Thyroid cancer is a malignancy originating in the thyroid gland, in the neck. It is one of the less common types of cancer, but its incidence has been rising in recent years. Thyroid cancer typically occurs when cells in the thyroid gland undergo uncontrolled growth, forming a tumor. There are several types of thyroid cancer, with papillary and follicular carcinomas being the most common.

The majority of thyroid cancers have a favorable prognosis, especially when diagnosed and treated early. Treatment options may include surgery, radioactive iodine therapy, targeted therapies, or, in some cases, chemotherapy. Regular monitoring and follow-up care are essential to manage and monitor the disease effectively. Thyroid cancer often presents as a painless lump in the neck, and early detection through screening and diagnostic tests is key to successful treatment outcomes.

Incidence: Thyroid cancer is one of the most rapidly increasing cancer types in many parts of the world. The incidence rates vary by geographic region, with higher rates reported in some areas, including the United States, South Korea, and certain parts of Europe. In the United States, it is one of the most common cancers among women.

Age and Gender: Thyroid cancer can affect individuals of all ages, but it is most diagnosed in the ages of 20 and 55. Women are more frequently diagnosed with thyroid cancer than men, with the female-to-male ratio being around 3:1.

Risk Factors: The risk factors including exposure to ionizing radiation, family history of thyroid cancer, certain genetic syndromes (e.g., familial adenomatous polyposis and multiple endocrine neoplasia type 2), and environmental factors.

Geographic Variation: There are geographic variations in the incidence of thyroid cancer, with higher rates in regions where there has been historical exposure to nuclear fallout or radiation, such as near nuclear power plants or following nuclear accidents.

Diagnostic Advances: The increased incidence of thyroid cancer is partially attributed to improved diagnostic techniques, such as ultrasound imaging and fine-needle aspiration biopsy, which can detect smaller thyroid nodules and cancers that might have gone unnoticed in the past.

Prognosis: Most cases of thyroid cancer have a favorable prognosis, especially when diagnosed at an early stage. The overall survival rate is high, with a 5-year survival rate exceeding 98% for papillary and follicular thyroid carcinomas.

Initiation: The exact cause of thyroid cancer is often unclear, but certain risk factors, such as exposure to ionizing radiation, genetic mutations, and family history, can initiate the process. Radiation exposure, especially during childhood, is a well-established risk factor, as it can damage the DNA within thyroid cells.

Genetic Mutations: Genetic mutations play a crucial role in thyroid cancer development. Mutations in specific genes can lead to uncontrolled cell division and tumor formation. The common mutations associated with thyroid cancer include BRAF and RAS mutations, which are frequently found in papillary thyroid carcinoma (PTC).

Thyroid Cell Transformation: In the initial stages, some thyroid cells undergo transformation, becoming cancerous. This transformation disrupts the normal regulatory mechanisms that control cell growth and apoptosis (programmed cell death).

Tumor Formation: The cancerous thyroid cells multiply and form a tumor within the thyroid gland. The size and characteristics of the tumor can vary, ranging from small nodules to larger masses.

Invasion and Metastasis: Invasive thyroid cancer cells can infiltrate surrounding tissues and structures in the neck, including lymph nodes, blood vessels, and the trachea. Some thyroid cancers have a propensity to metastasize to distant organs, like lungs, bones, and brain, through the bloodstream or lymphatic system.

Hormone Production: In some cases of thyroid cancer, cancerous cells may continue to produce thyroid hormones, which can affect the patient’s hormonal balance and thyroid function.

Radiation Exposure: Exposure to ionizing radiation, particularly during childhood, is the well-established risk factor for thyroid cancer. This exposure can result from various sources, including medical treatments (such as radiation therapy for head and neck cancers), nuclear fallout, or occupational exposure. Individuals living in areas near nuclear power plants may also have a slightly increased risk.

Genetic Predisposition: Genetic factors can play a role in thyroid cancer risk. Certain hereditary syndromes, like familial adenomatous polyposis (FAP) and type 2 multiple endocrine neoplasia, are associated with an elevated risk of medullary thyroid carcinoma (MTC). Additionally, specific gene mutations, such as BRAF and RAS mutations, are frequently found in papillary thyroid carcinoma (PTC).

