Prevalence of+Hereditary+Medullary+Thyroid+Cancer+in+Men

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=__**Purpose**__=

To determine whether if there is a genetic link in developing medullary thyroid cancer and to verify why women are more susceptible than men in acquiring medullary thyroid cancer. Also to investigate if there are any specific hormones that are contributing to the risk of developing a carcinoma and to verify if age is also a key factor in acquiring medullary thyroid cancer. = =

=__**Introduction**__= The thyroid gland is a butterfly shaped organ, which is located below the thyroid cartilage,the Adam's apple. The thyroid has two lobes, which the isthus connects the two lobes. The gland is important in producing proteins and controlling energy usage and secretion of hormones. The thyroid epithelial cells, follicular cells, are important for producing the hormones triiodothyronine (T3) and thyroxine (T4), which affect heart rate, metabolism, blood pressure, and weight. The epithelial cells are also important in taking up iodine and synthesizing thyroglobulin, a protein that is responsible for the production of T3 and T4. In addition, the thyroid also produces calcitonin, a hormone produced by the C-cells of the thyroid, which plays a key function in calcium metabolism.
 * What is the Thyroid gland?**

When cells have lost the capability to gather and produced normal tissue form and function, tumors arise. These malfunctioning cells might give raise to cancerous cells. Metastasis of thyroid tumors can spread through the lymph vessels to the lymph nodes. Also, thyroid tumors can travel by blood vessels to the bones, liver, and lungs, developing a secondary tumor.

There are four main types of thyroid cancer: papillary, follicular, medullary, and anaplastic. Papillary and follicular thyroid cancers have the highest carinomas among the four types (> 90%) then medullary carcinomas ( 2% to 3%) then anaplastic cancers (< 3%). Thyroid cancer can be developed from varies risk factors, such as a low diet in iodine, exposure to radiation, and familial conditions like medullary thyroid cancer.

=__**Medullary Thyroid Cancer**__=

**What is Medullary Thyroid Cancer?**
Thyroid cancer denotes about 3% of recent cancerous growths happening annually in the United States. It is estimated 56,460 patients are diagnosed with thyroid cancers and 1,780 thyroid cancer deaths per year. 2% to 3% of these diagnoses are medullary thyroid cancer. Medullary thyroid cancers develop from the parafollicular calcitonin-secreting cells of the thyroid gland. Medullary thyroid cancer arises in a hereditary form (25%) and in sporadic form (75%) and that may be lead through parafollicular cells (C-cell) hyperplasia.

**Survival Rates**
The 5-year survival rate for papillary and follicular thyroid cancer is 90% to 94%, which is higher than the average 5- year survival rate for medullary thyroid cancer that is 83%. However, the survival rate varies on when the patient was initially diagnosed and the stage at diagnosis. For instance, when diagnosed at an early stage, it will improve the prognosis and survival rate in medullary thyroid cancer. Also, there are other factors that contribute to enhance better survival rates in medullary thyroid cancer, such as small tumor size, diagnosis at an early age, genetic components versus non-genetic factors, and the diagnosis through biochemical screening versus. Survival rate also varies whether the cancer becomes metastasis or has confined to one location.For instance, the survival rate drops to about 35% for patients with distant metastases.

**Risk Factors**
Risk factors that are associated with medullary thyroid cancer include a mutation of the proto-oncogene, //RET.//The mutation can be passed down through generations, which causes an inherited risk factor for individuals to develop medullary thyroid cancer. In addition, individuals who are exposed to radiation have a higher risk in acquiring medullary thyroid, since the thyroid gland is extremely sensitive to radiation. Also, a low iodine diet is a risk factor in obtaining medullary thyroid cancer, because the thyroid gland is capable of storing iodine. Additionally, gender is factor that contributes in developing a medullary thyroid carcinoma.

