How Your Thyroid Works 
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Common Thyroid Problems
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Common Tests to  Examine
 Thyroid Gland Function
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Thyroid Hormone
    TSH / T3 / FT3 / T4 /
    FT4
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Normal Laboratory Values
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The thyroid gland is the biggest gland in the neck. It is situated in the anterior (front) neck below the skin and muscle layers. The thyroid gland takes the shape of a butterfly with the two wings being represented by the left and right thyroid lobes which wrap around the trachea. The sole function of the thyroid is to make thyroid hormone. This hormone has an effect on nearly all tissues of the body where it increases cellular  activity. The function of the thyroid therefore is to regulate the body's metabolism.
thyroid cancer tumor surgery operation condition thyroid parathyroid disease disease tumor

  Your thyroid gland is a small gland, normally weighing less than one ounce, located in the front of the neck. It is made up of two halves, called lobes, that lie along the windpipe (trachea) and are joined together by a narrow band of thyroid tissue, known as the isthmus.

The thyroid is situated just below your "Adams apple" or larynx. During development (inside the womb) the thyroid gland originates in the back of the tongue, but it normally migrates to the front of the neck before birth. Sometimes it fails to migrate properly and is located high in the neck or even in the back of the tongue (lingual thyroid) This is very rare. At other times it may migrate too far and ends up in the chest (this is also rare).

The function of the thyroid gland is to take iodine, found in many foods, and convert it into thyroid hormones: thyroxine (T4) and triiodothyronine (T3). Thyroid cells are the only cells in the body which can absorb iodine. These cells combine iodine and the amino acid tyrosine to make T3 and T4. T3 and T4 are then released into the blood stream and are transported throughout the body where they control metabolism (conversion of oxygen and calories to energy). Every cell in the body depends upon thyroid hormones for regulation of their metabolism. The normal thyroid gland produces about 80% T4 and about 20% T3, however, T3 possesses about four times the hormone "strength" as T4.



The thyroid gland is under the control of the pituitary gland, a small gland the size of a peanut at the base of the brain (shown here in orange). When the level of thyroid hormones (T3 & T4) drops too low, the pituitary gland produces Thyroid Stimulating Hormone (TSH) which stimulates the thyroid gland to produce more hormones. Under the influence of TSH, the thyroid will manufacture and secrete T3 and T4 thereby raising their blood levels. The pituitary senses this and responds by decreasing its TSH production. One can imagine the thyroid gland as a furnace and the pituitary gland as the thermostat. Thyroid hormones are like heat. When the heat gets back to the thermostat, it turns the thermostat off. As the room cools (the thyroid hormone levels drop), the thermostat turns back on (TSH increases) and the furnace produces more heat (thyroid hormones).


The pituitary gland itself is regulated by another gland, known as the hypothalamus (shown in our picture in light blue). The hypothalamus is part of the brain and produces TSH Releasing Hormone (TRH) which tells the pituitary gland to stimulate the thyroid gland (release TSH). One might imagine the hypothalamus as the person who regulates the thermostat since it tells the pituitary gland at what level the thyroid should be set.

The thyroid gland is prone to several very distinct problems, some of which are extremely common. These problems can be broken down into [1] those concerning the production of hormone (too much, or too little), [2] those due to increased growth of the thyroid causing compression of important neck structures or simply appearing as a mass in the neck, [3] the formation of nodules or lumps within the thyroid which are worrisome for the presence of thyroid cancer, and [4] those which are cancerous. Each thyroid topic is addressed separately and illustrated with actual patient x-rays and pictures to make them easier to understand. The information on this web site is arranged to give you more detailed and complex information as you read further.

• Goiters ~ A thyroid goiter is a dramatic enlargement of the thyroid gland. Goiters are often removed because of cosmetic reasons or, more commonly, because they compress other vital structures of the neck including the trachea and the esophagus making breathing and swallowing difficult. Sometimes goiters will actually grow into the chest where they can cause trouble as well. Several nice x-rays will help explain all types of thyroid goiter problems.
  

