Understanding Medullary Thyroid Carcinoma: Causes & Treatments

Thyroid cancer develops when certain cells in the thyroid gland grow in an uncontrolled manner. Cancer cells in the thyroid gland can develop due to various causes, including genetic and environmental factors. Learn more about What Causes Thyroid Cancer?

Medullary thyroid carcinoma (MTC) is a rare malignant thyroid tumor. It accounts for only about 1-2% of all thyroid cancers diagnosed in the United States. 

Medullary thyroid cancers are different from other types of thyroid cancers, such as papillary thyroid cancer, follicular thyroid cancer, and anaplastic thyroid cancer. It is called medullary thyroid carcinoma when the cancerous cells are C cells or parafollicular cells. These thyroid cells do not make thyroid hormone. Instead, they make another hormone called calcitonin, which controls the amount of calcium in blood. 

An elevated calcitonin level is, therefore, a hallmark feature of medullary thyroid cancer that is not seen in other types of thyroid cancers.

Approximately 75% of the cases of medullary thyroid cancer are random or sporadic MTC. The other 25% of the cases are familial or inherited and run in families. MTC is linked to a mutation in the RET proto-oncogene. This mutated or defective gene can be inherited from a parent. 

Familial medullary thyroid cancer may be linked to other endocrine tumors and genetic syndromes such as multiple endocrine neoplasia type 2 (MEN2). People with MEN2 have pheochromocytomas (tumors of the adrenal glands), parathyroid gland tumors, and neuromas (nerve cell tumors) in addition to medullary thyroid cancer. Learn more about the difference between a neoplasm vs a tumor.

The Importance of the Thyroid Gland in Your Body

The thyroid gland is a small, butterfly-shaped gland in the neck that makes and releases thyroid hormones. These hormones regulate many important functions in the body, including metabolism, temperature, weight, heart rate, and blood pressure. 

Key Terms Explained: Calcitonin, C Cells, and RET Proto-Oncogene

Calcitonin

Calcitonin is a hormone made by the C-cells in the thyroid gland. This hormone regulates calcium by decreasing levels in the blood. It has the opposite action to parathyroid hormone (PTH) which increases blood calcium levels.

C-Cells

C-cells, also called parafollicular cells, are types of thyroid cells that make and release calcitonin hormone into the bloodstream. They are different from follicular cells in the thyroid gland that make and release thyroid hormones.

RET Proto-Oncogene

Proto-oncogenes are genes that regulate normal cell growth. They can contribute to cancers if they get “switched on” by a mutation (change or defect) in the gene. People with medullary thyroid cancer (MTC) have a mutation in a proto-oncogene known as RET. 

Differences between Medullary Thyroid Carcinoma and Other Thyroid Cancers

Unique Characteristics of Medullary Carcinoma

• Medullary thyroid cancer (MTC) is a rare type of thyroid cancer. It accounts for only about 1-2% of all thyroid cancers in the U.S. 

• MTC develops in the parafollicular or C cells of the thyroid gland. These cells make calcitonin hormone, which regulates calcium levels in the blood.

• MTC can spread to surrounding lymph nodes and distant organs such as the liver and lungs. 

• Approximately 1 in 4 cases of MTC are inherited and run in families. The remaining 75% are random or sporadic MTC.

• People with MTC typically have a high calcitonin level because the cancerous C-cells make too much of the hormone. The higher the calcitonin level, the greater the chance of having medullary thyroid cancer diagnosed.

• Other clinical findings in MTC patients include the presence of a palpable solitary thyroid nodule (growth) in the neck. 

• An elevated tumor marker called CEA (carcinoembryonic antigen) may raise suspicion for MTC or other types of cancer. 

• Medullary thyroid cancer can occur with other endocrine tumors and genetic syndromes. 

• Family members of a person diagnosed with medullary thyroid cancer can undergo genetic testing for a mutation in the RET proto-oncogene. The presence of this mutation can help with early diagnosis and curative thyroid surgery for MTC.

Papillary and Follicular Thyroid Cancer vs. Medullary Thyroid Cancer

There are two main types of cells in the thyroid gland. Follicular cells that make thyroid hormones, and parafollicular C-cells that make calcitonin hormone. The key differences between medullary thyroid cancer and other types of thyroid cancers are:

• Origin: Papillary and follicular thyroid cancers arise from follicular cells in the thyroid. Medullary thyroid cancers arise from parafollicular C-cells.

