Treatments: Surgery and Post-Surgery
Most patients diagnosed with thyroid cancer will undergo surgery to remove the thyroid cancer and the surrounding normal thyroid tissue. Furthermore, if there is evidence that the thyroid cancer has spread to the lymph nodes in the neck, the surgeon will also remove lymph nodes as part of the initial surgery. For the past 30 years, most patients with thyroid cancer had their entire thyroid removed (total thyroidectomy). But the 2016 ATA Guidelines now allow for a more conservative option of removing only half of the thyroid for properly selected patients with tumor less than 4 cm that appear to be confined to the thyroid.
It is important for all members of the health care team and the patient to understand the risks and benefits of the various surgical options as the extent of thyroid surgery will have a significant impact on how follow-up is done after surgery. For example, radioactive iodine cannot be used if half of the thyroid remains and thyroglobulin will not be as sensitive to detect disease recurrence. But, removing half the thyroid may avoid the need to go on thyroid hormone pills after surgery and may be a slightly safer surgery since only one side of the neck is exposed to surgical complications.
An experienced thyroid surgeon should be consulted. This may be a general surgeon, an otolaryngologist (ear, nose and throat specialist) or endocrine surgeon, usually a general surgeon who has confined his/her practice to the treatment of endocrine tumors. In general, the more experienced the surgeon in the management of thyroid tumors, the more sophisticated and knowledgeable he or she is in the decision making, surgical technical ability and pre- and post-operative patient care.
Is thyroid surgery mandatory for all thyroid cancers?
While most thyroid cancers will require surgical removal, the rapid rise in the diagnosis of very small, intrathyroidal, incidental, asymptomatic thyroid cancers has led many clinicians to question whether or not they actually require immediate surgical removal. Our Japanese colleagues have demonstrated that an observational management approach can be safe and quite effective when very small thyroid cancers (< 1 cm) are incidentally discovered. Surprisingly, most of these small cancers either don’t grow (or grow very slowly) such that on about 10% required surgical removal because they slowly increased in size over several years. The other 90% have remained stable with continued observation. Importantly, the 10% that grew were very effectively treated with surgery at the time of progression making this a very safe approach. Obviously, not everyone is willing to observe a thyroid cancer once it is diagnosed even if would probably be safe to do so. So a careful discussion of the risk and benefits of observation versus immediate surgery is needed in all patients diagnosed with small, intrathyroidal papillary microcarcinomas.
What are the risks of thyroid surgery?
Like any major surgery, thyroidectomy is not without risks. These will be explained in great detail to you by your surgeon. In addition to the risks of bleeding and infection that are common to most surgeries, there is the risk of damaging the nerves that control the voice box and the glands that keep the serum calcium normal (parathyroid glands). In experienced hands the risk of permanent nerve damage is less than 1 % and the risk of permanent parathyroid gland injury is less than 10%. Postoperatively, temporary changes in the voice and low serum calcium levels are common and usually resolve over several weeks to months.
If the voice does not recover to normal after surgery, there are a variety of temporary and permanent options to improve the voice. Voice therapy is often recommended. In some patients, injections or surgery to the vocal cord may make the voice stronger and louder.
If the parathyroid glands are not functioning normal after thyroid surgery (surgical hypoparathyroidism), patients will have low blood calcium levels and can experience a multitude of symptoms including muscle cramps, and tingling around the mouth and in the hands and feet. These low calcium levels are commonly treated with oral calcium and prescription strength vitamin D supplements. If the oral calcium and vitamin D supplements are not effective in controlling the calcium levels, a synthetic form of injectable parathyroid hormone (NATPARA, from Shire) is now available. Studies demonstrate that injections of NATPARA can be very effective in controlling the calcium levels in the blood and urine in this situation. Because NATPARA was associated with the development of a malignant bone tumor (osteosarcoma) in rats, it is currently approved for use in the US only for patients that cannot be well controlled on calcium and VIt D and should be avoided in patients that have clinical conditions may put them at risk for osteosarcoma (such as Paget’s disease or the bone, young people with bones that are still growing, previous history of radiation to the bone, or rare hereditary disorders)
What is NATPARA? NATPARA is a synthetic form of injectable parathyroid hormone that can be used to normalize the blood and urine calcium levels in patients that have hypoparathyroidism (decrease function of parathyroid glands) after thyroid surgery that cannot be adequately controlled with calcium and vitamin D replacement therapy.