• Thyroid Cancer ~ Thyroid cancer is a fairly common malignancy, however, the vast majority have excellent long term survival. We now include a separate page on the characteristics of each type of thyroid cancer and its typical treatment, follow-up, and prognosis. Over 30 pages thyroid cancer.
  
  
• Solitary Thyroid Nodules ~ There are several characteristics of solitary nodules of the thyroid which make them suspicious for malignancy. Although as many as 50% of the population will have a nodule somewhere in their thyroid, the overwhelming majority of these are benign. Occasionally, thyroid nodules can take on characteristics of malignancy and require either a needle biopsy or surgical excision. Now includes risks of radiation exposure and the role of Needle Biopsy for evaluating a thyroid nodule. Also a new page on the role of ultrasound in diagnosing thyroid nodules and masses.
  

• Hyperthyroidism ~ Hyperthyroidism means too much thyroid hormone. Current methods used for treating a hyperthyroid patient are radioactive iodine, anti-thyroid drugs, or surgery. Each method has advantages and disadvantages and is selected for individual patients. Many times the situation will suggest that all three methods are appropriate, while other circumstances will dictate a single best therapeutic option. Surgery is the least common treatment selected for hyperthyroidism. The different causes of hyperthyroidism are covered in detail.
  
  
• Hypothyroidism ~ Hypothyroidism means too little thyroid hormone and is a common problem. In fact, hypothyroidism is often present for a number of years before it is recognized and treated. There are several common causes, each of which are covered in detail. Hypothyroidism can even be associated with pregnancy. Treatment for all types of hypothyroidism is usually straightforward.
  
  
• Thyroiditis ~ Thyroiditis is an inflammatory process ongoing within the thyroid gland. Thyroiditis can present with a number of symptoms such as fever and pain, but it can also present as subtle findings of hypo or hyper-thyroidism. There are a number of causes, some more common than others. Each is covered on this site.

Some information on this page is a little more advanced.
If you have trouble understanding the process of normal thyroid function,
please go to our page describing this process first.

As we have seen from our overview of normal thyroid physiology, the thyroid gland produces T4 and T3. But this production is not possible without stimulation from the pituitary gland (TSH) which in turn is also regulated by the hypothalamus's TSH Releasing Hormone. Now, with radioimmunoassay techniques it is possible to measure circulating hormones in the blood very accurately. Knowledge of this thyroid physiology is important in knowing what thyroid test or tests are needed to diagnose different diseases. No one single laboratory test is 100% accurate in diagnosing all types of thyroid disease; however, a combination of two or more tests can usually detect even the slightest abnormality of thyroid function.

For example, a low T4 level could mean a diseased thyroid gland ~ OR ~ a non-functioning pituitary gland which is not stimulating the thyroid to produce T4. Since the pituitary gland would normally release TSH if the T4 is low, a high TSH level would confirm that the thyroid gland (not the pituitary gland) is responsible for the hypothyroidism.

If the T4 level is low and TSH is not elevated, the pituitary gland is more likely to be the cause for the hypothyroidism. Of course, this would drastically effect the treatment since the pituitary gland also regulates the body's other glands (adrenals, ovaries, and testicles) as well as controlling growth in children and normal kidney function. Pituitary gland failure means that the other glands may also be failing and other treatment than just thyroid may be necessary. The most common cause for the pituitary gland failure is a tumor of the pituitary and this might also require surgery to remove.

• Modern measurement of thyroid hormones is done by a new technique, radioimmunoassay (RIA), discovered by Dr. Solomon Berson and Dr. Rosalyn Yallow. They were awarded the 1977 Nobel Prize in Medicine for this discovery which revolutionized the study of thyroid disease as well as the entire field of endocrinology.
  

Measurement of Serum Thyroid Hormones: T4 by RIA. T4 by RIA (radioimmunoassay) is the most used thyroid test of all. It is frequently referred to as a T7 which means that a resin T3 uptake (RT3u) has been done to correct for certain medications such as birth control pills, other hormones, seizure medication, cardiac drugs, or even aspirin that may alter the routine T4 test. The T4 reflects the amount of thyroxine in the blood. If the patient does not take any type of thyroid medication, this test is usually a good measure of thyroid function.

