Thyroid Molecular Markers Allow Patients To Avoid Surgery
We want to help patients find that perfect balance between under-treatment and over-treatment. The people-gram shows how molecular testing can help patients avoid unnecessary surgery.
Left Path: Before the use of molecular markers, everyone with an indeterminate biopsy went to surgery. Of those who went to surgery, cancer was found in only 25% of those cases . 75% of the surgical patients turned out not to have needed surgery at all because their nodules were benign .
Right Path: Today, if you have an indeterminate biopsy, you also undergo molecular testing.50% of patients were categorized as benign from the molecular test and safely avoided surgery. Of the surgical patients who received a suspicious molecular test result , cancer was found in 50% of those patients .
It is very rare that patients end up having cancer because of a false negative test. Still, it is UCLAs standard of care to have a safety net and follow every patient after molecular testing, regardless of their result. Those patients will get ultrasounds every 12 months to ensure that nodules do not grow or change in appearance.
Who Is At Risk For Hyperthyroidism
You are at higher risk for hyperthyroidism if you
- Are a woman
- Are older than age 60
- Have been pregnant or had a baby within the past 6 months
- Have had thyroid surgery or a thyroid problem, such as goiter
- Have a family history of thyroid disease
- Have pernicious anemia, in which the body cannot make enough healthy red blood cells because it does not have enough vitamin B12
- Have type 1 diabetes or primary adrenal insufficiency, a hormonal disorder
- Get too much iodine, from eating large amounts of foods containing iodine or using iodine-containing medicines or supplements
When You Might Need Additional Tests
In these cases, doctors may choose to order a comprehensive panel of thyroid function tests to measure thyroxine such as Free T4, Total T4, Total T3, and thyroid antibodies, in addition to the TSH. A critical part of obtaining the best possible TSH test results and thyroid treatment involves ensuring youre receiving the right diagnostic tests.;
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What Causes Tsh Level High It Typically Signals That The Thyroid Is Under Performing Also Known As Hypothyroidism That Requires Medical Treatment
TSH or thyroid stimulating hormone is a hormone produced in the anterior pituitary gland. This is used to help stimulate the thyroid to produce triiodothyronine or thyroxine , hormones that help stimulate the metabolism. If your pituitary gland is producing TSH trying to stimulate the thyroid but the thyroid does not respond, it can result in high;TSH level in the bloodstream. This can be caused by stress, illness, an obstruction or surgery causing the thyroid to malfunction or be sluggish.
Causes Of High Tsh Levels
Thyroid hormones operate on a negative feedback loop. Low thyroxine levels indicate to the pituitary gland to produce more TSH, but more TSH can further decrease thyroxine levels. Therefore, any issues that cause hypothyroidism, will in turn affect production from the pituitary gland.
One of the most common causes of hypothyroidism with a high TSH level is chronic autoimmune thyroiditis, also known as Hashimoto’s thyroiditis. White blood cells begin to attack the thyroid gland, which decreases the amount of thyroid hormone it produces.;
Other things that affect T4 levels, ultimately affecting TSH levels, include:
- Hormonal changes from hormonal birth control or a shift in estrogen levels
- Medications that cause thyroid dysfunction, like amiodarone or tyrosine kinase inhibitors
- Injury to the thyroid gland from radiation therapy
- Partial or complete removal of the thyroid gland
While the causes of thyroid diseases are widely researched and understood, it is less clear what can cause the elevated TSH levels if the pituitary gland is the source of the issue. One possible cause of elevated TSH levels are TSH-secreting adenomas. These are tumors on the pituitary that independently produce TSH, stimulating the thyroid gland to produce T4 and T3. However, these tumors are rare.
Swelling of the pituitary gland can also cause malfunction and hormonal imbalance, potentially affecting TSH levels. However, the condition is rare and usually affects other hormones produced by the pituitary.
What Does A Low Tsh Level Mean
A TSH level below 0.5 mIU/L can mean that your thyroid gland is overactive. This is hyperthyroidism, which can cause such symptoms as , heat intolerance, increased appetite, and bulging eyes.
