In order to better understand thyroid cancer, it is important to first understand the anatomy of the thyroid gland and the important surrounding structures. The thyroid gland sits in the midline of the neck, just beneath the skin and a few layers of thin muscles. It has 2 lobes, the right and left lobe, which are connected in the midline by an isthmus. Occasionally, the thyroid also has a prominent pyramidal lobe that extends upwards towards the hyoid bone and base of tongue. The pyramidal lobe is located in the midline in front of the larynx and connects to the isthmus.

The thyroid gland secretes thyroid hormones, which are important in regulating many metabolic functions of the body. These thyroid hormone levels are closely controlled by thyroid stimulating hormone (TSH), which is produced by the pituitary gland and causes cells to produce thyroid hormone. The pituitary gland responds to  levels of thyroid hormones in the bloodstream, producing more or less TSH to maintain metabolic function. However, thyroid hormones can still sometimes be over or under-produced. A simple blood test can measure these hormone levels. Cases of overproduction create hyperthyroidism, and cases of underproduction create hypothyroidism.

The gland is made up of follicular cells that take up iodine and produce thyroid hormone, which is stored in follicles inside the thyroid. The thyroid is also made up of another type of cell called parafollicular cells (C-cells). These cells form a hormone called calcitonin, which helps with calcium regulation. Cancer of these C-cells is called medullary thyroid caracinoma and will be discussed in a different section.

The blood supply to the thyroid gland comes from the inferior thyroid artery, a branch of the thyrocervical trunk, and the superior thyroid artery, a branch of the external carotid artery. In some rare cases, there exists an artery called the ima artery, which runs from below the clavicles on the top surface of the trachea towards the isthmus portion of the thyroid gland.

On the backside of the thyroid gland are four parathyroid glands (two on each side). These are, much like the thyroid gland, endocrine glands that produce and secrete hormones. Through the secretion of the parathyroid hormone, the parathyroid glands regulate calcium levels in the blood and bones. Additionally, parathyroid hormone controls levels of calcium absorption from the diet and calcium excretion from the kidneys into the urine. During thyroid surgery, it’s important for surgeons to carefully separate the parathyroids from the thyroid to maintain normal levels of parathyroid hormone in the blood.

The recurrent laryngeal nerves (one on each side) run upward from the vagus nerve toward the voice box (larynx) in the groove between the trachea (windpipe) and esophagus which is just deep to the thyroid gland. This nerve moves the vocal cords and is responsible for speaking and control of the vocal cords during breathing. In extremely rare cases, the right recurrent laryngeal nerve can emerge straight down from the vagus nerve. This is called a non-recurrent laryngeal nerve because it does not come from below. It is important for surgeons to locate and protect this nerve during surgery.

The superior laryngeal nerves (one on each side) run downward from the vagus nerve. The external branch supplies the cricothyroid muscle and helps with changing voice pitch and volume, whereas the internal branch controls the sensation of the larynx and aids in normal swallowing by protecting against aspiration.

The main lymph nodes associated with the thyroid are the central compartment lymph nodes (levels VI and VII) which lie in the middle portion of the neck in the tissue surrounding the thyroid gland. Occasionally, thyroid cancers can spread to the lateral neck or retropharyngeal lymph nodes (situated behind the upper part of the pharynx) as well.

There is often no definitive cause of thyroid cancer. It’s a combination of genetics and environmental factors. However, listed below are a few known risk factors for developing thyroid cancer:

Radiation

Radiation exposure—from previous medical treatments or from environmental disasters like power plant accidents or nuclear explosions—is a known risk factor for developing thyroid cancer. Head and neck radiation treatments during childhood have been associated with an increased risk of thyroid cancer; this risk is higher for larger doses and younger ages of a patient at the time of radiation treatment.

Family History

People with at least 2 first-degree relatives diagnosed with thyroid cancer are at an increased risk of developing thyroid cancer themselves. This risk factor applies to people regardless of whether or not they have a known genetic syndrome associated with thyroid cancer.

Inherited Medical Conditions

Patients with familial adenomatous polyposis (FAP), Cowden disease, or Carney complex type I may be at an increased risk of developing papillary or follicular thyroid cancer.

Low-Iodine Diet

Although most people in Australia obtain enough iodine in their diet due to iodised table salt and other food products that contain iodine, low-iodine diets are common in other parts of the world. Diets low in iodine may increase the risk of follicular and papillary thyroid cancer, especially if a person has also experienced some radiation exposure.

Thyroid cancers are usually detected by patients or doctors when they feel a lump in the thyroid gland or when an imaging test for an unrelated condition shows a lump in the thyroid gland. Other rare signs and symptoms of thyroid cancer include:

• A lump or bump somewhere else in the neck: A metastatic lymph node with a biopsy showing thyroid cancer is another way that thyroid cancer can be detected.
• Change in voice: Unlike benign tumours in the thyroid gland, thyroid cancers can invade the nerves to the voice box (larynx) or even the trachea and esophagus. This could lead to a hoarse voice.
• Difficulty with swallowing (dysphagia): If thyroid tumours become very large (or invade surrounding structures), they can cause difficulty with swallowing.

It is important to note that a patient could have one or more of these symptoms and NOT have thyroid cancer. There are several non-cancerous causes of the same symptoms. That is why it is important for patients to go see a medical specialist if they are experiencing any of these symptoms.

Diagnosis

Thyroid nodules are commonly discovered by a patient at home or by a physician during a routine physical exam. They are also often discovered incidentally on unrelated imaging studies such as a chest CT scan, an MRI of the cervical spine, or a doppler ultrasound study of the carotid arteries.

In general, the standard diagnostic approach for thyroid cancer includes a physical examination to identify a nodule, blood tests, imaging, and possibly a fine-needle biopsy. Patients can expect their doctor to have a discussion with them about the risks, benefits, and alternatives to each of the following approaches.

Physical Exam

To start, a physician will feel (“palpate”) the neck to detect any abnormal swelling, hardness, tenderness, or asymmetry. Vocal cord function and ease of swallowing may also be assessed depending on patient symptoms.

Blood Tests

Blood tests are used to detect the levels of thyroid hormone circulating in the body. Most thyroid nodules do not produce thyroid hormones. However, some nodules do make excess thyroid hormones, which can cause significant symptoms, and can be detected on a blood test.

Patients often undergo a number of blood tests before and/or after being diagnosed with thyroid cancer. These might include tests to detect thyroid stimulating hormone (TSH), thyroxine (T4),  and certain antibodies that suggest an autoimmune thyroid disease (e.g. Graves’ or Hashimoto’s disease).

• TSH is a hormone produced by the pituitary gland, which stimulates the thyroid to produce more thyroid hormone. TSH regulates the thyroid gland in order to maintain a hormone balance.
• Thyroxine, also known as T4, is the main hormone produced by the thyroid gland. It regulates metabolism and other functions throughout the body.

