Medullary thyroid cancer is the third most common of all thyroid cancers (around 3%). It can also be called “medullary thyroid carcinoma” since carcinoma implies a certain type of cancer. About 1/3 of patients with medullary thyroid cancer have a family history of a thyroid cancer, the other 2/3 obviously do not.
Even individuals with the inherited form of medullary thyroid cancer may not know that they inherited the cancer for a number of reasons. First, they may not know their effected relatives, second, they may be the first individual ever effected within a family.
All patients with medullary thyroid cancer should be counseled and offered genetic screening to determine whether they have the hereditary form of this cancer. For individuals with the inherited form a medullary thyroid cancer, genetic counseling and testing is available to test and screen for other family members which may possess the underlying genetic condition leading to medullary thyroid cancer.
Medullary thyroid cancer typically starts within the thyroid as growth, or bump (nodule) in the thyroid that grows out of the otherwise normal thyroid tissue. Medullary thyroid cancer is most commonly diagnosed as a lump in the neck. There is an extensive body of information that continues to expand as science and the understanding of the genetic mutations that medullary thyroid cancer continue to expand. (see genetics of medullary thyroid cancer)
- Medullary thyroid cancer is a rare cancer.
- Most thyroid surgeons rarely ever see a patient with medullary thyroid cancer, or certainly treated one.
- A medullary thyroid cancer patient should only be operated upon by a truly expert thyroid cancer surgeon.
- Medullary thyroid cancer surgery is not a surgery for the infrequent thyroid cancer surgeon or inexperienced thyroid cancer surgeon.
- Medullary thyroid cancer requires an interdisciplinary thyroid cancer team.
- Medullary thyroid cancer requires a comprehensive evaluation.
- A medullary thyroid cancer patient needs to be informed of their disease and understand the role of genetic testing and screening.
Frequently, small medullary thyroid cancers are not readily noticeable by either the patient or their doctors. Often medullary thyroid cancers produce no or very few symptoms. The reason this is the case is because frequently medullary thyroid cancers may be small and surrounded by normal thyroid tissue. Therefore, early diagnosis of medullary thyroid cancer is, in fact, not very common.
When it does produce symptoms, medullary thyroid cancer is unlike other thyroid cancers in that the lumps of medullary thyroid cancer are frequently tender to touch or examination. Calcitonin is a hormone produced by medullary thyroid cancers that can be measured in the blood as well. In very advanced cases of medullary thyroid cancer, patients may experience frequent bouts of diarrhea when their calcitonin levels are very high in the blood.
Medullary thyroid cancers very frequently spread to lymph nodes within the neck even with very small medullary thyroid cancers. The reported rate of lymph node spread for medullary thyroid cancer approximates 70%. For this reason, almost all experienced medullary thyroid cancer surgeons as well as guidelines for management of medullary thyroid cancer advocated for total thyroidectomy and central compartment lymph node removal as a minimum surgery for patients with medullary thyroid cancer. Unlike other thyroid cancers such as papillary and follicular thyroid cancer, when medullary thyroid cancer spreads to lymph nodes, survival of patients is significantly effected. Medullary thyroid cancer patients with disease localized to the thyroid gland have survival rates of nearly 90%, however, when neck lymph node spread is found, survival is reduced to approximately 70% after ten years.
Although thyroid cancer is clearly increasing in its incidence both in the United States and globally, the increasing numbers of thyroid cancers does not appear to be due to medullary thyroid cancers.
Medullary thyroid cancers are caused by genetic alterations of a special cell found within the thyroid gland called parafollicular C cells. The more common thyroid cancers such as papillary thyroid cancer and follicular thyroid cancer are derived from a totally different cell called follicular cells. These different cells which they are derived make all the differences between these two cancers.
Medullary thyroid cancers do not respond to the hormone, thyroid stimulating hormone (TSH), as compared to the more common thyroid cancers. That is because medullary thyroid cancer do not have something called a receptor for TSH. For this reason, other therapies such as radioactive iodine therapy and thyroid suppressive therapy (giving excess thyroid hormone to patients) has no role in the management of medullary thyroid cancer.
