Exploring the Causes of Thyroid Cancer: Insights & Facts

The Anatomy of the Thyroid Gland and Its Functions

The thyroid gland is a small, butterfly-shaped gland in the neck that belongs to the body’s endocrine system. It produces hormones that regulate many important body functions, including metabolism, heart rate, blood pressure, body temperature, and weight. 

Thyroid disease occurs when levels of thyroid hormones are too high or too low. Thyroid cancer develops in the cells of the thyroid gland when abnormal cells begin to grow uncontrollably. Read about 8 Signs You May Have A Thyroid Condition.

Thyroid Cancer Prevalence 

Approximately 44,000 people in the United States receive a thyroid cancer diagnosis each year. It is a highly treatable cancer with excellent cure rates. However, about 2,000 people die from this disease each year.

Defining Thyroid Cancer: Types and Characteristics

Different types of tumors can develop in the thyroid gland. Some of these are benign (non-cancerous) while others are malignant (cancerous). Malignant thyroid tumors can spread to nearby tissues and other parts of the body. 

There are two main types of cells in the thyroid gland:

• Follicular cells which use iodine to make thyroid hormones

• C-cells or parafollicular cells that make a hormone called calcitonin, which helps regulate the amount of calcium in the blood

Additional types of cells in the thyroid gland include stromal (supportive) cells and lymphocytes (immune system) cells.

Different types of thyroid cancers develop from different thyroid cells. Knowing which type of cancer is present is important because it influences the treatment and outlook.

Papillary Thyroid Cancer

Papillary thyroid cancer is the most common type and accounts for 70-80% of all thyroid cancers. This is a slow-growing cancer that develops from follicular cells. The outlook for papillary thyroid cancer is usually excellent, even if the tumor has spread to surrounding lymph nodes. These tumors are rarely fatal. Learn the difference between a neoplasm vs tumor.

Follicular Thyroid Cancer

Follicular thyroid cancer makes up approximately 10-15% of all thyroid cancers in the U.S. This type of thyroid cancer occurs in follicular cells and is slow-growing. It can spread through the bloodstream to other organs in the body, especially the bones and lungs. A variant of follicular thyroid cancer is called Hurthle cell thyroid cancer or Hurthle cell carcinoma (HCC). 

Papillary and follicular thyroid cancers are called differentiated thyroid cancers. This means the thyroid cancer cells look like normal cells when viewed under the microscope. A differentiated thyroid cancer tends to grow and spread more slowly than a poorly differentiated or undifferentiated tumor.

Medullary Thyroid Cancer

Medullary thyroid cancer (MTC) is a rare type of thyroid cancer, accounting for about 2% of all cases. It develops in the parafollicular or C-cells of the thyroid gland that produce the calcitonin hormone. MTC can spread to regional lymph nodes and distant organs such as the lungs and liver. 

Around 1 in 4 MTCs run in families and occur in association with other endocrine tumors. If a person is diagnosed with medullary thyroid cancer, their family members can be tested for a genetic mutation in a gene called RET proto-oncogene. The presence of this mutation can help with timely diagnosis and curative surgery for MTC. However, 3 out of 4 people with medullary thyroid cancer do not have the inherited form of the disease.

Anaplastic Thyroid Cancer

Anaplastic thyroid cancer is a rare, highly aggressive thyroid cancer that accounts for about 2% of all thyroid cancers. It can sometimes develop from existing papillary or follicular thyroid cancers. This is an undifferentiated tumor in which the thyroid cancer cells often spread to nearby lymph nodes and distant organs. It has a very poor outlook. 

What Causes Thyroid Cancer?

The Role of Genetic Mutations

Certain acquired changes in a person’s genes (DNA) can cause normal thyroid cells to become thyroid cancer cells and grow uncontrolled. These changes are called gene mutations. They occur due to damage to the DNA by environmental causes, such as radiation. Mutations can also be random without any external cause. In addition, certain mutated genes are inherited from one’s parents.

