What Is the Thyroid?
The thyroid is a gland in the low, front part of the neck which produces special "thyroid hormones" necessarily for life. The thyroid gets it's "instructions" on how much hormone to produce by a chemical message sent from the mid-brain pituitary gland. The thyroid is located in the middle of the low neck, overlying the windpipe ("trachea"). It is composed of 2 "lobes", with the lobes joined together at the lower third by by a connecting "Ithmus" and covered by cartilage, The thyroid connects to this tough, thick cartilage, called the "thyroid cartilage". This cartilage provides some barrier to the local spread of a thyroid cancer. The blood supply to the thyroid is from the "inferior" (lower) and "superior" (upper) thyroid arteries. These emanate from the "thyroid axis", which is a branch of the large "subciavian artery" coming off of the aorta from the heart. The thyroid veins that drain blood from the thyroid form a network ("plexus") on the surface of the organ and empty into the "jugular veins", which return it to the heart. Infections or cancer can thus be spead via the bloodstream ("hematogenously") to distant blody areas. The smallest blood vessels are where the arteries and veins join, these are called "capillaries". The fluid portion of the blood ("serum") migrates through the walls of the capillaries to bathe-individual ceiis with oxygen and nutrients. This serum is filtered by a series of "fymph glands" ("nodes") in the neck; these tend to swell ("lymphadenopathy") when invaded by the spread of infections or cancer.
The main hormones produced by the thyroid gland are thyroxine and calcitonin. A hormone is a chemical produced at one location in the body (by a gland) that has it's effects on another part of the body (like the heart or bone). Thus, a hormone is a "chemical messenger" that may,be produced either closeby or far distant to its "target tissue" area of action. Thyroxine controls the metabolic rate of the body, that is "how fast our machine runs". It is crucial for the developing child, and without it the child will be severely retarded ("cretin") and have stunted growth. An adult without any thyroxine will gradually go into a coma from too low of a metabolism. Signs that the thyroxine level is too low ("hypothyrold") include swelling in the neck (goiter), low heart rate, fatigue, getting obese, feeling of coldness, constipation and thickened hair. Conversely, signs that the thyroxine level is to high ("hyperthyrold") include a fast heart rate and palpitations, sweating, lots of energy, being thin, feeling of being hot, and diarrhea. Ideally people should be "euthyrold", meaning neither too much nor too little hormone is being produced. You can see that the thyroid hormone level must be tightly controlled for us to feel normal, and the pituitary gland in the brain does this bysensing the rate of metabolism and putting on "thyroid stimulating hormone" (TSH) which regulates the thyroid's production of thyroxine. Fortunately, even if the thyroid completely fails and no thyroxine is produced, it can be artificially replaced by taking a daily pill (levothyroxine). Thus the patient can still lead a normal life and not go into a coma ("myxedema") from lack of this crucial hormone. Too much thyroid
hormone can be controlled by chemically or radioactively destroying ("ablating") part of the thyroid to limit it's production of hormone. Thus, medical science is good at adjusting the thyroxine level if the body's regulation of it malfunctions.
The other critical hormone produced by different glands within the thyroid (called the "medullary glands") is calcitonin. This hormone regulates the calcium level in the blood. It's release causes the blood calcium to go down as it is deposited into the bones. Older individuals with severe bone thinning may benefit from calcitonin injections ("Calcimar") to which builds up the cortex (hard portion) of the bones. Blood calcium must be maintained within a narrow balance or the patient will first have abnormal reflexes, be very fatigued, and eventually go into a coma. Its intricate functions in governing proper metabolism make the thyroid a gland basic for life. It is fortunate that medical science can fairly well replace thyroid function with medications.
What Is Thyroid Cancer?
The thyroid, like other body organs, goes through a rapid development stage as we grow from infancy to adulthood. The thyroid cells grow and produce their hormones in a tightly controlled manner. In the adult, thyroid cells only divide to replace those lost through old age or injury. Thyroid cancer starts In just one cell. Something goes awry in the internal workings of this cell; in it's "genes". The genes contain the genetic information that controls the cell; they may be influenced by outside hormones. With specific types of gene damage, the cell starts dividing out of control, forming a tumor. A tumor simply means a swelling, and is not necessarily cancer. A benign tumor only grows in it's local area (although it can become very large); it is not cancer. However, a malignant tumor can spread ("metastasize") to other body areas and Is cancerous. It is this ability for malignant tumors to spread to other vital organs, and disturb their functioning, that makes cancer dangerous.
How Common Is Thyroid Cancer?
Each year in the U.S.A. there are 1 5,600 new cases of thyroid cancer causing 1,200 deaths. Thyroid cancer accounts for just 1.5% of new cancers in the U.S.A. Women are affected more than men three cases to two. The risk increases with age, the average patient is 50 years old. Thyroid cancer is rare in people younger than 30. Thyroid cancer is more common in people of Asian extraction,and the number of cases has Increased worldwide over the past decade.
What Causes or Increases the Risk for Thyroid Cancer?
Like any cancer, why any one person develops the disease and another does not remains unknown. However, several factors have been noted to Increase risk for thyroid cancer by studying groups of patients; these are called "risk factors":
1) Goiter simply means an enlarged thyroid gland. It can be either generally big or just have separate areas of enlargement (nodules). It the pituitary gland in the brain makes too much TSH, then the thyroid will enlarge. Goiters can be present at birth or develop later in life. Iodine is necessary for the the thyroid to make it's
hormones and with iodine insuff iciencency, a goiter will develop as the brain tries to stimulate the thyroid to make it's crucial hormones. In general, having a goiter increases the risk of thyroid cancer. In animals, thyroid cancer has been produced by severe iodine restriction, giving lots of TSH, and "goiterogen" foods (such as cabbage and rapeseed oil) that stimulate goiter.