**Symptoms**
Early of the cancer, one may not feel any symptoms or complications, however later as the tumor growths individuals may experience various problems, such as**:**
 * Breathing complications
 * Cough/ cough with blood
 * Diarrhea
 * Enlarged thyroid
 * Lump on thyroid gland
 * Hoarseness
 * Swollen lymph nodes
 * Swallowing complications
 * Neck pain
 * Throat pain
 * Mass in the front of the neck

**Diagnosis and Staging**
The following exams may be accomplished:


 * **Physical exam:** A physician exams one’s thyroid for any masses. In addition, the physician exams one’s lymph nodes and neck for inflammation.
 * **Blood tests:** A physician could exam for odd levels of TSH in the blood stream. Abnormal levels of TSH may indicate a carcinoma. In addition, the physician exams for excessive amounts of calcitonin in the blood.
 * **Ultrasound:** The sound waves create echoes that form a picture of one’s thyroid. The picture can illustrate the size and the shape of the tumor, which can indicate if the tumor is cancerous.
 * **Thyroid scan:** One consumes radioactive iodine, which the thyroid cells will absorb. If the tumor absorbs more radioactive iodine, than that tumor is not cancerous. However, if the tumor absorbs less radioactive iodine, that tumor is cancerous. Since medullary thyroid cancer produces a small amount of iodine, one can detect if the tumor is cancerous
 * **Biopsy:** A pathologist obtains a piece of one’s thyroid tissue and checks for cancerous cells, which can be accomplished with a thin needle.

Staging a patient may involve the following exams:
 * **Ultrasound:** A ultrasound exam of one’s neck can indicate if the tumor has become metastatic and invasion to the lymph nodes or other tissues.
 * **CT scan:** X-ray scan can indicate if the tumor has become metastatic and invasion to the lymph nodes or other tissues, or chest.
 * **MRI:** Scan has specific pictures of one’s neck and chest and if the tumor has become metastatic and invasion to the lymph nodes or other tissues.
 * **Chest x-ray:** X-ray can indicate if the tumor has travels to the lungs.
 * **Whole body scan:** Scan can if the tumor has become metastatic to other parts of the body, when one consumes radioactive iodine.

The staging system is a normal way to diagnose patients based on the size and metastasis of the tumor. There are 3 important parts of the TNM staging system.
 * The TNM Staging System **

**T:** Illustrates the size of the primary tumor **N:** Explains if the tumor has traveled to the lymph nodes **M:** Illustrates if the tumor has become metastasis to other tissues of the body

<span style="font-family: Arial,Helvetica,sans-serif;">The numbers 0-4 can give more information about a patient when using T,N,M. Increasing the number signifies the severity of the tumor. The letter X represents "cannot be assessed because the information is not available."

<span style="font-family: Arial,Helvetica,sans-serif;">**TX:** Primary tumor cannot be measured <span style="font-family: Arial,Helvetica,sans-serif;">**T0:** No indication of primary tumor <span style="font-family: Arial,Helvetica,sans-serif;">**T1**: Tumor has not traveled outside of thyroid and is 2cm crosswise <span style="font-family: Arial,Helvetica,sans-serif;"> **T1a:** Tumor has not traveled outside of thyroid and is 1cm crosswise <span style="font-family: Arial,Helvetica,sans-serif;"> **T1b**: Tumor has not traveled outside of thyroid and is larger than 1 cm crosswise <span style="font-family: Arial,Helvetica,sans-serif;">**T2:** Tumor has not traveled outside of thyroid and is between 2cm and 4cm crosswise <span style="font-family: Arial,Helvetica,sans-serif;">**T3:** Tumor has started to grow slightly into surrounding tissues and is larger than 4cm crosswise <span style="font-family: Arial,Helvetica,sans-serif;">**T4a:** Moderately advanced disease. Regardless of any tumor size, it has traveled to surrounding tissues such as the neck, trachea, esophagus, and the larynx’s nerve. <span style="font-family: Arial,Helvetica,sans-serif;">**T4b:** Very advanced disease. Regardless of any tumor size, it has traveled to the spine or surrounding large blood vessels.
 * <span style="font-family: Arial,Helvetica,sans-serif;">T Classifications for Medullary Thyroid Cancer **