Gender: Thyroid cancer is more common in women than in men, with a female-to-male ratio of approximately 3:1. The reasons for this gender disparity are not fully understood but may involve hormonal factors.

Family History: Having a family history of thyroid cancer can increase an individual’s risk, especially if a first-degree relative (parent, sibling, or child) has been diagnosed with the disease.

Hormonal Factors: Hormonal factors, such as reproductive history and hormonal therapy (e.g., estrogen replacement therapy), have been investigated as potential contributors to thyroid cancer risk, but the evidence remains inconclusive.

Obesity: Some studies have suggested a modest association between obesity and an increased risk of thyroid cancer, particularly PTC.

Histological Type: The specific histological type of thyroid cancer is a significant prognostic factor. Papillary thyroid carcinoma (PTC) & follicular thyroid carcinoma have more favorable outcomes compared to medullary thyroid carcinoma and anaplastic thyroid carcinoma, which tend to be more aggressive.

Tumor Size: The primary tumor size, often measured in centimeters, is an important prognostic factor. Smaller tumors (T1 and T2) are associated with better outcomes than larger tumors (T3 and T4).

Tumor Stage: The American Joint Committee on Cancer (AJCC) staging system is commonly used to stage thyroid cancer. Higher stages (III and IV) are associated with a worse prognosis than lower stages (I and II).

Lymph Node Involvement: The presence of cancer cells in regional lymph nodes (lymph node metastasis) is a strong prognostic factor. Patients with lymph node involvement may have a higher risk of recurrence and a potentially worse prognosis.

Age: Younger patients, particularly those under 45 years of age, tend to have better prognoses in thyroid cancer. Older age at diagnosis is associated with a higher risk of recurrence and a potentially worse outcome.

Gender: Thyroid cancer is more common in women, and they have better outcomes compared to men with the same stage and type of cancer.

Genetic Mutations: Specific genetic mutations, such as BRAF mutations in PTC or RET mutations in MTC, can impact prognosis. Some mutations may make tumors more aggressive.

Surgical Margin Status: The completeness of surgical removal (clear or positive margins) of the thyroid tumor can affect prognosis. Negative margins indicate a lower risk of recurrence.

Age: Thyroid cancer can occur at any age, but there are age-related patterns:

• Younger Patients: Thyroid cancer is often diagnosed in individuals between 20 and 55 years, with peak incidence in the 40s and 50s.
• Pediatric Patients: In rare cases, thyroid cancer can occur in children and adolescents. In these cases, the diagnosis may be more challenging.

Gender: Thyroid cancer is more common in women, and they account for a significant majority of cases. Therefore, the patient’s gender is relevant to the clinical history.

Family History: Inquiring about a family history of thyroid cancer or other endocrine-related disorders, such as multiple endocrine neoplasia (MEN) syndromes, is important, as a positive family history can increase the risk.

Previous Medical History: Understanding the patient’s overall health, including any comorbidities or chronic medical conditions, is essential for tailoring treatment plans. Certain comorbidities, such as autoimmune thyroid diseases like Hashimoto’s thyroiditis or Graves’ disease, may be associated with thyroid cancer.

Symptoms: Patients may present with various symptoms or signs, such as:

• Neck Mass or Nodule: The most common presentation is the discovery of a painless lump or nodule in the neck.
• Voice Changes: Thyroid nodules or tumors pressing on the vocal cords may lead to voice changes.
• Swallowing Difficulties: Large thyroid masses can cause difficulty swallowing or a lump sensation in the throat.
• Neck Pain: Discomfort or pain in the neck, particularly in the region of the thyroid gland.

Thyroid Function: Assessing thyroid function through blood tests, including thyroid hormone levels (TSH, T3, T4), is crucial to determine if the thyroid gland is functioning normally or if there are abnormalities that may be related to thyroid cancer.

Duration of Symptoms: Understanding how long the patient has experienced symptoms or noticed the neck lump can help gauge the acuity of presentation.

Inspection of the Neck:

• Visual Examination: The healthcare provider will visually inspect the patient’s neck for any visible abnormalities or asymmetry.
• Skin Changes: Look for any skin changes, such as redness or swelling, over the thyroid gland area.
• Neck Mass or Nodule: Palpate (feel) the neck for the presence of a neck mass or thyroid nodule. Note the location, size, and consistency of the nodule. Thyroid nodules are often found in the lower front of the neck, just above the collarbone.