Certain genes called oncogenes help cells to grow and live longer. Other genes called tumor suppressor genes slow down growth and ensure cell death at the appropriate time. Cancers occur when genetic mutations cause oncogenes to switch on or tumor suppressor genes to switch off.

For example, DNA mutations in the RET gene, BRAF gene, and NTRK1 gene have been linked to papillary thyroid cancers. Changes in the RAS oncogene and PAX8–PPAR-γ rearrangement cause some follicular thyroid cancers. People with medullary thyroid carcinoma have mutations in different parts of the RET gene than those with papillary carcinoma. Those with familial MTC inherit the RET mutation from a parent. People with anaplastic thyroid cancers may have some of the genetic changes described above and/or mutations in the TP53 tumor suppressor gene. Genetic testing may be available to determine any potential risk of developing these types of cancers based on your genetic profile.

Radiation Exposure: Risks and Realities

There is a known association between radiation exposure and thyroid cancer. The two main risk factors are the radiation dose and the age at exposure. The higher the radiation dose, the greater the risk of thyroid cancer. Also, exposure to radiation during childhood poses a greater risk than exposure during adulthood. Thyroid cancer typically develops 5-10 years after radiation exposure. The most common type associated with radiation exposure is papillary thyroid carcinoma with changes in the RET/PTC genes. 

Family History and Genetic Syndromes

Several inherited genetic syndromes have been linked to different types of thyroid cancer. In addition, people with a family history of the disease are at a higher risk of developing it. 

Most people with thyroid cancer do not have a family history or genetic syndrome.

If a loved one is diagnosed with thyroid cancer, read our tips for supporting family members with cancer.

Multiple Endocrine Neoplasia

About 20-25% of cases of medullary thyroid cancer occur in people with an inherited mutated gene. This is known as familial medullary thyroid carcinoma (FMTC). It can occur alone or in combination with other tumors of the endocrine glands, such as pheochromocytomas (tumors of the adrenal glands), parathyroid gland tumors, and neuromas (tumors of nerve cells). This syndrome is called multiple endocrine neoplasia type 2 (MEN 2).

Cowden Disease

Cowden disease is a genetic syndrome caused by defects in the PTEN gene. People with this mutation are at an increased risk of benign growths such as hamartomas as well as thyroid cancer, breast cancer, uterine cancer, and other cancers. The thyroid cancer type in Cowden syndrome is either papillary or follicular.

Familial Adenomatous Polyposis

Familial adenomatous polyposis (FAP) is a genetic syndrome associated with changes in the APC gene. People with this syndrome develop multiple polyps in the colon and have a very high risk of colon cancer. They are also at an increased risk of papillary thyroid cancer. A variant of FAP is called Gardner syndrome and is associated with benign tumors.

Carney Complex, Type I

People with Carney Complex Type I have mutations in the PRKAR1A gene. They develop benign tumors and hormonal disturbances and are at an increased risk of thyroid cancer (papillary and follicular type). 

Familial Non-Medullary Thyroid Carcinoma

Changes in chromosomes 19 and 1 are linked to an inherited condition that runs in some families. Papillary thyroid carcinoma tends to develop at an early age in individuals with these DNA changes.

Non-Modifiable Risk Factors: Gender and Age

Women are at a three times higher risk of thyroid cancer than men. The disease is commonly diagnosed in women in their 40s and 50s and men in their 60s and 70s. But people of any age can develop thyroid cancer, including children.

Other Factors: Iodine Deficiency and Environmental Influences

Iodine Deficiency

There may be a link between iodine deficiency and thyroid cancer. The thyroid gland needs iodine to make thyroid hormone. When iodine is deficient, thyroid hormone levels fall. This results in TSH (thyroid-stimulating hormone) secretion by the pituitary gland. Chronic TSH stimulation can cause uncontrolled growth of thyroid follicular cells, resulting in cancer. More research is needed, and other mechanisms may also be involved.