Thyroid hormone tests (TSH and T4) will help doctors determine the next steps in the workup of a thyroid nodule.

Imaging

Once a nodule has been identified, the blood tests described above can help doctors determine which imaging studies should be used to further evaluate the nodule. Imaging of the neck will be required to determine the size and location of a thyroid nodule, and is a vital step prior to any treatment decision.

• Generally, patients with hyperthyroidism (low TSH and elevated T4) will be ordered to have an ultrasound and an I-131 uptake scan. Through the uptake scan, the doctor will determine whether the nodule in question is the cause of thyroid hormone overproduction. Nodules that produce thyroid hormones in excess are called “functional” nodules, and are unlikely to be malignant. Therefore, functional nodules do not need to be biopsied and can be followed with regular ultrasounds.
• On the other hand, patients with normal (euthyroidism) or low (hypothyroidism)  thyroid hormone function are more likely to have malignant nodules. Therefore, ultrasound  is the study of choice in these cases. If the ultrasound of the nodule shows worrisome characteristics or demonstrates involvement of lymph nodes, a biopsy should be performed.

For thyroid cancer, the gold standard initial imaging test is an ultrasound. Ultrasounds are always used to evaluate thyroid nodules, and often lymph nodes in the surrounding neck area.  In some cases, a doctor may also recommend more advanced imaging studies such as a CT scan,  MRI, PET/CT, or I-131 uptake scan (as described above).

Biopsy

The best way to determine if a thyroid nodule is cancerous is with a fine needle aspiration (FNA) biopsy to remove a small piece of tissue and examine it under a microscope. This procedure is performed with local numbing medicine under the guidance of an ultrasound, and is essentially risk free.

The majority of thyroid nodules are benign (not cancerous). Only about 5-15% of nodules are found  to be cancerous after a biopsy. Since benign thyroid nodules are very common, not all nodules need to be biopsied, especially if they are very small (< 1 cm). However, nodules that grow or appear “suspicious” on ultrasound should be evaluated further with follow-up ultrasounds and a biopsy.

The results of thyroid nodule FNA biopsies are reported using the Bethesda System, which is a 1-6 scale used to predict how likely it is that the biopsied nodule is cancerous. It is important to know that a doctor will not be completely sure about the pathology for the nodule until it has been surgically removed and examined under the microscope. Keep in mind that the Bethesda System is different than cancer staging.

Molecular Testing

Multiple molecular tests are now available to help better assess the risk of malignancy in certain thyroid nodules that are not well characterised on the basis of cytology alone.  These tests look for genetic mutations in the biopsied cells that can be found in thyroid cancers. Molecular testing is commonly recommended when biopsies return as Bethesda III or IV (see above). There are multiple types of molecular assays available which have been shown to have similar accuracy in detecting possible malignancy.

Type

First, it is important to remember that not all lumps and lesions in the neck are cancer. Some nodules are benign (non-cancerous), and there are some tumours that are on the borderline between benign and malignant (cancerous).  Often, the definitive diagnosis of the type and sub-type of cancer is not fully determined until after the thyroid is removed.   This is because the pathologist sometimes needs to see the entire nodule within the thyroid gland before being able to determine if the nodule is benign or malignant.

There are a few different types of well-differentiated thyroid cancers, as well as a few sub-types or variants within each type.

Papillary Thyroid Cancer

Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid cancer, representing approximately 85% of cancers of the thyroid gland. There are several different sub-types of PTC.

• Classical
  Classical variant, also known as conventional variant, is the most common sub-type of papillary thyroid cancer. Approximately half of all papillary thyroid cancers are classical variant. These cells have finger-like projections and contain enlarged, overlapping nuclei. This variant of papillary thyroid cancer grows slowly and has an excellent prognosis.
• Follicular Variant
  Follicular variant is the second most common variant of papillary thyroid cancer, and has a prognosis similar to that of classical variant papillary thyroid cancer. Follicular variant cells have features that resemble both papillary and follicular thyroid cancer cells. However, these cells do not have papilla (finger-like projections), and typically grow in clusters.
• Tall Cell Variant
  Tall cell variant is a sub-type of papillary thyroid cancer that is associated with less favourable outcomes. The tall cell variant is characterised by a predominance of tall columnar tumour cells whose height is at least 3 times their width. These tumors often present in individuals that are of older age and at a more advanced stage than classic papillary carcinoma.
• Hobnail Variant
  Hobnail variant of papillary thyroid carcinoma is rare and described by a specific “hobnail” appearance of the cells. This type is known to often spread to the rest of the body, especially the lungs, and has a worse prognosis than classic papillary carcinoma.
• Columnar Cell Variant
  Columnar cell variant of papillary thyroid carcinoma is characterised by mostly “column like” cells. These tumours also have a higher risk of spread to the rest of the body.
• Diffuse Sclerosing Variant
  Diffuse sclerosing variant of papillary thyroid carcinoma is characterised by widespread involvement of the thyroid gland and is more likely to spread to lymph nodes in the neck and to the rest of the body. Patients with this type of cancer do slightly worse than those with classic papillary carcinoma; however, response to treatment is generally excellent.

Follicular Thyroid Cancer

This is another well-differentiated thyroid cancer. It is the second most common form of thyroid cancer, after papillary thyroid cancer, representing approximately 12% of cancers of the thyroid gland. The diagnosis of follicular thyroid carcinoma can really only be made after the gland (or at least half of the gland) is analysed under a microscope. The diagnosis is made when follicular cells are seen invading through the cover (capsule) of the nodule or into blood vessels. If this is not seen, then it is considered a benign (non-cancerous) follicular tumour called “non-invasive follicular thyroid neoplasm.”

• Hurthle Cell Carcinoma
  This is a variant of follicular thyroid cancer. When observed under the microscope, these cells have a different appearance than other follicular tumours. This variant is associated with a more aggressive behaviour overall.

Grade

The grade of a cancer is usually only determined after the tumour has been removed and examined by a pathologist. The grade of cancer relates to how healthy or unhealthy the cells look under a microscope. In other words, a pathologist will determine the grade of cancer by comparing the amount of the healthy-looking tissue to the amount of cancerous tissue.  If most of the tumour cells look like normal tissue, then the cancer is “well-differentiated” or “low-grade.” However, if the tumour cells look very different from normal tissue, then the cancer is considered “poorly-differentiated”, “undifferentiated”, or “high-grade.” The grade of the cancer may help to predict how quickly the cancer may spread.

The focus of this section is on well-differentiated thyroid cancers, which are, by definition, considered to  be of a lower grade. However, some “well-differentiated” thyroid cancers may have portions that are “poorly differentiated.” Adjustments to postoperative treatment may be made if this is found on final pathology.  Overall, this is an uncommon scenario.

Stage

The stage of a cancer is determined by the TNM staging system:

• The ‘T’ stands for tumour size.
• The ‘N’ stands for lymph node involvement.
• The ‘M’ stands for distant metastases, or cancer spread to other areas of the body.