Sporadic (not inherited) medullary thyroid cancer effects women more commonly than men and has a peak incidence at the 40-50 years of age range. The inherited form of medullary thyroid cancer will effect women equally to men. Again, although thyroid cancer is now the fifth most common malignancy among women (and seventeenth among men) in the United States, if you have recently undergone biopsy suggesting medullary thyroid cancer, this is a rare cancer and you need to identify a real expert in this disease. If you have already undergone surgery and the diagnosis of medullary thyroid cancer was a surprise, don’t worry, this page has been created just for you.
Our Introduction to Thyroid Cancer page has a great general overview of all types of thyroid cancer--read it if you haven't already!
Medullary Thyroid Cancer Occurs in 2 Major Settings: Quick Facts:
Sporadic (not inherited) Medullary Thyroid Cancer
- Accounts for 75% of all medullary thyroid cancers
- Effects women more commonly than men (3:2)
- Peak occurrence 40-60 years of age
- Worse prognosis in those greater than 50 years of age
- High incidence of spread to neck lymph nodes (70%)
- Nearly 1/3 will present with diarrhea caused by the disease due to hormones (and other secreted by the cancer (calcitonin, prostaglandins, serotonin, VIP)
Hereditary (inherited) Medullary Thyroid Cancer
- MEN stands for multiple endocrine neoplasia syndrome. A syndrome is three or more characteristics which are associated with each other repeatedly.
- Inherited in an autosomal dominant fashion (50% chance that offspring will inherit the disease
- Woman effected equally to men
- Of the Hereditary type of Medullary Thyroid Cancer-There are Three Types
What are the Three Types of Inherited Medullary Thyroid Cancers?
MEN2A (also called Sipple’s Syndrome)
- Medullary thyroid cancer
- Tumors of the adrenal gland called pheochromcytoma (benign tumors of the adrenal gland that secrete hormones that can make blood pressure become very high)
- Hyperparathyroidism (a benign tumor that makes your calcium get very high)
- Disease usually seen by 30 years of age
- Medullary thyroid cancer
- Tumors of the adrenal gland called pheochromcytoma (benign tumors of the adrenal gland that secrete hormones that can make blood pressure become very high)
- Mucosal ganglioneuromas which produce benign lumps around the lips, tongue, oral cavity and eyelids
- A marfanoid appearance which is characterized by elongated arms, generally tall thin stature and very predictable facial features
- Syndrome manifested during the first decade of life
Inherited medullary thyroid cancer (without any other associated endocrine abnormalities)
- Peak incidence is between 40 and 50 years of age
- Generally a less aggressive form of inherited medullary thyroid cancer as compared to MEN2B
Medullary Thyroid Cancer: Who Gets It?
You really need to think about medullary thyroid cancer as two different diseases: The more common is those that are sporadic (not hereditary). In those instances, which approaches 80% of cases, you did nothing wrong. Medullary thyroid cancer is not associated with smoking, alcohol, radiation or occupational exposures based upon our current fund of knowledge. It is a rare thyroid cancer and also is not associated with any other diseases. It is caused by an abnormality in the RET gene (as is the inherited form of medullary thyroid cancer) although somehow this mutation of the gene occurs spontaneously in affected medullary thyroid cancer patients. In sporadic forms of medullary thyroid cancer, the premalignant form of medullary thyroid cancer called C cell hyperplasia is almost never seen.
In the hereditary (or inherited forms) of medullary thyroid cancer, the children of parents with medullary thyroid cancer have a 50% risk of inheriting the mutated RET gene. This is the whole reason for genetic counseling and genetic testing. If you have inherited the mutated RET gene from one of your parents, you have the disease!!! Whether you are showing any evidence of disease at that time, well that is another issue. Independent of which inherited form of medullary thyroid cancer the individual has inherited, they have a lifetime risk of developing medullary thyroid cancer. Those individuals with mutated inherited RET genes can develop a premalignant condition called C cell hyperplasia (overgrowth of the parafollicular C cells of the thyroid gland). This can occur throughout the thyroid gland and may also appear in the blood of those with this condition with elevated calcitonin levels. The concept of the onset of the development of medullary thyroid cancer and the role of prophylactic surgery to prevent and cure medullary thyroid cancer is discussed much more in the section Medullary Thyroid Cancer Genetics. Lastly, although some patients may have an inherited form of medullary thyroid cancer (they possess the Mutated RET gene in all of their body’s cells), they may be the first individual in their family that has this disease due to a spontaneous event that occurred in the earliest phase of conception). Although this is very very rare, it is possible and further supports the need for all medullary thyroid cancer patients to seriously consider genetic testing. For more details on who gets medullary thyroid cancer, the incidence, and ages of patients affected, go to our page on the Medullary Thyroid Cancer Diagnosis.