Palpation of the Thyroid Gland:

• Thyroid Nodule: If a thyroid nodule is detected, the healthcare provider will assess its characteristics, such as whether it is soft, firm, or hard. They will also check if it is mobile or fixed in place.
• Tenderness: Assess whether the thyroid gland or any associated lymph nodes are tender to the touch.

Lymph Node Examination:

• Neck Lymph Nodes: Palpate the cervical lymph nodes, especially in the neck regions where lymph nodes are commonly found (e.g., the sides of the neck). Enlarged or palpable lymph nodes may suggest regional spread of thyroid cancer.

Voice Changes:

• Hoarseness: Inquire about and assess for hoarseness of the patient’s voice, which can occur if a thyroid nodule is compressing or invading the recurrent laryngeal nerve.

Swallowing Difficulties:

• Ask the patient about any swallowing difficulties or the sensation of a lump in the throat, which can result from pressure from a large thyroid mass.

Neck Pain:

• Inquire about neck pain or discomfort, as this can sometimes be associated with thyroid cancer.

Thyroidectomy: The primary treatment is surgical removal of thyroid gland. The extent of the surgery depends on the type and stage of the cancer.

• Total Thyroidectomy: Removal of entire thyroid gland
• Lobectomy: Removal of one lobe of thyroid gland (used for some early-stage cancers).
• Lymph Node Dissection: If cancer spread to nearby lymph nodes, they may be removed during surgery.

Lymph Node Evaluation: Surgeons often examine and remove nearby lymph nodes to determine if they contain cancer cells.

Radioactive Iodine (RAI) Therapy:

• Radioactive iodine is used after surgery to destroy any remaining thyroid tissue and cancer cells (ablation) and to detect and treat any distant metastases.
• RAI therapy is particularly effective for papillary and follicular thyroid cancers, which often take up iodine.

Hormone Replacement Therapy:

• After total thyroidectomy, patients require lifelong thyroid hormone replacement therapy (levothyroxine) to maintain normal thyroid hormone levels in the body.
• This hormone therapy also helps suppress the production of thyroid-stimulating hormone (TSH), which can stimulate any remaining thyroid cancer cells.

External Beam Radiation Therapy (EBRT):

• EBRT may be used in certain cases, such as when thyroid cancer has spread to the surrounding tissues or lymph nodes, or when RAI therapy is not effective.
• It is less commonly used in well-differentiated thyroid cancers but may be employed for more aggressive types.

Targeted Therapies:

• Targeted therapies, such as tyrosine kinase inhibitors (e.g., lenvatinib, sorafenib), may be prescribed for advanced or recurrent thyroid cancer, particularly for patients with specific genetic mutations.
• These medications target specific molecular pathways involved in the growth of cancer cells.

Chemotherapy:

• Traditional chemotherapy is generally less effective in treating thyroid cancer but may be considered for certain aggressive or advanced cases, particularly in anaplastic thyroid carcinoma (ATC).

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Lifestyle modifications: 

Healthy Diet: A well-balanced diet can help support your overall health and immune system. Consider these dietary guidelines: 

• Eat a variety of fruits & vegetables for essential vitamins and minerals. 
• Include lean protein sources like poultry, fish, beans, and legumes. 
• Limit processed foods, sugary snacks, and high-fat foods. 

• Stay well-hydrated by drinking plenty of water. 

Thyroid Hormone Replacement: If you’ve had a thyroidectomy or radioactive iodine therapy, you’ll likely need thyroid hormone replacement medication (usually levothyroxine). Properly managing thyroid hormone levels is essential for your overall well-being. 

Stress Management: Managing of stress is important for mental and emotional health. Stress-reduction techniques like meditation, deep breathing exercises, yoga, or mindfulness practices can help you cope with anxiety and stress. 

Physical Activity: Engage in regular physical activity, as approved by your healthcare provider. Exercise can improve energy levels, mood, and overall well-being. 

Smoking Cessation: If you smoke, consider quitting. Smoking can have a detrimental effects on overall health and can interfere with the effectiveness of cancer treatments. Seek support & resources to quit smoking if required. 