• Prevalence: Papillary and follicular cancers are the most common types. They account for 70-80% and 10-15%, respectively, of thyroid cancers. Medullary thyroid cancers account for around 1-2% of all thyroid cancer diagnoses.

• Type of Cancer: Papillary and follicular thyroid carcinomas are differentiated thyroid cancers. They tend to grow and spread more slowly than non-differentiated cancers like MTC.

• Potential to Spread: Papillary thyroid cancer may spread to surrounding lymph nodes. Follicular thyroid cancer can spread to nearby lymph nodes and distant organs such as the lungs and bones. Medullary thyroid cancer can spread to regional lymph nodes and distant sites such as the liver and lungs. 

• Genetic Mutations: Approximately 25% of MTCs are familial and linked to an inherited mutation in a gene called the RET proto-oncogene. People who have papillary thyroid carcinoma also have a mutation in the RET gene, but it is in a different part of the gene than those with MTC.

Common Symptoms of Medullary Thyroid Carcinoma

Many patients with medullary thyroid cancer do not have any symptoms. Some people may notice a new lump or growth in their neck. Less commonly, MTC causes hoarseness or changes in voice, persistent cough, problems with swallowing (such as a sensation of pills getting stuck in the throat), and shortness of breath when lying flat.

Diagnostic Tests and Their Significance

Blood Test for Calcitonin Levels and Carcinoembryonic Antigen (CEA)

If a thyroid nodule is discovered on a routine neck examination, your doctor will obtain a detailed personal and family medical history. They will order blood tests such as T3, T4, and TSH (thyroid stimulating hormone) to check your thyroid function. Most people with thyroid cancer are euthyroid (i.e., they have normal thyroid function). What is a TSH blood test?

If your doctor suspects medullary thyroid cancer, they will order blood calcitonin and CEA levels. Calcitonin levels are elevated in people with MTC. This blood test also provides clues about the severity of the disease. In general, the higher the level of detectable calcitonin, the poorer the disease prognosis. High levels of tumor markers, specifically CEA (carcinoembryonic antigen), are also a sign of aggressive medullary thyroid cancer.

Fine-Needle Aspiration Biopsy

Ultrasound-guided fine-needle aspiration biopsy is a minimally invasive test for medullary thyroid cancer. It is relatively safe and fairly accurate. The test involves obtaining a sample of thyroid cells using a fine needle. The tissue biopsy is then examined under the microscope in the laboratory to check for evidence of tumor cells. The FNAC test is usually done on an outpatient basis, and complications are rare.

Genetic Testing

The presence of a hallmark mutation in the RET proto-oncogene with genetic testing can lead to an early diagnosis of medullary thyroid cancer. Family members of a person found to have this mutation should undergo genetic testing. Such individuals can be offered preventive treatment with thyroid surgery. Therefore, monitoring and genetic testing of people with a positive family history of MTC is very important.

The Role of Imaging in Diagnosing Thyroid Nodules

A thyroid ultrasound is usually the first imaging study done to investigate a palpable thyroid nodule that is felt on clinical examination. This imaging study can help differentiate between cysts, multinodular goiter, and potentially cancerous thyroid nodules. Interventions such as fine-needle aspiration (FNA) are also performed under ultrasound guidance. Learn key difference between cysts vs tumors.

Other imaging studies that may be ordered in patients with suspected thyroid cancer include scintigraphy (this is done using a radioactive tracer), plain X-rays, and CT (computed tomography) or MRI (magnetic resonance imaging) scans for staging the disease.

The Influence of RET Mutation in Medullary Thyroid Carcinoma

If you have an inherited RET gene mutation, you are at a greater risk of developing certain cancers, including medullary thyroid cancer. Your siblings have a 50% chance of having this mutation. There is also a 50% chance that you will pass on this mutation to each of your children. Other family members are also at risk of having the RET mutation and should undergo genetic counseling and testing for hereditary MTC.

Familial vs. Sporadic Forms of MTC: Understanding the Genetic Link

Nearly everyone with familial (inherited) MTC has a RET mutation. People with familial MTC and genetic syndromes such as MEN2 inherit the RET mutation from a parent. They can pass the mutation on to their children. Inherited mutations are present in every cell in the body and can be detected by genetic tests.