2) Nodules of the thyroid are simply "bumps" or uneven areas of enlargement. It there are many nodules, the thyroid may enlarge ("multinodular goiter"). About 4% of the American population has thyroid nodules. Clinically speaking, a lump is called a "nodule" If it is more than 1 cm. (1/2") in size. While any growing nodule in the thyroid is suspicious for cancer, most are benign. Nodules may be either "hot" (function to produce thyroid hormone), "cold" (don't function to make hormones) or "warm" (make a little hormone, but not much). Over 90%
of thyroid nodules are "OK. Even though a "cold" nodule Is more likely to be cancerous than a "hof'one, only 1 0% of cold nodules are cancerous. A single nodule is more likely to be cancer than multiple nodules, Larger nodules (over 5 cm. or -2 inches) are more likely to be cancerous than small ones. A "cold" nodule in a male under 30 years old is particularly worrisome for cancer. Nevertheless, all suspicious nodules should be checked for cancer!
3) Radiation Exposure is a risk factor for developing thyroid cancer. Radiation causes changes in the genes of the thyroid cells, and increases the chance for nodules. Young people (under 30 years old) who get radiation to the neck area are at highest risk. Some young Japanese who survived the atomic bomb later developed it. Radiation is linked to slow growing thyroid cancer that often takes 10 - 30 years after the exposure to become apparent. Radioactive lodine-1 31 used for to destroy (ablate) thyroid tissue for treatment of hyperthyroldism has not been linked to later development of cancer.
4) Family History of thyroid cancer in first degree (close) relatives or rare familial
5) Genetic diseases like "multiple endocrine neoplasia" ("MEN" syndrome) raises thyroid cancer risk. Twenty percent of thyroid cancer patients have a family history of goiter. Goiter was much more common in the "Goiter Belt" (Midwest) of the U.S.A. prior to salt being "iodized".
Chronic Infections or Inflammation of the thyroid, as from Hashimoto's Thyrolditis (an "auto-immune" disease where the body's own Immune system turns agains the thyroid tissue) increase cell division in the thyroid. The more often cells divide, the more likely a change ("mutation") will arise in its genes, and certain mutations presage cancer. Anything that irritates the thyroid gland over time will increase cancer risk.
***Alcohol and Tobacco use havn't been linked to getting thyroid cancer.
What are the Signs and Symptoms of Thyroid Cancer?
The way a patient appears when they first come to medical attention is called their "presentation". This is described by "signs" which are things that can be measured (such as the size of a nodule or fever), and "symptoms" which are things the patient feels (such as pain or decreased appetite). A high "suspicion Index" is the first step.
Early thyroid cancer usually has no symptoms, it is just a small lump in the thyroid.
As the cancer grows, it may produce the following symptoms:
1) Neck Mass-- The patient (or their doctor) may notice a mass or goiter in the neck. doctors should feel ("palpate") for thyroid nodules as part of a complete physical examination. One-third of thyroid cancers are discoved from a routine exam of the neck. Eventually 75% of theyrold cancer patients will develop a noticeable swelling In the neck.
2) Hoarseness-- If the cancer invades a nerve controlling the voicebox, called the "recurrent laryngeal nerve", hoarseness of voice will result. About 15% of patients with thyroid cancer have hoarseness.
3) Neck Pain-- A pain or pressure sensation in the low neck Is found in 10% of patients due to the cancer invading nerves of the neck.
4) Swallowing Difficulty-- This "dysphagis" is found in 15% of patients and is
due to a growing tumor pressing upon the esophagus (foodpipe). Actual pain on swallowing ("odynophagia") Is a later sign of deep nerve invasion.
5) Breathing Difficulty-- This "dypnea" is found In 10% of patients and is due to
_growing tumor pressing upon the trachea (windpipe).
6) Swollen Glands-- This Illymphadenopathyll can represent spread of the
cancer to the lymph gland in the neck. These lymph glands are part of the immune system that filters blood serum and destroys germs ("pathogens") They are normally bean sized, but can swell up to large masses If invaded by infection or cancer (or both). Neck lymph gland swelling may be the first sign of thyroid cancer, but is much more commonly due to benign conditions.
7) Signs of Distant Spread-- If the cancer has spread out of it's local area, it
may "seed" to bone, lung, liver, brain or virtually any other location in the body, causing symptoms there from a "metastatsis" (distant cancer spread).
How Is Thyroid Cancer Detected and Evaluated?
As mentioned above, about 1/3 of thyroid cancers are discovered during a routine physical examination. Only by getting an actual sample piece of the tumor ("biopsy") can the diagnosis be made with certainty. If a patient presents to the doctor with signs or symptoms suggestive of thyroid cancer, the following "workup" is routinely done:
1) Complete Physical Examination documenting the size, location and consistency of any nodules and checking the lymph glands in the neck for enlargement. Shining a simple strong light ("transillumination") may show that the nodule is a fluid-filled cyst and less likely to be cancerous. On the other hand, a mass that is "complex" (has both solid and liquid portions) is more likely to be a cancer. Using a special mirror to look down the throat ("indirect laryn-
goscopy") shows the vocal cords and should be done routinely. The doctor should also look for any signs of spread to bone, liver or lungs.