Alcohol Moderation: If you consume alcohol, do so in moderation. Excessive alcohol intake can impact overall health and may interact with certain medications. 

Sun Protection: If you’ve undergone radioactive iodine therapy, your skin may be more sensitive to sunlight. Use sunscreen and the protective clothing when outdoors to prevent sunburn. 

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Thyroid Hormone Suppression Therapy: 

• Thyroid hormone suppression therapy involves administering a synthetic form of thyroid hormone thyroxine (T4), which is known as levothyroxine (brand names include Synthroid, Levoxyl, and others). 
• The goal of this therapy is to suppress the thyroid-stimulating hormone (TSH) production from the pituitary gland by providing the body with an adequate amount of thyroid hormone. TSH is a hormone that can stimulate the growth of thyroid tissue, including any residual thyroid cancer cells. 
• By keeping TSH levels low through the administration of levothyroxine, the therapy aims to reduce the stimulation of any remaining thyroid cancer cells, slowing down their growth and potentially preventing recurrence or progression of the cancer. 

Determination of Dosage: 

• The dosage of levothyroxine is carefully tailored to each patient’s individual needs. The goal is to achieve TSH suppression within a specific target range while avoiding overmedication, which can lead to side effects such as hyperthyroidism. 

Monitoring and Adjustments: 

• Patients undergoing thyroid hormone suppression therapy are regularly monitored by their healthcare team through blood tests to assess thyroid hormone levels and TSH levels. 
• The dosage of levothyroxine may be adjusted as needed to maintain the desired level of TSH suppression and to ensure that the patient’s thyroid hormone levels remain within the target range. 

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Radioactive Iodine Uptake: 

• RAI therapy takes advantage of the fact that thyroid cells, including thyroid cancer cells, readily absorb and concentrate iodine. In this treatment, a radioactive form of iodine, typically iodine-131 (I-131), is used. 

Preparation: 

• Before undergoing RAI therapy, patients may be placed on a low-iodine diet and may receive thyroid hormone withdrawal therapy. This process increases the uptake of radioactive iodine by thyroid tissue, including any remaining thyroid cancer cells. 

Radioactive Iodine Administration: 

• Patients receive a carefully calculated dose of radioactive iodine as a pill or liquid. The radioactive iodine is taken orally, and it is absorbed by the thyroid cells, including any cancerous cells. 
• The radioactive iodine emits radiation that damages and destroys thyroid tissue, including thyroid cancer cells. 

Targeted Treatment: 

• RAI therapy is targeted and specific to thyroid tissue. The radiation primarily affects the thyroid gland and thyroid cancer cells while sparing surrounding healthy tissues. 

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Multikinase Inhibitors: 

• Lenvatinib (Lenvima): Lenvatinib is a multikinase inhibitor used to treat advanced, progressive, or metastatic thyroid cancer that is refractory to radioactive iodine therapy. It targets multiple tyrosine kinases involved in angiogenesis (blood vessel formation) and tumor growth. 
• Sorafenib (Nexavar): Sorafenib is another multikinase inhibitor used in the treatment of advanced thyroid cancer. It targets tyrosine kinases involved in the growth and spread of cancer cells. 
• Cabozantinib (Cabometyx): Cabozantinib is approved for the treatment of progressive, metastatic medullary thyroid cancer. It targets multiple receptors involved in cancer growth, angiogenesis, and metastasis. 

RET Inhibitors: 

• Selpercatinib (Retevmo): Selpercatinib is a targeted therapy approved for the advanced or metastatic RET fusion-positive thyroid cancer, which includes some cases of papillary thyroid cancer. It specifically inhibits the RET protein, which is involved in cancer growth. 

TRK Inhibitors: 

• Larotrectinib (Vitrakvi): Larotrectinib is indicated for the treatment of solid tumors, including thyroid cancer, that have a specific genetic alteration called NTRK fusion. This is a rare genetic event but can be present in some cases of thyroid cancer. 
• Entrectinib (Rozlytrek): Similar to larotrectinib, entrectinib is approved for NTRK fusion-positive cancers, including thyroid cancer, when no satisfactory alternative treatments are available. 