One of the most common causes of hyperthyroidism is Graves disease, an autoimmune disorder in which your bodys immune system mistakenly attacks the thyroid gland. also can be caused by or taking certain medications.
Other Diseases Associated With Autoimmune Thyroiditis And Elevated Anti
Not only will high levels of anti-TPO antibodies damage your thyroid, but it also is important to identify because the presence of this autoimmune disease increases your risk of developing other autoimmune diseases.
Studies have shown that patients with Hashimotos and autoimmune thyroiditis conditions have a very large increase of developing other diseases like Celiac disease , type I diabetes mellitus, pernicious anemia and even adrenal insufficiency.
For this reason, the early detection of thyroidal antibodies becomes very important.
Treating and reducing the immune and inflammatory component to this disease can help reduce the risk of developing these other autoimmune diseases.
The presence of TPO antibodies in your blood should prompt your physician to order other tests to evaluate your autoimmune status.
This is particularly important in the case of Celiac disease which is so often undiagnosed and underappreciated .
Below Ive included an example of a patient of mine who had elevated anti-TPO antibodies on initial testing and further evaluation of her antibodies to gluten revealed she also had antibodies to the gluten protein.;
You can see above the high titers to tissue transglutaminase and gliadin antibody, both of which can be markers of the condition Celiac disease.;
Its always very important to identify the gluten sensitivity in patients because the removal of gluten can be curative in this autoimmune disease .;
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How Is Thyroid Stimulating Hormone Controlled
When thyroid stimulating hormone binds to the receptor on the thyroid cells, this causes these cells to produce thyroxine and triiodothyronine and release them into the bloodstream.;These hormones have a negative effect on the pituitary gland and stop the production of thyroid stimulating hormone if the levels of thyroxine and triiodothyronine are too high.;They also switch off production of a hormone called thyrotropin-releasing hormone.;This hormone is produced by the hypothalamus and it also stimulates the pituitary gland to make thyroid stimulating hormone.;
What Is Thyroid Medication
Thyroid Hormone Treatment Levothyroxine is thestandard of care in thyroid hormone replacement therapy and treatment of hypothyroidism. Levothyroxine is equivalent to the T4 form of naturally occurring thyroid hormone and is available in generic and brand name forms.
How do I take levothyroxine? To optimize absorption of your thyroid medication, it should be taken with water at a regular time each day. Multiple medications and supplements decrease absorption of thyroid hormone and should be taken 3-4 hours apart, including calcium and iron supplements, proton pump inhibitors, soy, and multivitamins with minerals. Because of the way levothyroxine is metabolized by the body, your doctor may ask you to take an extra pill or skip a pill on some days of the week. This helps us to fine tune your medication dose for your body and should be guided by an endocrinologist.
For patients with celiac disease or gluten sensitivity, a gluten free formulation of levothyroxine is available.
Some individuals may have genetic variant that affects how the body converts T4 to T3 and these individuals may benefit from the addition of a small dose of triiodothyronine.
Liothyronine is replacement T3 thyroid hormone. This medication has a short half-life and is taken twice per day or in combination with levothyroxine. Liothyronine alone is not used for treatment of hypothyroidism long term.
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What Are Thyroid Antibodies
Sometimes the immune system mistakenly attacks your thyroid gland with antibodies. This damages your thyroid and can lead to inflammation of the thyroid gland , symptoms of hypothyroidism or hyperthyroidism, and if left unchecked, autoimmune thyroid disease.
Hashimotos is diagnosed by blood tests looking for:
You have autoimmune hypothyroidism if you have elevated thyroid antibodies and also have:
- Low T4
- Elevated thyroid stimulating hormone levels.
Not everyone who has thyroid antibodies is hypothyroid, but some people with elevated TPO or TG antibodies will eventually become hypothyroid. The question is, how likely is it you will become hypothyroid if your antibodies are elevated?
How Is Hypothyroidism Diagnosed
Your health care provider may use many tools to make a diagnosis:
- A medical history, including asking about your symptoms
- A physical exam
- Imaging tests, such as a thyroid scan, ultrasound, or radioactive iodine uptake test. A radioactive iodine uptake test measures how much radioactive iodine your thyroid takes up from your blood after you swallow a small amount of it.
