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Thyroid Cancer

Definition:
Thyroid cancer develops in your thyroid, a butterfly-shaped gland located at the base of your neck, just below your Adam's apple. Although your thyroid gland is small, it produces hormones that regulate every aspect of your metabolism, from your heart rate to how quickly you burn calories.

Sometimes you may develop one or more solid or fluid-filled lumps called nodules in your thyroid. Most of these are noncancerous (benign) and cause no symptoms. But a small percentage are cancerous (malignant). Serious complications are possible in thyroid cancer.

The prognosis is often excellent for thyroid cancer. The most common types of thyroid cancer can often be completely removed with surgery. But the important first step is to know the symptoms of thyroid cancer and see your doctor.

Causes:
Your thyroid gland is composed of two lobes that resemble the wings of a butterfly separated by a thin section of tissue called the isthmus. The thyroid takes up iodine from the food you eat and uses it to manufacture two main hormones, thyroxine (T-4) and triiodothyronine (T-3). These hormones maintain the rate at which your body uses fats and carbohydrates, help control your body temperature, influence your heart rate and regulate the production of
protein. Your thyroid gland also produces calcitonin, a hormone that regulates the amountof calcium in your blood.

The thyroid contains two main types of cells. Follicle cells make the thyroid protein thyroglobulin and produce and store thyroxine and triiodothyronine. Other cells, called C cells (parafollicular cells), produce calcitonin. The distinction is important because each type can give rise to different types of cancer.

Papillary and follicular cancers develop in follicle cells. They account for the great majority of thyroid cancers, can usually be completely removed with surgery and generally result in an excellent prognosis. Medullary cancer, on the other hand, arises in the thyroid's C cells and is generally more aggressive and harder to treat than papillary and follicular cancers are.

The types of thyroid cancer include:
  • Papillary cancer
  • Follicular cancer
  • Medullary cancer
  • Anaplastic cancer
  • Thyroid lymphoma
Papillary cancer (papillary carcinoma, papillary adenocarcinoma)
This is the most common type of thyroid cancer. It develops from thyroid follicle cells and usually appears as a single mass in one lobe of the thyroid. Anyone, including children, can develop papillary cancer, but it's most common in women who are between 30 and 50 years of age.

Although most papillary cancers grow slowly, they often spread to the lymph nodes early in the course of the disease. This usually doesn't affect the outlook for recovery, which is generally excellent when the cancer is small and its spread limited to the lymph nodes in your neck. The prognosis isn't as positive for people with very large tumors or in the rare cases when papillary cancer has invaded tissues other than the lymph nodes. But even papillary tumors that have spread to the lungs or bone often can be successfully treated with radioactive iodine (radioiodine).

Follicular cancer (follicular carcinoma, follicular adenocarcinoma)
This type of cancer is more aggressive and affects a slightly older population than does papillary cancer. Follicular tumors don't usually spread to the lymph nodes but are likely to invade the veins and arteries within the thyroid. From there, they may spread to organs such as your lungs and bone.

Medullary cancer (medullary carcinoma)
Rather than arising from follicle cells, this type of thyroid cancer develops in calcitonin-producing C cells. These tumors usually make calcitonin along with carcinoembryonic antigen (CEA) — a protein produced by certain cancers. Both are released into the bloodstream and can be detected by blood tests. But in many cases, medullary cancer may spread to the lymph nodes or other organs before a lump is detected or blood tests show an increase in calcitonin or CEA.

There are three main types of medullary cancer:
  • Sporadic. Sporadic tumors make up the great majority of medullary cancers. They primarily affect people between the ages of 40 and 60 and are not inherited.
  • Multiple endocrine neoplasia, type II (MEN 2). MEN 2 medullary cancers are passed from one generation to the next and usually appear much earlier in life than do other thyroid cancers. In addition to thyroid tumors, people with MEN 2 usually have tumors in other endocrine glands, such as the adrenal or parathyroid glands. MEN 2 has two subtypes, MEN 2A and MEN 2B.