While RET mutation is present in virtually all cases of medullary thyroid carcinoma (MTC) caused by MEN2 syndrome, the prevalence of RET mutation in sporadic MTC varies by population, ranging from about 19 to 89%.  This mutation is not inherited from a parent. Most people with sporadic MTC only have the gene mutations in their cancer cells. The mutations do not get passed on to their children. 

Risk Factors Beyond Genetics: Family History and Multiple Endocrine Neoplasia

Risk factors are traits that can increase your risk of getting thyroid cancer. Having a risk factor does not mean that you will definitely develop cancer. It means you are more likely to develop cancer compared to someone who doesn’t have the risk factor.

Non-Modifiable Risk Factors for MTC (Which Can’t Be Changed)

• Gender and Age: Thyroid cancers are three times more common in women than in men. They tend to affect women in their 40s and 50s and men in their 60s and 70s.

• Hereditary Conditions: Inherited genetic syndromes such as multiple endocrine neoplasia type 2 (MEN2) are caused by mutations in the RET gene. People with MEN 2 have medullary thyroid cancer and other cancers such as pheochromocytomas (adrenal gland tumors), tumors of the parathyroid glands, and neuromas. 

• Family History: Having a first-degree relative (parent, sibling, or child) with a history of thyroid cancer is a risk factor for developing thyroid cancer. This risk is present even in the absence of a known inherited syndrome.

Modifiable Risk Factors for MTC (Which Can Be Changed)

• Iodine: Too much or too little iodine in diet has been linked to some types of thyroid cancers (papillary and follicular types) but not specifically to medullary thyroid cancer.

• Radiation Exposure: Exposure to radiation (during medical procedures or from a nuclear fallout) is a known risk factor for thyroid cancer. Radiation exposure at a very young age carries a higher risk than exposure during adulthood.

• Obesity: People who are overweight or obese are at an increased risk of thyroid cancer.

Survival Rate and Prognosis for Medullary Thyroid Carcinoma Patients

The 5-year relative survival rate for medullary thyroid carcinoma depends on the stage of the cancer:

• Localized MTC with no cancer outside the thyroid gland: More than 99.5%

• MTC with regional spread to nearby structures: 92%

• MTC with metastases to other parts of the body: 43%

• All stages combined: 91%

Note: A 5-year relative survival rate of 99% means that 99% percent of people who are diagnosed today will still be alive 5 years from now. 

Treatment Options and Management

Surgical Approaches: Total Thyroidectomy and Lymph Node Removal

The primary treatment for thyroid cancers in most patients is thyroidectomy or thyroid removal surgery. This can be a complete or incomplete surgical resection, depending on the size and location of the tumor. It may include central neck dissection to remove enlarged lymph nodes. Lymph node dissection is done to lower the risk of cancer recurrence if thyroid cancer cells have spread to nearby lymph nodes.

The Role of Radiation Therapy in MTC Treatment

Various types of high-energy rays, including external beam radiation, can be used to selectively destroy medullary thyroid cancer cells that may be left behind after surgery. The radiation dosing regimen can range from several days to several weeks. 

Radioactive Iodine Treatment

Radioactive iodine (RAI) is a treatment in which iodine labeled with a radioactive substance (I-123 or I-131) is used to find and destroy cancer cells. RAI may be offered following thyroid surgery to destroy any remaining cancer in surrounding tissues. 

Targeted Therapy Options: Vandetanib and Cabozantinib

Aggressive medullary thyroid cancers may need to be treated with systemic therapies such as chemotherapy and targeted therapy. These are drugs that destroy cancer cells throughout the body. They are recommended for people who have thyroid cancers with distant metastases to other parts of the body. Examples include:

• Selective RET kinase inhibitors such as selpercatinib (Retevmo)

• Chemotherapy drugs such as doxorubicin, cisplatin, carboplatin, paclitaxel, and docetaxel. 

• Antiangiogenic multikinase inhibitors (aaMKIs), , targeted therapy for medullary thyroid cancer, such as vandetanib (Caprelsa) and cabozantinib (Cometriq).

Importance of Follow-Up and Monitoring for Recurrence

Your doctor will monitor you with regular follow-ups every 6-12 months after your treatment for medullary thyroid cancer has finished. At these visits, you may undergo a physical examination, laboratory tests, and imaging studies. 