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Multikinase Inhibitors: 

• Vandetanib (Caprelsa): Vandetanib is a multikinase inhibitor used for the treatment of advanced, unresectable MTC. It targets multiple receptors, including RET, which is often mutated in MTC, as well as other kinases involved in cancer growth and angiogenesis. 
• Cabozantinib (Cabometyx): Cabozantinib is also a multikinase inhibitor approved for progressive, metastatic MTC. It targets various receptor tyrosine kinases associated with tumor growth and angiogenesis. 

RET Inhibitors: 

• Selpercatinib (Retevmo): Selpercatinib is a highly specific RET inhibitor approved for advanced or metastatic RET-mutant MTC, as well as other RET fusion-positive solid tumors. It is particularly effective in tumors driven by RET alterations. 

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Multikinase Inhibitors: 

• Dabrafenib (Tafinlar): Dabrafenib is a multikinase inhibitor that targets specific genetic mutations, including BRAF V600E, which can be present in some cases of anaplastic thyroid cancer. It is often used in combination with trametinib. 
• Trametinib (Mekinist): Trametinib is another multikinase inhibitor that may be used in combination with dabrafenib for the treatment of anaplastic thyroid cancer with the BRAF V600E mutation. 

RET Inhibitors: 

• Selpercatinib (Retevmo): Selpercatinib is a highly specific RET inhibitor that has shown promise in the treatment of RET-altered thyroid cancers, including anaplastic thyroid cancer. It is typically considered when the tumor has a RET gene fusion or mutation. 

TRK Inhibitors: 

• Larotrectinib (Vitrakvi): Larotrectinib is indicated for the treatment of solid tumors, including thyroid cancer, that have a specific genetic alteration called NTRK fusion. While not specific to anaplastic thyroid cancer, it may be considered in cases with NTRK fusion alterations. 
• Entrectinib (Rozlytrek): Similar to larotrectinib, entrectinib is approved for NTRK fusion-positive cancers, which can include rare cases of anaplastic thyroid cancer. 

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The use of thyroidectomy (surgical removal of the thyroid gland) with or without radioactive iodine ablation (131-I ablation) is a common approach in the treatment of thyroid cancers such as papillary and follicular thyroid cancer.

The decision to use radioactive iodine ablation or not is based on several factors, including the type and stage of the cancer, the extent of disease, and individual patient characteristics. Here’s an overview of both approaches: 

Thyroidectomy Without 131-I Ablation: 

• In some cases of well-differentiated thyroid cancer, particularly when the cancer is small, localized, and does not spread to lymph nodes, thyroidectomy may be the primary treatment. After surgery, patients may not receive radioactive iodine ablation. 

• Thyroid hormone replacement therapy (levothyroxine) is prescribed to replace the missing thyroid hormone production, and the goal is to maintain a stable thyroid-stimulating hormone (TSH) level within the normal range. 
• This approach is often used for low-risk thyroid cancers where the risk of recurrence or progression is low, and the potential benefits of radioactive iodine therapy may not outweigh the risks. 

Thyroidectomy With 131-I Ablation: 

• In other cases, especially for higher-risk thyroid cancers or when there is evidence of residual thyroid tissue, lymph node involvement, or distant metastasis, thyroidectomy is followed by radioactive iodine ablation. 
• Radioactive iodine ablation involves the administration of a carefully calculated dose of radioactive iodine-131 (I-131) with the goal of destroying any remaining thyroid tissue, including cancer cells. 
• This treatment is used to reduce the risk of recurrence and to target any microscopic thyroid cancer cells that may be left behind after surgery. 
• The decision to use 131-I ablation is typically based on factors such as cancer type, tumor size, extent of disease, and individual risk factors. 

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Lobectomy, the surgical removal of one of the two lobes of the thyroid gland, is a treatment option for certain cases of thyroid cancer.  