Staging helps doctors determine how serious the cancer is and how best to treat it. For well-differentiated thyroid cancers (such as papillary thyroid carcinoma and follicular thyroid carcinoma), the staging is determined based on the patient’s age, with different staging systems for patients under and over 55 years of age.

At first, you will be given a clinical stage based on all of the available information.

Clinical staging (cTNM) is determined from any information your doctor might have about how extensive the cancer is BEFORE starting any treatment. Stage is determined based on your doctor’s physical exam, imaging studies, laboratory work and biopsies. Classification of clinical stage is described using the lowercase prefix c (e.g., cT, cN, cM).

If there is surgical removal of the cancer as part of your treatment, a pathologist will analyse the tumour and any lymph nodes that may have been removed. You will then be assigned a pathological stage.

Pathological staging (pTNM) provides more data. Classification of pathology stage is described using the lowercase prefix p (e.g., pT, pN, pM). This may or may not differ from the clinical stage.

There are also several other lowercase prefixes that might be used in the staging of your cancer.

• The subscript y(yTNM) is used to assign a cancer stage after some sort of medical, systemic or radiation treatment is given (Post therapy or Post neoadjuvant Stage). It is typically combined with either a clinical or pathological stage. For example, ycT2N0M0 indicates that after some sort of non-surgical therapy, the new clinical stage is T2N0M0.
• The subscript r(rTNM) is used when the tumour has recurred after some period of time in which it was gone. This is called Re-treatment Classification Stage. Your doctor will use all the available information to assign you a re-treatment stage.

Treatment Plan

There are multiple different options for the treatment of thyroid cancers that can be used alone or in combination:

• Active Surveillance
• Surgery
• TSH suppression therapy
• Radiation
• Chemotherapy

Active Surveillance for Low Risk Thyroid Cancer

Thyroid nodules smaller than 1cm and thyroid cancers that are small (<1 cm in size), show no evidence of lymph node involvement, and are not located on the back surface of the gland (near the recurrent laryngeal nerve) are considered “low risk thyroid cancers” and may be eligible to undergo active surveillance. Active surveillance is when doctors closely monitor a patient’s thyroid condition or cancer over time without giving any treatment. Doctors will intervene with treatment if there is evidence that the cancer has grown, or if the patient’s condition begins to change.  Another term for active surveillance is “watchful waiting.” With active surveillance, some patients may be able to avoid surgery, as their cancer may remain small and never grow to a concerning size.  Studies have shown that this is a very reasonable option for thyroid nodules smaller than 1cm, and even for those nodules that appear to be cancerous based on ultrasound features or are biopsy-proven papillary thyroid cancer.

Surgery 

For nodules greater than 1cm with worrisome characteristics on ultrasound and biopsy results suggestive of cancer, surgery is the preferred treatment choice. Occasionally, in select cases with large, symptomatic nodules greater than 4 cm,  surgery may be chosen without the need for a biopsy to confirm thyroid cancer. The extent of surgery will depend on multiple factors, including the size of the tumour, the histologic type, the location, and the involvement of regional lymph nodes or local structures.

Possible surgeries might include:

Hemithyroidectomy: This is the removal of only one of the thyroid lobes. A Hemithyroidectomy can be considered for some small cancers (< 4 cm) with no evidence of a tumour in the remaining lobe and no evidence of regional lymph node involvement on imaging studies. The remaining lobe should be followed closely with routine ultrasounds after surgery. It is important to note that this procedure is only chosen for low-risk thyroid cancers with no signs of invasion to other tissues.  The goals of this procedure are to preserve healthy thyroid tissue and to avoid the need for lifelong thyroid hormone replacement therapy.

Total thyroidectomy: This is the removal of the entire thyroid gland. This is performed in larger tumours (> 4 cm), when there are nodules in both lobes, or if part of the treatment will include giving radioactive iodine (RAI).

Central compartment lymph node neck dissection: This is a type of neck dissection, which involves removing the central compartment lymph nodes, including the lymph nodes next to the trachea and in front of the larynx. This might be recommended if a patient has known cancer in the thyroid gland or enlarged lymph nodes in the area.

Lateral compartment lymph node neck dissection: This is a type of neck dissection, which involves removing lymph nodes from the sides of the neck. This would be done if there is known cancer spread to that area.

Revision thyroid surgery: This is an additional surgery, or re-operation, in the thyroid bed or at the lymph node sites, which could be required if there is evidence that the cancer has recurred, or come back. Recurrence can be picked up on follow-up imaging studies or blood tests.

TSH suppression therapy

Following a total thyroidectomy, patients will need to undergo lifelong thyroid hormone replacement. TSH (Thyroid Stimulating Hormone) is a hormone produced by the brain to stimulate the growth of thyroid tissue and the production of thyroid hormone. When the thyroid gland is removed, the body is unable to produce thyroid hormone naturally. The brain will therefore start producing more TSH to try to increase the production of thyroid hormone. However, elevated TSH can also stimulate the growth of remnant thyroid tissue, which could increase the risk of recurrent thyroid cancer.

After surgery, TSH suppression therapy may be used to decrease a patient’s future risk of disease recurrence. In this type of therapy, patients are given a much larger dose of thyroid hormone (levothyroxine) than is necessary to fulfil their body’s needs. Giving this “larger-than-needed” dose signals the brain to stop producing TSH (as there is already more than enough thyroid hormone in the body), and therefore prevents the growth of additional thyroid tissue. When combined with surgery and RAI (when needed), this treatment has been shown to lower the risk of thyroid cancer recurrence.  The side effects of this treatment include a fast and irregular heartbeat and a loss of bone density, which leads to an increased risk of fractures. Doctors will evaluate a patient’s TSH levels, along with other clinical factors, in order to determine the optimal thyroid suppression levels for each individual patient.

Radiation 

Radiation for thyroid cancer comes in two main forms: radioactive iodine (RAI) and external beam radiation therapy.

Radioactive iodine: The main function of iodine in the body is to be used by thyroid cells to make thyroid hormone. Thyroid cells use essentially all of the iodine in the body for hormone production. Well-differentiated thyroid cancer cells also have the ability to take in iodine, just like healthy thyroid cells. Radioactive iodine (I-131) treatment involves administering I-131 (a radioactive isotope of iodine) to a patient either as a drink or in a capsule. The radioactive iodine is then taken up by thyroid cells, both healthy and cancerous. Since it is radioactive iodine, it will damage the thyroid cells and prevent them from growing. This radioactive iodine will affect all thyroid cells, no matter where in the body they are located, but will not damage normal tissue. This treatment is only given to patients who have previously undergone a total thyroidectomy, because these patients should not have any remaining healthy thyroid tissue. This means that that any existing thyroid tissue is likely to be cancerous. In these cases, radioactive iodine is useful because the I-131 will damage the cancerous thyroid cells and prevent them from growing, without affecting any other cells in the body.