2) Blood Tests include a complete blood count ("COC") to check for anemia (low red blood cell count) and infection (usually manifested by a high white blood cell count. A chemistry panel ("SMA") is an inexpensive way to check sodium, potassium, glucose, calcium, phosphorus, cholesterol, liver and kidney
function, and evidence of recent heart damage by the enzyme CPK. Any patient with suspected thyroid problems will get a "thyroid function panel". This routine blood test measures thyroid activity and includes "T3, T4, and TSH". TS and T4 (sometimes put together as "T7") are the thyroxine hormones produced by the thyroid that control body metabolism. The TS H (thyroid stimulating hormone) is made by the pituitary gland in the brain and stimulates the thyroid to produce T3 and T4. Normally, the T3 and T4 "feedback on the pituitary, stopping it from putting out excessive TSH, preventing hyperthyroldism. A pituitary tumor can cause excess TSH production and hyperthyroidism! Patients with Hashimoto's Thyroiditis initally put out excess thyroid hormone, and as the gland is slowly destroyed hormone production fails to produce clinical hypothyroidism. However, in thyroid cancer, the thyroid function panel results are usually normal. If surgery is being considered the surgeon usually wants a "coagulation panel" (PT, PTT and bleeding time) to see how well the patient's blood clots.
3) Imaging Tests are done in the radiology (X-ray) department and include X-
rays of the neck to check the appearance of the tumor, and look to see if it is pressing upon the windpipe ("tracheal stenosis"). A "barium swaillow' may be ordered; it shows esophagus function and may show a goiter "fixed upon" the trachea, which is suspicious for cancer, CT scan of the neck (which uses a series of multiple X-ray beams to construct an image) Is a relatively standard test for any suspected cancer in the neck. it helps show I lymph glands are en-
larged in the neck which remain too small to be apparent by physical exam. The CT may be gotten with contrast, which is given through an arm vein and helps better define the soft tissues and blood vessels in the neck. If getting a CT with contrast, insist upon "omnlpaquell brand or equivalent contrast- it is more costly but also more comfortable and less likely to cause allergic reactions or kidney damage than older types of contrast. Another test is Magnetic Resonance Imaging (MRI) which uses magnetism instead of radiation. it is recommended to check the extent of the tumor into the cartilage and other soft tissues of the neck, and is usually somewhat clearer (and much more expensive) than CT scan. The MR I may also be given with another type of contrast which also highlights the blood vessels, called "gadolinium". These advanced imaging scans can help guide a future surgery. Conversely, older Ultrasound of the thyroid adds cost, provides little information and Isn't recommended. if thyroid cancer diagnosed, a "metastatic survey" is ordered to look for cancer spread to other body areas. This includes Chest X-ray to took for spread to the lungs, a "Bone Scan" which looks for spread to bone (by injecting an intravenous radioactive dye which is attracted to bone tumors and then taking special whole body scan in the Nuclear Medicine department). Another way of checking for the spread to bone is by taking plain X-rays of the entire skeleton ("skeletal survey")-- following radioactive iodine-1 31 Injection into the patienvs veins (as part of the test below called "thyroid scan"). CT scans of the brain, liver or spleen scan, or other exdtic tests cannot be recommended symptoms in those areas. In aeneral, no test should be ordered unless it has the potential to change the planned therapy!
4) Thyroid Scan means radioactive iodine-131 is injected into a vein and special pictures are taken of the thyroid. The iodine-131 is taken up by "hot' or "warm" functioning nodules (which are hungry for the iodine or necessary to make the thyroid hormones), This can help rule-out cancer, since "hof'or "warm" nodules are rarely malignant, but rathe rmerely excess thyroid tissue which has grown under constant TSH stimulation. Recall that 900/o of thyroid nodules are "cold", thus more suspicious for cancer. Therefore, many doctors go to the biopsy test discussed below for diagnosis, since the thyroid scan cannot confirm nor deny cancer. A Thyroid scan is not done ("contraindicated") during pregnancy.
5) Biopsy of the Tumor is the only way to absolutely confirm the diagnosis of cancer and must be done prior to any therapy. A "f lne-needle" placed through the skin of the neck into the tumor under fluoroscopic or CT scan guidance. This can be done under local anesthesia. If a larger sample needs to be gotten, a "cutting needle" or "large needle" biopsy can be done. Needle biopsies are over 900/o accurate in diaonos'na thyroid cancer (they only miss -5% of the
time). If an adequate sample cannot be gotten with the needle then an "open biopsy" (a small surgery to remove a piece of the tumor often (under general anesthesia) by a head and neck surgeon ("otolaryngologist") is necessary. The sample taken is then examined by a "cytopathologist" (a physician who specializes in making diagnosis from small tissue samples). After several days the "pathology report" comes back from the laboratory which tells if the tumor was cancerous, and if so what particular type of cancer is, and how malignant ("aggressive") or benign ("indolent") it looks under the microscope. Cancer may manifest a spectrum of behaviors. Highly malignant cancers usually have lots of cellular division and poorly resemble their normal tissue of origin (it this case thyroid tissue); slower growing "Indolent" cancers have few cellular divisions and usually closely resemble their normal tissue counterpart. "Grading" of the cancer based upon its microscopic appearance Is described below.
What are the Types of Thyroid Cancer?
There are several types of thyroid cancer, and have have different behaviors and outcomes, and sometimes different treatments:
1) Papillary Carcinoma is the commenest type, making up more than 50% of adult thyroid cancers and over 80% of children's thyroid cancers. It tends to stay localized in the thyroid for many years, growing as a nodule. It then spreads to lymph glands in the neck and chest, and to the lungs. It gets more aggressive
in the older patient, and rarely is deadly before age 45 years. It is strongly linked to goiter and radiation exposure at a young age. Papillary cancers are graded, as described below, and can be mixed with foillcular carcinoma too.
