Thyroid Cancer

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The thyroid gland is an endocrine gland in the neck that produces thyroid hormones. If the cells of the thyroid gland start to divide uncontrollably, then it is considered as thyroid cancer. Normally the hypothalamus, which is located at the base of the brain secretes thyrotropin-releasing or TRH into the hypophyseal portal system. This is a network of capillaries linking the hypothalamus to the anterior pituitary. The anterior pituitary will then be releasing a hormone of its own which is called Thyroid-stimulating hormone, thyrotropin, or the TSH. The TSH stimulates the thyroid gland which is a gland found in the neck that looks like 2 thumbs hooked together in the shape of a V. If we look at it the entire gland is covered with a thin tough membrane which is called the fibrous capsule. If we look at it more closely into the thyroid gland we are going to see thousands of follicles that are small hollow spheres the walls of which are lined with follicular cells and usually are separated by a small amount of connective tissue. Follicular cells convert thyroglobulin which is a protein found in follicles into iodine-containing hormones triiodothyronine or T3 and thyroxine or T4. Once it is released from the thyroid gland usually these hormones will tend to enter the blood and they usually bind to circulating plasma proteins. Only a small amount of T3 and T4 will travel unbound in the blood. And these 2 hormones get picked up by nearly every cell in the body. Once inside the cell T4 is mostly converted into T3 at which point it can exert its effect. The T3 will usually speed up the basal metabolic rate, for example, they might end up producing more proteins and will tend to burn up more energy which is in the form of sugars and fats. It is kind of where the cells are in a bit of frenzy. If we look at the T3 it will increase the cardiac output, stimulate bone resorption which then will thin out the bones and activate which we observe in the sympathetic nervous system, which is the part of the nervous system that is mainly responsible for our fight or flight response. Thyroid hormone is very important and when there is an occasional increase is like getting a boost to fight. The thyroid hormones are usually involved in various types of things like controlling sebaceous and as well as the sweat gland secretion, growth of hair follicle, and protein regulation and synthesis of the mucopolysaccharides by skin fibroblast. In general, the thyroid is made up of parafollicular or we can say the C cells which we see near the follicles. These cells produce calcitonin which is a hormone that lowers blood calcium levels by inhibiting osteoclasts. Osteoclasts are bone cells that break down bone tissue which frees up the calcium to enter the bloodstream. The calcitonin usually also inhibits renal tubular cell reabsorption of calcium which then allows for the calcium in order to be excreted in the urine. The DNA mutations are the once that usually cause thyroid cells to become cancerous, let us see an example, if we look at the mutation it might change a proto-oncogene like RET and BRAF, that genes which code for proteins that promote cell growth and the proliferation into oncogenes. That would mean that the protein forces the cells to be stuck in the “on” position always dividing and that causes the thyroid cells to turn into a tumor. There are other genes called tumor suppressor such as PTEN that normally slow down cell division or make cells die if they divide uncontrollably. DNA mutations might also turn off tumor suppressor genes, which allow thyroid cells that try to divide uncontrollably to go unchecked. Over time a thyroid cell that divides cells uncontrollably will lead to a lump of cells within the thyroid called a nodule. Most often the nodules are non-functional, so they don’t produce thyroid hormone and these are called “cold” nodules. There are 3 main types of thyroid cancer differentiated, medullary, and anaplastic. In differentiated thyroid cancer arises from the follicular cells and is known as differentiated because the cancer cells look and act like normal thyroid cells. Within the differentiated thyroid cancer, there are 3 groups papillary, follicular, and Hurthle cell carcinoma. When we look at the first group papillary carcinoma it usually represents the most common form of thyroid cancer which is associated with RET and BRAF gene mutations this even caused due to exposure to ionizing radiation at the time of childhood. As was seen in kids near the Chernobyl nuclear power plant accident. The name papillary refers to the fact that these tumors have finger-like prolongation of the follicle cells known as papillae that tend to grow slowly towards nearby lymphatic vessels and invade nearby lymph nodes in the neck. Under the microscope, the nuclei of papillary carcinoma cells contain very few proteins and a small amount of DNA and that gives the appearance of the empty nucleus sometimes known as the “Orphan Annie eye” nuclei which is based on a famous old character that we see in the cartoon. Another feature is the psammoma bodies which are calcium deposits within the papillae. The second type of follicular carcinomas also known as the follicular adenocarcinomas represents the second most common type of thyroid cancer. This type of thyroid cancer is more frequently associated with countries with low dietary iodine but is also associated with the RAS oncogene or the deactivation of the tumor suppressor gene in PTEN. In follicular carcinomas, the tumor develops from the follicular cells and grows until it breaks through the fibrous capsule. From there the follicular carcinomas can invade into nearby blood vessels and spread to other parts of the body like the lungs, liver, and brain. But interestingly they don’t invade the nearby lymph nodes. The third type of Hurthle cell carcinoma is a rare type of cancer and is considered a variant of follicular carcinoma. A tumor can often cause the immune cells to attack it causing inflammation. Follicular cells in the thyroid adapt to cellular stress like inflammation by becoming Hurthle cells. They do so by increasing the production of mitochondria which fills up their cytoplasm and gives it a granular appearance and stains pink. These cells are also seen in disorders like Hashimoto’s thyroiditis where the thyroid is also inflamed. Like in follicular carcinoma Hurthle cells form neoplastic tumors that break through the fibrous capsule and invade via the bloodstream.   