External beam radiation therapy: While it remains the standard of care in many cancers of the head and neck, external beam radiation is not often recommended for thyroid cancer. For well-differentiated thyroid cancers, radioactive iodine is preferred because it is a more targeted form of radiation that attacks only thyroid cells and has fewer side effects than external beam radiation.

External beam radiation therapy might be considered in the following circumstances:

• Patients who are over the age of 55 and have T4 disease (gross extra-thyroidal extension).
• Patients who have an aggressive cancer that cannot be completely resected and is not sensitive to radioactive iodine (either in the neck, in the thyroid bed or recurrent disease).
• Patients who have a distant metastasis that is causing significant symptoms and cannot be surgically resected (spine, brain, thorax).

Chemotherapy & Biologic Medications

Currently, very little research has been done on the use of chemotherapy as a treatment for well differentiated thyroid cancer. For patients who have persistent disease despite conventional treatments (surgery, TSH suppressive therapy, and RAI), additional treatment options include watchful observation (discussed above) and  systemic chemotherapy. The goal of chemotherapy is to stabilise, or slow, the progression of metastatic disease. In other words, it attempts to prevent the disease from spreading throughout the body. Chemotherapy is considered a disease modifying drug because it is expected to stop disease progression, but it is not expected to improve disease prognosis or provide a cure. Chemotherapeutic drugs can have significant toxic effects that might vary according to the specific chemotherapeutic agent used and the administered dose. Therefore, it is important to limit the use of systemic treatments to only those patients who are at significant risk for morbidity or mortality due to advanced disease.

If recurrent disease is evident after standard treatment, other local treatment therapies can be offered. These other treatments may be able to improve a patient’s quality of life when their disease is symptomatic. If the disease continues to progress despite all previously mentioned therapeutic options, chemotherapeutic drugs may be offered to select patients through clinical trials.

For more information about new therapies for thyroid cancer speak to your medical practitioner.

Prognosis

A prognosis is a prediction of the outcome of one’s disease. How likely is survival? Will the cancer come back? These are the big questions on most people’s minds after receiving a diagnosis of well-differentiated thyroid cancer. In general, there are several characteristics of the tumour that can inform a patient about their chances of being cured.

Factors That Affect Prognosis

Stage

This is the most important factor that affects a patient’s chance of being cured.

Site

The location and size of the tumour in the thyroid gland can affect the surgeon’s ability to resect the tumour with adequate margins of healthy tissue around it.

Type and Grade

Both the type and grade of the tumour determine the amount of treatment necessary and the ultimate prognosis.

Spread to Lymph Nodes

This helps determine stage, but even without other factors, spread to lymph nodes in the neck decreases the chance of cure, especially if there is evidence of growth of cancer outside of the lymph node. Both the number and size of lymph nodes are also important, as a low number of small lymph nodes may not increase a patient’s risk significantly.

Age

A patient’s age at diagnosis is a significant factor in determining stage.  Patients younger than 55 years old can only be Stage I or II.

While each of these factors contributes to one’s outcome, patients should have a discussion with their doctor to determine their overall prognosis. Giving a percentage of survival is challenging because cancer research often looks at multiple types of cancer and may include a large range of patients who underwent a variety of treatments.

The chance of recurrence should be reevaluated at each follow-up visit after primary treatment. Perhaps contrary to what one might think, recurrent cancer can often be successfully treated and does not always lead to a higher risk of dying from disease.

The most recent (2015) American Thyroid Association (ATA) Guidelines for papillary and follicular thyroid cancer identify the following factors which indicate low, intermediate, or high-risk disease.

Low Risk Factors

• Cancer limited to the thyroid gland.
• ≤5 lymph node micrometastases (<0.2 cm in size) (small spread of tumour into lymph nodes).

Intermediate Risk Factors

• Aggressive histology (microscopic changes in the tumour that indicate aggression).
• Minimal extension of tumour outside the thyroid gland.
• Vascular invasion (spread of tumour into blood vessels).
• >5 involved lymph nodes (0.2-3.0 cm in size).

High Risk Factors

• Gross extension of tumour outside the thyroid gland.
• Incomplete tumour resection.
• Distant metastases (spread of thyroid cancer to another part of the body).
• Lymph node metastasis >3cm in size.

What to Expect After Treatment

After patients have completed treatment for well-differentiated thyroid cancer, they will need to have close follow-up with their doctor. Initially, an endocrinologist will help screen for possible endocrine, or hormonal, complications resulting from surgery.

Finding the right dosage of thyroid hormone replacement after surgery is essential. Thyroid hormone replacement is important for two main reasons. Firstly, since some or all of the thyroid gland has been removed, this therapy helps restore the thyroid hormone levels in the body. Secondly, thyroid hormone therapy keeps TSH levels low, which helps to reduce the risk of disease recurrence. Doctors will periodically order blood tests and imaging studies in order to monitor the disease.

Thyroglobulin & Thyroglobulin Antibodies 

Thyroglobulin (Tg) is a protein found in thyroid tissue, it is an essential ingredient in thyroid hormone production. Normally, Tg drops significantly in patients after total thyroidectomy and RAI treatment. Therefore, postoperative elevation in Tg levels is considered an indirect sign of disease recurrence or progression, and requires further investigation.

Anti-Tg antibodies (TgAb) are also helpful in the evaluation of disease recurrence. When anti-Tg antibodies are high, the results from Tg assays are not considered trustworthy, since the appearance of anti-Tg antibodies in the blood can cross react with Tg and give false results.

After initial surgery Tg and anti-Tg antibodies should be monitored periodically and, if at all possible, by the same laboratory, to avoid variables that could make interpretation difficult. Initially serum Tg should be measured every 6–12 months, or more frequently in high-risk patients.

It is important to note that for many patients who have undergone a hemi-thyroidectomy, their thyroid function will remain normal, despite the removal of half of the thyroid gland. For these patients, thyroglobulin should not be used as a marker of disease status, as levels found might not reflect the course of the disease. These patients should be monitored with imaging studies, as explained below.

Imaging studies

Doctors will perform imaging in the first 6 months after treatment. This is usually an ultrasound, and the first ultrasound will serve as a “baseline” study for the purpose of comparing future studies. During every follow-up visit after “baseline” evaluation, patients will be sent for imaging studies to help monitor for  the presence of disease.

Occasionally, when ultrasound exams are normal, but blood tests (Tg and anti-Tg antibodies) are elevated, other imaging studies can be used such as a CT, MRI, or PET/CT scan. If something suspicious comes up, a biopsy might be helpful to rule out disease recurrence.

RAI uptake scans, or functional tests may also be used, because uptake of radioactive iodine can help to localise any recurrent disease in the neck or distant metastasis elsewhere in the body.