2) Follicular Carcinoma is -25% of all thyroid cancers and usually occurs
in middle age. It rapidly spreads through the bloodstream to lung and bones, but has little tendency to invade lymph glands. Sometimes, however, follicular carcinoma behaves in a milder fashion, more like papillary cancer. Follicular cancer's behavior depends upon it's "Grade". The grade is assigned by the pathologist
who examines the cancer sample under a microscope. "Grade 1 " means the cancer looks indolent (non-aggressive) under the microscope, that is much like normal thyroid tissue. "Grade III" means the cancer looks very aggressive, with rapid cell division and invasion of nearby structures, it is very "cancerous@ and probable spread quickly. "Grade II" is intermediate in appearance and behavior. Mixed follicular and papillary carcinoma has an indolent course.
3) Medullary Carcinoma is much less common at just 511/a of thyroid cancers. It arises from the "C-cells!' of the thyroid that make the hormone calcitonin, rather than from the thyroid follicules as do the cancers above. It's risk factors, testing, and behavior is thus different than for papillary or follicular carcinoma. It comes either as familial forms (25%) associated with the "MEN" syndromes, or as a spontaneous cancer in 75% of cases. The familial form occurs at younger age and is less aggressive than the sporadic form. Testing for medullary carcinoma can be done based on the calcitonin hormone it produces (although a biopsy is still needed to confirm the diagnosis). The specific test is a "thyrocalcitonin assay" a positive test needs to be followed up with a surgical neck exploration for cancer regardless of results on a "thyroid scan". Patients with a confirmed medullary cancer should have tests to look for the other cancers in the "MEN" syndromes, like pituitary gland and adrenal gland cancers. The treatment for
medullary carcinoma is different than for the papillary or follicular types, as will be discussed.
4) Anal2lastic Carcinoma is about 10% of thyroid cancers and is the worse type. It arises from long-standing goiter, sometimes from a "transformation" of a less aggressive papillary carcinoma, or from a rare variant of follicular cancer
called the "Hurthle Cell" type. It usually strikes patients over 60 years of age, and rapidly spreads to lymph glands and distant organs. The term "anaplastic" means that the thyroid follicle cells in this cancer very poorly resemble their normal tissue of origin, and thus we expect the cancer to behave aggressively.
5) Rare Cancers of the thyroid include lymphomas and Hodgkin's Disease (from immune cells in the gland) sarcomas (from muscles, fat or cartilage in
the gland) and cancers of other organs (i.e. lung, colon, pancreas) spread to the thyroid. If a cancer spreads to the thyroid from a different body area, it is not considered "primary thyroid cancer". If thyroid cancer spreads to other body areas, however, it is still called mprimary thyroid cancer" irrespective of the extent or location of spread. The treatment for the various rare thyroid cancers follows their standard treatment as in other body areas where they are commoner.
How Is the Extent of Thyroid Cancers Gauged?
Like all cancers, the extent of thyroid cancer is given by the "Stage". These stages take into consideration the size of the tumor, it's spread to lymph glands, andto distant organs. The commonest staging system used in the U.S.A. is the American Joint Cancer Committee ("AJCC") staging. The stage is used to help predict appropriate treatment, and expected survival:
For Papillary and Follicular thyroid cancers, under age 45 years of age
Stage Definition 15 year survival
I Any cancer, Any size, no spread to distant organs 95%
II Any cancer, Any size, with spread to distant organs 75%
For Papillary and Follicular cancers, patient age 45 years or older
Stage Definition 15 year survival
I Cancer smaller than 1 cm, limited to thyroid 95%
II Cancer larger than 1 cm, limited to thyroid 85%
III Cancer invades thyroid capsule and/or lymph nodes 70%
IV Cancer has spread to distant organs 50%
For Anaplastic thyroid cancer-- all patients are stage IV, 5 year survival less than 1 0%, average survival is only 7 months.
For Medullary thyroid cancer
Stage Definition 15 year survival
I Cancer smaller than 1 cm, limited to thyroid 90%
II Cancer larger than 1 cm, and/or invades capsule 80%
III Cancer invades local lymph nodes in neck 40%
IV Cancer has spread to distant organs 200/0
It is important to remember that the above survival numbers are just textbook averages, and include demise during the 15 year time period from all causes, including heart attacks, accidents, or other cancers. Survival statistics say nothina about how any individual will do. Each cancer tends to behave different in each patient. Predicting lifespan is both poor science and poor medical practice; we are M.D.'s, not M. Dieties. Moreover, individuals often live long and satifying lives even with "incurable" disease.
What are the Important factors that Determine Outcome?
These are called prognostic factors and are elucidated by studying groups of patients. Particular factors that are WORSE for thyroid cancer include:
1 ) Age older than 45 years.
2)Tumor fails to take up iodine (since radioactive iodine is used treat them).
3)Tumor is larger than 5 cm. (~2 inches--compared with smaller than 2 cm.)
4)Tumor extends into thyroid capsule or has spread to lymph nodes.
5)Tumor causes actual symptoms, such as hoarseness or pain on swallowing.
6)Anaplastic or Medullary cancer compared to the Papillary or Follicular types.
7)Poor "response" of the cancer to initial treatment
8)Obviously, spread of the cancer to distant organs, although many are still cured. In fact, thyroid cancer is still one of the most curable cancers even after spread.