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Types of Thyroid Cancer

The thyroid is said to be a cancerous disease that begins in your thyroid gland. Your thyroid gland is located over your larynx or voice box. It wraps around your trachea or windpipe, your thyroid produces 2 hormones called thyroid hormone and calcitonin and secretes them directly into your bloodstream. Inside your thyroid gland, follicular cells make thyroid hormone. Your body uses the thyroid hormone to increase your energy and raise your body temperature when necessary. For example, these effects offset the heat your body loses when exposed to cold weather perifollicular cells in your thyroid make calcitonin. Calcitonin is thought to stimulate the formation of new bones. If you have thyroid cancer, it may be one of 4 types depending upon the thyroid cell in which cancer started and the appearance of the cancer cells. When we talk about papillary carcinoma which is one of the most common thyroid cancers, it usually begins in the follicular cells. Talking about the follicular carcinoma which is accounting for 1 in 10 cases and it also begins in follicular cells. The medullary carcinoma is said to be less common and it usually begins in parafollicular cells. When we look at the anaplastic thyroid carcinoma which is said to be a rare and one of the more dangerous forms of thyroid cancer. Thyroid cancer like all cancers results in an unrestrained growth of cells due to damaged genetic material in the cell’s nucleus. A tumor forms as the cells begin to accumulate, over time lymph forms in your thyroid as the tumor enlarges. You will usually feel there is a lump in your neck over to the thyroid gland. You may have neck or throat pain hoarseness and trouble swallowing as the tumor grows around your trachea. In order to treat thyroid cancer, the doctor may recommend surgery which is followed by thyroid hormone therapy, chemotherapy. or radiation therapy. Surgery is the most common treatment for almost all types of thyroid cancer. If you have surgery your doctor will remove your entire thyroid gland, your doctor may remove the nearby lymph nodes as well. Once the surgery is completed, your doctor will usually recommend you to go for thyroid hormone therapy. Without your thyroid, your body will have low levels of thyroid hormones. This condition stimulates the pituitary gland in your brain to release the thyroid-stimulating hormone. Increased levels of thyroid-stimulating hormones cause any remaining thyroid cancer cells to grow even faster. If you take thyroid it will reduce the amount of thyroid-stimulating hormones circulating in your body which will prevent the cancer cells from growing. In case you are having anaplastic thyroid cancer and have already undergone surgery, your doctor, in this case, will recommend you go for radiation therapy which is an external beam radiation therapy. Radiation damages and kills any remaining thyroid cancer cells. Once the surgery is over, your doctor will put you on a pill which usually contains another type of radiation therapy which is called radioactive iodine. Any remaining thyroid cancer cell absorbs the radioactive iodine which kills them. Your doctor may recommend chemotherapy for anaplastic thyroid cancer that does not respond to therapy or radiation and has spread. Chemotherapy uses drugs to stop the progression of cancer by either killing the cancer cells or preventing further growth.        