Follow-up Schedule

Patients should visit their specialist on a regular basis (or earlier if they have any concerning symptoms). This allows doctors to examine for any sign that the cancer has returned. The best timeline for follow-up will be determined by the doctor.

Standard Follow-up Schedule

• For the first year, go every 1–3 months.
• For the second year, go every 2–6 months.
• For the third to fifth year, go every 4–8 months.
• After five years, start going once annually.

According to the results of the blood tests and imaging studies, patient’s response to therapy will be re-assessed at every follow up visit in order to plan subsequent visits or any necessary future treatments.

When discussing thyroid cancer, it’s important to first understand the anatomy of the thyroid gland and the important surrounding structures. The thyroid gland sits at the midline of the neck, just beneath the skin and a few layers of thin muscles. It has 2 lobes, the right and left lobe, which are connected in the midline by the isthmus. Occasionally, the thyroid may have a prominent pyramidal lobe that extends upwards in the midline, towards the hyoid bone and base of tongue.

The thyroid gland produces and secretes thyroid hormones, that are important in regulating many metabolic functions of the body. Thyroid hormone levels are closely controlled by the body, but can sometimes be over or under produced. A simple blood test can measure hormone levels. Cases of overproduction create hyperthyroidism, and cases of underproduction create hypothyroidism.

The gland is made up of follicular cells that take up iodine and produce thyroid hormone, which is stored in follicles inside the thyroid. The thyroid is also made up of another type of cell called parafollicular cells (C-cells). These cells produce a hormone called calcitonin, which helps regulate circulating calcium levels. Cancer that arise from C-cells is called medullary thyroid carcinoma.

The blood supply to the thyroid gland comes from the inferior thyroid artery, a branch of the thyrocervical trunk, and the superior thyroid artery, a branch of the external carotid artery. In some rare cases, there exists an artery called the ima artery, which runs from below the clavicles on the top surface of the trachea towards the thyroid gland.

On the backside of the thyroid gland are four parathyroid glands (two on each side). These are, much like the thyroid gland, endocrine glands that produce and secrete hormones. Through secretion of parathyroid hormone, the parathyroid glands regulate calcium levels in the blood and bones. Additionally, parathyroid hormone controls levels of calcium absorption from the diet and calcium excretion from the kidneys into the urine. During thyroid surgery, it’s important for surgeons to carefully separate the parathyroids from the thyroid in order to maintain normal levels of parathyroid hormone in the blood.

The recurrent laryngeal nerves (one on each side) run upward from the vagus nerve toward the voice box (larynx) in the groove between the trachea (windpipe) and esophagus which is just deep to the thyroid gland. This nerve moves the vocal cords and is responsible for speaking and control of the vocal cords during breathing. In extremely rare cases, the right recurrent laryngeal nerve can emerge from the vagus nerve higher in the neck and run straight down from the vagus nerve. This is called a non-recurrent laryngeal nerve because it does not come from below. It is important for surgeons to locate and protect this nerve during surgery.

The superior laryngeal nerves (one on each side) arise from the vagus nerve higher in the neck and run downward in close proximity to the superior pole of the thyroid gland. The external branch supplies the cricothyroid muscle and helps with changing vocal pitch and volume, whereas the internal branch controls the sensation of the larynx and aids in normal swallowing and prevention of aspiration.

The main lymph nodes associated with the thyroid are the central compartment lymph nodes (levels VI and VII) which lie in the middle portion of the neck in the tissue surrounding the thyroid gland. Occasionally, thyroid cancers can spread to the lateral neck or retropharyngeal lymph nodes, which lie behind the upper part of the pharynx, as well.

There is often no definitive cause of thyroid cancer. However, listed below are a few known risk factors for developing Medullary Thyroid Cancer.

Genetic Factors

Medullary Thyroid Cancer (MTC) can be either sporadic or hereditary. Approximately 80% of cases are sporadic, meaning that there was no family history of MTC. The exact etiology, or cause, of sporadic MTC is not fully understood.

The remaining 20% of cases of MTC are hereditary, meaning that the disease occurs due to genetic mutations that are inherited from family members. These inherited forms of MTC usually occur at a younger age (childhood or early adulthood) and can be categorised as one of 3 main syndromes: Multiple Endocrine Neoplasia 2A (MEN 2A), Multiple Endocrine Neoplasia 2B (MEN 2B), and Familial MTC (FMTC).

MEN 2A

Patients MEN 2A tend to have MTC, along with additional growths (parathyroid hyperplasia) or tumours in the parathyroid and adrenal glands. One example is pheochromocytomas, which are rare, hormone-secreting tumors in the adrenal gland that produce epinephrine and norepinephrine, causing symptoms such as sweating and headaches, among others.

MEN 2B

Patients MEN 2B tend to have MTC and pheochromocytomas, as well as benign growths of nerve tissue within the oral cavity or elsewhere, called mucosal neuromas.  Medullary thyroid carcinomas related to MEN 2B are often more aggressive.

Familial Medullary Thyroid Cancer

Patients with FMTC present with cancer only in the thyroid and/or associated metastatic lymph nodes. FMTC is not associated with any other tumours or altered hormonal production, as are MEN 2A and MEN 2B.

RET Proto-oncogene Mutations

Genetic mutations in the RET proto-oncogene are known to be the most prevalent risk factor in the development of MTC. These mutations occur in both hereditary and sporadic MTC. If this mutation is detected, screening for other related tumours (such as those present in MEN 2A and MEN 2B) should be performed. The presence of RET proto-oncogene mutations is associated with both an earlier age of presentation and a more aggressive disease.

Signs & Symptoms

Thyroid cancers are usually detected by patients or doctors when they feel a lump in the neck or when an imaging test for an unrelated condition shows a lump in the thyroid gland. Other rare signs and symptoms of thyroid cancer include:

• A lump or bump somewhere else in the neck: A metastatic lymph node with a biopsy showing thyroid cancer is a rare way that thyroid cancer can be detected.
• Change in voice: Unlike benign tumours in the thyroid gland, thyroid cancers can invade the nerves to the voice box (larynx) or even adjacent structures such as the trachea and esophagus. This could lead to a hoarse voice or difficulty breathing.
• Difficulty with swallowing (dysphagia): If thyroid tumours become very large (or invade surrounding structures), they can cause difficulty with swallowing.

It is important to note that a patient could have one or more of these symptoms and NOT have thyroid cancer. There are several non-cancerous causes of the same symptoms. That is why it is important for patients to go see a doctor if they are experiencing any of these symptoms.

Medullary thyroid cancer is diagnosed using the same standard methods as other types of thyroid cancer. Thyroid nodules are commonly discovered by a patient at home or by a physician during a routine physical exam. They may also be discovered incidentally on unrelated imaging studies such as a chest CT scan, an MRI of the cervical spine, or a Doppler ultrasound study of the carotid arteries.

In general, the standard diagnostic approach for thyroid cancer includes: physical examination, imaging, blood tests, and a fine-needle biopsy. Patients can expect their doctor to have a discussion with them about the risks, benefits and alternatives to each of these approaches.