What Is the Conventional Treatment for Papillary and Follicular Cancer?
There are several ways of managing early thyroid cancer, which is likely to be quite indolent (not aggressive). The treatment shouldn't be worse than the disease!
Surgery was and remains the conventional treatment for operable thyroid cancers. Once a diagnosis of cancer has been established, the traditional operation is called a "thyroldectomy", which simply means removal of the thyroid gland. The gland may be entirely removed ("total thyroldectomy") or partially removed ("subtotal thyroldectomy"). While the subtotal thyroidectomy has less side effects, it also has double the relapse rate (nrecurrence rate") than when the whole thyroid is removed, for papillary and follicular cancers. Thus, total thyroldectomy is the cancer operation of choice, and is recommended for all but the smallest cancers. Besides removing the thyroid, any suspicious lymph nodes in the neck should be removed (suspicious means larger than 1 cm. or 1/2 inch). While suraical "neck dissections" were done in the past to remove all of the maior lymph nodes in the neck, they were not found to increase sury4val, but iust make more coml2licatwons. Neck dissections leave ugly scarring and are best limited in papillary and follicular cancers to removal of only suspicious or grossly abnormal lymph nodes. Papillary cancers have lymph nodes involved in 50% of patients at surgery, while follicular cancers have lymph nodes involved in less than 20%.
Complications of surgery occur in 15% of patients getting total thyroidectomy and 10% of those getting subtotal thyroidectomy. As mentioned, relapse of the cancer is twice as likely in those getting only part of the thyroid removed; the worst "complication" of surgery (besides a 1% risk of operative death ) is recurrence of the cancer afterward. Thus, surgeons want to perform an operation which balances the need for total cancer removal with the increased complications of more extensive surgery. If an extensive neck dissection (removing even normal appearing lymph nodes) is done, then the major complication rate of surgery rises to 40%. Since this neck dissection has not increased survival, it is not recommended. The major complications of the standard total thyroidectomy are "hypoparathyroldism" and vocal cord paralysis. Hypoparathyroidism comes from removal of the parathyroid glands, the 4 of which are embeded within the tissue on the back of the thyroid gland. These glands regulate the body's calcium balance, making a hormone called "parathyrold hormone" or "PTH" for short. PTH raises blood calcium by causing it to be re-absorbed from bone. It's effects are balanced by "calcitonin", which is the hormone put out by the medullary cells of the thyroid that causes calcium from the bloodstream to be layed down into bone. This is a delicate balance, since too high or low blood calcium can lead to lethargy, muscle spasms, and eventual coma, muscle paralysis and death. Fortunately, the hypoparathyroid glands removed during total thyroidectomy can be re-implanted elsewhere in the body and continue their function. They are usually put into the forearm, and this works 90% of the time. If it doesn't, however, then the patient will need to take supplemental calcium to live. Vocal Cord Paralysis comes from damage to the recurrent laryngeal nerve, which tenses the v6cai cords for $peach. These nerves are paired; one for each vocal cord. If just one nerve is destroyed, then the patient will only be hoarse since they still have one functioning vocal cord. If both nerves are destroyed, the patient will not be able to speak without
special training (learning how to belch up air and mouth words) or an artificial larynx ("prosthesis"). Also, it the larynx does not work, it raises the risk for swallowed food or stomach acid to get into the lungs, causing "aspiration pneumonia". Fortunately, complete vocal cord paralysis is rare (1 %).
Healing is expected from surgery within 3 - 4 weeks, and strain to the neck should be avoided before then. The results of surgery alone (total thyroidectomy) shows a recurrence rate of 20% at 5 years and 30% at 10 years, with an overall death rate from the cancer itself of 12% over time. Clearly, while the majority of patients are cured by surgery alone, the risk of recurrence makes surgery alone inadequate treatment for many patients, Surgery is usually combined with radioactive and hormonal therapy, as will be discussed below.
Radioactive Iodine (1-131) is used to treat many papillary, follicular, mixed papillary- follicular, and Hurthle cell cancers. Patient's with these tumors will usually have iodine preferentially uptaken by the cancer. The Iodine-131 delivers a high radiation dose to both normal and thyroid cancer cells. Thyroid "ablation" (destruction) may be performed with lodine-1 31, usually after surgery to remove the bulk of thyroid tissue. This destruction of residual thyroid tissue has been shown to decrease the recurrence, and Increase survival, in papillary and follicular thyroid cancers. Iodine-
131 treatment is appropriate for patients with any remaining thyroid tissue after surgery, this is called "thyroid ablation" for patients with inoperable tumor, residual disease in the neck, lymph node involvement, thyroid capsule invasion, and distant spread. In practice, nearly all patients with thyroid cancer are suitable to get Iodine-
131, to reduce the risk of recurrence and increase survival.