Why do I have thyroid tissue left after my surgery?
Depending on the specific details of your thyroid cancer presentation you and your surgeon will have decided on only half or on complete removal of your thyroid gland. The usual surgery is complete removal of the thyroid gland. Despite the term “complete” and despite expert surgical skills the surgeon will usually leave behind a small amount of thyroid tissue and cells to avoid injuring important structures, namely the nerve that control your voice box and the parathyroid glands which help maintain normal calcium levels in your blood.
What evaluations will be done before thyroid surgery?
In addition to a careful history and physical examination, you will have a neck ultrasound that is designed to carefully evaluate both the thyroid gland and the various lymph node chains in the neck. Thyroid cancer commonly spreads to lymph nodes in the neck. Therefore, it is important that a careful neck ultrasound be done in order for the surgeon to plan the appropriate surgery for you with regard both to removing the thyroid gland, but also the lymph nodes if they are involved with thyroid cancer.
While not usually necessary, a CT or MRI with contrast of the neck may be requested if there is any question that the thyroid cancer may be invading important structures in the neck or if there is extensive abnormal lymph nodes on exam or ultrasound evaluation. Depending on the preference of your surgeon, your vocal cords may be evaluated for normal function by either physical examination, direct examination of the vocal cords or with an ultrasound.
How important is the microscopic evaluation of the thyroid cancer that is removed by the surgeon?
The pathologic microscopic examination of any thyroid surgical specimen is very important and demanding. There are multiple pitfalls encountered in deriving a precise and accurate diagnosis. That diagnosis significantly impacts upon subsequent investigation, treatment and ultimate prognosis. The more experienced the pathologist, the more likely the diagnosis will be accurate and complete.
Once my surgery is over, is my cancer gone forever?
In cases of small thyroid cancers confined to the thyroid, surgery alone has a very high cure rate. When the thyroid cancers are larger, or spread outside the thyroid gland, the risk of recurrence can vary between 5-30% depending on the specifics of the individual tumor and patient.
Sometimes thyroid cancer can come back or spread to other parts of the body – even many years after surgery. That is why your doctor needs you to come in for regular checkups especially in the first 5 to 10 years after your surgery.
How is thyroid cancer typically treated after surgery?
While nearly all patients with thyroid cancer require thyroid surgery, the use of other treatments is quite variable and depends on the specifics of each individual tumor and patient. Most patients will require thyroid hormone replacement in the form of a single pill that needs to be taken daily. Depending on the risk of recurrence, radioactive iodine may be used to destroy any residual microscopic thyroid cancer that was not visible to the surgeon at the time of the operation.
Chemotherapy and/or external beam irradiation is rarely used in papillary, follicular thyroid or medullary thyroid cancer but is commonly part of the treatment regimen in anaplastic thyroid cancer.
Risk stratification in thyroid cancer
The 2016 ATA thyroid cancer guidelines emphasizes the importance of risk stratification in nearly all management decisions related to the initial evaluation, retreatment, and follow-up of thyroid cancer. While there are several risk stratification systems that work well, we prefer to use the ATA risk system to define the risk of recurrence (low, intermediate or high) and the AJCC/TNM system to define the risk of dying from thyroid cancer (Stage I II, III, or IV).
In 2016, the AJCC/TNM system for papillary and follicular thyroid cancers was updated to the 8th edition so that all patients less than 55 years of age at diagnosis without evidence of distant metastases are Stage I. Patients less than 55 years of age with distant metastases are Stage II. Patients older than 55 years of age at diagnosis are Stage I if the thyroid cancer is confined to the thyroid, Stage II if the tumor involves neck lymph nodes, Stage III if the tumor is growing into the major structures of the neck (such as wind pipe and food pipe), and Stage IV if they have distant metastases. Thus the updated AJCC staging system classifies the vast majority of thyroid cancer patients as being at low risk of dying from thyroid cancer (Stage I or II).