Medullary Thyroid Cancer: How is it Diagnosed?
Medullary thyroid cancer starts as a growth of abnormal cancer cells within the thyroid. These special cells are the parafollicular C cells. In the hereditary form of medullary thyroid cancer, the growth of these cells is due to a mutation in the RET gene which was inherited. This mutated gene may first produce a premalignant condition called C cell hyperplasia. The parafollicular C cells of the thyroid begin to have unregulated growth. In the inherited forms of medullary thyroid cancer, the growing C cells may form a bump or a “nodule” in any portion of the thyroid gland. Unfortunately, even in cases of hereditary medullary thyroid cancer, many patients are not diagnosed until the medullary thyroid cancer has spread to the lymph nodes of the neck and presented with a “lump in the neck”.
Although medullary thyroid cancer may develop in any portion of the thyroid gland, the knowledge that parafollicular C cells are most dense in the upper thyroid is very important to the expert thyroid cancer surgeon. In patients with a RET gene mutation, removing the entire thyroid gland can provide the diagnosis of C cell hyperplasia and even early medullary thyroid cancers can completely cure the medullary thyroid cancer component of their disease or syndrome.
For those individuals undergoing prophylactic thyroidectomy to prevent the development of medullary thyroid cancer or total thyroidectomy to treat an established inherited medullary thyroid cancer, all of the upper portions of the thyroid gland must be completely removed. If not, the individual with the inherited mutated RET gene has had the wrong surgery!! Only expert thyroid cancer surgeons should be doing this surgery.
For patients with a sporadic (not hereditary) form of medullary thyroid cancer, they may form a bump or "nodule" within the thyroid that often sticks out of the side or front of the thyroid gland. For this reason, most medullary thyroid cancers, like all thyroid cancers, are diagnosed after a doctor feels the neck of a patient. Usually the doctor stands behind the patient to feel the thyroid for nodules or bumps. Sometimes, these growths and nodules can be seen when looking at the neck of thin women as a small bump under the skin that moves when the person swallows. Sometimes people are undergoing scans or x-rays of the neck for some other reason and a nodule or worrisome area of the thyroid is seen. Either way, your physician feeling this mass or seeing it as a surprise on some other scan will typically order a thyroid ultrasound to look at the thyroid closely and take pictures of the mass or nodule.
An ultrasound is a way to use sound waves to look underneath the skin. It exposes the patient to absolutely no radiation. If the nodule has some worrisome characteristics the next step is almost always a needle biopsy. We have several pages on needle biopsies of thyroid nodules and ultrasound of the thyroid. If you have recently undergone a thyroid needle biopsy or are scheduled to have a needle biopsy, these pages are for you.
Ultrasound for medullary thyroid cancer is far more sensitive than any of the most experience of hands. It is critically important in determining the extent of the medullary thyroid cancer. Since medullary thyroid cancer spreads so commonly to the lymph nodes of the central neck and sides of the neck, very close examination of these areas is required in every neck ultrasound for medullary thyroid cancer. If there are any suspicious lymph nodes in the side(s) of the neck, needle biopsy should be performed. This will assist the thyroid cancer surgeon in knowing the exact extent of surgery required to address all the medullary thyroid cancer patient’s neck disease in a single surgery!!! Failure to have a high quality ultrasound and expert thyroid cancer surgeon will greatly increase the medullary thyroid cancer patient’s risk for persistent or recurrent disease.
For all medullary thyroid cancer patients, because the cancer may so commonly spread to lymph nodes along the sides of the neck, the patient is frequently diagnosed with a lump in the neck that is actually spread of the cancer to the neck lymph nodes. Fine needle aspiration biopsy of a neck lymph node can adequately provide a diagnosis such that biopsy of the thyroid abnormality may not be required when the neck lymph node biopsy has already provided that information.