Environmental Risk Factors for Thyroid Cancer

Some external factors linked to thyroid cancer include:

• Radiation exposure (medical radiation or nuclear weapon fallout)

• Chemical toxins, including pesticides

• Metals such as cadmium that are present in air, water, or food

• Nitrites and nitrates present in food and water

• Air pollution

Medical Conditions

Certain health conditions can increase the risk of thyroid cancer, such as:

• Goiter (enlarged thyroid)

• Thyroiditis (inflammation of the thyroid gland)

• Obesity

Common Symptoms of Thyroid Cancer

Symptoms of thyroid cancer may include:

• A lump or growth in the neck

• Throat or neck pain

• A sensation of tickling in the throat

• Hoarseness and other voice changes

• A persistent cough

• Swollen lymph nodes in the neck

• Difficulty breathing or swallowing

Additional symptoms in people with advanced thyroid cancer may include:

• Fatigue

• Loss of appetite

• Unexplained weight loss

• Nausea

• Vomiting

Diagnosing Thyroid Cancer

Blood Tests

Thyroid function tests (blood tests such as T3, T4, and thyroid stimulating hormone or TSH) cannot diagnose thyroid cancer. This is because the thyroid gland usually continues functioning normally even when cancer is present. However, a high calcitonin level may raise suspicion for medullary thyroid carcinoma.

Ultrasound and Radioiodine Scans

If you or your healthcare provider feel a nodule (growth) in your neck, your provider may order a thyroid ultrasound. This study uses sound waves to obtain a picture of your thyroid gland. It is a painless test that does not involve radiation exposure. Thyroid ultrasound can be used to diagnose cysts, goiter, and thyroid cancer.

Fine-Needle Aspiration Cytology

Ultrasound-guided fine needle aspiration cytology (FNAC) is a minimally-invasive procedure in which doctors use a very fine needle to obtain a tissue sample from a suspicious thyroid nodule. The tissue sample is then examined in the laboratory under the microscope to see what types of thyroid cells are present. The test is typically done on an outpatient basis. 

FNAC is generally accepted as the most effective diagnostic test for thyroid nodules. It helps to identify patients with thyroid cancer who require surgery. It also reduces unnecessary thyroid surgery in patients with benign nodules. 

Understanding Stages of Thyroid Cancers

Healthcare providers use the AJCC (American Joint Committee on Cancer) TNM system for staging most cancers, including thyroid cancer. This system takes into account three key factors: 

• T: The size of the tumor

• N: The spread of the tumor to adjacent lymph nodes

• M: The metastasis of the tumor to distant organs such as the lungs or liver

The higher the number in TNM, the more advanced the cancer. Therefore, a T1N0M0 thyroid cancer is in the early stages, whereas a T4N1M1 tumor is a late-stage cancer.

Younger people will have a lower risk of dying from papillary or follicular thyroid cancer, and the TNM stage groupings consider this fact. Remember that the TNM staging system uses the “pathologic stage” or “surgical stage,” determined by the tissue removed during surgery. However, in many cases, surgery is not a viable option at the time or at all, so the “clinical stage” will be used instead. 

Receiving a cancer diagnosis is devastating, and cancer staging is complex. Not to mention, many other factors contribute to the uniqueness of each case. Therefore, your doctor is a great resource who can explain this to you in a way that applies to you and that you can understand thoroughly.

Treatment Options for Thyroid Cancer

Surgery: Thyroidectomy and Lobectomy

Thyroidectomy (thyroid removal surgery) is the recommended treatment for most thyroid cancers. Your healthcare team will develop a personalized treatment plan for you to eliminate the cancer and maintain thyroid function whenever possible. 

A thyroidectomy is done through a small incision (cut) in the neck. This incision can be placed in a natural skin crease so that the scar is less visible. You may be able to go home the same day or spend a night in the hospital.

There are two types of thyroid surgery for cancer, depending on how much of the thyroid gland is removed. This depends on the size, stage, and location of the tumor.