However, these initial estimates of risk of recurrence and risk of dying from thyroid cancer need to be adjusted over time. As new data becomes available during follow-up, the clinician is able to assess the current risks based on the natural history of the disease and the response to previous therapies. The 2016 ATA guidelines endorse a response to therapy staging system that classifies patients as either excellent (remission), biochemical incomplete (abnormal tumor marker with no identifiable structural disease), structural incomplete (persistent or recurrent structural disease) or indeterminate (non specific findings on imaging studies or tumor markers that cannot be confidently classified as excellent or incomplete responses). The long term follow up plan is based both on the initial risk assessments and also on the response to therapy classification.
Thyroid hormone replacement after thyroid surgery
Why do I need to take thyroid hormone after my thyroid surgery?
As previously mentioned, patients that had their entire thyroid removed start taking thyroid hormone after their surgery. If only half of the thyroid was removed, thyroid blood tests are usually done 4-8 weeks after surgery to determine if the half of thyroid is producing enough thyroid hormone to make you feel normal.
Thyroid hormone pills replace the normal hormones that the thyroid gland used to make. Taking thyroid hormone prevents you from experiencing hypothyroidism, which can cause a variety of symptoms, such as depression, difficulty in concentrating, tiredness, forgetfulness, dry skin and hair, puffy face and eyes, inability to tolerate the cold, weight gain, constipation, and heavy menstrual periods in women. These symptoms of hypothyroidism vary from patient to patient.
Another reason to take thyroid hormone after thyroidectomy is that TSH (thyroid stimulating hormone made by the pituitary gland) may cause thyroid cancers to grow. Taking thyroid hormone tablets sends a signal to the pituitary gland to make less TSH. Your goal TSH level will be based on your initial risk assessment and your response to therapy classification. But it is very few patients that require the TSH to be completely undetectable. Most patients initially start with a TSH goal of about 0.1 to 0.5 mIU/L which then changes to 0.5 to 1.5 mIU/L once they demonstrate an excellent response to therapy (remission)
So, taking the thyroid hormone tablets helps in two ways:
(1) It replaces the thyroid hormone that your body used to make on its own, so that you will not become hypothyroid.
(2) It tells the pituitary to make less TSH, so that if thyroid cancer cells are present, they will have less growth stimulation.
Are there any special instructions regarding how to take thyroid hormone?
Yes. Thyroid hormone is best taken on an empty stomach at least 30-60 minutes before eating. When thyroid hormone is taken with food or supplements (iron, calcium), it is less well absorbed into the blood stream.
Are generic thyroid hormone products interchangeable with brand name products?
While generic thyroid hormone products may be acceptable in the treatment of mild hypothyroidism, we prefer the branded products for most patients with thyroid cancer. Consistent use of a single brand minimizes variability between products and yields the most consistent thyroid hormone replacement and TSH suppression which are a critical part of the treatment of thyroid cancer.
What is armour thyroid?
Armour thyroid is ground up normal animal thyroid gland. It contains several thyroid hormones and is more variable than the more commonly used synthesized thyroid hormone preparations (levothyroxine). Because it is more difficult to tightly control the TSH level with armour thyroid, we prefer thyroid cancer patients use one of the branded levothyroxine products.
What is cytomel?
Cytomel is the commercial name for the thyroid hormone, T3 (liothyronine). The normal thyroid produces predominantly T4 (levothyroxine) and a very small amount of T3. Most of the T3 used by the body is produced inside the various cells in the body from the T4 that is circulating in the blood stream. The vast majority of patients are very nicely replaced with T4 (levothyroxine) alone. Because T3 is much shorter acting, has more variability, and is produced by each cell from T4, we usually do not have to use cytomel.
Is thyroid hormone replacement always needed after thyroid surgery?