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How Does The Thyroid Gland Function
The major thyroid hormone secreted by the thyroid gland is thyroxine, also called T4 because it contains four iodine atoms. To exert its effects, T4 is converted to triiodothyronine by the removal of an iodine atom. This occurs mainly in the liver and in certain tissues where T3 acts, such as in the brain. The amount of T4 produced by the thyroid gland is controlled by another hormone, which is made in the pituitary gland located at the base of the brain, called thyroid stimulating hormone . The amount of TSH that the pituitary sends into the bloodstream depends on the amount of T4 that the pituitary sees. If the pituitary sees very little T4, then it produces more TSH to tell the thyroid gland to produce more T4. Once the T4 in the bloodstream goes above a certain level, the pituitarys production of TSH is shut off. In fact, the thyroid and pituitary act in many ways like a heater and a thermostat. When the heater is off and it becomes cold, the thermostat reads the temperature and turns on the heater. When the heat rises to an appropriate level, the thermostat senses this and turns off the heater. Thus, the thyroid and the pituitary, like a heater and thermostat, turn on and off. This is illustrated in the figure below.
What Makes Tsh Fluctuate
The release of TSH is first stimulated by a hormone called TRH.
Once the thyroid stimulating hormone makes its way to your thyroid, levels are largely dictated by the amount of T3 and T4 in your blood.
When T3 and T4 levels are low, the body produces more TSH to stimulate the thyroid. But when T3 and T4 levels are high, the body produces less .
Image . Click to enlarge.
Several other factors can also influence TSH levels:
- Inflammation of the thyroid gland
Those with Graves disease have high low TSH and subsequent high thyroid hormone levels. Hashimotos disease is the opposite.
Summary: Low TSH typically;indicates excessive thyroid hormone levels, while high TSH indicates thyroid hormone deficiency.
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What Should Your Tsh Level Be
Normal TSH levels for the average adult range from 0.4 4.0 mIU/L .
However, many organizations agree that a reading of 2.5 or less is truly ideal for normal thyroid levels, with anything 2.5 4.0 mIU/L considered at risk.
For those on thyroxine, the ideal TSH normal range is between 0.5 to 2.5 mU/L.
The reference ranges alter slightly as we grow older and if you are pregnant:
TSH Normal Range By Age:
For premature birth;
- 0.727 mIU/L
- Birth to 4 days: 139 mIU/L
- 220 weeks: 1.79.1 mIU/L
- 21 weeks to 20 years: 0.764 mIU/L
- 2154 years:;0.44.2 mIU/L
- 5587 years:;0.58.9 mIU/L
- First trimester:;0.34.5 mIU/L
- Second trimester:;0.34.6 mIU/L
- Third trimester:;0.85.2 mIU/L
Small variations in results can occur depending on the laboratory and its methods used, as well as the time of day your blood was taken.
Summary: Normal levels range from 0.4 4.0 mIU/L for the average adult.
How Is A Thyroid Biopsy Performed
A thyroid biopsy, also called a fine needle aspiration , uses a small needle to take a little sample of the cells in the thyroid nodule. The possible outcomes from a biopsy are:
Non-diagnostic: Non-diagnostic is a technically failed biopsy. There were not enough cells taken during the biopsy so the cytologist was not able to determine anything. These usually need to be repeated.
Benign: Most thyroid nodule biopsies come back benign, meaning your doctor is highly re-assured that it’s not cancerous. Patients can almost always avoid surgery unless the nodule is large and pushing on adjacent structures like the airway.
Indeterminate:; Indeterminate means there was enough cells taken during the biopsy, but the cytopathologist was not sure if it is benign or malignant. Indeterminate results occur in about 20% of thyroid biopsies. This is a gray zone and means that the risk of cancer is about 10-30%. These nodules require additional work-up such as a repeat biopsy, molecular marker test, or surgical removal.
Suspicious for Malignancy or Malignant: Results categorized in these two categories are a strong indicator that there is cancer present and usually require surgical removal.