<span style="font-family: Arial,Helvetica,sans-serif;">**NX:** Surrounding lymph nodes cannot be measured <span style="font-family: Arial,Helvetica,sans-serif;">**N0:** Has not travel to the surrounding lymph nodes <span style="font-family: Arial,Helvetica,sans-serif;">**N1:** Tumor has traveled to surrounding lymph nodes <span style="font-family: Arial,Helvetica,sans-serif;">**N1a:** Traveled to the lymph nodes near the thyroid in the neck <span style="font-family: Arial,Helvetica,sans-serif;">**N1b:** Traveled to the lymph nodes in the neck, or the lymph nodes behind the throats, or the upper chest.
 * <span style="font-family: Arial,Helvetica,sans-serif;">N Classifications for Medullary Thyroid Cancer **

<span style="font-family: Arial,Helvetica,sans-serif;">**M0:** No metastasis <span style="font-family: Arial,Helvetica,sans-serif;">**M1:** Metastasis to other tissues of the body
 * <span style="font-family: Arial,Helvetica,sans-serif;">M Classifications for Medullary Thyroid Cancer **


 * <span style="font-family: Arial,Helvetica,sans-serif;">Specific Stages for Medullary Thyroid Cancer **
 * <span style="font-family: Arial,Helvetica,sans-serif;">**Stage I** (T1, N0, M0):
 * <span style="font-family: Arial,Helvetica,sans-serif;">**Stage II:** One of the following may include:
 * <span style="font-family: Arial,Helvetica,sans-serif;">T2, N0, M0:
 * <span style="font-family: Arial,Helvetica,sans-serif;">T3, N0, M0:
 * <span style="font-family: Arial,Helvetica,sans-serif;">**Stage III** (T1 to T3, N1a, M0)
 * <span style="font-family: Arial,Helvetica,sans-serif;">**Stage IVA:** One of the following may include:
 * <span style="font-family: Arial,Helvetica,sans-serif;">T4a, any N, M0
 * <span style="font-family: Arial,Helvetica,sans-serif;">T1 to T3, N1b, M0
 * <span style="font-family: Arial,Helvetica,sans-serif;">**Stage IVB** (T4b, any N, M0)
 * <span style="font-family: Arial,Helvetica,sans-serif;">**Stage IVC** (any T, any N, M1)

=__Genetic Medullary Thyroid Cancer__=

As previously stated, Medullary Thyroid Cancer makes up about 3% of all thyroid cases presented within the United States, of this 3% a very interesting phenomenon occurs; hereditary caused cancer! Of all Medullary Thyroid Cancer cases in the United States, 20-25% are passed down from one generation to the next within families(<span style="background-color: #ffffff; color: #333333; font-family: Arial,Tahoma,Helvetica,FreeSans,sans-serif;">[|Kloos, Eng, et al]). This form of the cancer is caused by what has been come to be called germline mutations.