If you have undergone a total thyroidectomy (removal of the entire thyroid gland), you will need to take thyroid hormone replacement therapy lifelong. People who undergo a partial removal of their thyroid may or may not need thyroid replacement medicine, depending on their thyroid hormone levels.

Living with Medullary Thyroid Carcinoma

Lifestyle Adjustments and Dietary Considerations Post Diagnosis and Treatment

You may have side effects from your medullary thyroid cancer treatments. These will slowly improve over time. Some healthy lifestyle changes can help you recover faster, such as:

• Eating well.

• Keeping active.

• Getting enough sleep.

• Stopping smoking.

• Limiting alcohol intake.

• Managing stress by spending time with loved ones and practicing relaxing activities like deep breathing, meditation, and yoga. 

Navigating Emotional and Psychological Impacts

It is normal to continue to feel anxious even after your treatment for medullary thyroid cancer is over, especially before doctors’ appointments. The support of family and friends can help you manage these emotions. Additionally, talk therapy is another excellent resource for receiving professional recommendations and coping strategies to help you navigate these challenging times. 

Support Systems: Connecting with Others and Finding Resources

While resources such as the National Cancer Institute (NIH) are a valuable source of credible information to understand your health journey better, joining a support group may be beneficial in a unique way since you can learn directly from those going through the same challenges as you.

Support groups for medullary thyroid cancer can help you learn more about your condition. They can also connect you with others who have been diagnosed with the disease. This will make you feel less alone. You may also learn some tips on coping with the illness. Some useful resources include:

• ThyCa (Thyroid Cancer Survivors’ Association)

• Rare Disease Advisor

• AnCan 

• National Cancer Institute (NIH)

Frequently Asked Questions

What is the survival rate for stage 3 medullary thyroid cancer?

The 5-year relative survival rate for stage 3 medullary thyroid cancer is 92%. This is the survival rate for an MTC with SEER stage “Regional,” where the cancer has spread outside the thyroid gland to surrounding structures.

What is the difference between thyroid cancer and medullary thyroid cancer?

Thyroid cancer can be of many different types, one of which is medullary thyroid cancer. The other types include papillary thyroid cancer, follicular thyroid cancer, and anaplastic thyroid cancer.

How serious is medullary thyroid cancer?

The prognosis for medullary thyroid cancer is not usually as good as differentiated thyroid cancers (papillary and follicular types). If MTC is discovered early, it can be cured with surgery. People with metastatic disease have a poorer outlook.

How does medullary thyroid cancer present?

Medullary thyroid cancer (MTC) is frequently diagnosed on routine physical examination as a solitary neck nodule. This thyroid nodule often does not cause any symptoms. 

Prevention and Early Detection Strategies

The Significance of Early Genetic Screening for High-Risk Individuals

A mutation in the RET gene is a hallmark of medullary thyroid cancer. Genetic testing to detect this mutation can lead to early detection in high-risk and asymptomatic individuals. This includes:

• People who have the RET mutation but don’t have MTC yet.

• People who have the RET mutation and have developed MTC but don’t have any symptoms. 

If a person has been diagnosed with MTC, others in their family should undergo genetic counseling and testing. Such individuals can have medullary thyroid cancer treated preemptively with thyroid surgery.

Thyroid Ultrasound Screening for Early Detection of Thyroid Nodules

Your doctor may order a neck ultrasound imaging test if they note a thyroid nodule. Thyroid nodules are also sometimes discovered incidentally on imaging tests done to evaluate other conditions in the neck. Nodules found in imaging studies are usually smaller than those discovered in a physical exam.

Lifestyle Choices That Could Influence Thyroid Health and Cancer Risk

Iodine deficiency and excess have been linked to increased thyroid cancer risk. Most people who eat a healthy, balanced diet get the right amount of iodine from dietary sources. However, if you have a deficiency, talk to your healthcare provider about eating iodine-rich foods such as seafood or seasoning your food with small amounts of iodized salt. 

Radiation is another known risk factor for thyroid cancer. To limit exposure, your healthcare providers will only order radiating imaging studies such as X-rays and CT scans when absolutely necessary. 

Obesity has been linked to an increased risk of thyroid cancer. Keep your weight in a healthy range by eating healthy and engaging in regular physical activity.

Note: Some people develop medullary thyroid cancer even when they don’t have any risk factors. Early diagnosis and treatment is the key to a good outcome. Seek care from a medical professional without delay if you see or feel a lump or growth in your neck.