The actual treatment is given in the hospital, in a special room where radioactive substances can be administered without danger to other patients. It is generally given 2 months after the thyroidectomy surgery, at such time as the patient is "clinically hypo-thyrold" (meaning any residual thyroid tissue or cancer will avidly uptake the radiactive iodine). Alternatively, the patient can be made artificially hypothyroid by injecting them for several days with thyroid stimulating hormone while depriving them of iodine. Iodine-131 is a liquid injected into a vein. Residual hyroid (along with any cancer) picks up the Iodine-131, which delivers a powerful local dose of radiation to these cells. The usual dose depends upon how much thyroid tissue (or cancer) is thought to remain, and ranges from 1 00 to I 000 "millicuries" (a radiation unit). The patient is usually in the hospital for 4 or 5 days. Several treatments may be required, repeated at 6 month intervals. The need for repeat treatments is based upon residual thyroid tissue or thyroid-hormone producing cancer cells making detectable thyroid hormone, which can be picked up on a blood test. Naturally, after successful thyroid destruction, the patient will need to be started on thyroid hormone pills ("thyroxine") to restore balanced metabolism, since thyroid hormone is essential to live. The doctor checks whether repeat treatment will be necessary by discontinuing the thyroid pills, waiting for hypothyroidism to develop (about 3 weeks), and giving a "scan" with I - 5 millicuries of Iodine-131. This scan will show the location of any residual thyroid tissue (or thyroid cancer cells) anywhere in the body, and tell whether a full ablative dose of
Iodine-131 needs to be repeated. This scan, and treatment, is repeated every 6 - 12 months until negative scans are obtained, afterwhich a simple blood test for thyroglobulln (the protien which carries thyroid hormone in the bloodstream) can be used as a marker for any thyroid which happens to regrow. The patient is also monitored for any signs of hypoparathyroidism.
Actual treatment with Iodine-131 is painless. Possible side effects are divided into "acute" and "late" reactions. "Acute" reactions occur within hours to 3 months after treatment. Within 12 hours there may be nausea, fatigue, headache and swelling and tendness of any residual thyroid tissue being treated (" radiation thyrolditis"). An effect on the bone marrow ("meylosuppression") is seen with temporary low red cell count ("anemia") and low white blood cell count ("leukopenia"), this raises the risk for infection. The salivary glands may swell ("sialidenitis") leading to dry mouth ( "xerostomia"), with a metallic taste ("dysgeusia). This can last for days to years. When getting Iodine-131, patients are asked to urinate every at least every 2 hours (even at night) to help avoid the bladder getting irritated from the treatment ("cystitis"). Rarely, patients may get temporary vocal cord paralysis or neck, swelling, or signs of swelling and bleeding at sites of distant cancer spread, where the cancer is being destroyed by the iodine-131. "Late" reactions include continued dry mouth ("xerostomia") which may be relieved by water sprays, humidiers, artificial saliva (salivart) or sometimes pilocarpine pills. The bone marrow generally recovers, but rarely is permanently damaged in patients who have been given large quantities of Iodine-131 and had spread of thyroid cancer to their bones. There used to be much concern about 12atients later developing leukemia, but this has been shown to only happen rarely (less than 2%). If leukemia does develop, it is more likely to occur in patients over 50 years old who get a preceeding "pre-leukemic" condition. The most frequent type of leukemia after thyroid treatment is "Acute Myelogenous" (AML). Lung damage ("radiation pneumonitis") is shown by shortness of breath, fever, and cough, and is more likely in patients who had spread of thyroid cancer to their lungs. This condition is treated with steroids (i.e. cortisone) but may progress to be fatal. It is fortunately quite rare (1%). Both women and men Generally remain fertile after treatment with 1-131, but it is recommended that they wait at least 6 months after treatment before tryina to conceive a child. This is because the most active egg (ova) or most recently produced sperm at the time of the therapy are likeliest to show a mutation (genetic change) attibutable to radiation, and the effect dissipates over time.
The results of Iodine-131 after surgery show that the recurrence rate is lowered to about 1 0%, compared with 20 - 30 % when surgery only is used. Reasons for failure of Iodine-131 therapy include inadequate surgery prior to treatment, insufficient hypothyroidism at the time of treatment (so the Iodine-131 doesn't get into the thyroid cells) and too low a dose of Iodine-131 for the first treatment (150 millicuries is usually required). A scan is routinely performed 5 - 10 days after giving the Iodine-131 to try to localize and document the location of any cancer spread. Overall, Iodine- 1 31 is a safe and effective treatment, useful even for widespread ("disseminated") thyroid cancer which uptakes iodine. Patients with spread to the lung have apparently been cured with this treatment, often surviving over 20 years after initial diagnosis.
Medical Therapy is given with thyroid hormone. This is actually therapeutic because it will suppress the growth and production of thyroid hormone by residual thyroid or cancer cells remaining in the body after surgery and Iodine-131 administration. In general, if the body is given something easily, as in a pill, it won't go through the costly biochemical hassel of trying to synthesize it. When aiven in coneuctoon with surae[y and Iodine - 131, thyroid hormone further reduces the risk of recurrence to about 5% over tbA. In some studies with surgery only, the recurrence rate has been as high as 40% with a death rate of 13%. This is compared to a recurrence rate of 3% and a death rate of 0% when both Iodine-131 and thyroid hormone were used in conjunction after surgery. Thus you can see the clear advantage of this extra ("adjuvant") treatment after surgery. Also, when giving thyroid hormone we can closely monitor the amount given, to ensure that the patient stays "euthythyrold" (normal) without metabolic swings from improper hormone balance. This will require periodic physician visits to ascertain the way the patient is feeling, physical exam for signs of hormone imbalance, and blood levels of TSH to ensure proper TSH suppression by oral thyroid pills. This type of "follow-up" is commonly done by an expert Endocrinologist, but some "Primary Care" (i.e. Internal Medicine and Family Practice physicians) are comfortable with it. It is also useful to have the close "follow up" to quickly detect any evidence of thyroid cancer recurrence.