 * Background: What is a Germline Mutation? **

According to the National Cancer Institutes Dictionary of Cancer Terms, a germline mutation is "A gene change in a body's reproductive cell (egg or sperm) that becomes incorporated into the DNA of every cell in the body of the offspring" ("Germline Mutation")<span style="background-color: #ffffff; color: #333333; font-family: Arial,Tahoma,Helvetica,FreeSans,sans-serif;">. Essentially, mutations that occur within the sex cells of a parent, will not actually affect the parent, but rather, will have a chance of affecting the offspring through reproduction. If these mutations are passed onto the next generation, the mutation will definitively be found in every cell of the offspring's body due to the manner in which <span style="background-color: #ffffff; color: #333333; font-family: Arial,Tahoma,Helvetica,FreeSans,sans-serif;">fertilization, meiosis, and mitosis occur. <span style="background-color: #ffffff; color: #333333; font-family: Arial,Tahoma,Helvetica,FreeSans,sans-serif;">It may be obvious that the second generation has a much greater chance of developing a disease from the mutation, as it has been incorporated into every cell within their bodies, but it is also true that the third generation has an even greater chance of getting the mutation based disease. This is because between the first and second generation, there is an x chance (depending on whether the mutation comes from the mother or the father) that the mutation will be received, but if the mutation is passed on, between the second and third generation there is a greater chance of the mutated gene being passed onward. Also, the status of each parent in the offspring's genetic pool, in terms of being a carrier or being actually affected by the disease influences the chance of receiving the mutation for the offspring. The figure to the above shows how the chances of receiving the mutated gene are different from each parent, as well as the fact that the sex of the offspring also drastically alters the probability. There are also other confounding factors, including crossing over of chromosomes, that add to the complexity of the mutated gene being passed on to the next generation. Germline mutations rarely are able to overcome these odds and make the entire generation present the mutation, rather, there is usually a mix of those who present the mutation, carry the mutation, and those who are mutation free.


 * How does this relate to cancer? **

These germline mutations can occur in regards to both proto-oncogenes and cancer repressor genes. In the case of a proto-oncogene, a mutation would cause the formation of an oncogene, resulting in cancerous cells. In the case of a cancer repressor gene, a mutation could possibly cause the gene to be rendered useless or off and therefore, cancerous cells would be formed. The Sanger Institute has thus far cataloged 488 different cancer causing germline mutations (Sanger Institute). The Institute has created an extensive table of these mutated genes that actually includes the HRPT 2 gene associated with hyperthyroidism, and over active thyroid disorder, which can eventually cause cancerous results.


 * What are the Mutations that Cause Familial Medullary Thyroid Cancer? **

The RET gene, found on the tenth chromosome, which codes for the RET protein, was discovered in 1985 and soon afterword in 1993 and 1994, the three types of genetic mutations causing MTC (MEN 2A, FMTC, and MEN 2B) were linked to germ line RET mutations (Kloos, Eng, et al) The RET protein is a tyrosine kinase receptor responsible for binding to Glycophosphatidylinositol (GFL) and a GFR-alpha receptor, dimerizing, and beginning a signal transduction cascade and its coding gene is a proto-oncogene. If the mutation is in fact a germline mutation, it can come in three forms; FMTC paired with MEN2A, FMTC paired with MEN2B, and FMTC alone. The Image to the right visually explains that RET has to bind to the GFR-alpha receptor and a specific ligand, and then dimerize in order to form a Heterocomplex and precipitate a signal transduction cascade, in this case, consisting of two different pathways.

MEN 2 or Multiple Endocrine Neoplasia, itself, is a major class of concern for the larger grouping of medullary thyroid cancer. It exists as an autosomal dominant cancer form and therefore has a 50% to be inherited by the offspring of a carrier. This fact makes it the main focus of RET genetic screening (Kloos Eng, et al). MEN2 can be can be sorted into two groups, A and B. MEN2A is defined as and medullary thyroid cancer carcinoma occurring alongside phechromocytom and parathyroid adenomas, where MEN2B is defined as a medullary thyroid cancer carcinoma occurring alongside a marfanoid habitus and pheochromocytoma. The third term and other MEN2 subtype, FMTC, is used when only medullary thyroid cancer occurs (Elisei, Romei, Cosci et al), which is most often a familial/hereditary occurrence.

The FMTC with MEN2A sub-type is most often attributed to the RET mutation known as C634, causing 90% of MEN2A medullary thyroid cancer. The FMTC with MEN2B sub-type is created by a completely different RET mutation, the largest gene mutation contributor being the M918T mutation, causing 90% of MEN2B medullary thyroid cancer (Thyroid Cancer). Both of these genes can also be attributed to sporatic cases of thyroid cancer, but are much more likely to cause these two main forms of hereditary thyroid cancer.