    People with MEN 2A often develop adrenal gland tumors (pheochromocytomas) and tumors of the parathyroid glands — four glands that sit behind the thyroid and produce a hormone that helps maintain the proper balance of calcium and phosphorus in the body. Although these associated tumors are usually benign, they can lead to serious complications. Adrenal gland tumors, for example, can cause high blood pressure, and parathyroid tumors can contribute to dangerously high levels of calcium as well as to osteoporosis and kidney stones.

    People with MEN 2B also have adrenal gland tumors, but not parathyroid gland problems. Instead, they develop benign nerve tissue growths (neuromas), mainly on their tongues, the underside of their eyelids and in the intestines. They may also have thick lips and thickened eyelids. The thyroid cancer that occurs in people with MEN 2B syndrome is particularly aggressive and usually develops at a very young age.

  • Familial. Familial medullary cancers are inherited, but unlike MEN 2 cancers, affect only the thyroid gland. They are usually slower growing than MEN 2 tumors, and they primarily affect people who are in their 40s and 50s.
Anaplastic cancer (anaplastic carcinoma)
This rare form of thyroid cancer is sometimes called undifferentiated cancer because it looks very different from normal thyroid tissue under a microscope. It appears to develop from an existing, undiagnosed papillary or follicular cancer. Anaplastic cancer is extremely aggressive, spreads rapidly to the lymph nodes and trachea, and then to other organs, especially the lungs and bone. For that reason, it's often not curable surgically by the time it's diagnosed. Unfortunately, other therapies, such as radiation, aren't usually successful in controlling anaplastic cancer.

Thyroid lymphoma
This rare type of cancer doesn't develop from thyroid follicular cells or C cells. Instead, it starts in immune system cells called lymphocytes. Although most lymphomas begin in the lymph nodes, some occasionally appear in other organs, such as the thyroid.

What causes thyroid cancer?
Healthy cells grow and divide in an orderly way. This process is controlled by DNA — the genetic material that contains the instructions for every chemical process in your body. When DNA is damaged or altered, changes occur in these instructions. One result is that cells may begin to grow out of control and eventually form a tumor — a mass of malignant cells.

In the case of thyroid cancer, DNA damage can occur from exposure to environmental contaminants such as radiation, from the aging process or, in medullary cancers, from genetic Causes:
  • Radiation. If you've been exposed to radiation, you have a greater risk of thyroid cancer, but it may not appear for decades after exposure. Children who received high doses of radiation to treat conditions such as acne, enlarged tonsils and scalp infections between the 1920s and 1950s are at higher risk of thyroid cancer and thyroid nodules than are those who didn't receive these treatments. Also at high risk of thyroid cancer are people who have been exposed to radioactive particles from atomic weapons tests and nuclear power plant accidents such as the 1986 Chernobyl disaster in the former Soviet Union.

    The greatest cancer risk comes from a component of fallout called iodine 131, a radioactive isotope of naturally occurring iodine that concentrates in the thyroid gland. Iodine 131 is especially harmful to children, whose thyroid glands are still developing.

  • Genetic causes. Familial medullary cancer and MEN 2 medullary thyroid cancer result from a genetic defect — a mutation of a gene that controls cell growth (oncogene) called RET. The mutation is inherited, and each child of a parent with the defect has a 50 percent chance of inheriting it as well. Before the discovery of the RET gene, people with a family history of medullary thyroid cancer were screened using tests that measure levels of calcitonin and carcinoembryonic antigen. Now, genetic testing allows doctors to discover an inherited tendency to thyroid cancer much earlier — before symptoms or abnormal blood tests ever develop.

    Most people with the RET mutation go on to develop cancer. A few families who don't have the RET genetic defect also develop and pass on medullary thyroid cancer and MEN 2.