Physical Exam

To start, a physician will feel (“palpate”) the neck to detect any abnormal swelling, hardness, tenderness, or asymmetry. Vocal cord function and ease of swallowing may also be assessed depending on patient symptoms.

Imaging

Imaging scans provide doctors with an inside view of the body. Imaging of the neck will be required to determine the size and location of a thyroid nodule and to get information about the surrounding thyroid tissue and the nearby structures such as lymph nodes, blood vessels, nerves and muscles. It is a vital step prior to any treatment decision. For thyroid cancer, the gold standard initial imaging test is an ultrasound.

In some cases, doctors may also recommend more advanced imaging studies such as a CT scan or an MRI.  These studies are especially important in evaluating patients with medullary thyroid carcinoma who have significantly elevated levels of calcitonin (>500 pg/mL) which may indicate disease outside of the thyroid gland and neck.

Blood Tests

Blood tests are used to detect thyroid hormone levels circulating in the body. Generally, thyroid nodules do not make thyroid hormone. However, some nodules do make excess thyroid hormone, which can cause significant symptoms, and can be detected on a blood test.

If medullary thyroid cancer is suspected preoperatively, doctors may order additional tests, such as Calcitonin (a hormone produced by the thyroid which helps regulate blood calcium and phosphate levels) and Carcinoembryonic antigen (a blood marker that has been shown to increase in certain cancers, such as MTC).

Patients with suspected MTC will likely also undergo genetic screening for certain mutations.

Biopsy

The best way to determine if a thyroid nodule is cancerous is with a fine needle aspiration (FNA) biopsy to remove a small piece of tissue and examine it under a microscope. This procedure is performed with local numbing medicine under the guidance of an ultrasound, and is essentially risk free. 

The majority of thyroid nodules are benign (not cancerous). Only about 5–15% of nodules are found  to be cancerous after a biopsy. Since benign thyroid nodules are very common, not all nodules need to be biopsied, especially if they are very small (< 1 cm). However, nodules that grow or appear “suspicious” on ultrasound should be evaluated further with follow-up ultrasounds and a biopsy.

A diagnosis of medullary thyroid cancer can be made with an FNA alone about 50–80% of the time. Otherwise, the diagnosis will require pathologic examination under the microscope following surgery.  If the biopsy is suspicious but not certain, sometimes the tumour cells from the FNA will be stained and tested for calcitonin to best detect and confirm the medullary carcinoma diagnosis.

However, in some cases, the diagnosis of medullary thyroid cancer cannot be made until the thyroid nodule is surgically removed.

In general, FNA results are reported using the Bethesda System, which is a 1–6 scale used to predict how likely it is that the biopsied nodule is cancerous. It is important to know that a doctor will not be completely sure about the pathology for the nodule until it has been surgically removed and examined under the microscope. Keep in mind this is different than cancer staging.

Type, Grade & Stage

Type

It is important to remember that not all lumps and bumps in the neck are cancer. Some thyroid nodules are benign (non-cancerous), and others are on the borderline between benign and malignant (cancerous). Often, the definitive diagnosis of the type of cancer is not fully determined until after the thyroid nodule has been surgically removed.  This is because a pathologist will need to examine the entire nodule within the thyroid gland before being able to determine for sure if the nodule is benign or malignant.

Medullary Thyroid Cancer (MTC)

Overall this is a rare form of thyroid cancer, making up approximately 1-2% of all thyroid cancers. Medullary thyroid cancers (MTC) grow from cells in the thyroid called parafollicular cells. These cells produce the hormone calcitonin, which helps regulate calcium levels in the blood. Approximately 80% of medullary thyroid cancers are considered to be “sporadic cases,” meaning that the patients did not have a family history of MTC. The remaining 20% are cases of hereditary MTC, meaning that the disease is related to a genetic mutation that can be passed down from family members. In this heritable form of MTC, there is a mutation in a gene called the RET proto-oncogene, which can be detected with a blood test. This mutation is inherited in an autosomal dominant way, meaning that if one parent has the mutation, there is a 50% chance that each child will inherit the disease. MTC can also be associated with genetic syndromes such as MEN 2a and  MEN 2b, which generally appear at an earlier age and tend to be more aggressive. Learn more about the genetic syndromes that can lead to MTC.

Grade

Medullary Thyroid Carcinoma (MTC) is generally considered to be of low to intermediate grade. However, there is no formal grading system for MTC.

The stage of a cancer is determined by the TNM staging system:

• The ‘T’ stands for tumour size.
• The ‘N’ stands for lymph node involvement.
• The ‘M’ stands for distant metastases, or cancer spread to other areas of the body.

Staging helps doctors determine how serious the cancer is and how best to treat it. Staging systems often reference very specific anatomical structures. Please see the anatomy page to learn about these terms.

Staging is generally based on the American Joint Committee on Cancer (AJCC) 8th edition guidelines. To learn more, see the AJCC TNM Staging Table and the TNM Staging Tool below.

Determining the Stage of the Cancer
The final step before discussing treatment options is a determination of the stage of the cancer. Like with all cancers of the head and neck, in Australia it is mandatory for doctors to use the AJCC Cancer Staging Manual (7th Ed) to determine the stage based on three factors.

At first, you will be given a clinical stage based on all the available information.
 Clinical staging (cTNM) is determined from any information your doctor might have about how extensive the cancer is BEFORE starting any treatment. Stage is determined based on your doctor’s physical exam, imaging studies, laboratory work and biopsies. Classification of clinical stage is described using the lowercase prefix c (e.g., cT, cN, cM).
If there is surgical removal of the cancer as part of your treatment, a pathologist will analyse the tumour and any lymph nodes that may have been removed. You will then be assigned a pathologic stage.
Pathologic staging (pTNM) provides more data. Classification of pathology stage is described using the lowercase prefix p (e.g., pT, pN, pM). This may or may not differ from the clinical stage.
There are also several other lowercase prefixes that might be used in the staging of your cancer.

• The subscript y(yTNM) is used to assign a cancer stage after some sort of medical, systemic or radiation treatment is given (Posttherapy or Postneoadjuvant Stage). It is typically combined with either a clinical or pathologic stage. For example, ycT2N0M0 indicates that after some sort of non-surgical therapy, the new clinical stage is T2N0M0.
• The subscript r(rTNM) is used when the tumour has recurred after some period in which it was gone. This is called Retreatment Classification Stage. Your doctor will use all the available information to assign you a retreatment stage.

 T stage: the main tumour mass
Based on a physical examination and review of any imaging, your doctor should be able to give you a T stage that falls within one of the following categories.

 N stage: spread of cancer to the lymph nodes in the neck
Next, your doctor will use all the available information and assign you an N stage. This is based on the assessment as to whether the cancer has spread to lymph nodes in the neck.