If the entire thyroid is removed, thyroid hormone treatment will always be required after surgery. In the case of small thyroid cancers, sometimes only half of the thyroid is removed. If only half of the thyroid is removed, thyroid blood tests will be required after surgery to determine if thyroid hormone replacement is required.
What are the risks of prolonged thyroid hormone suppressive therapy?
Suppression of the serum TSH with thyroid hormone is a part of therapy for most thyroid cancer patients. Most patients can tolerate thyroid hormone suppression for several years with little problems. After several years without evidence of recurrence, the dose of thyroid hormone is often decreased resulting in less TSH suppression.
In young patients this appears to cause little problems. However, in older patients, prolonged thyroid hormone suppressive therapy can be associated with abnormal heart rhythms (atrial fibrillation) and thinning of the bones (osteopenia/osteoporosis). Therefore, it is important to tailor the degree of thyroid hormone suppression to the risk of the cancer keeping the patients other medical problems in mind.
What is the risk of recurrence or death from thyroid cancer?
After initial treatment, are recurrences common?
Unfortunately, yes. While most patients have a very small risk of dying from thyroid cancer, the risk of recurrence can be as high as 30% depending on the specifics of the individual tumor and patient. The good news is that most recurrences appear in lymph nodes in the neck and are usually readily treated with either additional surgery or more radioactive iodine.
What is the risk of death from thyroid cancer?
With appropriate initial therapy, 30 year survival rates for thyroid cancer are usually more than 95%. The risk of dying from thyroid cancer is highest in older patients (>60 yrs old) with thyroid cancer that either cannot be completely removed surgically or has spread to the lungs or the bones (8th edition AJCC stage III or IV). As noted above, anaplastic thyroid cancer is a much more aggressive tumor than the more common thyroid cancers and is associated with significantly higher disease specific mortality rates.
How will recurrent thyroid cancer be found?
In the past, radioactive iodine whole body scans were the primary tool used to detect recurrent thyroid cancer. However, the primary tools used today include the blood test marker of thyroid cancer (serum thyroglobulin for papillary and follicular thyroid cancers or calcitonin and CEA for medullary thyroid cancer) and the neck ultrasound. If the serum thyroglobulin is elevated and the disease is not localized with a neck ultrasound, other radiologic studies are often used to identify the site of disease. These studies may include CT, MRI, and/or FDG PET scanning.
What are the treatment options for recurrent thyroid cancer?
Probably more than 90% of the recurrences in papillary and medullary thyroid cancer develop in the neck. Usually these are detected as abnormal or enlarged lymph nodes on ultrasound examinations that may contain thyroid cancer. Large lymph nodes suspected of containing thyroid cancer are removed surgically. Small lymph nodes are less likely to require surgical removal and may be followed with careful observation or a repeat dose of radioactive iodine. Rarely, external beam irradiation is used for an aggressive recurrence that cannot be surgically removed and is unlikely to respond to additional radioactive iodine.
Imaging modalities commonly used in the diagnosis and ongoing management of thyroid cancer
What is a thyroid ultrasound (US)?
A thyroid ultrasound is a sound wave picture (like a radar) of the thyroid. It is usually the best test to evaluate the size and structure of the thyroid. Since the test uses sound waves (and not radiation) it is very safe and can be used repeatedly without complications.
In addition to evaluating the thyroid gland, ultrasonography is now commonly used during follow up to detect recurrent thyroid cancer in the neck.
What is FDG PET scanning?
FDG PET scanning is a newer testing modality in which radioactive sugar (FDG) is detected using a special scanner (PET scan). FDG PET scanning is particularly good at localizing thyroid cancer that no longer concentrates radioactive iodine. In young patients, FDG PET scanning is rarely required since the thyroid cancer in young patients usually concentrates radioactive iodine very well and seldom uses enough glucose to allow detection with the PET scanner. Conversely, more poorly differentiated thyroid cancers that often arise in older patients often fail to concentrate radioactive iodine and since they use more sugar than the surrounding normal cells are often readily detected with FDG PET scanning.
It is important to note many other benign and malignant conditions can also cause nodules and lymph nodes to concentrate high levels of glucose and therefore may be positive on the FDG PET scan. Therefore, biopsy of lesions found on the PET scan are usually required before one can be certain that the lesion found is actually thyroid cancer.
