Medullary thyroid cancer is a rare form of thyroid cancer that develops in special hormone-producing cells within the thyroid gland. Unlike more common thyroid cancers, it requires a different approach to diagnosis and treatment, and in some families, it can be passed down through generations.

Understanding Medullary Thyroid Cancer

Medullary thyroid cancer, often shortened to MTC, develops in a specific type of cell inside the thyroid gland. The thyroid is a small, butterfly-shaped organ located at the base of your neck, just below the Adam’s apple. While most thyroid cancers start in cells that produce thyroid hormone, medullary thyroid cancer originates from something different. It begins in parafollicular C cells, which are special cells that produce a hormone called calcitonin. This hormone plays a minor role in regulating calcium levels in the blood and bone growth.^[1]

What makes this cancer unique is that calcitonin levels can be measured in the blood, which helps doctors both diagnose the disease and monitor for its return after treatment. Because calcitonin’s effect on the body is relatively weak, patients don’t need to replace it after their thyroid is removed, unlike thyroid hormone itself.^[2]

How Common Is Medullary Thyroid Cancer?

While thyroid cancer overall is fairly common, medullary thyroid cancer specifically is quite rare. In the United States, approximately 4 percent to 10 percent of all thyroid cancers are medullary type. This means that roughly 1,000 people receive a diagnosis of MTC each year in the United States.^[1] In other parts of the world, the numbers are similar, with MTC representing between 1 and 5 percent of all thyroid cancer cases.^[2]

In Korea, medullary thyroid cancer accounts for only 0.6 percent of all thyroid cancers, although the incidence has been increasing steadily over recent years. Despite thyroid cancer being the most commonly diagnosed cancer in Korea in 2013, medullary thyroid cancer remains an uncommon variant.^[4]

Although thyroid cancer is more common in women overall, medullary thyroid cancer shows different patterns. It tends to affect both men and women, though research suggests that it may be slightly more common in females.^[2]

What Causes Medullary Thyroid Cancer?

The causes of medullary thyroid cancer fall into two main categories: sporadic and hereditary. Understanding which type you have is important because it affects both treatment and whether family members might be at risk.

About 75 percent of medullary thyroid cancer cases are sporadic. This means the cancer occurs randomly in people who don’t have a family history of the disease. Scientists haven’t yet figured out exactly why sporadic MTC develops. However, research shows that between 40 and 50 percent of people with sporadic MTC have acquired mutations in a gene called RET. These mutations develop during a person’s lifetime rather than being inherited from parents.^[1]

The remaining 25 percent of cases are hereditary, meaning they run in families. These cases are linked to an inherited condition called multiple endocrine neoplasia type 2, or MEN2. When someone has MEN2, they carry a mutation in the RET gene from birth, which they inherited from a parent. This genetic change dramatically increases their risk of developing medullary thyroid cancer, often at a young age.^[1]

There are different forms of MEN2. In MEN2A, people have a 90 percent chance of developing medullary thyroid cancer during their lifetime. They may also develop tumors in other glands, such as pheochromocytomas (tumors of the adrenal glands) or parathyroid adenomas (tumors of the parathyroid glands). MEN2B is even more aggressive. People with MEN2B have essentially a 100 percent chance of getting medullary thyroid cancer at a very young age. They may also develop pheochromocytomas and neuromas, which are benign growths of nerve tissue in the lining of the mouth or digestive tract.^[1]

Risk Factors for Medullary Thyroid Cancer

The strongest risk factor for medullary thyroid cancer is having a family history of the disease. If a parent, sibling, grandparent, or child has been diagnosed with MTC, your risk increases significantly. Even without a known genetic syndrome, having a close relative with medullary thyroid cancer raises your risk between 2 and 10 times higher than the general population.^[2]

People who carry a mutation in the RET proto-oncogene face the highest risk. This genetic change is present in all hereditary cases and causes not only medullary thyroid cancer but sometimes other tumors as well. If you have a known RET mutation, your doctor may recommend preventive surgery to remove your thyroid gland before cancer has a chance to develop.^[1]

Unlike other types of thyroid cancer, radiation exposure to the neck during childhood does not appear to be a strong risk factor for medullary thyroid cancer. This is different from papillary and follicular thyroid cancers, which are more likely to be caused by radiation. However, medullary thyroid cancer is less common overall.^[8]

Age also plays a role. Sporadic medullary thyroid cancer typically develops in older adults, while hereditary forms can appear in children and young adults. People with MEN2B, in particular, can develop medullary thyroid cancer very early in life, sometimes even in infancy.^[2]

Recognizing the Symptoms

Many people with medullary thyroid cancer have no symptoms at all, especially in the early stages. The tumor can remain small and undetected for a long time. However, as the cancer grows, certain signs may appear.^[1]