 M stage: spread of cancer outside the head and neck
Finally, based on an assessment on the entire body, you will be assigned an M stage.

 Your cancer stage
After TNM staging, your doctor can assign a cancer stage based on the following chart.

 Your clinical stage
Once the diagnostic tests are completed, before deciding what type of treatment you are going to undergo, you should be given a clinical stage that will look like the example below.

 * The lowercase subscript c indicates that this is a CLINICAL STAGE, the stage assigned based on all information available to your doctor before starting treatment.
After surgery, you should get a pathologic stage of your tumour. It will look almost like the clinical stage you received before starting treatment, but notice the “p” that indicates the stage group is based on an analysis of the entire tumour, with or without lymph nodes, under a microscope by a pathologist. In many cases, the pathologic stage will be the same as the clinical stage, but sometimes it will change.
After surgery, and after the pathologist has evaluated all of the tumour that was removed, you should be given a pathologic stage that looks something like this:

 The lowercase subscript p indicates that this is a PATHOLOGIC STAGE, the stage assigned after tumour removal and confirmation of cancer by a pathologist.
 Note also that the M stage is usually clinical, based on all available data without actually analysing any tissue.

Treatment Plan

There are multiple different options for the treatment of thyroid cancers that can be used alone or in combination:

• Active Surveillance
• Surgery
• TSH suppression therapy
• Radiation
• Chemotherapy

Active Surveillance for Low Risk Thyroid Cancer

Thyroid nodules smaller than 1cm and thyroid cancers that are small (<1 cm in size), show no evidence of lymph node involvement, and are not located on the back surface of the gland (near the recurrent laryngeal nerve) are considered “low risk thyroid cancers” and may be eligible to undergo active surveillance. Active surveillance is when doctors closely monitor a patient’s thyroid condition or cancer over time without giving any treatment. Doctors will intervene with treatment if there is evidence that the cancer has grown, or if the patient’s condition begins to change.  Another term for active surveillance is “watchful waiting.” With active surveillance, some patients may be able to avoid surgery, as their cancer may remain small and never grow to a concerning size.  Studies have shown that this is a very reasonable option for thyroid nodules smaller than 1cm, and even for those nodules that appear to be cancerous based on ultrasound features or are biopsy-proven papillary thyroid cancer.

Surgery 

For nodules greater than 1cm with worrisome characteristics on ultrasound and biopsy results suggestive of cancer, surgery is the preferred treatment choice. Occasionally, in select cases with large, symptomatic nodules greater than 4 cm,  surgery may be chosen without the need for a biopsy to confirm thyroid cancer. The extent of surgery will depend on multiple factors, including the size of the tumour, the histologic type, the location, and the involvement of regional lymph nodes or local structures.

Possible surgeries might include:

Hemithyroidectomy: This is the removal of only one of the thyroid lobes. A Hemithyroidectomy can be considered for some small cancers (< 4 cm) with no evidence of a tumour in the remaining lobe and no evidence of regional lymph node involvement on imaging studies. The remaining lobe should be followed closely with routine ultrasounds after surgery. It is important to note that this procedure is only chosen for low-risk thyroid cancers with no signs of invasion to other tissues.  The goals of this procedure are to preserve healthy thyroid tissue and to avoid the need for lifelong thyroid hormone replacement therapy.

Total thyroidectomy: This is the removal of the entire thyroid gland. This is performed in larger tumours (> 4 cm), when there are nodules in both lobes, or if part of the treatment will include giving radioactive iodine (RAI).

Central compartment lymph node neck dissection: This is a type of neck dissection, which involves removing the central compartment lymph nodes, including the lymph nodes next to the trachea and in front of the larynx. This might be recommended if a patient has known cancer in the thyroid gland or enlarged lymph nodes in the area.

Lateral compartment lymph node neck dissection: This is a type of neck dissection, which involves removing lymph nodes from the sides of the neck. This would be done if there is known cancer spread to that area.

Revision thyroid surgery: This is an additional surgery, or re-operation, in the thyroid bed or at the lymph node sites, which could be required if there is evidence that the cancer has recurred, or come back. Recurrence can be picked up on follow-up imaging studies or blood tests.

TSH suppression therapy

Following a total thyroidectomy, patients will need to undergo lifelong thyroid hormone replacement. TSH (Thyroid Stimulating Hormone) is a hormone produced by the brain to stimulate the growth of thyroid tissue and the production of thyroid hormone. When the thyroid gland is removed, the body is unable to produce thyroid hormone naturally. The brain will therefore start producing more TSH to try to increase the production of thyroid hormone. However, elevated TSH can also stimulate the growth of remnant thyroid tissue, which could increase the risk of recurrent thyroid cancer.

After surgery, TSH suppression therapy may be used to decrease a patient’s future risk of disease recurrence. In this type of therapy, patients are given a much larger dose of thyroid hormone (levothyroxine) than is necessary to fulfil their body’s needs. Giving this “larger-than-needed” dose signals the brain to stop producing TSH (as there is already more than enough thyroid hormone in the body), and therefore prevents the growth of additional thyroid tissue. When combined with surgery and RAI (when needed), this treatment has been shown to lower the risk of thyroid cancer recurrence.  The side effects of this treatment include a fast and irregular heartbeat and a loss of bone density, which leads to an increased risk of fractures. Doctors will evaluate a patient’s TSH levels, along with other clinical factors, in order to determine the optimal thyroid suppression levels for each individual patient.

Radiation 

Radiation for thyroid cancer comes in two main forms: radioactive iodine (RAI) and external beam radiation therapy.

Radioactive iodine: The main function of iodine in the body is to be used by thyroid cells to make thyroid hormone. Thyroid cells use essentially all of the iodine in the body for hormone production. Well-differentiated thyroid cancer cells also have the ability to take in iodine, just like healthy thyroid cells. Radioactive iodine (I-131) treatment involves administering I-131 (a radioactive isotope of iodine) to a patient either as a drink or in a capsule. The radioactive iodine is then taken up by thyroid cells, both healthy and cancerous. Since it is radioactive iodine, it will damage the thyroid cells and prevent them from growing. This radioactive iodine will affect all thyroid cells, no matter where in the body they are located, but will not damage normal tissue. This treatment is only given to patients who have previously undergone a total thyroidectomy, because these patients should not have any remaining healthy thyroid tissue. This means that that any existing thyroid tissue is likely to be cancerous. In these cases, radioactive iodine is useful because the I-131 will damage the cancerous thyroid cells and prevent them from growing, without affecting any other cells in the body.

External beam radiation therapy: While it remains the standard of care in many cancers of the head and neck, external beam radiation is not often recommended for thyroid cancer. For well-differentiated thyroid cancers, radioactive iodine is preferred because it is a more targeted form of radiation that attacks only thyroid cells and has fewer side effects than external beam radiation.

