Medullary Thyroid Cancer

June 15, 2024 
This page was reviewed under our medical and editorial policy by Sasan Fazeli, M.D., assistant clinical professor in the Department of Diabetes, Endocrinology and Metabolism, and Karen Tsai, M.D., assistant clinical professor in the Department of Diabetes, Endocrinology and Metabolism, City of Hope^® Cancer Center Duarte.

Medullary thyroid cancer (MTC) is a rare type of cancer that develops in the thyroid gland. This small gland makes hormones that regulate important bodily functions, such as metabolism and growth. It’s located at the base of the front portion of the neck, where thyroid cancer symptoms often first appear.

MTC accounts for about 4% of all thyroid cancers. It may occur as part of genetic conditions known as multiple endocrine neoplasia (MEN) syndromes or other family gene mutations, but it most often occurs on its own.

What Is Medullary Thyroid Cancer?

Unlike other types of thyroid cancer, medullary thyroid cancer begins in the parafollicular cells of the thyroid gland. Also known as C cells, these cells make calcitonin, a hormone that helps regulate the body’s calcium levels.

Medullary thyroid cancer comes in two forms: sporadic (unknown origin) or hereditary (runs in families due to a gene mutation). About 75% of medullary thyroid cancers are sporadic, meaning doctors are not sure what made the cancer begin to grow. Sporadic MTC often affects only one side of the thyroid, while hereditary MTC tumors typically appear on both sides of the gland.

Metastatic Medullary Thyroid Cancer

In metastatic medullary thyroid cancer, cancer has spread beyond the thyroid gland to other parts of the body. This often includes nearby lymph nodes — small, bean-shaped structures strung throughout the lymphatic system that carry fluid and cellular waste around the body. MTC may also spread to distant organs, such as the lungs, liver, brain or bones.

Medullary Thyroid Cancer Symptoms

The symptoms of medullary thyroid cancer may include:

• A lump or nodule in the neck
• Hoarseness or difficulty speaking
• Difficulty swallowing
• Persistent cough, with or without blood
• Swollen lymph nodes in the neck
• Neck enlargement
• Wheezing, shortness of breath
• Facial flushing
• Diarrhea

What Causes Medullary Thyroid Cancer?

The exact cause of medullary thyroid cancer is not fully understood. Most of the time it occurs without a known cause.

But in about 25% of cases, or 1 out of 4 patients, certain inherited gene mutations play a significant role in its development.

In hereditary MTC (also called familial MTC), patients usually have a mutation in the RET proto-oncogene, which helps cells grow and divide. This flawed gene, inherited from a parent, is found throughout the body and is linked to what are known as multiple endocrine neoplasia (MEN) syndromes. These genetic syndromes increase the risk of medullary thyroid cancer and other conditions. There are two types of hereditary MEN syndromes: MEN2A and MEN2B, both of which impact the RET gene and may lead to medullary thyroid cancer.

A blood test may confirm whether MTC is hereditary, and screening may help diagnose it early in relatives who are at risk.

In sporadic cases of MTC (instances without a familial genetic abnormality), some patients do have an RET mutation. This genetic abnormality does not transfer to other family members, and it occurs in the thyroid tumor cells only. A comprehensive molecular and genetic analysis of the tumor cells may be used to find out whether the tumor cells have any known genetic changes, and this genetic test may be useful in selecting which targeted therapies to use.

Medullary Thyroid Cancer Diagnosis

Diagnosing medullary thyroid cancer typically involves a combination of imaging tests, blood tests and biopsies.

Imaging tests such as ultrasound, computed tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI) scans may help doctors visualize the thyroid gland and any potential tumors.

Biopsy involves removing some tissue from the thyroid nodule to look for cancer cells under a microscope. Biopsy results help confirm the diagnosis of MTC.

Blood tests may be performed to measure levels of calcitonin, the hormone that is often elevated in patients with MTC. Another marker that may be elevated in MTC is CEA (carcinoembryonic antigen). This protein is measured in the blood to help diagnose and monitor MTC.

Medullary Thyroid Cancer Treatment

Treatment for medullary thyroid cancer is aligned with each patient based on several factors, including the stage of the disease and whether it has spread to other parts of the body. Staging describes the extent or spread of cancer in the body, and it helps doctors plan patient care accordingly.

Surgery is the primary treatment for localized MTC (cancer that has not spread beyond the thyroid gland) and may involve removing part or all of the thyroid gland (thyroidectomy), as well as any affected lymph nodes.

In cases of metastatic MTC, treatment may include surgery, targeted therapy, radiation therapy and/or chemotherapy after careful review with each patient.

Targeted therapies disrupt proteins and block signals that tell cancer cells to grow. Two general targeted therapies have been approved to help treat all types of medullary thyroid cancer: Caprelsa® (vandetanib) and Cometriq® (cabozantinib).

More selective targeted therapy against RET gene mutations have also been used. Retevmo® (selpercatinib) and Gavreto® (pralsetinib) are the two RET inhibitors which have been approved for MTC cases with RET mutations, both familial or sporadic, and a new generation of RET inhibitors is under development.

It is important to know that, while radioactive iodine may be used to treat many other thyroid cancers, it is not a treatment option for MTC, since the cells affected do not respond to iodine uptake.

Medullary Thyroid Cancer Survival Rate

The survival rate for medullary thyroid cancer varies according to the stage at diagnosis and whether the cancer has spread.

Five-year relative survival rates are estimates based on the percentage of patients who were still living five years or more after their initial diagnosis in the most recent past. For medullary thyroid cancer, the overall five-year relative survival rate is 91%, according to the American Cancer Society.

Advanced cancers are more challenging to treat. The five-year relative survival rate when medullary thyroid cancer has spread to distant parts of the body is 43%.

It is important to note that these estimates are based on past data from large numbers of patients, and they are not a prognosis for any individual patient.

Medullary thyroid cancer is a rare form of thyroid cancer that requires prompt diagnosis and treatment. Advances in treatment options have improved the outlook for those with MTC, but early detection is the key to improving survival rates.