Symptoms of Medullary Thyroid Cancer
It is important to know that early disease in medullary thyroid cancer usually has no symptoms. It almost never causes hyperthyroidism (increased thyroid function) or hypothyroidism (decreased thyroid function). It doesn't make people feel bad. Thus, the early detection of sporadic (not hereditary) medullary thyroid cancer is found is by a patient noticing a lump in their neck or throat, or a doctor feeling a lump or nodule when examining a patient's thyroid gland. Because sporadic early medullary thyroid cancers don't usually cause any symptoms, how long the cancer has been growing can be hard to determine.
As medullary thyroid cancer progresses it commonly can produce other symptoms. Although rare among other thyroid cancers, medullary thyroid cancers are frequently tender to the touch and can even be painful either where they started in the thyroid or where they spread to lymph nodes in the neck. You must understand that almost all cancers that spread to the neck lymph nodes do not produce discomfort. If a lymph node in the neck is cancer and it is tender, the first suspicion should be medullary thyroid cancer. Since medullary thyroid cancer is so rare, you then understand what a bold statement that is then.
Medullary thyroid cancer produces many proteins and other shed molecules that produce another common symptom of advanced medullary thyroid cancer-which is diarrhea. The cause of the diarrhea is likely an interaction of several factors including calcitonin, prostaglandins, VIP, and the like. The diarrhea can be managed with effective surgical therapy if the disease is primarily located in the neck only. In those patients with medullary thyroid cancer which has spread to distant sites outside of the neck, medical management can often significantly improve these symptoms.
Medullary Thyroid Cancer: What About Lymph Nodes?
We have lymph nodes all over our body that are made up of groups of infection-fighting and cancer fighting immune cells. We all have had "swollen glands" in our neck when we had a sore throat or tonsils. These same glands that get swollen when we have a neck infection can help fight cancer by preventing the cancer cells from spreading from the thyroid to the rest of the body.
Medullary thyroid cancer can grow slowly for years and has time for the medullary thyroid cancer to spread into the lymph nodes which are doing their job of capturing the cancerous cells before they can spread further. The medullary thyroid cancer basically gets “stuck” in the lymph node something like a filter. Our bodies don’t have any ability to remove the cancer from this filter system and therefore the medullary cancer cells begin growing within the lymph nodes.
In medullary thyroid cancer surgery for untreated patients, the lymph nodes of the sides of the neck called lateral or anterolateral lymph nodes are more of a point of debate among experts. Certainly, any suspicious lymph nodes on ultrasound of the lateral neck should be biopsied. Any evidence of spread to the lateral neck lymph nodes should therefore include the modified neck dissection for thyroid cancer which I have written extensively for you in thyroid cancer surgery. The real question is when is an elective dissection indicated of the lateral neck for the initial treatment of medullary thyroid cancer. Prior to high resolution ultrasound, bilateral neck dissections for patients was argued by many. Today, with a negative high resolution ultrasound of the lateral neck, the lateral neck is not routinely prophylactically dissected unless the thyroid mass itself is so large that it requires a lateral neck dissection in order to get “around” the thyroid cancer where it began in a three dimensional fashion.
In a common sense fashion, if you are already going to “be there” to remove the medullary thyroid cancer, the you are better off removing the lymph nodes because the subsequent scarring will make further surgery in the area more difficult and the risk for microscopic metastatic disease is so high in the local lymph nodes. In our opinion, in these circumstances, done and out is good!
Medullary thyroid cancer which has spread to lymph nodes of the neck may be associated with a higher chance that the cancer may come back months or years later (a higher recurrence rate). Medullary thyroid cancer which has spread to the neck is also associated with a greater risk of developing distant spread of the cancer as well as a higher mortality rate.
Hereditary medullary thyroid cancers can have quite predictably outcomes regarding how the cancer may behave. For example, some genetic mutations of the RET gene may be associated with:
- Different ages of onset of disease
- Associated endocrinopathies
- Vary rates of lymph node spread
- Risk of death with disease
The overview of the importance of lymph nodes in medullary thyroid cancer ends here, but if you have this problem, then please continue reading our page on Medullary Thyroid Cancer Staging.
How Can I Make Sure That I Have The Best Outcome Possible?
What is critically important to you is that you are evaluated and managed by a highly experienced thyroid cancer team whom are experts in the imaging (ultrasound and Xrays), staging, pathologic analysis (the way individual cells look under a microscope) and surgery management of medullary thyroid cancer.