The most common symptom, present in 75 to 95 percent of people at diagnosis, is a thyroid nodule. This appears as a lump on the front of the neck, in the area where the thyroid gland sits. You might notice this lump yourself, or your doctor might discover it during a routine physical examination. The nodule is usually painless, but it’s important not to ignore any new lump in your neck.^[1]

About 70 percent of people with medullary thyroid cancer have swollen lymph nodes in their neck at the time of diagnosis. Lymph nodes are small, bean-shaped structures that are part of your immune system. When cancer spreads to nearby lymph nodes, they can become enlarged. These swollen nodes might feel like firm lumps on the sides or front of your neck.^[1]

In rarer cases, when a thyroid nodule grows large enough, it can press on surrounding structures and cause additional symptoms. Some people experience hoarseness or changes in their voice. This happens when the tumor affects the nerves that control the vocal cords. Others may have difficulty swallowing, with food or pills feeling like they get “stuck” when swallowed. Breathing problems can occur if the tumor grows large enough to narrow the airway. Some people feel pressure or shortness of breath, especially when lying flat.^[1]

In advanced cases where the cancer has spread beyond the thyroid, symptoms related to high levels of calcitonin may develop. These can include persistent diarrhea and flushing of the skin. The diarrhea can be severe and doesn’t respond to typical treatments. The flushing looks similar to what happens in other hormone-producing tumors and can be accompanied by itching.^[7]

How to Prevent Medullary Thyroid Cancer

For most people with sporadic medullary thyroid cancer, there are no known specific prevention strategies because the exact cause isn’t clear. However, for people with hereditary forms of the disease, prevention is possible and can be lifesaving.

If you have a family history of medullary thyroid cancer or MEN syndrome, genetic testing should be your first step. This testing looks for mutations in the RET gene. If you test positive for a RET mutation, your doctor may recommend preventive surgery to remove your thyroid gland before cancer develops. This is called a prophylactic thyroidectomy. The timing of this surgery depends on the specific type of RET mutation you have, with some requiring surgery in early childhood and others allowing for later intervention.^[1]

Family members of someone diagnosed with medullary thyroid cancer should also undergo genetic testing, even if they feel healthy. Because the condition is inherited in an autosomal dominant pattern, there’s a 50 percent chance that each child or sibling of an affected person carries the mutation. Finding out who has the mutation allows for early intervention before cancer develops.^[2]

For those at risk, regular screening with blood tests measuring calcitonin levels can help detect the disease early. Early detection is crucial because medullary thyroid cancer spreads more readily to lymph nodes and other parts of the body compared to other thyroid cancers. Catching it early improves the chances of complete surgical removal and cure.^[4]

Unlike some other thyroid cancers, limiting radiation exposure doesn’t appear to significantly reduce the risk of medullary thyroid cancer. However, anyone undergoing medical procedures involving radiation, especially to the head, neck, or chest, should discuss the benefits and risks with their healthcare provider.^[8]

How the Body Changes: Understanding Pathophysiology

To understand what goes wrong in medullary thyroid cancer, it helps to know what normally happens in the thyroid gland. The thyroid contains different types of cells with different jobs. Most thyroid cells are follicular cells that produce thyroid hormone, which regulates metabolism. Scattered throughout the thyroid are parafollicular C cells, which produce calcitonin.^[6]

In medullary thyroid cancer, the C cells begin to grow out of control. This uncontrolled growth happens because of changes in the RET proto-oncogene. The RET gene normally provides instructions for making a protein that helps control cell growth and development. When mutations occur in this gene, the protein it produces becomes overactive. This causes C cells to multiply inappropriately and form tumors.^[7]

As the tumor grows, the cancerous C cells continue to produce calcitonin, often in very high amounts. This is why blood calcitonin levels are elevated in people with medullary thyroid cancer and why measuring calcitonin is useful for diagnosis and monitoring. Unlike normal C cells, however, these cancer cells don’t respond to the body’s usual signals to stop dividing.^[1]

Medullary thyroid cancer behaves differently from other thyroid cancers in important ways. It doesn’t take up iodine the way follicular cells do, which means radioactive iodine treatment (commonly used for papillary and follicular thyroid cancers) doesn’t work for MTC. The cancer also tends to spread earlier to lymph nodes in the neck. From there, it can travel through the bloodstream to distant organs, particularly the liver, lungs, and bones.^[2]

When medullary thyroid cancer produces very high levels of calcitonin and related substances, these can cause symptoms throughout the body. The hormone can affect the digestive system, leading to diarrhea that can be difficult to control. It can also cause blood vessels to dilate, producing flushing and sometimes itching of the skin. These symptoms become more common when the cancer has spread to other organs, particularly the liver.^[7]

The tumor may also deposit a substance called amyloid in the surrounding tissue. Amyloid is an abnormal protein that can accumulate between cells. When pathologists examine medullary thyroid cancer tissue under a microscope, they often see these amyloid deposits, which help confirm the diagnosis.^[7]