Thyroid cancer and pregnancy
What happens if I am diagnosed with papillary thyroid cancer during pregnancy?
Because thyroid cancer is one of the most common cancers in women of childbearing age, it is not uncommon for someone to be diagnosed with thyroid cancer during pregnancy. In most cases, it is very safe to observe the thyroid cancer during the pregnancy and perform the thyroid surgery after the baby is born. However, if the thyroid cancer has spread outside the thyroid or if the patient prefers to have it removed, thyroid surgery can be safely performed during the second trimester of pregnancy. Several studies have demonstrated that a delay in thyroid surgery until after delivery is associated with the same excellent outcomes as immediate surgery.
Will pregnancy increase my risk of recurrence?
We consider pregnancy to be a very mild stimulus to the thyroid (both the normal thyroid and potentially to thyroid cancer cells). Therefore, we prefer if women can wait at least 6-12 months after initial therapy before getting pregnant. That being said, we have had many patients get pregnant in just a few months after surgery and RAI and have completely normal, healthy pregnancies. While the data is somewhat conflicting, there may be a slightly higher miscarriage rate in the first 6-12 months after RAI.
We usually say that pregnancy never made anyone have a recurrence that was not destined to have a recurrence in the years to come. However, it is possible that the mild stimulation of pregnancy may make the recurrence become clinically apparent a little sooner than would have otherwise happened. We have had many women have healthy, uncomplicated pregnancies after therapy for their thyroid cancer.
How long should I wait to become pregnant after RAI therapy?
Contraception is advised for the first 6-12 months after RAI therapy. There may be a transient effect of RAI on the ovarian/gonadal function immediately after therapy, although this does not seem to have any significance in the long term. In our view, the main reason to avoid pregnancy within the first year after initial treatment is to allow flexibility if additional treatment and/or scans are needed within that time.
What is radioactive iodine?
What is radioactive iodine?
Radioactive iodine is one of the principal tools used for both treatment and detection of persistent/recurrent disease. The normal thyroid cell (and most thyroid cancers) need iodine to make thyroid hormone. Thyroid cells have a highly specialized pump that actively concentrates iodine inside the thyroid cell. Since the pump cannot differentiate normal iodine from radioactive iodine, the radioactive iodine pumped into the cell can be used in very small doses to localize and identify thyroid cancer anywhere in the body and can be used in larger doses to destroy those same cells. Unfortunately, medullary thyroid cancer and anaplastic thyroid cancer cells do not have this iodine pump and therefore we cannot use radioactive iodine to treat medullary or anaplastic thyroid cancer.
Whole body radioactive iodine scan
Another test that checks for the return or spread of the cancer is called a whole body scan, or WBS. In this test, you will be asked to take a pill or drink with a small, safe amount of radioactivity, called 131I (“eye-one-thirty-one”). After you have taken the pill or drink, you will lie down under a large camera that takes an x-ray picture (scan) of your body. If any thyroid cells are present in your body, they will show up as spots on the film.
It is important to note that this “whole body scan” is only useful for detecting thyroid cancer. Other cancers do not concentrate radioactive iodine and are therefore not detected by radioactive iodine whole body scanning. Furthermore, with the improved ability to detect disease recurrence with highly sensitive thyroglobulin assays and neck ultrasonography, we seldom do routine follow up whole body radioactive iodine scans as part of follow-up.
Is radioactive iodine harmful?
Radioactive iodine has been used in thousands of patients with both benign and malignant thyroid disease since the late 1940’s. While multiple, large doses of radioactive iodine appear to very slightly increase the risk of other types of cancers later in life, we do not believe that the usual one or two doses of radioactive iodine used in the typical thyroid cancer patient result in any significant increased cancer risk.