    Genetic testing is controversial, especially when a disease can't be prevented or successfully treated. But medullary thyroid cancer can be prevented by surgically removing the thyroid gland (thyroidectomy) before problems occur. Children at risk of MEN 2A may have this surgery around age 7 or 8, and children at risk of MEN 2B, as early as 1 year of age. You can live a normal life without a thyroid gland, although you must take thyroid hormone for life to replace what your thyroid would ordinarily produce. And because MEN 2 is a syndrome involving other types of tumors, children who have their thyroid glands removed still need to be monitored for other potential problems.

    If you have a family history of medullary thyroid cancer, consider talking to a genetic counselor. He or she can explain the advantages and disadvantages of genetic testing and the risks and benefits of thyroid surgery.


Risk Factor:

Although the exact cause of many cases of thyroid cancer isn't known, certain factors increase your risk:
  • Exposure to radiation. This includes radiation you may have received as a treatment for acne or other childhood diseases as well as radiation from nuclear fallout. If you're concerned about possible radiation exposure, talk to your doctor. Or contact the National Cancer Institute's Cancer Information Service at (800) 4-CANCER, or (800) 422-6237, for more information.
  • Family history. Having a parent with MEN 2A, MEN 2B or familial medullary cancer means you have a 50 percent chance of having the genetic mutation that causes these diseases. If you have one of these types of cancer yourself, your children have a 50 percent chance of developing cancer. Your doctor or a genetic counselor can give you more information and answer any questions you may have regarding genetic screening and treatment.
  • Certain inherited conditions. Your risk of papillary thyroid cancer increases if you have Gardner's syndrome or familial adenomatous polyposis — genetic disorders in which large numbers of precancerous polyps develop throughout your colon and upper intestine. Untreated, Gardner's syndrome and familial adenomatous polyposis usually lead to colon cancer. Having Cowden disease, a rare, inherited disorder that causes lesions on your face, hands and feet, and inside your mouth, also increases your risk of developing thyroid cancer and breast cancer.
  • Your sex. For reasons that aren't clear, women are two to three times as likely as men to develop thyroid cancer.
  • Reproductive history. Women whose last pregnancy occurs at age 30 or later appear to be at higher risk of thyroid cancer than are women who have children earlier in life.
  • Age. Papillary and follicular thyroid cancers can develop at any age but are more common in young adulthood. Sporadic medullary thyroid cancer usually occurs in adults. MEN 2 and familial medullary cancer also occur in adults but can affect children and infants as well.
  • Race. White Americans are more likely to develop thyroid cancer than black Americans are.

When to seek medical advice:
See your doctor if you develop any of the symptoms of thyroid cancer, including a lump in your neck near your Adam's apple, hoarseness, or trouble swallowing or breathing. And don't hesitate to talk to your doctor if you think you may be at risk of thyroid problems or are worried about radiation treatments you received in childhood.

Symptoms:
Most often, you won't have signs and symptoms in the early stages of thyroid cancer. But, as the cancer grows, you may experience one or more of the following thyroid cancer Symptoms:

  • A lump — sometimes growing rapidly — in the front of your neck, just below your Adam's apple
  • Hoarseness or difficulty swallowing
  • Trouble breathing
  • Swollen lymph nodes, especially in your neck
  • Pain in your throat or neck, sometimes spreading up to your ears
Having one or more of these symptoms doesn't mean you have thyroid cancer. Other conditions — including a benign thyroid nodule, an infection or inflammation of the thyroid gland, and a benign enlargement of the thyroid (goiter) — can cause similar problems, all of which are highly treatable.

Dignosis:
Although it's possible that you may see or feel a lump (nodule) in your thyroid yourself — usually just to the lower right or left of your Adam's apple — it's more likely that your doctor will discover a lump during a routine medical exam. You're usually asked to swallow while your doctor examines your thyroid because the thyroid moves up and down during swallowing, making nodules easier to feel.

Sometimes a thyroid nodule is detected as an incidental finding when you have an imaging test to evaluate another condition in your head or neck. Nodules detected this way are usually too small to be found during a physical exam.

