USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 45-year-old woman is brought to her primary care physician's office because of fevers and weight loss for the past 3 months. Physical examination shows a hard and nontender thyroid nodule with cervical lymphadenopathy. A complete metabolic panel and complete blood count is ordered and the results show no abnormalities. A positron emission tomography shows pulmonary metastasis. Fine-needle aspiration of the thyroid mass shows concentric laminar calcified collections. Which of the following is the most likely diagnosis?
Contributors:Pauline Rowsome, BSc (Hons), Tanner Marshall, MS, Sam Gillespie, BSc, Miguel Quintana, MD
If the cells of the thyroid gland start to divide uncontrollably, then that’s considered a thyroid cancer.
Normally, the hypothalamus, which is located at the base of the brain, secretes thyrotropin-releasing hormone, or ΤRH, into the hypophyseal portal system - which is a network of capillaries linking the hypothalamus to the anterior pituitary.
The anterior pituitary then releases a hormone of its own, called thyroid-stimulating hormone, thyrotropin or simply TSH.
TSH stimulates the thyroid gland which is a gland located in the neck that looks like two thumbs hooked together in the shape of a “V”.
The entire gland is covered in a thin, tough membrane called the fibrous capsule.
If we zoom into the thyroid gland, we’ll find thousands of follicles, which are small hollow spheres whose walls are lined with follicular cells, and are separated by a small amount of connective tissue.
Follicular cells convert thyroglobulin, a protein found in follicles, into two iodine-containing hormones, triiodothyronine or T3, and thyroxine or T4.
Once released from the thyroid gland, these hormones enter the blood and bind to circulating plasma proteins.
Only a small amount of T3 and T4 will travel unbound in the blood, and these two hormones get picked up by nearly every cell in the body.
Once inside the cell T4 is mostly converted into T3, and it can exert its effect. T3 speeds up the basal metabolic rate.
T3 increases cardiac output, stimulates bone resorption - thinning out the bones, and activates the sympathetic nervous system, the part of the nervous system responsible for our ‘fight-or-flight’ response.
Thyroid hormone is important - and the occasional increase is like getting a boost to fight off a zombie or to stay warm during a snowstorm!
Thyroid hormones are also involved in a number of other things, like controlling sebaceous and sweat gland secretion, hair follicle growth, and regulating proteins and mucopolysaccharide synthesis by skin fibroblasts.
The thyroid is also made up of parafollicular or C cells, which are near the follicles.
Osteoclasts are bone cells that break down bone tissue which frees up the calcium to enter the bloodstream.
Calcitonin also inhibits renal tubular cell reabsorption of calcium, allowing the calcium to be excreted in the urine.
DNA mutations can cause thyroid cells to become cancerous.
For example, a mutation might change a proto-oncogenes like RET and BRAF, which are genes that code for proteins that promote cell growth and proliferation, into oncogenes.
That would mean that the proteins force the cell to be stuck in the "on" position, always dividing, and that causes the thyroid cell to turn into a tumor.
There are other genes, called tumor suppressors, such as PTEN and that slow down cell division or make cells die if they divide uncontrollably.
DNA mutations might also turn off tumor suppressor genes, which allows thyroid cells that try to divide uncontrollably to go unchecked.
Over time, a thyroid cell that divides uncontrollably, will lead to a lump of cells within the thyroid, called a nodule.
Most often, nodules are non-functional, so they don't produce thyroid hormones, and these are called "cold" nodules.
Now, there are three main types of thyroid cancer: differentiated, medullary, and anaplastic.
In differentiated thyroid cancer, the cancer arises from follicular cells, and it's known as differentiated because the cancer cells look and act like normal thyroid cells.
Within the differentiated thyroid cancers there are three groups: papillary, follicular, and Hṻrthle cell carcinoma.
The first group, papillary carcinomas, represents the most common form of thyroid cancer and is associated with RET and BRAF gene mutations as well as exposure to ionizing radiation during childhood, as seen in kids near the Chernobyl nuclear power plant accident.
The name “papillary” refers to the fact that these tumors have finger-like prolongations of 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 carcinomas cells contain very few proteins and a small amount of DNA, and that gives the appearance of an empty nucleus, sometimes called an “Orphan Annie eye” nucleus based on an old famous cartoon character.
Another feature are psammoma bodies, which are calcium deposits within the papillae.
The second type, follicular carcinomas, also known as follicular adenocarcinomas, represent the second most common form of thyroid cancer.
This type of thyroid cancer is more frequent associated with countries where people have low dietary iodine , but is also with the activation of RAS oncogene or the deactivation of the tumor suppressor gene PTEN.
In follicular carcinomas, the tumor develops from the follicular cells and grows until it breaks through the fibrous capsule.
From there, follicular carcinomas can invade into nearby blood vessels and spread to other parts of the body like the lungs, liver, bone, and brain, but interestingly they don’t typically invade nearby lymph nodes.
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