What Is Medullary Thyroid Cancer?

Medullary thyroid cancer (MTC) is a rare and aggressive subtype of thyroid cancer that begins when the parafollicular C cells of the thyroid begin to grow abnormally. Medullary thyroid cancer makes up approximately 3% of all thyroid cancers and may be hereditary or sporadic.

The sporadic form accounts for approximately 70% of all cases of the disease. The hereditary form of MTC is a result of a mutation in the RET gene and is part of a multiple endocrine neoplasia type 2 disorder. In the inherited types, other conditions (e.g., pheochromocytoma or parathyroid hyperplasia) may be present.

Medullary thyroid cancer is more common in women than in men (with the exception of inherited MTC). Unlike other thyroid cancers, it is not associated with exposure to radiation.

Symptoms

Symptoms are rare in the early stages of medullary thyroid cancer, and this may be one reason that this subtype of thyroid cancer has a tendency to be diagnosed after it has spread to other parts of the body.

As the parafollicular C cells of the thyroid begin to grow at a rapid rate, a nodule is formed. In the early stages of medullary thyroid cancer, this lump in the neck may be the only symptom. The nodule may be tender if it is palpated. Surrounding lymph nodes may become tender to the touch if cancer has spread. MTC first spreads to the surrounding lymph nodes and then commonly metastasizes to the liver, lung, bone, and brain.

Parafollicular C cells are responsible for the production of a hormone called calcitonin. As the disease progresses, alterations in the production of calcitonin may result in other symptoms, including diarrhea. In its advanced stages the following symptoms of MTC may occur:

• Difficulty swallowing
• Hoarseness
• Breathing problems
• Cushing syndrome
• Carcinoid syndrome
• Weight loss
• Lethargy
• Bone pain

Diagnosis

The first steps in diagnosing medullary thyroid cancer are obtaining an accurate report of your symptoms and medical history as well as performing a physical examination.

During the physical examination, your healthcare provider may find a lump in your neck. Many conditions can cause a lump in the thyroid area of the neck and most are more common than MTC. To identify the exact nature and cause of a thyroid nodule or goiter, follow up testing may include:

• Ultrasound of the neck and surrounding lymph nodes
• Fine needle aspiration (biopsy) of the tumor or lymph nodes

Another important test used to diagnose medullary thyroid cancer is a blood calcitonin level which serves as a type of tumor marker for MTC. Calcitonin levels are usually very high in individuals with MTC. The more advanced the stage of cancer, the higher the calcitonin levels tend to be. While calcitonin is an important tumor marker used in diagnosing and monitoring MTC it should be noted that other health conditions including other types of thyroid cancer, autoimmune thyroiditis, and thyroid goiters can also be a cause of elevated calcitonin.

In the case of inherited forms of MTC DNA testing for the RET gene may be a beneficial diagnostic tool.

Treatment

Due to the rarity of medullary thyroid cancer it is important to seek out a specialized healthcare provider with knowledge of this specific type of thyroid cancer. Treatment of MTC differs significantly from other types of thyroid cancer including papillary thyroid carcinoma or follicular thyroid carcinoma. It also has a higher mortality rate than these other types of cancer but a better prognosis than anaplastic thyroid cancer.

Surgical Removal of the Thyroid

Total thyroidectomy is a first-line treatment for medullary thyroid cancer. Sometimes individuals who have not been diagnosed with MTC but who have been tested and found to have the RET mutation opt to have a total thyroidectomy to prevent MTC.

In cases of confirmed MTC, lymph nodes or other tissue in the surrounding area are often removed at the same time as the thyroid. This may depend on the size of the tumor and other individual circumstance.

If the tumor is small and confined to the thyroid, surgery may be the only treatment necessary for MTC. Following a total thyroidectomy, it is necessary to take levothyroxine (an oral pill to replace your thyroid hormone) for the remainder of your life since you no longer have a thyroid gland to produce thyroid hormones for you.

Your experience following a total thyroidectomy will be individual and depend on whether or not your healthcare provider found it necessary to remove lymph nodes in your neck or other tissues simultaneously. Most people can expect to have a small incision on the front lower portion of the neck, (called a collar incision) approximately 6 to 8 centimeters (cm) in length. Immediately after total thyroidectomy, you can expect to have some throat pain and hoarseness. Most people stay overnight in the hospital.

The parathyroid glands, which play an important role in calcium regulation, are located nearby or embedded within the thyroid gland. These glands may have to be removed or may go into shock following thyroidectomy. For this reason, your calcium levels are closely monitored following surgery.

Additional Surgery

Additional surgery may be necessary if cancer recurs or if it has spread to other parts of the body. Whether or not MTC can be surgically removed from other parts of the body depends on the exact location and size of the tumor and other factors.

External Beam Radiation Therapy

External beam radiation therapy (EBRT) may be used if cancer has spread or if remaining cancer is found following surgery or if cancer recurs. This type of radiation uses a machine to provide a localized beam of radiation to a small area of the body. Medullary thyroid cancer is susceptible to this type of radiation, so it can kill cancer cells or control the growth of tumors.

The treatment only lasts a few minutes and is not painful. However, side effects may occur since radiation not only kills cancerous cells but healthy cells as well. Regardless of the area of the body where EBRT was used, you may experience pain and tenderness of your skin similar to that of a sunburn. Fatigue is another common side effect. If EBRT is used directly over the thyroid or your neck, you may also have hoarseness, difficulty swallowing, or dry mouth.

Tyrosine Kinase Inhibitors

Tyrosine kinase inhibitors (TKIs) are a group of anticancer drugs sometimes used to treat medullary thyroid cancer. These medications, which inhibit the growth of cancer cells, include cabozantinib, vandetanib, sorafenib, and sunitinib.

Tyrosine kinase inhibitors are usually given as a tablet or capsule and like many other anticancer drugs can cause unpleasant side effects including: skin problems such as folliculitis, loss of hair (particularly at the hairline or eyebrows), splinter hemorrhages (tiny blood clots under the fingernails), anemia, thrombopenia, and neutropenia, nausea, vomiting, and diarrhea. Heart problems have been reported.

Radioactive Iodine

While radioactive iodine is a common treatment for other types of thyroid cancer, it is not an effective treatment for medullary thyroid cancer. This is due to the fact that the parafollicular C cells involved in MTC do not absorb iodine the same way that some other thyroid cells do.

Chemotherapy

Chemotherapy drugs are not often used in the treatment of medullary thyroid cancer and are usually only tried if other treatments have failed. Studies have shown that MTC has a poor response rate to chemotherapy, and given the high rate of side effects associated with these drugs, they are not typically used for this type of cancer. Cytotoxic chemotherapy, of which dacarbazine-based regimens are preferable, is an alternative option for patients who cannot tolerate multiple TKIs.

The best possible prognosis is achieved when MTC is diagnosed in the early stages of the disease, particularly if cancer is able to be completely surgically removed.

Follow-Up Care

Following treatment for medullary thyroid cancer, you will need long-term monitoring to make sure that your cancer has not come back. Blood levels of calcitonin and carcinoembryonic antigen (CEA) levels are checked periodically, as elevated levels may be an indication that MTC has returned. These blood tests are typically done every six to 12 months. If the levels are elevated other tests may be warranted, such as ultrasound.

Other tests that are often used as follow-up care for MTC may include physical examinations, periodic ultrasounds of the neck or annual chest X-rays. You must work closely with a knowledgeable physician to perform necessary follow-up care. In the case of any recurrence of MTC, early detection will provide the best possible outcomes.