To aid in diagnosis, you may have one or more of the following tests:
  • Ultrasound scan. This imaging technique uses high-frequency sound waves to outline the neck anatomy and detect abnormal growths. While very good at identifying whether a growth or nodule is present, ultrasound scans can't tell for sure whether it's malignant or benign. Ultrasound is safe, with virtually no complications associated with its use.
  • Fine-needle aspiration (FNA) biopsy. This test is generally considered the most sensitive for distinguishing between benign and malignant thyroid nodules.

    During the procedure, your doctor places a thin needle through your skin and into a nodule and removes a sample of cells. Several passes are usually needed to obtain tissue from different parts of the nodule. If you have more than one nodule, your doctor is likely to take samples from as many as possible. Often, your doctor will use ultrasound to help guide the placement of the needle. The samples are then sent to a laboratory and analyzed under a microscope.

    Only a small percentage of biopsied nodules are malignant. This diagnosis is based on the characteristics of individual cells and patterns in clusters of cells that are different from normal thyroid tissue. In some cases, a pathologist can determine specific types of cancer from an FNA biopsy sample.

  • Blood tests. If your doctor suspects medullary cancer, you may have tests that check for high levels of calcitonin in your blood. Other tests can provide information about the function of your thyroid gland. For example, you may have a test that measures thyroid-stimulating hormone (TSH), a hormone made by the pituitary gland that regulates thyroid hormones.
Staging tests
If you receive a diagnosis of thyroid cancer, you're likely to have tests to help determine whether the cancer has spread (metastasized) — a process known as staging. The stage of cancer helps your doctor determine the best course of treatment and the outlook for your recovery. The staging tests you have may vary, depending on the type of thyroid cancer.

Tests such as ultrasonography, computerized tomography (CT) and magnetic resonance imaging (MRI) may help your doctor to see whether the cancer has spread to the lymph nodes or other areas of your neck. Sometimes you may have an octreotide scan — a test that uses a radioactively tagged hormone to check for the spread of medullary cancer.

Screening tests
If you have medullary cancer, consider having DNA testing, which checks a blood sample for the known genetic defects that cause familial and MEN-associated medullary thyroid cancer. A genetic counselor can help determine what a positive or negative test result may mean for your family.

If you have medullary thyroid cancer but don't test positive for the RET gene, it's still important that your close family members have their calcitonin levels tested. This is generally done using a calcium infusion test. Although the calcitonin level of healthy people rises slightly after an injection of calcium, it's much higher in people with medullary thyroid cancer.

The calcium infusion test usually takes between 15 and 20 minutes and is done on an outpatient basis. You'll have a small amount of blood drawn before the injection of calcium and again at two, five, 10 and 15 minutes after the injection.

Complication:
Thyroid tumors can lead to a number of complications, including:
  • Difficulty swallowing and breathing. Some thyroid cancers, particularly fast-growing anaplastic tumors and thyroid lymphomas, can cause hoarseness and difficulty breathing or swallowing when they spread to or press on your windpipe or esophagus.
  • Hoarseness. The nerves that control your vocal cords lie next to your thyroid gland. Aggressive thyroid cancers can irritate or damage these nerves, leading to a hoarse voice.
  • Diarrhea. Medullary thyroid cancer can cause severe diarrhea, which may be related to calcitonin production. It's usually controlled with drugs that reduce the activity of the intestine, such as Lomotil or Imodium.
  • Spread of cancer (metastasis). The most serious complication of thyroid cancer is the spread of the cancer to other tissues and organs. This is especially likely in anaplastic cancer, which has often spread to the windpipe or lungs by the time it's diagnosed. Follicular and papillary cancers also may spread to distant organs such as the lungs, bone and liver.
Treatment:
Thyroid cancer treatment generally includes one or more of the following:

Surgery
Surgery is the main type of treatment for thyroid cancer. Most surgeons use a procedure called near-total thyroidectomy — an operation that removes practically the entire thyroid with the exception of small rims of tissue around the parathyroid glands to reduce the risk of parathyroid damage. If you have enlarged lymph nodes as a result of thyroid cancer, your operation may be extended to remove the affected lymph nodes.