• Unilateral Thyroid Cancer: Lobectomy is often considered when thyroid cancer is confined to one lobe of the thyroid gland and has not spread to the other lobe. In this situation, removing the affected lobe (along with the isthmus, a bridge of tissue that connects the two lobes) can effectively treat the cancer while preserving the function of the remaining thyroid tissue. 
• Papillary Thyroid Cancer: Lobectomy is more commonly used for well-differentiated thyroid cancers, such as papillary thyroid cancer, which tends to be less aggressive and may be confined to one lobe. This approach is guided by medical guidelines that consider tumor size, location, and extent. 
• Preservation of Thyroid Function: One of the advantages of lobectomy over total thyroidectomy is the potential preservation of thyroid function. With one lobe of the thyroid remaining, some patients may continue to produce thyroid hormones without the need of lifelong thyroid hormone replacement therapy (levothyroxine). This can help maintain hormonal balance and quality of life. 
• Careful Selection: The selection of lobectomy as a treatment option requires careful consideration of factors such as the type and stage of cancer,size and location of tumor, and the patient’s age and overall health. Multidisciplinary teams, including endocrinologists and surgeons, play a crucial role in making this decision. 

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Thyroglobulin antibodies (TgAb) are not used in the treatment of thyroid cancer. Instead, they are used as diagnostic and monitoring tools to assess thyroid cancer status and treatment response. 

• Thyroglobulin as a Tumor Marker: Thyroglobulin is a protein produced by thyroid cells, including thyroid cancer cells. After thyroid surgery (thyroidectomy), the goal is to have undetectable or very low levels of thyroglobulin in the blood, as this suggests the absence of thyroid tissue and thyroid cancer. 

• Thyroglobulin Antibodies (TgAb): In some thyroid cancer patients, especially those with autoimmune thyroid diseases like Hashimoto’s thyroiditis, thyroglobulin antibodies (TgAb) can be present in the blood. TgAb can interfere with the accurate measurement of thyroglobulin levels. 
• Interference with Thyroglobulin Measurement: TgAb can lead to falsely elevated thyroglobulin results when measured using standard assays. This interference can make it challenging to accurately assess a patient’s response to treatment or detect recurrence based solely on thyroglobulin levels. 

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Acute Phase: 

• Diagnosis and Staging: The acute phase begins with the diagnosis of thyroid cancer. This includes a thorough evaluation of the patient’s medical history, physical examination, imaging studies (such as ultrasound, CT scans, or MRI), and often a fine-needle aspiration (FNA) biopsy of thyroid nodules to confirm the presence of cancer. 
• Surgery (Thyroidectomy): The primary treatment for most thyroid cancers is surgery, typically a thyroidectomy, which involves the removal of part or all of the thyroid gland. The extent of surgery depends on the type, size, and stage of the cancer. 
• Lymph Node Dissection: In cases where lymph nodes are affected or suspicious, lymph node dissection (neck dissection) may be performed during thyroidectomy to remove affected lymph nodes for further evaluation. 

• Radioactive Iodine Therapy (RAI): For some types of thyroid cancer (e.g., papillary and follicular), radioactive iodine therapy may be recommended after surgery. This treatment is used to target any remaining thyroid tissue or cancer cells and reduce the risk of recurrence. 
• Hormone Replacement Therapy: After thyroidectomy, patients will require lifelong thyroid hormone replacement therapy (usually levothyroxine) to replace the missing thyroid hormone. Hormone levels are carefully monitored to maintain normal thyroid function. 

Chronic Phase: 

• Follow-Up Care: After the acute phase, patients enter a chronic phase of management that involves regular follow-up appointments with an endocrinologist, thyroid specialist, or oncologist. These appointments include physical examinations, blood tests (thyroid function tests and thyroglobulin levels), and imaging studies (e.g., neck ultrasound). 
• Monitoring for Recurrence: The primary goal of the chronic phase is to monitor for cancer recurrence. Elevated thyroglobulin levels or suspicious findings on imaging may prompt further evaluation or treatment. 
• Management of Recurrence: If thyroid cancer recurs, treatment options such as additional surgery, radioactive iodine therapy, targeted therapies, or external beam radiation therapy may be considered, depending on the specific circumstances. 
• Long-Term Surveillance: Thyroid cancer survivors require long-term surveillance to detect and manage any recurrent or persistent disease. The frequency and duration of follow-up appointments depend on the patient’s risk factors, cancer type, and treatment history. 
• Management of Hormone Levels: Ensuring that thyroid hormone levels remain within the normal range is essential for the patient’s overall health and well-being. Adjustments to thyroid hormone replacement therapy may be made as needed.