Measurement of Serum Thyroid Hormones: T3 by RIA. As stated on our thyroid hormone production page, thyroxine (T4) represents 80% of the thyroid hormone produced by the normal gland and generally represents the overall function of the gland. The other 20% is triiodothyronine measured as T3 by RIA. Sometimes the diseased thyroid gland will start producing very high levels of T3 but still produce normal levels of T4. Therefore measurement of both hormones provides an even more accurate evaluation of thyroid function.

Thyroid Binding Globulin. Most of the thyroid hormones in the blood are attached to a protein called thyroid binding globulin (TBG). If there is an excess or deficiency of this protein it alters the T4 or T3 measurement but does not affect the action of the hormone. If a patient appears to have normal thyroid function, but an unexplained high or low T4, or T3, it may be due to an increase or decrease of TBG. Direct measurement of TBG can be done and will explain the abnormal value. Excess TBG or low levels of TBG are found in some families as an hereditary trait. It causes no problem except falsely elevating or lowering the T4 level. These people are frequently misdiagnosed as being hyperthyroid or hypothyroid, but they have no thyroid problem and need no treatment.

Measurement of Pituitary Production of TSH. Pituitary production of TSH is measured by a method referred to as IRMA (immunoradiometric assay). Normally, low levels (less than 5 units) of TSH are sufficient to keep the normal thyroid gland functioning properly. When the thyroid gland becomes inefficient such as in early hypothyroidism, the TSH becomes elevated even though the T4 and T3 may still be within the "normal" range. This rise in TSH represents the pituitary gland's response to a drop in circulating thyroid hormone; it is usually the first indication of thyroid gland failure. Since TSH is normally low when the thyroid gland is functioning properly, the failure of TSH to rise when circulating thyroid hormones are low is an indication of impaired pituitary function. The new "sensitive" TSH test will show very low levels of TSH when the thyroid is overactive (as a normal response of the pituitary to try to decrease thyroid stimulation). Interpretations of the TSH level depends upon the level of thyroid hormone; therefore, the TSH is usually used in combination with other thyroid tests such as the T4 RIA and T3 RIA.

 More information about TSH Test


TRH Test. In normal people TSH secretion from the pituitary can be increased by giving a shot containing TSH Releasing Hormone (TRH...the hormone released by the hypothalamus which tells the pituitary to produce TSH). A baseline TSH of 5 or less usually goes up to 10-20 after giving an injection of TRH. Patients with too much thyroid hormone (thyroxine or triiodothyronine) will not show a rise in TSH when given TRH. This "TRH test" is presently the most sensitive test in detecting early hyperthyroidism. Patients who show too much response to TRH (TSH rises greater than 40) may be hypothyroid. This test is also used in cancer patients who are taking thyroid replacement to see if they are on sufficient medication. It is sometimes used to measure if the pituitary gland is functioning. The new "sensitive" TSH test (above) has eliminated the necessity of performing a TRH test in most clinical situations.

 More information about TRH Test


Iodine Uptake Scan. A means of measuring thyroid function is to measure how much iodine is taken up by the thyroid gland (RAI uptake). Remember, cells of the thyroid normally absorb iodine from our blood stream (obtained from foods we eat) and use it to make thyroid hormone (described on our thyroid function page). Hypothyroid patients usually take up too little iodine and hyperthyroid patients take up too much iodine. The test is performed by giving a dose of radioactive iodine on an empty stomach. The iodine is concentrated in the thyroid gland or excreted in the urine over the next few hours. The amount of iodine that goes into the thyroid gland can be measured by a "Thyroid Uptake". Of course, patients who are taking thyroid medication will not take up as much iodine in their thyroid gland because their own thyroid gland is turned off and is not functioning. At other times the gland will concentrate iodine normally but will be unable to convert the iodine into thyroid hormone; therefore, interpretation of the iodine uptake is usually done in conjunction with blood tests.