** What is the means of inheritance of these mutation? ** The inheritance of the RET mutations revolves around the fact that everyone gets one RET gene from each parent. People with familial medullary thyroid cancer usually receive one mutated form and one healthy form of the gene. Although it is possible to survive with only one healthy version of the gene, it is still much more likely for the patient to develop medullary thyroid cancer as only one proto-oncogene needs to be mutated in order for the cancer to present. If only one parent has familial medullary thyroid cancer, there is a 50% chance that their offspring with inherit the mutated gene (American Cancer Society). A person with only one healthy version of the disease is therefore much more likely to develop medullary thyroid cancer than someone who has two healthy versions of the gene. It takes more mutations to create oncogenes in two RET genes than it does to create one RET oncogene. Due to the genetic factor of medullary thyroid cancer predisposition, those individuals with any family medical history of the disease should be tested as soon as possible. People who have been given a mutated RET gene from their parents present this mutation in every cell in their body and therefore, are easily tested and diagnosed through a blood sample.

=__Why are women more likely to have the hereditary form of MTC?__=

Are there hormones that are contributing? If so, which ones and how?
Women are three times more likely than men in acquiring thyroid cancer. This suggests that perhaps sex hormones may be a contributing factor. As mentioned before, parafollicular C cells secrete the hormone calcitonin. Calcitonin’s expression is promoted in the response to estrogen. Estrogen is a sex hormone primarily in women and is a key factor in thyroid regulation. The hormone increases the thyroxine-bind-globulin, which is responsible for transporting the thyroid hormones in the blood stream, and is used for women with hypothyroidism.

Estrogen has two receptors, ERα and ERβ. After ERα and ERβ bind to estrogen (or Estradiol E2), the receptor dimerizes and becomes activated. It can now initiate estrogen response elements to encode specific genes. Also when ERα and ERβ are activated, it can also signal to other transcription factors that can encode other genes. Estrogen receptors have been present in both normal and abnormal human thyroid cells. Also when estrogen binds to ERα it promotes cell proliferation and cell growth. When estrogen binds to ERβ, it signals apoptosis, cell death. The expression of ERα and ERβ were noticed in medullary thyroid cancer, which suggest a promising factor in tumorigenesis.

There were studies that investigated the ERα and ERβ in normal and abnormal tissue. There have been illustrations of ERα protein and ERβ mRNA in normal and metastatic thyroid tissues which confirms the theory that the likelihood of estrogen being a direct component in thyroid tissues and tumors.Studies have also observed the expression of ERβ in normal parafolliciular C cell and medullary thyroid cancer. Also they have noticed the existence of mRNA for ERα and ERβ in human medullary thyroid cancer tissues. Also a study have also illustrated that existence of ERα and the loss of ERβ expression in medullary thyroid cancer and revealed interesting data. They demonstrated that the expression of ERβ mRNA decreased and as well as the ERβ protein decreased. Concluded that the ERα/ERβ mRNA ratio increased in tumor tissues opposed to normal tissues, which implies a promising factor in tumor growth and progression. However, there were other studies that showed the expression of ERβ and the absence of ERα. The presence of ERβ have demonstrated a more promising prognosis and a lower severity of developing a tumor and a higher disease-free survival rate.There is indication that estrogen may contribute in human thyroid cells by regulation proliferation and thyroid function. The ERα and ERβ expression plays a key role in thyroid cancer cell proliferation and the development of a cancerous tumor.

**Does age have a factor? If so, what age is effected the most and why this age?**
Age is not a significant factor that contributes in obtaining medullary thyroid cancer. However, there are certain time periods when women are more prone in acquiring the disease. During post-postural and puberty women are more susceptible because hormones, such as estrogen, are increasing the chances in acquiring medullary thyroid cancer. Also, women that have the RET mutation from birth, are highly susceptible in getting medullary thyroid cancer, and genetic testing must be accomplished.