Because the salivary glands in the mouth that make saliva also have the pump that concentrates radioactive iodine, it is quite common to have alterations in taste, pain/discomfort in the salivary glands that develops shortly after taking the radioactive iodine. Less commonly the damage to the salivary glands can be more severe and result in dry mouth. While these salivary gland side effects can develop in as many as 30-40% of patients, they usually resolve, with fewer than 5-6% of patients having persistent problems after RAI treatment. Rarely, the radioactive iodine will cause irritation and blockage of the tear ducts which can result in tears spilling over the lower eyelid and onto the face.
Radioactive iodine appears to have little, if any, impact on subsequent fertility in either men or women. While we often ask that patients not get pregnant for 6-12 months after a dose of radioactive iodine, we expect normal fertility after the usual one or two doses of radioactive iodine that may be needed.
Is radioactive iodine treatment required for all thyroid cancer patients?
No. Patients staged as low risk do not significantly benefit from routine use of radioactive iodine therapy in terms of having any meaningful impact on the already very low rates of recurrence and disease specific mortality. Radioactive iodine is only recommended if it is anticipated that treatment will result in decreased recurrence rates, improved survival or a clinically meaningful increased ability to detect and treat recurrent disease.
What is the criteria for not needing radioactive iodine?
Your doctor will review the details of your thyroid cancer including the size and number of tumors, whether or not it invaded structures outside of the thyroid including blood vessels and lymph nodes, an assessment of the presence or lack of features (variant) that may suggest a more aggressive type of tumor, and consideration of how and where you will be followed for your cancer. Thyroid cancer may be a small size, confined to the thyroid and lack any local invasion/spread or other features that your doctor views as higher risk. When this is the case, your doctor will weigh the potential risks and or benefits of giving you additional treatment with radioactive iodine. If he or she does not see any significant benefit in achieving the goals of radioactive iodine, they will not recommend it.
What is the goal of radioactive iodine therapy?
(1) The goal of radioactive iodine can vary depending on the patient to whom it is given, but in general it is given for the following: to decrease the risk of recurrence of your cancer by treating any remaining cancer cells and/or tissue left behind after your surgery.
(2) To improve the long-term survival of some patients with thyroid cancer.
(3) To treat and/or detect any thyroid cancer that has spread to other parts of the body. The detection portion requires a whole body scan, which is always done after treatment with radioactive iodine. “Ablating” (eliminating) any remaining normal thyroid tissue may also make future treatments for thyroid cancer more effective.
(4) To aid your doctor in the ability to detect recurrent disease. Radioactive iodine may help, but is not always required, to bring the thyroid cancer marker (thyroglobulin) we measure in the blood to an undetectable level so that if the cancer comes back we see it as a rise in the tumor marker. Thyroglobulin is a protein made by the follicular cells of the thyroid that stores thyroid hormone. Its presence or absence in some patients with thyroid cancer patients may indicate the presence or absence of thyroid cancer, respectively.
Will this testing have an impact on my life?
Yes. Patients treated with radioactive iodine will be radioactive for several days after treatment. While the specific radiation safety precautions will vary from patient to patient, usually it is necessary to avoid close contact with children and pregnant women for 2-5 days after treatment with radioactive iodine.
What is Thyrogen (recombinant human thyroid hormone stimulating hormone) ?
Thyrogen is just like the TSH that the body produces naturally, although it is made in a laboratory. Because Thyrogen is just like TSH, you do not have to stop taking your thyroid hormone therapy or risk going through weeks of unpleasant symptoms before being tested. You can keep taking your thyroid hormone therapy. In other words, you will not have to become hypothyroid. This is especially important in the first years after thyroidectomy, since patients may require repeated testing for the return or spread of the cancer during this period.
Side effects of taking Thyrogen (thyrotropin alfa for injection) are few and generally mild. Some people experience nausea, headache, weakness, or vomiting after their injection. A few people have experienced itching or rash at the site of the injection. Please see the section entitled adverse reactions in the complete prescribing information. If you experience any side effects or have any questions, contact your doctor.
Why might Thyrogen be prescribed?