Radiation Therapy is occasionally used to treat thyroid cancer, especially when it is inoperable, the patient is not suited for surgery due to other problems, or the disease relapses after surgery, Iodine - 131 and thyroid hormone treatment. It is also useful if the cancer does not uptake Iodine-131. Radiation is given by "External Beam" (meaning a beam of photons is aimed at the thyroid or to sites of spread) and is prescribed by a "Radiation Oncologist" (a cancer doctor who specializes in giving radiation). Prior to treatment, the area to be treated is marked out on a replica machine, this process is called "Simulation" and takes about an hour. Watercolor marks, and eventually small pinpoint tattoos, are placed on the patient's skin to indicate the treatment area. Information from previous scans, and the Simulation, is put into a "treatment planning computer" and a "plan" is generated. This plan tells how much radiation is going to the cancer, and how much to surrounding normal tissues. Special lead blocks may be cut to shield areas that do not need to be treated; these blocks fit into the head of the treatment machine. The actual machine is usually a "Linear Accelerator" (Linac for short) but some departments still use cobalt-60 machines. The patient comes in for their "treatment start" which takes about 40 minutes. They lay on a hard table, are aligned with laser lights, and X-rays are taken to confirm positioning. The actual treatment only takes several minutes. The treatment is usually given from several different directions, the patient remains still since the machine head pivots to the proper area. The patient usually comes in Monday through Friday for 6 - 7 weeks, spending about 15 minutes each day in the radiation oncology department. The total dose given is commonly 70 Gray (units of radiation) to the tumor, at a rate of 2 Gray per treatment day. In general, the larger the tumor, the larger the dose needed. For advanced disease where relief of symptoms is the goal, 30 Gray
given over 10 days may be adequate. The lower the dose given each day ("fraction size") the less will tend to be the side effects, discussed below. Of course, this must be balanced with the speed with which the patient needs relief from a growing tumor.
When getting radiation to the neck area, patients do not become radioactive, get sick, or lose their scalp hair. The side effects ("toxicity") of External Beam radiation are Generally limited to the actual area being treated. Acute effects which may occur during the period of treatment include neck skin redness (which may progress to peeling), sore throat, loss of taste, dry mouth, salivary gland swelling, and fatigue. Late effects include skin color changes, skin thickening, prolongued dry mouth with taste changes, higher risk for dental problems (cavities), and of course hypothyroidism if hormone pills are not taken. Special care is taken to avoid excessive radiation to the spinal cord, which only tolerates about 45 Gray-- exceeding this can lead to neurological problems or even paralysis ("transverse myelitis"), although this is very rare. In general, radiation treatment is easy to get and well tolerated, Radiation is very effective for bone pain or other symptoms caused by spread of the tumor to distant sites, and can dramatically reduce the amount of pain medication needed. In general, External Beam radiation is only used for those with advanced or relapsed disease, and for those with medullary or anaplastic cancer of the thyroid, so it is not compared "head to head" with surgery and Iodine - 131 for early disease. Radiation does tend to be less effective in patients whose tumors do not uptake iodine, but this often be compensated for by giving a higher dose of radiation.
Chemotherapy has been tried but does not have a major role in papillary and follicular thyroid cancers. The most effective single drug is Adriamycin ("Doxorubicin"), a red liquid which can cause severe heart and lung problems-- it's administration is carefully monitored. It s dose is generallyl restricted to 500 milligrams per square meter of body area (patients are between 1 and 2 square meters). Heart function is usually tested with a MUGA scan before Adriamycin is given. About one-
third of patients oettina adriamycqn had significant tumor shrinkage with prolooed survival. and another one-third had a temporary arrest of their progressive disease. The chemotherapy is only offered to patients with advanced disease, there is no sense in giving dangerous drugs to patients who are probably going to be cured anyway.There is rational for giving chemotherapy for patients with locally advanced disease, who cannot get surgery, and following the chemotherapy with External Beam radiation treatment. This has resulted in local cumor control at one year in 85% of patients so treated. At Memorial-Sloan Kettering Cancer center in New York, patients with extensive papillary and follicular cancers got low - dose Adriamycin once a week during radiation therapy, they had an average survival of 5 years. Unfortunately, the combination of adriamycin and radiation in the neck markedly increases the skin and tissue reactions there-- usually manifested by skin redness ("erythema"), peeling ("desquamation") and intense soreness especially on swallowing ("odynophagia"). In other words, chemotherapy intensifies the acute reactions of radiation therapy. Interestingly, this increased reaction is even noted when the radiation is given months after chemotherapy ("recall reactions"). The main uses for chemotherapy are in medullary and anaplastic thyroid cancers (see below).
Since medullary cancers arise from the C-cells of the thyroid and do not uptake iodine, their treatment is different than for papillary and follicular cancers. Patients should have a total thyroidectomy, since the chance for recurrence after partial thyroidectomy for medullary cancer (30%) is greater than for the papillary or follicular types. Furthermore, the disease often involves both halves of the thyroid. It is important that the pre-operative evaluation exclude the MEN syndromes with their accompanying pituitary, pancreas or adrenal tumors. If lymph nodes are not involved, the survival rate is 90%, but 70% of patients do have lymph nodes involved at surgery, lowering the survival to 40%. Unlike papillary and follicular cancer, medullary cancer demands a full dissection of the lymph nodes in the central neck. If these nodes are grossly involved, then a modified radical neck dissection is done. Doing radical neck dissection has not been shown to increase survival over the modified type, and it is more morbid. Patients with disease limited to the thyroid can actually benefit from Iodine-131 administration. This is thought to be due to the fact the even through medullary cancer doens't uptake iodine, the nearby papillary and follicular cells do, and shine their radiation on their medullary neighbors, killing them. More often, patients get external beam radiation, to 60 Gray given over 6 weeks. While it is not as sensitive as papillary carcinoma, it is more sensitive than anaplastic disease.
