What is Medullary Thyroid Cancer?
Medullary thyroid cancer is a type of cancer that starts from specific cells in the thyroid gland known as parafollicular or C cells. This type of cancer is known for producing a hormone called calcitonin, and a notable sign of this cancer is having high levels of this hormone in your body. These C cells are originally born from parts of the body that form our nervous system.
Recent breakthroughs in understanding how diseases develop on a molecular and genetic level have helped doctors categorize patients based on their risk levels. It has also helped find potential areas for treatment. For patients who have genetic mutations that put them at high risk, doctors recommend a preventive surgery known as a prophylactic thyroidectomy, which involves removing the thyroid gland.
For medullary thyroid cancer that has advanced or spread to other parts of the body, a type of drug called tyrosine kinase inhibitor is approved for use. These drugs work by blocking certain proteins that help cancer cells grow.
What Causes Medullary Thyroid Cancer?
About 75-80% of medullary thyroid cancers happen spontaneously without any known cause, and the rest are inherited, often as part of conditions like multiple endocrine neoplasias (MEN) 2A, MEN 2B, or familial medullary thyroid cancer (FMTC). Changes in the RET gene in the neural crest tissue in the thyroid gland – which is tissue important for the development of the body – can cause medullary thyroid cancer. The changes in the gene that we inherit from our parents are associated with MEN2 and FMTC-type medullary thyroid cancers. Also, 40-50% of those medullary thyroid cancers that occur spontaneously have acquired changes in the RET gene.
Risk Factors and Frequency for Medullary Thyroid Cancer
Medullary thyroid cancer makes up 4% to 10% of all thyroid cancers in the US. Typically, this type of cancer generally appears most often in people in their 50s and 60s. However, in cases linked with either MEN 2A or MEN 2B syndrome, the peak incidence is in the 2nd or 3rd decade of life.
Signs and Symptoms of Medullary Thyroid Cancer
Most individuals with medullary thyroid cancer, around 75% to 95%, have a lump in the upper part of the thyroid gland, where specific cells called C cells are found. About 70% of cases also have swollen lymph nodes in the neck area. Some patients may experience symptoms like trouble swallowing, voice changes, or difficulty breathing due to the pressure from the enlarged thyroid gland. In less than 10% of cases, the cancer might have spread to other parts of the body. Common areas where the cancer can spread include the liver, bones, lungs, and brain. Just a small number of patients might have diarrhea due to high levels of a hormone called calcitonin.
In the case of familial medullary thyroid cancer (FMTC) and multiple endocrine neoplasia (MEN) syndrome, the occurrences are similar to medullary thyroid cancer that happens randomly. However, it’s common for them to be diagnosed at an earlier age.
Testing for Medullary Thyroid Cancer
A medical procedure known as fine needle aspiration (FNA) can be used to test a solitary or dominant thyroid nodule to help identify the cause of the problem. If the results from the FNA are inconclusive, a thyroid lobectomy (removal of part of the thyroid) can be performed and the removed tissue can be studied further. The test could indicate abnormal spindle-shaped cells that don’t form follicles, a sign that these tumor cells originated from the parafollicular C cells of the thyroid.
It may be tempting to measure a protein called serum calcitonin before the FNA, but this can lead to misleading results due to a high rate of false positives. However, once the diagnosis of medullary thyroid cancer is confirmed using tissue examination, it’s important to measure both serum calcitonin and carcinoembryonic antigen (CEA) levels. These measurements can help identify a tumor that is producing too much protein, and comparing the pre-operative and post-operative levels can help track the success of the treatment after total thyroidectomy (surgical removal of the entire thyroid gland). Measuring how quickly the calcitonin and CEA levels double after the operation can also provide us with warning signs of the disease progressing.
Once a diagnosis is confirmed, it’s recommended to use ultrasound or other imaging techniques like CT scans to check for potential lymph node involvement in the neck. Patients who are suspected of having cancer spread to other parts of the body, or who have lymph node involvement and high calcitonin levels may need further tests such as CT scans or MRI scans of the liver. PET scans and nuclear scans are not typically used as the first line of evaluation for metastatic disease as their sensitivity can vary.
Doctors should discuss with patients the potential risks and benefits of genetic testing in these cases, specifically focusing on sequencing of certain sections (exons 10, 11, and 13 to 16) of a gene called RET proto-oncogene. This is particularly appropriate for patients with an overgrowth of parafollicular C cells or sporadic medullary thyroid cancer.
As genetic test results often aren’t available before surgery in sporadic cases, it’s recommended to also perform a biochemical assessment for other potential tumors linked with MEN2 syndromes before the operation. This can be achieved by testing for hyperparathyroidism and pheochromocytoma using serum calcium and plasma metanephrines tests. Such screenings are particularly important for patients with an unidentified RET mutation status and a confirmed hereditary RET status.
The American Joint Committee on Cancer has a system for classifying and assessing thyroid cancer severity. The system uses a tumor-node-metastasis (TNM) classification for differentiated and anaplastic thyroid cancer. According to this system, the five-year survival rate for stages I, II, and III medullary thyroid cancer is 93%, while it drops to 28% for stage IV.