Effective use of radioactive iodine requires both a low iodine diet and an elevated TSH (thyroid stimulating hormone). We usually recommend a low iodine diet for up to 1 week prior to the use of radioactive iodine in order to deplete the normal iodine from the body: thereby increasing the chance that a thyroid cell will grab onto radioactive iodine rather than normal iodine. Your physician will give you specific instructions on how long to remain on the low iodine diet as well as resources that provide a detailed description of a low iodine diet.
In addition, since thyroid cancer cells often don’t concentrate radioactive iodine as well as normal thyroid cells, we use an elevated TSH level to help stimulate the thyroid cells to concentrate radioactive iodine. In the past, whenever people were tested for the return or spread of thyroid cancer (especially if they had a whole body scan), they had to stop taking their thyroid medication for 2 to 6 weeks before the test. This allowed their body to produce enough TSH to make the tests as accurate as possible. But it also caused patients to become hypothyroid. Plus, even when the testing was done and they started taking their thyroid medication again, many people continued to feel hypothyroid until the level of thyroid hormone in their bloodstream returned to normal. All in all, some people felt the symptoms of hypothyroidism for up to 10 to 12 weeks.
The availability of Thyrogen (recombinant human TSH) allows us a method to raise the TSH through intramuscular injections without having to stop the patient’s thyroid hormone pills. Therefore, most patients can receive radioactive iodine scanning and initial therapy using Thyrogen rather than going through thyroid hormone withdrawal.
What can be done to make radioactive iodine work better?
To maximize the effectiveness of radioactive iodine, we routinely place patients on a low iodine diet and treat only when the TSH is elevated (either by stopping thyroid hormone pills, or more commonly with Thyrogen). However, exciting work the last several years has shown the potential of using other medicines for a few weeks prior to radioactive iodine therapy that blocks specific pathways within the thyroid cancer cells and causes some of the thyroid cancers to dramatically increase the amount of radioactive iodine they absorb. Currently, these medications are being evaluated as part of clinical trials (research). We hope that in the near future, that one of more of these drugs can be used as part of the preparation for radioactive iodine therapy both to maximize its effectiveness in tumors that can concentrate radioactive iodine but also to restore radioactive iodine uptake in tumors that have lost that ability.
What are the tumor markers commonly used in thyroid cancer?
What is the Thyroglobulin (Tg) blood test?
A thyroglobulin test is a blood test that measures the amount of thyroglobulin, a protein that stores thyroid hormone, in your blood. Thyroid cells are the only cells in your body that make thyroglobulin. So if thyroglobulin shows up in your blood test, then you know that normal thyroid cells or thyroid cancer cells are present somewhere in your body. Since thyroglobulin is made in the normal thyroid, it cannot be used to diagnose thyroid cancer. However, after surgery to remove the thyroid and radioactive iodine therapy to destroy any residual thyroid cells, the serum thyroglobulin should be nearly zero in cured patients. A detectable or rising serum Tg after initial therapy may indicate persistent thyroid cancer.
What are anti-thyroglobulin antibodies?
As many as 20-25% of thyroid cancer patients have an antibody in their blood stream that is directed at the thyroglobulin protein. While the antibody itself does not cause any medical problems, it does interfere with the testing procedure that we use to measure the serum thyroglobulin. If anti-thyroglobulin antibodies are present, the value obtained for serum thyroglobulin is unreliable. In most cases the anti-thyroglobulin antibodies make the measured serum thyroglobulin appear lower than it really is. This could make it look like someone is cured (very low measured serum thyroglobulin) when the actual serum thyroglobulin is quite elevated.
The gradual disappearance of anti-thyroglobulin antibodies is a good sign and usually indicates the patient is cured of thyroid cancer. However, it may take years for the anti-thyroglobulin antibodies to gradually resolve.
The method of testing for thyroglobulin may vary slightly from laboratory to laboratory. To minimize the variability of results based on differences in laboratories and methodology, your doctor will recommend being consistent with the laboratory where you have your thyroglobulin measured.
What are calcitonin and CEA?
Calcitonin and CEA are tumor markers that are produced by medullary thyroid cancer. Unlike thyroglobulin, calcitonin and CEA can be produced at sites outside the thyroid. So a rise in either is suggestive of medullary thyroid cancer in the right clinical setting but could also represent other conditions (less commonly)
After initial diagnosis and treatment, what follow-up is needed?