• Total thyroidectomy involves the removal of the entire thyroid gland. 

• Partial thyroidectomy involves removing only one side of the thyroid where the cancer is present. This may be a lobectomy surgery in which the surgeon removes one of the two lobes of the thyroid. 

If thyroid cancer cells have spread to nearby lymph nodes in the neck, the surgeon may remove affected lymph nodes to reduce the risk of the cancer coming back. This is called a lymphadenectomy procedure.

Radioactive Iodine Treatment

The thyroid gland needs a mineral called iodine to make thyroid hormone. Thyroid cancer cells also absorb iodine. Therefore, specialists in nuclear medicine can use radioactive iodine (RAI), a type of iodine that emits radiation, to destroy cancer cells. Different isotopes (types) of radioactive iodine, such as I-123 and I-131, are used to diagnose and treat thyroid cancer.

Radioactive iodine therapy may be used after thyroid surgery to destroy any remaining cancer cells that may have spread to surrounding tissues. 

After RAI treatment, your body continues to emit radiation for some time. Consequently, you need to take certain precautions to protect the people around you.

External Radiation Therapy 

Healthcare providers can use high-energy rays to destroy cancer cells that may remain after surgery, without affecting normal thyroid tissue. There are various types of radiation for thyroid cancer, including external beam radiation therapy, intensity-modulated radiation therapy, proton therapy, and stereotactic body radiotherapy. 

The duration of radiation therapy for thyroid cancer depends on the specific type of radiation and dosing schedule. It can be anywhere from several days to several weeks. Your doctors will create an individualized treatment plan for you.

Systemic Therapy

People with aggressive thyroid cancers may be prescribed systemic therapies. These treatments involve the use of drugs that find and destroy cancer cells throughout the body. They are offered to people with thyroid cancers that have metastasized (spread to other organs in the body). There are two types of systemic therapy:

Chemotherapy

Chemotherapy drugs destroy cancer cells throughout the body. They are given by IV injection into a vein. Examples of chemotherapy drugs used in thyroid cancer patients include doxorubicin, carboplatin, cisplatin, docetaxel, and paclitaxel. Chemotherapy also destroys healthy cells and can, therefore, cause side effects. Learn more about common chemotherapy side effects.

Find out How Long Does It Take for Chemo to Start Working?

Targeted Therapy

Targeted therapy drugs find cancer cells and prevent them from growing. Depending on the type of thyroid cancer, treatment may include: 

• Kinase inhibitors such as sorafenib, lenvatinib, and cabozantinib (Cabometyx)

• BRAF inhibitors such as dabrafenib (Tafinlar) and vemurafenib (Zelboraf)

• NTRK inhibitors such as entrectinib (Rozlytrek) and larotrectinib (Vitrakvi)

• RET inhibitors such as pralsetinib (Gavreto) and selpercatinib (Retevmo)

Learn the most affordable medications to fight cancer.

Managing Thyroid Cancer

Long-Term Monitoring and Thyroid Hormone Replacement

Follow-up after treatment for thyroid cancer typically includes regular physical examinations, laboratory tests, and imaging studies. Your doctors will want to keep track of your thyroid gland for several years afterwards. People who are treated for thyroid cancer usually need to return to their doctor's office every 6-12 months for follow-ups.

If you undergo a total thyroidectomy, you will need to take thyroid hormone replacement medicine lifelong. If you undergo a partial thyroidectomy, you may or may not need to take daily thyroid hormone therapy for life. It will depend on how much of your thyroid was removed and your thyroid hormone levels, 

The Role of Support and Resources in Cancer Care

A cancer diagnosis can be a frightening and overwhelming experience. Having a support system in place can help cancer patients find a safe space to be heard, express their feelings, and receive empathy and understanding. This reduces the emotional burden of cancer. Support groups and forming connections with other people who have been diagnosed with similar medical problems can also be extremely helpful.

Frequently Asked Questions: Thyroid Cancer

What is the risk of Thy3f cancer?