Treatment Options for Medullary Thyroid Cancer
Surgery is the primary treatment for a type of thyroid cancer called medullary thyroid carcinoma. This particular tumor type does not respond to radioactive iodine treatments or usual chemotherapy. Treatment to suppress thyroid-stimulating hormones isn’t needed because the cancer cells (known as C cells) don’t carry the hormone receptor that would respond to it. Every patient should be checked for other health conditions such as hyperparathyroidism and pheochromocytoma before surgery. If a pheochromocytoma, a rare type of adrenal gland tumor, is found, it should be removed before the thyroid surgery.
Total thyroid removal, or total thyroidectomy, is recommended for all patients with medullary thyroid cancer. If the tumor is bigger than one centimeter, surgery should also include removing lymph nodes on both sides of the neck. This might also be considered for smaller and one-sided tumors. Total thyroidectomy makes it easier to monitor for tumor recurrence using a hormone called calcitonin in the blood after surgery.
In cases where the disease is inherited, preventive total thyroid removal is recommended by age five or as soon as a certain mutation is found in the patient. This is particularly important with RET mutations, specific types of genetic changes. It’s recommended even earlier, by age one, in very high-risk mutations. For patients with less risky mutations and no family history of aggressive disease, surgery can be postponed if annual evaluations are done and the family agrees to delay it.
A few months after surgery, it’s necessary to check blood levels of calcitonin and a protein called Carcinoembryonic Antigen (CEA). If both are normal, the patient is thought to be free from the disease and has the best prognosis. Check-ups should continue once a year to make sure everything is still okay.
However, if there are abnormal levels of calcitonin or CEA after surgery, this is a sign of remaining cancer cells. The neck should be evaluated through an ultrasound, and with calcitonin levels greater than 150pg/ml, CT scans of the neck, chest, and abdomen might be needed. If these tests don’t show anything, the patient should be monitored closely with regular physical exams and blood tests. If the results from the imaging are positive and the patient has symptoms, then surgery to remove the remaining cancer spots is required. If the disease cannot be completely removed, radiation therapy can be used to help control the symptoms.
In cases where the disease can’t be removed and symptoms are present, tyrosine kinase inhibitors like vandetanib and cabozantinib might be used. These are medications that stop certain proteins from helping cancer cells divide and grow. In the studies, these drugs have shown to delay disease progression.
What else can Medullary Thyroid Cancer be?
If you are experiencing symptoms that are similar to medullary thyroid cancer, they could be stemming from other, similar health conditions. Here are some other conditions that might need to be ruled out by your doctor:
- Anaplastic thyroid carcinoma
- De Quervain thyroiditis
- Follicular thyroid carcinoma
- Graves’ disease
- Intestinal carcinoid tumor
- Multiple endocrine neoplasia (MEN) Type 2
- Papillary thyroid carcinoma
- Thyroid lymphoma
- Thyroid nodule
- Thyrotoxicosis
- Toxic nodular goiter
This list contains all the main conditions that doctors consider when diagnosing and treating symptoms similar to medullary thyroid cancer.
What to expect with Medullary Thyroid Cancer
The likelihood of recovery from this condition depends on a few things, including the patient’s age, the severity of the disease based on a medical test (histologic grade), and how successful the surgical removal of the disease was. Older people, those with a severe level of disease, or those where the disease wasn’t completely removed during surgery tend to have a harder time recovering.
Looking at survival rates five years after diagnosis, 93% of people in stages 1 to 3 are still alive, compared to 28% for those in stage 4. There have been advances in genetic screening to detect a gene difference (RET proto-oncogene) that can cause this condition, but so far, this hasn’t shown to make a big difference in recovery rates.
One study found that younger patients with a hereditary form of the disease were most likely to stay disease-free if the staging of their disease was done correctly (TNM staging) and they had a pre-operations level of a hormone called calcitonin that was below 30 picograms/milliliter.
Possible Complications When Diagnosed with Medullary Thyroid Cancer
Permanent low thyroid function (also known as hypothyroidism) and regular loss of voice box nerve function (also known as recurrent laryngeal nerve palsy) are reported to happen in fewer than 2% of individuals undergoing a first-time neck operation. A repeated operation, or reoperation, has a higher probability of causing these conditions.
Complications of Neck Surgery:
- Permanent hypothyroidism (low thyroid function)
- Recurrent laryngeal nerve palsy (regular loss of voice box nerve function)
- Increased risk of these complications with reoperation
Preventing Medullary Thyroid Cancer
Educating patients is essential when they have undergone a total thyroid removal surgery, because they will need to take a medication called thyroxine for the rest of their lives. It’s also recommended that patients get a physical check-up twice a year for the first two years after their surgery, and then once a year after that. This is to ensure their overall health is good.
In addition, they should have their levels of serum calcitonin and CEA (which are types of proteins that can indicate certain health issues) monitored twice a year for the first two years, and then once a year subsequently. This helps in identifying if the cancer has returned or spread to other parts of the body.
If the levels of calcitonin are high, further tests may be needed, like a neck ultrasound or a Computerized Tomography (CT) scan, which are types of imaging tests that can help detect abnormalities.
The main goal of these recommendations is to ensure the patient is recovering well and to detect any potential health problems early so they can be treated promptly.