Patients usually wait one week for the cytopathologist to examine the cellular characteristic of the biopsy sample. If your doctor is reassured that it’s benign based on the biopsy result, further work-up is stopped and serial ultrasound surveillance is recommended usually once a year.
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In People Without Known Thyroid Disease
A high TSH in people who are not undergoing thyroid disease treatment usually indicates the presence of primary hypothyroidism.
This is by far the most common form of hypothyroidism, and it occurs because the thyroid gland produces an inadequate amount of thyroid hormones. The pituitary gland senses these low levels and increases the production of TSH.
An elevated TSH may also occur with normal thyroid function due to the presence of antibodies, proteins made by the immune system.
What Is A Normal Thyroid Level
Tests often used to assess thyroid hormone status include TSH and FT4 tests. The normal value for a laboratory test is determined by measuring the hormone in a large population of healthy individuals and finding the normal reference range. Normal ranges for thyroid tests may vary slightly among different laboratories, and typical ranges for common tests are given below.
TSH normal values are 0.5 to 5.0 mIU/L. Pregnancy, a history of thyroid cancer, history of pituitary gland disease, and older age are some situations when TSH is optimally maintained in different range as guided by an endocrinologist.
FT4 normal values are 0.7 to 1.9ng/dL. Individuals taking medications that modify thyroid hormone metabolism and those with a history of thyroid cancer or pituitary disease may be optimally managed with a different normal FT4 range.
Total T4 and Total T3 levels measure bound and free thyroid hormone in the blood. These levels are influenced by many factors that affect protein levels in the body, including medications, sex hormones, and liver disease. A normal Total T4 level in adults ranges from 5.0 to 12.0g/dL. A normal Total T3 level in adults ranges from 80-220 ng/dL.
Free T3 assays are often unreliable and not routinely used to assess thyroid function.
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Problems Caused By Low Or High Tsh Levels
There can be complications in the body if the person has imbalanced TSH levels. This may lead to hypothyroidism or hyperthyroidism.
Hypothyroidism occurs when the thyroid does not produce enough T3 and T4 hormones. This means that the thyroid is underactive, which may lead to energy loss and lethargy. The body may also experience changes, such as dry skin and brittle, dull hair.
The person who is experiencing hypothyroidism may also have difficulty in losing weight. It may also affect the bodys reproductive system. Men run the risk of infertility and high cholesterol. On the other hand, women may have chances of birth defects or miscarriage.;;
Hyperthyroidism is the state in which the thyroid gland is overactive and produces too much T3 and T4 hormones. Having too much thyroid hormones in the body is just as bad as having too little thyroid hormones as it may cause a barrage of ill effects as well. An individual suffering from hyperthyroidism may experience restlessness, hyperactivity, anxiety, irritability, and palpitations and may have a high risk of developing a goiter.
Thyroxine Triiodothyronine And Tsh Levels
The main job of the thyroid gland is to make the hormone thyroxine, also known as T4 because it has four iodine molecules. The thyroid also makes the hormone triiodothyronine, known as T3 because it has three iodine molecules, but in smaller amounts, explains Cathy Doria-Medina, MD, an endocrinologist with HealthCare Partners Medical Group in Torrance, California. The thyroid gland makes mostly T4, the T4 has to be converted to T3, because T3 is the part of thyroxine that actually does the work, she says.
The pituitary gland at the base of the brain controls hormone production in your body. It makes thyroid-stimulating hormone , which tells the thyroid gland how much T4 and T3 to produce. The TSH level in your blood reveals how much T4 your pituitary gland is asking your thyroid gland to make. If your TSH levels are abnormally high, it could mean you have an underactive thyroid, or hypothyroidism. Thats because it indicates your pituitary gland is producing more TSH in an effort to stimulate your thyroid to produce thyroid hormone, according to the Mayo Clinic.
TSH levels go in the opposite direction of your thyroid hormone, Dr. Doria-Medina explains. If youre making too little thyroid hormone, your TSH will go up. If youre making too much thyroid hormone, your TSH will go down.
If your TSH is higher than 4.0 mU/L on repeat tests, you probably have hypothyroidism.
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