Doctors use a test called fine-needle aspiration cytology (FNAC) to obtain a sample of cells from a suspicious thyroid nodule (growth). The result sometimes comes back as indeterminate cytology (THY3a-f). This means a formal histological evaluation is required to confirm whether the growth is benign or malignant. Studies have shown that 1 in 5 patients with a suspicious follicular neoplasm (THY3f) is diagnosed with a thyroid carcinoma. The risk is much lower for THY3a. Doctors recommend thyroid surgery for all patients with THY3f cytology.

What causes TIRADS 3?

TI-RADS stands for Thyroid Imaging Reporting and Data System. It is a method of stratifying risk for thyroid lesions based on ultrasound features.

• TI-RADS 1: Normal thyroid gland

• TI-RADS 2: Benign lesions with 0% risk of malignancy

• TI-RADS 3: Probably benign nodules (less than 5% risk of malignancy)

• TI-RADS 4: Suspicious nodules (5-80% risk of malignancy)

• TI-RADS 5: Probably malignant nodules (more than 80% risk of malignancy)

• TI-RADS 6: Biopsy-proven malignancy

Can you survive stage 3 thyroid cancer?

A stage 3 thyroid cancer is a cancer of any size that may be growing outside the thyroid gland and may have spread to lymph nodes in the neck but which does not involve nearby structures or distant sites. The 5-year survival rate for stage 3 thyroid cancers ranges between 99% for papillary thyroid cancer to 98% for follicular thyroid cancer, 92% for medullary thyroid cancer, and 11% for anaplastic thyroid cancer. A 5-year survival rate of 99% means that people who have cancer are about 99% as likely to live for at least 5 years compared to people who don’t have cancer.

Preventive Measures and Lowering Your Risk

Monitoring Radiation Exposure

In many thyroid cancer cases, there are no known risk factors. So, it may not be possible to lower the risk of developing thyroid cancer or to prevent thyroid cancer. 

However, radiation exposure, particularly early in life, is a known thyroid cancer risk. Because of this, healthcare providers do not use radiation to diagnose or treat diseases unless absolutely necessary. Imaging tests such as X-rays and CT scans expose you to radiation, while those such as ultrasound and MRI do not. When exposure to radiation is necessary, doctors use the lowest dose possible.

Diet and Lifestyle Adjustments

The evidence is conflicting, but low iodine intake may be a risk factor for thyroid cancer. In addition, goitrogenic foods, for example, cruciferous vegetables (cauliflower, cabbage, broccoli), are a potential risk factor for thyroid cancer. Other potential risks include certain meats (chicken, pork) and micronutrients such as nitrates. Certain fruits, such as tangerines and persimmons, may have a protective effect. Further studies are needed to investigate the link between these dietary factors and thyroid cancer risk. 

Regular Check-Ups and Screenings for At-Risk Individuals

If you have a family history of medullary thyroid cancer, it is important to seek care from a specialist in genetic counseling and genetic testing for this disease. If the disease is discovered in one member of a family, other family members can be tested for the inherited gene mutation and treated. 

Sometimes, removing the thyroid gland in people who carry an abnormal inherited gene is recommended. This can prevent a potentially fatal thyroid cancer in the future. Genetic tests allow most familial medullary thyroid carcinomas to be prevented or treated. 

The Importance of Awareness and Early Detection

By reading about the causes of thyroid cancer and learning more about this disease, you have taken the first step toward awareness and early detection. Being aware of the symptoms of thyroid cancer can help you seek timely medical care. 

Early detection of thyroid cancer gives most patients more treatment options and increases the chances of successful treatment.  However, not all early thyroid cancers cause signs and symptoms that can be noticed. Nonetheless, it’s important not to ignore any symptoms and to seek medical care in a timely manner.

Further Research and Consultation with Healthcare Providers

Do not ignore any suspicious thyroid cancer symptoms. Most thyroid cancers are treatable. You can increase your chances of a good outcome by seeking timely medical care.