Cancer is less likely to return or spread after thyroidectomy than after less complete operations, and in experienced hands, the risks of the surgery are low. The greatest risk associated with the operation is unintended nerve injury. Such injury could cause permanent damage to your voice, but this occurs rarely. Another potential risk is damage to the parathyroid glands, resulting in low calcium levels.

In some cases, the type of cancer can't be diagnosed until the affected tissue is examined. Sometimes, this can be done during surgery using a technique called frozen section, which takes less than 10 minutes to complete and which is performed while you're still anesthetized. When this procedure isn't available, surgeons are likely to remove the lobe of the thyroid that contains the nodule (lobectomy) and send it to a pathologist, who examines it under a microscope. If the nodule is malignant, the next step is near-total thyroidectomy.

Thyroid hormone therapy
After any type of surgery for thyroid cancer, you'll need to take the thyroid hormone medication levothyroxine (Levothroid, Synthroid, others) for life. This has two benefits: It supplies the missing hormone your thyroid would normally produce, and it suppresses the pituitary's production of TSH, which signals your thyroid to manufacture hormones. High TSH levels could conceivably stimulate any remaining cancer cells to grow.

You'll likely have blood tests to check your thyroid hormone levels every few months until your doctor finds the proper dosage for you. Too much hormone can cause unintended weight loss, palpitations, tremors, osteoporosis and frequent bowel movements. Too little may lead to weight gain, sensitivity to cold, and dry skin and hair.

Radioactive iodine (radioiodine) follow-up screening and therapy
After surgery, radioiodine may be used in small doses for a follow-up test called a thyroid scan. During the test, a radioactive isotope is injected into the vein on the inside of your elbow. You then lie on a table while a special camera produces an image of your thyroid on a computer screen. The scan can detect any remaining normal thyroid tissue. A thyroid scan also may detect thyroid cancer cells that have spread and that could not be identified at the time of surgery or on other imaging, both in the neck and in other parts of your body.

If any normal tissue remains, moderate doses of radioiodine can be used to eliminate the normal tissue (remnant ablation). Larger doses can be used to destroy any cancerous cells that have spread beyond the thyroid gland. Because radioiodine is taken up primarily by thyroid tissue — including thyroid cancer cells — other parts of your body are less affected. Normal thyroid tissue must be removed first because it absorbs more iodine than do cancer cells, and its presence would make the treatment against cancer cells less effective.

With radioiodine therapy, you take a capsule containing iodine 131. Before you undergo radioiodine therapy, you need high blood levels of TSH in order for cancer cells to take up radioactive iodine. For that reason, you normally discontinue taking thyroid hormones for up to two weeks before therapy or your doctor may recommend a synthetic version of a hormone that artificially elevates blood levels of TSH.

Radioactive iodine therapy is typically administered about six weeks after surgery, generally as an outpatient procedure. Higher doses of this treatment may require hospitalization for two or three days.

You may have a sore throat, nausea and vomiting immediately after radioiodine treatment. You may also have a dry mouth or pain in your cheeks and neck because your salivary glands may absorb some of the radioactive iodine. And because iodine 131 can affect the thyroid gland of a developing fetus or infant, you shouldn't have radioiodine therapy if you're pregnant or breastfeeding.

Radioiodine treatments aren't an option for people with medullary cancer because thyroid C cells don't absorb iodine.

External beam radiation
Like radioiodine therapy, external beam radiation uses radioactivity to destroy cancer cells. But in this case, the rays come from a source outside your body — a high-energy X-ray machine called a linear accelerator. The cancer cells are targeted with a high dose of radiation for a few minutes at a time, usually five days a week, over the course of six to eight weeks. The goal is to destroy the cancer cells while minimizing damage to healthy tissue. You're likely to feel very tired later in the course of treatment, and your skin may become red and tender in the treated area, as if you had a bad sunburn. You may also feel hoarse or have trouble swallowing.