If women are not more susceptible to all cancer, what makes MTC different?
Human chorinonic gonadotropin (hCG) is a hormone that is made during pregnancy, and the cells that develop the placenta secrete this hormone. hCG levels are high at 10-12 weeks of a normal pregnancy, and there is a inhibition of serum thyroid stimulationg hormone levels (TSH). This is because there is an inverse relationship between hCG and TSH at early pregnancy when hCG levels are high. The high levels of hCG increasing free T4 and free T3. Researchers have concluded that hCG causes the increase of free thyroid hormone levels, thus hCG is suppressing TSH. Therefore, hCG is a thyroid stimulator in early normal pregnancy. hCG functions has a thyroid stimulator in early pregnancy because hCG and TSH belong to a family of hereodimeric glycoproteins that have a similar α subunit. However, hCG is not regulated by thyroid hormones, but rather when the levels of hCG are high it increases the thyroid hormone secretion, and TSH is suppress. The high levels of the thyroid hormones can cause hyperthyroidism which can lead to medullary thyroid cancer. This can be reason why women are more susceptible in developing medullary thyroid cancer oppose to other cancers.

=__Genetic Testing for Medullary Thyroid Cancer__=


 * How do these systems work? **

In the case of Medullary Thyroid Cancer Genetic Testing of the RET gene and its possible mutations center on the tenth chromosome of the human genome. The prevelent MEN2A RET mutation, C634 can be found within exon 11 of the chromosome, while the prevelent MEN2B RET mutation, M918T can be found within exon 16(Thyroid Cancer); each of the two exons' mutations also create protein alterations in their each domain of the chromosome. These protein shape changes may create the actual problem, but it is the mutation in the gene that can be tested for. Laboratories will take a patient's tissue, in this case, usually in the form of a blood test, and add a fluorescent DNA probe, a short sequence of DNA complementary to the RET gene. This probe allows for a certain amount of mis-pairing in order to allow the probe to find the healthy and mutated forms of the gene. Then, the lab technitions can give a DNA read out of the sections of these exons that contain the probe's fluorescent dye (Gene Testing), which can then be interpreted by a doctor or genetic counselor. These health professionals can tell the patient the status of their predisposition for the cancer, based off the presence of the mutation or lack there of, and then help guide the patient through the resulting process.


 * Are these systems making a difference, especially in early detection of the cancer? **

The entire reason behind creating and using genetic testing systems for hereditary medullary thyroid cancer is to ensure the patients knowledge of their status if they happen to be predisposed. If they know they have a predisposition for the cancer, there should be a better chance of them finding signs of the cancer at earlier stages, they should be able to catch the disease before it progress into stages III and IV. But is this the case?

Over the last 13 years, the department of endocrinology at the University of Pisa has RET screened 807 individuals; a little over half of the diagnosed patients showed sporadic MTC, 289 were patients' relatives, and the rest, 37 patients, with evidence of clinical MEN 2 MTC. On top of the already known MEN 2 patients, 35 of the sporadic MTC patients turned out to have a germ line mutation, increasing the overall proportion of those with hereditary cancer in the study, and of the 37 who were already classified as clinical MEN 2 patients, RET germ line mutations occurred in 36 cases. These 72 total hereditary cases could be traced through different families of patients. As part of the study, the department also began tracking the stage in which each cancer was diagnosed. Unfortunately,there has been no significant decrease in cancer stage or TNM measurement in the last decade, which means only half of patients being diagnosed before stage III and IV even today (Elisei, Romei, Cosci et al). This begs the question of why patients are not being diagnosed earlier. Some evidence shows that because many people do not discover their cancer until stage III or IV, many of their family members do not get tested until this point and therefore have a larger chance of already having a later stage version of the cancer themselves. Also, the many easily visible symptoms of thyroid cancer (Lump in neck, Swollen Lymph nodes, horse voice, difficulty swallowing, neck pain, and throat pain) are not prevalent till later stages or TNM ratings, specifically when the tumor reaches a large size and begins spreading to the lymph nodes (Walker), which theoretically would contribute to a cycle of one person not knowing if they have medullary thyroid cancer until a later stage and their relatives then not getting tested until then, giving them a better chance of having a later stage cancer themselves.
 * Who should get tested? **