What is the usual follow up in the first 2 years after diagnosis and treatment?
After appropriate thyroid surgery, a decision is made regarding whether radioactive iodine therapy is needed. If needed, this usually happens about 1-3 months after surgery. If radioactive iodine is being considered for therapy, you may also see a nuclear medicine specialist, as well.
If all goes well, the usual follow up pattern is to see the endocrinologist and thyroid surgeon about every 6 months for the first 2 years. At each visit blood tests are drawn to check the thyroid hormone levels, thyroglobulin and thyroglobulin antibodies (or calcitonin/CEA if medullary thyroid cancer). Often times serum calcium and PTH is measured if there was any problem with the calcium levels in the immediate post-operative period.
Usually a neck ultrasound is done 1 and 2 years after surgery to rule out recurrence in the neck. Whole body radioactive iodine scans are no longer routinely performed on every thyroid cancer patients, but may be done in patients at higher risk of persistent/recurrent disease.
What is the usual long term follow up?
With our modern follow up tests, most significant recurrences are detected within the first 2 years of diagnosis and treatment. Therefore, patients who have no evidence of disease at the 2 year point are often seen every 1-2 years with blood tests (TSH, Free T4, thyroglobulin, anti-thyroglobulin antibodies) and the occasional neck US (every 3-5 few years or less often). If the serum thyroglobulin remains essentially undetectable, other radiology tests or nuclear medicine tests are usually not required. However, thyroid cancer recurrence may be detected as late as decades after the initial treatment and appropriate follow-up should be lifelong.
What treatment options are available if surgery and radioactive iodine are not effective?
What treatments are available if RAI is no longer working?
We prefer to use localized therapies as long as possible. These may include surgical resection of metastatic disease, external beam irradiation, or embolization. However, if multiple sites are getting larger or if the site of enlargement is not amenable to treatment with a localized therapy, systemic therapy should be considered.
In the past, the systemic treatment options were very limited and not very effective. Usually some combination of chemotherapies (e.g. doxorubicin or platinum based regimens) would be offered with realistic success rates of less than 5-10%. In the past several years, there has been an explosion in the number of target therapies that are being used in thyroid cancer.
Currently, there are two medications approved by the FDA for the treatment of progressive or symptomatic radioactive iodine refractory differentiated thyroid cancer (sorafenib and lenvatinib) and two agents approved for progressive or symptomatic medullary thyroid cancer (vandetinib and cabozantinib). In large, placebo controlled, phase III randomized clinical trials, each of these medications significantly improved progression free survival compared to the placebo arm..In clinical use, these agents appear to cause disease stabilization (or sometimes regression) in up to 70% of patients. The duration of effectiveness is usually in the 12-18 month range but many patients have remained on these medications for years with prolonged disease stabilization.
These medications are not recommended for treatment of elevations in tumor markers alone (thyroglobulin, calcitonin, or CEA) and should not be used if there is effective localized therapies available (surgery, external beam irradiation, embolization). Their use is restricted to patients with known structural disease that is increasing significantly in size over the last several months.
While these new targeted agents are not as toxic as traditional chemotherapy, they are not without side effects. The side effects appear to be dose related and are reversible when the medication is stopped. The most common side effects include high blood pressure, rash, fatigue and diarrhea.
Is molecular characterization of advanced thyroid cancer helpful?
We don’t recommend routine molecular characterization of all patients with thyroid cancer at the time of diagnosis. In most cases, the molecular findings provide only marginal information with regard to risk stratification and seldom change our treatment or follow-up recommendations.
However, we do see value in evaluating the molecular profile of advanced thyroid tumors to help us provide more individualized treatment recommendations. At MSKCC, tumors from patients with advanced thyroid cancer are evaluated for mutations in more than 400 specific genes. The results of this analysis allows us to more rationally select either an approved drug or a clinical trial alternative that is likely to be effective. Clinical trials or approved therapies are available for each of these specific mutational changes.