Chemotherapy
Chemotherapy, the use of drugs to kill cancer cells that have spread to other parts of the body, may be used in some cases, such as for medullary thyroid cancer, which doesn't respond to radioiodine therapy. Not every person with medullary thyroid cancer responds to chemotherapy, but in some cases a combination of cancer drugs may shrink tumors or slow their growth.

Chemotherapy may also be used for anaplastic thyroid cancer, the most aggressive and fastest growing type of thyroid cancer. Anaplastic cancer often can't be helped by surgery by the time it's diagnosed. Radiation or chemotherapy may shrink tumors slightly and make you more comfortable.

Follow-up care
When the cancer hasn't spread, the outlook after surgery is excellent. If the cancer has spread to other organs, treatment depends on several factors, including the size of the tumor, how quickly it's growing, and the extent of the spread. For example, your doctor might choose not to surgically remove a small tumor in the liver, lung or bone. Such tumors sometimes grow slowly for years without causing any symptoms. Large or rapidly growing tumors, on the other hand, may need surgery or other treatment. In that case, you and your doctor will work together to decide on the best type of therapy. Thyroid cancer can recur as many as 20 or 30 years after the original diagnosis, although if you've remained cancer-free for five years, the recurrence rate is low.

You'll likely have periodic blood tests to monitor your level of thyroglobulin, a protein that stores thyroid hormone. Elevated levels of this hormone could indicate that the cancer has returned. You may also have imaging tests, such as ultrasound of the neck or other tests, that help your doctor check for a recurrence of cancer.

Clinical trials
If you have anaplastic cancer, you may want to consider participating in a clinical trial. This is a study that tests new forms of therapy — typically new drugs or surgical procedures, or novel treatments such as gene therapy. Cancer clinical trials are closely monitored to ensure that they're conducted as safely as possible. And they offer access to treatments that wouldn't otherwise be available to you. The risk is that treatments used in clinical trials haven't yet been shown to be effective. They may have serious or unexpected side effects, and there's no guarantee you'll benefit from them.

If you're interested in finding out more about clinical trials, talk to your doctor. You can also call the National Cancer Institute's Cancer Information Service at 800-4-CANCER, or 800-422-6237. The call is free, and trained specialists are available to answer your questions.

Prevention:
It's often not possible to prevent thyroid cancer. But the following measures may reduce or eliminate your risk:
  • Preventive (prophylactic) surgery. If you've inherited a defective RET gene, you may choose to have your thyroid gland surgically removed, even though the gland appears to be healthy. This pre-emptive approach eliminates the risk of medullary thyroid cancer but doesn't reduce the likelihood of adrenal or parathyroid tumors in people with MEN 2 syndrome.
  • Potassium iodide tablets. Heightened concerns about national security have focused attention on nuclear power plants in the United States. Current government guidelines recommend that people within 10 miles of these plants be provided with potassium iodide tablets.

    Taken just before or immediately after exposure to nuclear fallout, potassium iodide protects your thyroid gland from iodine 131, though not from other radioactive material. Children are most at risk from exposure to radioactive iodine, and potassium iodide is safe and effective for even very young children when taken in the proper dosage.

    Short-term side effects, which are more common in adults than in children, include intestinal problems, allergic reactions and minor rashes. You shouldn't take potassium iodide if you have multinodular goiter, Graves' disease or autoimmune thyroiditis.

  • A healthy diet. A diet high in fruits and vegetables and low in animal fat can reduce your risk of many types of cancer. The American Cancer Society recommends eating at least five servings of fruits and vegetables every day. They contain antioxidants, which protect your cells from damage that occurs as a result of normal metabolism.

    In addition, emphasize unsaturated fats (omega-3 fatty acids), especially those found in salmon and other fish, because they may help protect against cancer. Maintaining a healthy weight can also help protect against many diseases, including cancer of the thyroid.

Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.
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