use this treatment depends upon the type and extent of the thyroid cancer and the levels of thyroid stimulating hormone (TSH) produced by the pituitary gland.

Radiation

In certain thyroid cancers, where the tumor does not take up iodine, radiation therapy may be considered in place of radioactive iodine. Radioactive iodine update tests performed before surgery can assess whether or not iodine is taken up by the thyroid gland.

Chemotherapy

Chemotherapy is not commonly used for most thyroid cancers but may be used in certain clinical situations when the thyroid cancer does not respond to other treatments.

Targeted therapy

Targeted therapy for thyroid cancer uses specially developed drugs that are effective on cancers that express certain genetic alterations.

There are many types of thyroid cancer, and outcome depends upon the type of thyroid cancer, its stage, and the type of thyroid cancer treatment received.

Patients who have papillary or follicular cancer that is confined to the thyroid gland may expect a normal life expectancy with treatment. Prognosis may be better for women who are younger than 40 years of age. The 5-year survival rate is nearly 100% for people with localized papillary, follicular, and medullary thyroid cancers. Thyroid cancer that has spread to nearby tissues or organs and/or the regional lymph nodes is called regional thyroid cancer. The 5-year relative survival rate for regional papillary thyroid cancer is 99%, for regional follicular cancer is 98%, and for regional medullary cancer, the rate is 92%. 

Patients with anaplastic cancer do poorly, with many surviving only a few months after diagnosis. The five-year survival rate for this cancer is less than 5%.

What is the likelihood of thyroid cancer recurrence?

The recurrence rate of thyroid cancer depends upon whether the cancer remains localized within the thyroid gland or whether it has spread or metastasized to local structures in the neck or to distant sites in the body.

In general, the recurrence risk of a cancer that has not spread is very low. For example, Italian researchers found that among patients with papillary cancer of the thyroid gland, those with a low risk of disease had a recurrence rate of about 1.4% at eight years.

Researchers from the Mayo Clinic followed patients for up to 15 years and concluded that low risk patients had a recurrence rate of 3%-5%. However, they noted that more recently, thyroid cancer was being diagnosed much earlier and with the appropriate surgery, cure was much more likely and survival rate after surgery was very high.

There is little one can do to prevent thyroid cancer aside from avoiding excessive exposure to radiation.

Research continues regarding the best treatment for the different types of thyroid cancers. New drugs are being developed that specifically target the thyroid cancer cells by attacking specific genes or proteins.

Clinical trials continue to enroll patients with many diseases, including thyroid cancer. If appropriate, your health care professional may be a resource in finding a clinical trial that may be beneficial. Clinical trials that are enrolling patients can be found at the U.S. National Cancer Institute web site (https://www.cancer.gov/about-cancer/treatment/clinical-trials/search).

Support

Patients, families, and friends are all affected by a diagnosis of cancer is made. Support is available not only for the patient but for all those who are close to the patient. Hospitals, clinics, and health care professionals' offices often have specially trained staff to help patients and families address their physical, emotional, and spiritual needs.

It is important for the patient and family to understand the disease, the treatment options, the expected outcomes, and the journey that will occur with cancer. Family members will benefit from being present for provider visits during the diagnosis and treatment, as well as with follow-up appointments. This allows all to be involved in advocating for the patient, since there is so much information to understand and absorb; it can be overwhelming.

There are many community resources available as well. The American Cancer Society is a good place to begin. They have local offices and may be contacted online.