According to the Cleveland Clinic's genetic counseling department, these people would receive the most benefits from getting tested:


 * Patients with Medullary Thyroid Cancer
 * People with several relatives who are affected by thyroid or other endocrine gland cancers
 * People who have or have had several types of cancer
 * People who have or have had a Clustering of cancers or tumors that are known to be genetically related (such as thyroid and other endocrine tumors or thyroid and breast, uterine, or colon cancers)
 * People who have a known cancer-causing genetic mutation in the family (e.g., a blood relative with a known RET mutation)
 * The test for genetic condition can be adequately interpreted ([|The Genetics of Thyroid Cancer])

Getting genetic testing as a cancer patient isn't only about helping yourself, but rather, it is about helping your entire family understand their predisposition as well as your own treatment and lifestyle options. Alongside genetic testing, a thorough understanding of someones medical family history can be extremely valuable. The figure to the right contains four different example family histories of medullary thyroid cancer, which were published as part of an article called "High Penetrance of Pheochromocytoma Associated with the Novel C634Y/Y791F Double Germline Mutation in the RET Protooncogene" in the journal of clinical endocrinology and metabolism. The patient who received the genetic counseling is shown with an arrow next to their particular symbol; those who are shaded, present or presented medullary thyroid cancer or other forms of related cancers. These four family histories are from four completely unrelated families who all present the germline mutation within their family genome. In these cases, the only genetic counseling patients who were tested were those who already had the disease and were most likely doing the testing on behalf of their family members, or for family planning reasons. Clearly, a in depth medical history is a very powerful tool that can be used alongside, as well as before a genetic test in order to get a bigger picture of the medullary thyroid cancer within themselves and their families.

=__ Treatment __= <span style="font-family: Arial,Helvetica,sans-serif; font-size: 12px;">When caught early enough, Thyroid cancer is one of the easier cancers to treat and survive. The routine method of dealing with thyroid cancer involves both the cutting and burning methods and the removal of the entire thyroid organ.

The removal of the thyroid completely, is the best treatment for medullary thyroid cancer. The procedure, total tyroidectomy is high recommended, for patients that have localized medullary thyroid carcinoma. Also, physicians may perform a total tyroidectomy with central neck dissection, which they remove the thyroid and the lymph nodes that are surrounding the gland. Additionally, physicians may perform a modified radical neck dissection if the neck lymph nodes are involved in the medullary thyroid cancer. Damage to the parathyroid gland may cause low calcium levels. Operation may result in blood clots of the deep vein thrombosis, infection, and pain.
 * Treatment for Localized Carcinoma **
 * Surgery **
 * Possible Complications May Include: **

The treatment involves high-energy particles to kill cancer cells or decrease growth. This therapy is unique because this treatment is used for cancer that does not take up iodine, therefore this therapy is used for only anaplastic and medullary thyroid cancer. However, for the individuals that have a deficiency iodine, put them in risk for metastatic cancer. External-beam radiation therapy is used after surgery to reduces the reoccurring tumor, to help treat the cancer. Skin change, fatigue, diarrhea, hair loss, mouth problems, nausea, vomiting, sexual changes, swelling, trouble swallowing, urinary changes and bladder changes.
 * External-Beam Radiation Therapy **
 * Side Effects May Include: **