Medullary Thyroid Cancer Staging
Medullary thyroid cancers are not all alike. Some are big and some are small. Some have thick capsules, some have cancer that has extended into local tissues by spreading outside of the thyroid gland itself. Most will have spread to lymph nodes of the neck to some extent or another. To separate out the cancers that are easy to cure from those that are more difficult to cure, doctors have come up with a grading or "staging" system. All cancers have their own staging system, but medullary thyroid cancer has a staging system that is not like other cancers. The staging system also includes the size of the medullary thyroid cancer in the thyroid gland itself and whether or not the cancer has spread into lymph nodes around the thyroid gland and/or sides of the neck. The staging system for medullary thyroid cancer also includes whether or not the cancer has spread into the fat and muscles around the thyroid (called local extension).
The last component of medullary thyroid cancer staging is the presence of distant metastases, which means whether the cancer has spread to distant (far away) areas like the lungs, liver or bones. If you or someone you know has medullary thyroid cancer, then please read our more detailed page on Medullary Thyroid Cancer Staging. The stage of the cancer will determine how aggressive the cancer operation needs to be, and other things like whether or not radioactive iodine should be given.
What extent of Surgery is Needed for Medullary Thyroid Cancer?
Medullary thyroid cancer is almost always treated with surgery as its first therapy. It is important to understand that the best chance of cure is to have an expert thyroid cancer surgeon from the beginning. A surgeon who performs surgery for thyroid cancer several times per week (or more often) has a higher cure rate and much lower complication rate than a surgeon who performs thyroid surgery once or twice per week, or does primarily other types of thyroid surgery (like for goiters). Surgery for thyroid cancer has become very specialized so it is important for you to be comfortable with your choice of surgeon.
Medullary thyroid cancer surgery includes a total thyroidectomy and central compartment dissection. A very detailed description of what they surgery means and includes has been written for you in the section of Thyroid Cancer Surgery. But this is the minimum surgery.
- The size of the medullary thyroid cancer (greater than 4cm cancers should be electively dissected)
- The ultrasound and FNA findings of the lateral neck
- The CT scan findings of the neck
For patients with hereditary medullary thyroid cancers, which have no biochemical (calcitonin is not elevated) or ultrasound evidence of cancer, the preferred surgical procedure is a prophylactic total thyroidectomy. The recommendations and timing of this surgery are described in depth in the section Medullary Thyroid Cancer Genetics. Prophylactic total thyroidectomy in children should only be performed by the most experienced thyroid cancer surgeons. Occasional thyroid surgeons should never perform total thyroidectomy on infants or children (or on adults for that matter). The risk of injury to the nerves of the voice box (recurrent and superior laryngeal nerves) and the glands that control calcium (parathyroid glands) are far to high among inexperienced surgeons. An infant, young child or adult with difficulty maintaining their blood calcium levels has lifelong implications. Bilateral nerve injuries to the voice box can cause life long issues regarding breathing, speaking and swallowing!!! Get the best thyroid cancer surgeon that you can!
What About Thyroid Hormone Pills After Medullary Thyroid Cancer Surgery?
Essentially all patients undergoing surgery for medullary thyroid cancer will require life long thyroid hormone replacement unless for some reason they did not undergo complete removal of their thyroid gland. Unlike the other more common thyroid cancers (papillary thyroid cancer and follicular thyroid cancer), there is no benefit of giving slightly higher doses of thyroid hormone to suppress thyroid stimulating hormone (TSH). Therefor medullary thyroid cancer patients should be normalized with thyroid hormone such that their hormone levels are within the normal range and their “sense of well-being” is similarly being met.
What is the Long Term Follow-up of Medullary Thyroid Cancer?
Essentially all people who had surgery for medullary thyroid cancer will need to see a doctor for many years to have exams and certain blood tests to make sure the cancer has been cured, and to detect any return of the cancer as soon as possible should it return. Many people with medullary thyroid cancer will need to be monitored by experts in medullary thyroid cancer including routine high resolution ultrasound of the neck, blood tests for markers of medullary thyroid cancer including calcitonin and CEA, and CT scan imaging when indicated to screen or examine for distant spread of disease. Much more is written about long term follow-up of medullary thyroid cancer. We have several very important pages on these topics for you to review.