Signs and Symptoms of Thyroid Cancer     

The thyroid is the 8th most form of cancer diagnosed worldwide, the incidence is rising. It is also a bit more frequent in women than in women. It tends to be more aggressive in African-Americans than the rest of the population. It tends to be more aggressive if you tend to be male versus female. So most cases thyroid cancer is detected either on a routine physical exam without causing any symptoms or on a routine scan which is frequently obtained for totally unrelated reasons. That does not mean that you have thyroid cancer if somebody finds a nodule. In fact, the majority of the thyroid nodules are actually benign. Nonetheless, this should prompt a workup to make sure that this is not thyroid cancer. Because the thyroid gland is so close to the surface it is actually easy to examine your thyroid gland yourself. It is located right below the voice box, it is a little butterfly shape organ and if you. If you put your hands on your neck and swallow you feel something moving slightly up and down, which is your thyroid gland. The most common signs and symptoms of thyroid cancer are just the swellings of the thyroid gland. Often feeling of pressure or something just being stuck in the throat or below the throat. If cancer progresses to a certain size, it can start interfering with the functioning of the voice box. There can be hoarseness, there can be difficulty swallowing although these are typical signs of some advanced thyroid cancer. Now we need to keep in mind that these are common symptoms that every one of us experiences at some point in our lives and it does not necessarily mean that you have thyroid cancer in fact, most likely you don’t. However, if these symptoms persist, then we need to have those checked out by our physician.           

Signs That Thyroid Cancer Has Spread 

Evaluating thyroid cancer for the spread involves a couple of things. The first is to see your surgeon and have them do a physical exam. Feel for any enlarged lymph nodes in the neck. Every patient should have an ultrasound of the neck and that should include the evaluation of the lymph nodes both in the central neck and in the middle as well as those on the lateral neck on both sides. It is very important that this is done not always are the lymph nodes assessed when a patient gets an ultrasound initially just looking at the thyroid nodule itself. So those are the mainstays of evaluation if there are several enlargement nodes or they are particularly large, then a surgeon may also want to get a CT scan to further evaluate for any lymph node spread. 

FAQ (Frequently Asked Questions)

Q1. How can You be Sure if Your Cancer is Gone.

Ans: These are set at the beginning and they never change. A stage one patient is a stage one for the rest of their life you can't change stage over time. So we don’t change the stage or the initial risk recurrence that stays with you. But what can change at every single visit is the dynamic classification of response to therapy. This is a very important concept, so low thyroglobulin, negative antibodies, negative ultrasound, and if we do a whole-body scan that is negative. If you stimulate that thyroglobulin either by taking away the thyroid hormone or thyroid unit it doesn’t go up very high, it goes up to less than one. Consider if you are at stage one, say you start out as an intermediate-risk disease but now you have an excellent response to therapy. The intermediate-risk could be upwards of 20% risk of it coming back. Once you have an excellent response to therapy it is 1 to 2% or less. The intermediate-risk meaning may be that you have a little bit of thyroglobulin measurable, the antibodies are positive, and they are kind of staying at a low level and not changing. We see something on the ultrasound if you see these indeterminate lymph nodes that are little big, little funny looking but not scary looking that is considered an indeterminate response. Biochemically incomplete, they will be using a tumor marker thyroglobulin. In fact now if you have high thyroglobulin, and they can’t find the disease that is called a biochemically incomplete response. Technically if you are on thyroid hormone therapy it is above one the thyroglobulin and once you stimulate it is above 10 which is technically what is called the biochemically incomplete response. When we don’t see it on imaging and if we see it on imaging we can do a biopsy and say it is cancer that is structurally incomplete. You have a lymph node in your neck that we biopsy and it is cancer that is called a structurally incomplete response.  

Q2. Which is the Best Way of Detecting Thyroid Cancer?

Ans: Ultrasound is the best way for deducting the nodules, finding them 20 to 65% of the time. But the 7 to 15% of the nodules detected are cancerous. UAB Medicine has nationally recognized thyroid cancer surgeons and oncologists who have made major discoveries in thyroid cancer research.