** Palliative chemotherapy ** Vandetanib, a small molecule inhibitor, which patients may be treated with a targeted therapy. Vandetanib is the only FDA-approved drug for advanced medullary thyroid cancer. In medullary thyroid cancer, overexpression of vascular endothelial growth factor receptor (VEGF) is associated with metastasis. Vandetanib is a 4-anilinoquinazoline, a tyrosine kinase inhibitor (TKI) that affects the signaling cascade. It targets the VEGF receptors 2 and 3, RET, and at higher concentrations, epidermal growth factor receptor (EGFR). It works by docking to the ATP-binding site of the RET kinase, which creates an inhibition. However, the toxicity of Vandetanib is very high, and it is strictly regulated. Diarrhea, rash, acne, nausea, hypertension, headache, fatigue, decrease appetite, abdominal pain, dry skin, vomiting, asthenia, insomnia, cough, hypocalcemia, dyspepsia, pharyngitis, pruritus, weight decrease, depression, and proteinuria.
 * Treatment for Metastasis Carcinoma **
 * Adverse Reactions: **

=__**Is There a Way to Prevent Thyroid Cancer?**__=

There is no explicit method to prevent medullary thyroid cancer, since individuals may develop a carcinoma regardless of avoiding all the possible risk factors. However, individuals can attempt of developing thyroid cancer several ways. Since one form of medullary thyroid cancer is familial and may be inherited though generations, one should obtain a genetic screening to attempt prevention on medullary thyroid cancer. It is highly recommended for multiple endocrine neoplasia (MEN) type IIA, and carriers of inherited Rearranged during Transfection (RET) mutation, as early as 6 years old to be tested. Also, if there is a family history of developing a thyroid carcinoma, one could have a surgerical removal of the thyroid to prevent a cancer. In addition, thyotropin testing can prevent medullary thyroid cancer. The test screens if one has hyperthyoidism or hypothyrodism. Expressing excessive amounts of triiodothyronine (T3) and thyroxine (T4), or expressing a small amount, is a symptom of acquiring medullary thyroid cancer. Since, the thyroid gland is extremely sensitive to radioactive radioiodine exposure, one must try to avoid the exposure. Additionly, since //NIS// encodes a protein that is in charge for the uptake of iodine to the thyroid, it is important that one must have a diet that contains iodine. However, having a moderate amount or excessive amount of iodine can lead to a thyroid disease, which is extremely important one must acquire the correct amount of iodine.

**References**
"Do we Know what causes thyroid Cancer?." American Cancer Society. American Cancer Society, 20 Jan 2012. Web. 5 Jun 2012. Elisei, Rossella, Christina Romei, et al. "RET Genetic Screening in Patients with Medullary Thyroid Cancer and Their Relatives: Experience with 807 Individuals at One Center." Journal of Clinical Endocrinology & Metabolism. 92.12 (2007): 4725-4729. Print.

"Gene Testing." genomics.energy.gov. U.S. Department of Energy, 17 sep 2010. Web. 5 Jun 2012.

"Germline Mutation." Dictionary of Cancer Terms. Web. 5 Jun 2012. <http://www.cancer.gov/dictionary?cdrid=46384>.

"Germline mutated cancer genes." Sanger Institute. The Sanger Institue, 13 Mar 2012. Web. 5 Jun 2012. <http://www.sanger.ac.uk/genetics/CGP/Census/germline_mutation.shtml>.

Kloos, Richard T., CharisEng, et al. "Medullary Thyroid Cancer: Management Guidelines of the American Thyroid Association." THYROID. 19.6 (2009): n. page. Print.

"The Genetics of Thyroid Cancer." Cleveland Clinic. The Cleveland Clinic, n.d. Web. 5 Jun 2012. <http://my.clevelandclinic.org/disorders/thyroid_cancer/hic_the_genetics_of_thyroid_cancer.asp&xgt

"Thyroid Cancer." My Cancer Genome. Vanderbilt-Ingram Cancer Center, 1 Jan 2012. Web. 5 Jun 2012. <http://www.mycancergenome.org/content.php?disease=7&gene=20&variant=128>.

Walker, Kamiah. "Thyroid Cancer Symptoms." endocrineweb. Vertical Health, 9 Mar 1012. Web. 5 Jun 2012.

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