External beam radiation therapy might be considered in the following circumstances:

• Patients who are over the age of 55 and have T4 disease (gross extrathyroidal extension).
• Patients who have an aggressive cancer that cannot be completely resected and is not sensitive to radioactive iodine (either in the neck, in the thyroid bed or recurrent disease).
• Patients who have a distant metastasis that is causing significant symptoms and cannot be surgically resected (spine, brain, thorax).

Chemotherapy & Biologic Medications

Currently, very little research has been done on the use of chemotherapy as a treatment for well differentiated thyroid cancer. For patients who have persistent disease despite conventional treatments (surgery, TSH suppressive therapy, and RAI), additional treatment options include watchful observation (discussed above) and  systemic chemotherapy. The goal of chemotherapy is to stabilise, or slow, the progression of metastatic disease. In other words, it attempts to prevent the disease from spreading throughout the body. Chemotherapy is considered a disease modifying drug because it is expected to stop disease progression, but it is not expected to improve disease prognosis or provide a cure. Chemotherapeutic drugs can have significant toxic effects that might vary according to the specific chemotherapeutic agent used and the administered dose. Therefore, it is important to limit the use of systemic treatments to only those patients who are at significant risk for morbidity or mortality due to advanced disease.

If recurrent disease is evident after standard treatment, other local treatment therapies can be offered. These other treatments may be able to improve a patient’s quality of life when their disease is symptomatic. If the disease continues to progress despite all previously mentioned therapeutic options, chemotherapeutic drugs may be offered to select patients through clinical trials.

For more information about new therapies for thyroid cancer speak to your medical practitioner.

A prognosis is a prediction of the outcome of one’s disease. How likely is survival? Will the cancer come back? These are the big questions on most people’s minds after receiving a diagnosis of well-differentiated thyroid cancer. In general, there are several characteristics of the tumour that can inform a patient about their chances of being cured.

Factors That Affect Prognosis

Stage

This is the most important factor that affects a patient’s chance of being cured.

Site

The location and size of the tumour in the thyroid gland can affect the surgeon’s ability to resect the tumour with adequate margins of healthy tissue around it.

Type and Grade

Both the type and grade of the tumour determine the amount of treatment necessary and the ultimate prognosis.

Spread to Lymph Nodes

This helps determine stage, but even without other factors, spread to lymph nodes in the neck decreases the chance of cure, especially if there is evidence of growth of cancer outside of the lymph node. Both the number and size of lymph nodes are also important, as a low number of small lymph nodes may not increase a patient’s risk significantly.

Age

A patient’s age at diagnosis is a significant factor in determining stage.  Patients younger than 55 years old can only be Stage I or II.

While each of these factors contributes to one’s outcome, patients should have a discussion with their doctor to determine their overall prognosis. Giving a percentage of survival is challenging because cancer research often looks at multiple types of cancer and may include a large range of patients who underwent a variety of treatments.

Although the TNM staging system is intended to define the risk of mortality associated with thyroid cancer, the American Thyroid Association (ATA) has developed a system that is intended to determine the risk of developing recurrent thyroid cancer. The chance of recurrence should be reevaluated at each follow-up visit after primary treatment. Perhaps contrary to what one might think, recurrent cancer can often be successfully treated and does not always lead to a higher risk of dying from disease.

Low Risk Factors

• Cancer limited to the thyroid gland.
• ≤5 lymph node micrometastases (<0.2 cm in size) (small spread of tumour into lymph nodes).

Intermediate Risk Factors

• Aggressive histology (microscopic changes in the tumour that indicate aggression).
• Minimal extension of tumour outside the thyroid gland.
• Vascular invasion (spread of tumour into blood vessels).
• >5 involved lymph nodes (0.2-3.0 cm in size).

High Risk Factors

• Gross extension of tumour outside the thyroid gland.
• Incomplete tumour resection.
• Distant metastases (spread of thyroid cancer to another part of the body).
• Lymph node metastasis >3cm in size.

What to Expect After Treatment

After patients have completed treatment for well-differentiated thyroid cancer, they will need to have close follow-up with their doctor. Initially, an endocrinologist will help screen for possible endocrine, or hormonal, complications resulting from surgery.

Finding the right dosage of thyroid hormone replacement after surgery is essential. Thyroid hormone replacement is important for two main reasons. Firstly, since some or all of the thyroid gland has been removed, this therapy helps restore the thyroid hormone levels in the body. Secondly, thyroid hormone therapy keeps TSH levels low, which helps to reduce the risk of disease recurrence. Doctors will periodically order blood tests and imaging studies in order to monitor the disease.

Thyroglobulin & Thyroglobulin Antibodies 

Thyroglobulin (Tg) is a protein found in thyroid tissue, it is an essential ingredient in thyroid hormone production. Normally, Tg drops significantly in patients after total thyroidectomy and RAI treatment. Therefore, postoperative elevation in Tg levels is considered an indirect sign of disease recurrence or progression, and requires further investigation.

Anti-Tg antibodies (TgAb) are also helpful in the evaluation of disease recurrence. When anti-Tg antibodies are high, the results from Tg assays are not considered trustworthy, since the appearance of anti-Tg antibodies in the blood can cross react with Tg and give false results.

After initial surgery Tg and anti-Tg antibodies should be monitored periodically and, if at all possible, by the same laboratory, to avoid variables that could make interpretation difficult. Initially serum Tg should be measured every 6–12 months, or more frequently in high-risk patients.

It is important to note that for many patients who have undergone a hemi-thyroidectomy, their thyroid function will remain normal, despite the removal of half of the thyroid gland. For these patients, thyroglobulin should not be used as a marker of disease status, as levels found might not reflect the course of the disease. These patients should be monitored with imaging studies, as explained below.

Imaging studies

Doctors will perform imaging in the first 6 months after treatment. This is usually an ultrasound, and the first ultrasound will serve as a “baseline” study for the purpose of comparing future studies. During every follow-up visit after “baseline” evaluation, patients will be sent for imaging studies to help monitor for  the presence of disease.

Occasionally, when ultrasound exams are normal, but blood tests (Tg and anti-Tg antibodies) are elevated, other imaging studies can be used such as a CT, MRI, or PET/CT scan. If something suspicious comes up, a biopsy might be helpful to rule out disease recurrence.

RAI uptake scans, or functional tests may also be used, because uptake of radioactive iodine can help to localise any recurrent disease in the neck or distant metastasis elsewhere in the body.

Follow-up Schedule

Patients should visit their specialist on a regular basis (or earlier if they have any concerning symptoms). This allows doctors to examine for any sign that the cancer has returned. The best timeline for follow-up will be determined by the doctor.

Standard Follow-up Schedule

• For the first year, go every 1–3 months.
• For the second year, go every 2–6 months.
• For the third to fifth year, go every 4–8 months.
• After five years, start going once annually.

According to the results of the blood tests and imaging studies, patient’s response to therapy will be re-assessed at every follow up visit in order to plan subsequent visits or any necessary future treatments.