Since lymph nodes over the collarbone ("supraclavicular"), the armpit ("axillary") and the chest ("mediastinal") are often involved, the radiation fields may be quite large.This may result in more radiation side effects, which increase along with field size, total dose and daily dose, Tumor shrinkage following radiation is quite slow, necessitating years of follow-up to determine the results. When Adriamycin chemotherapy is given for advanced or relapsed medullary cancer, about 1/2 of of patients show some response lasting an average of 2 years. Some patients will have permanent responses, and thus parent cure.
Conventional Treatment - Anaplastic Cancer
Anaplastic cancer of the thyroid has historically been one of the most deadly cancers known. With an average survival of just 7 months, many things have been tried. There is some hope for these patients with very aggressive therapy, using everything we have ("multimodality treatment"). Firstly, the patient should get surgery to remove the thyroid. After maximal surgical removal of the tumor, the patient is sent for External Beam radiation. This is given to at least 60 Gray, but at this point is rarely (though occasionally) curative. Either during or after radiation treatment, chemotherapy is started. Combined chemo-radiotherapy may be the best hope for these patients. The best chemotherapy today uses a "combination" of agents which usually includes Adriamycin, Melphalan, Bleomycin and Vincristine. About 60% of patients respond to this. In Europe, a three drug regimen of Bleomycin, Cyclophosphamide, and Adriamycin along with radiation therapy resulted in an apparent cure rate of 12%, and a doubling of average survival time compared to patients who recieved no chemotherapy. While these results cannot be called "good", they are the first significant increase in survival we have seen for anaplastic or spindle-cell carcinoma.
What Is the Latest Effective Treatment for Thyroid Cancer?
The latest treatment is the maximization of conventional treatments, tailored to each particular patient. We have shown that combining Iodine-131 and thyroid hormone with surgery has improved survival. In the 1930's, before Iodine-131 was routinely used, the death rate from papillary and follicular-cancers was about 12%. By the 1960's, when use of iodine-131 became routine, the death rate droped to 3%. In many series now it is less than 1% for non-aggressive papillary and follicular cancers. Besides for new combinations of radiation and chemotherapy to salvage those with advanced disease, some newer treatments are worthy of mention:
1)Hyperthermia means heating the cancer to about 115 degrees F. just before giving radiation therapy. This has been shown by the Nationwide Radiation Oncology Therapy Group (RTOG) to double the local control rates as radiation alone; it is off ered at many University Academic Radiation Oncology departments.
2)lmmunotherapy means using agents which stimulate the bodies immune system to fight the cancer. Besides good nutrition and a good attitude on the part of the patient (depression lowers immunity), chemicals like the BCG vaccine have been tried in poor-risk thyroid cancer. It has very little risk, is a simple injection, and has so far had inconclusive results. Nonetheless, immune-stimulatana vaccines can be
recommended due to their low risk and poss"ble great benefit for particular Qatients. Another recent method is taking special antibodies, called "monoclonal antibodies" with a radioactive tracer. These antibodies go specifically to thyroid cancer cells, wherever they may be in the body. They can both be used to show the location of the cancer cells, though a nuclear medicine scan to see where they have gone, or can even be tagged with enough radiation to kill the cancer cells once the antibody joins with them.
3)Gene Therapy for solid tumors, including thyroid cancer, is the subject of active trials at the Dana Farber Cancer Center, M.D. Anderson Cancer Center, Thomas Jefferson Medical Center and Memorial Sloan Kettering. If we can insert a correct copy of a mutated gene into a tumor cell, using a virus, we may be able to reverse the process of uncontrolled division-- without untoward side effects on other cells. This is NOT yet a widely accepted option, but given the low risks of gene therapy it is worth considering for advanced, otherwise untreatable thyroid cancer.
For the patient diagnosed with thyroid cancer, it is important not to rely on a single pill or ray, but utilize a "combination" approach. This means utilizing a program for improved nutrition, exercise and spiritual renewal. It is worthwhile to select a safe, affordable Alternative Therapy that the patient can believe in-- and that doesn't interfere with getting the latest effective treatment. CancerAnswers.com has an In-
Depth Transcript describing reasonable Alternative Therapies available via our Website. Overall, there is more hope than ever before for patient's with thyroid cancer, and the overall survival is now over 90% for the average patient. Patients with the poorer-risk types have the best chance for survival by combining treatment modalities. Continued advancements against thyroid cancer offer better hope than ever before for patients and families of those stricken, and effective therapy for this once often fatal disease makes it a landmark in the fight against cancer.
This is the full transcript, offered freely in the spirit of internet sharing, of CancerAnswers' report on Thyroid Cancer. Much more, including latest
additional treatments for Thyroid Cancer can be found on our order page. Thank you for using CancerAnswers as
your information resource.
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ADDITIONAL TOPICS
Acute Leukemia
Anal Cancer
Bladder Cancer
Bone Cancer
Brain Cancer
Breast Cancer: Early
Breast Cancer: Advanced
Cartilage Cancer
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Chronic Leukemia
Colo-rectal Cancer
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Ovarian Cancer
Pancreas Cancer
Penile Cancer
Plasmacytomia
Prostate Cancer
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Thyroid Cancer
Tongue Base and Tonsil
Cancer of Unknown Origin
Uterine Cancer
Vaginal Cancer
Vulvar Cancer
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