Thyroid Scan. Taking a "picture" of how well the thyroid gland is functioning requires giving a radioisotope to the patient and letting the thyroid gland concentrate the isotope (just like the iodine uptake scan above). Therefore, it is usually done at the same time that the iodine uptake test is performed. Although other isotopes, such as technetium, will be concentrated by the thyroid gland; these isotopes will not measure iodine uptake which is what we really want to know because the production of thyroid hormone is dependent upon absorbing iodine. It has also been found that thyroid nodules that concentrate iodine are rarely cancerous; this is not true if the scan is done with technetium. Therefore, all scans are now done with radioactive iodine. Both of the scans above show normal sized thyroid glands, but the one on the left has a "HOT" nodule in the lower aspect of the right lobe, while the scan on the right has a "COLD" nodule in the lower aspect of the left lobe (outlined in red and yellow). Pregnant women should not have thyroid scans performed because the iodine can cause development troubles within the baby's thyroid gland.

• Two types of thyroid scans are available. A camera scan is performed most commonly which uses a gamma camera operating in a fixed position viewing the entire thyroid gland at once. This type of scan takes only five to ten minutes. In the 1990's, a new scanner called a Computerized Rectilinear Thyroid (CRT) scanner was introduced. The CRT scanner utilizes computer technology to improve the clarity of thyroid scans and enhance thyroid nodules. It measures both thyroid function and thyroid size. A life-sized 1:1 color scan of the thyroid is obtained giving the size in square centimeters and the weight in grams. The precise size and activity of nodules in relation to the rest of the gland is also measured. CTS of the normal thyroid gland In addition to making thyroid diagnosis more accurate, the CRT scanner improves the results of thyroid biopsy. The accurate sizing of the thyroid gland aids in the follow-up of nodules to see if they are growing or getting smaller in size. Knowing the weight of the thyroid gland allows more accurate radioactive treatment in patients who have Graves' disease.

Identifying nodules and determining if they are 
                  "hot" or "cold".

Measuring the size of the goiter prior to treatment.

Follow-up of thyroid cancer patients after surgery.

Locating thyroid tissue outside the neck, i.e. base of the 
                 tongue or in the chest.



Thyroid Ultrasound. Thyroid ultrasound refers to the use of high frequency sound waves to obtain an image of the thyroid gland and identify nodules. It tells if a nodule is "solid" or a fluid-filled cyst, but it will not tell if a nodule is benign or malignant. Ultrasound allows accurate measurement of a nodule's size and can determine if a nodule is getting smaller or is growing larger during treatment. Ultrasound aids in performing thyroid needle biopsy by improving accuracy if the nodule cannot be felt easily on examination. Several more pages are dedicated to the use of ultrasound in evaluating thyroid nodules.

Thyroid Antibodies. The body normally produces antibodies to foreign substances such as bacteria; however, some people are found to have antibodies against their own thyroid tissue. A condition known as Hashimoto's Thyroiditis is associated with a high level of these thyroid antibodies in the blood. Whether the antibodies cause the disease or whether the disease causes the antibodies is not known; however, the finding of a high level of thyroid antibodies is strong evidence of this disease. Occasionally, low levels of thyroid antibodies are found with other types of thyroid disease. When Hashimoto's thyroiditis presents as a thyroid nodule rather than a diffuse goiter, the thyroid antibodies may not be present.

Thyroid Needle Biopsy. This has become the most reliable test to differentiate the "cold" nodule that is cancer from the "cold" nodule that is benign ("hot" nodules are rarely cancerous). It provides information that no other thyroid test will provide. While not perfect, it will provide definitive information in 75% of the nodules biopsied. A very extensive discussion of Thyroid Needle Biopsy is found on another page.

Since Euthyrox or Synthroid (and most other thyroid pills) behave exactly as normal human thyroid hormone, they are not rapidly cleared from the body as other medications are. Most thyroid pills have a half life of 6.7 days which means they must be stopped for four to five weeks (five half lives) before accurate thyroid testing is possible. An exception to the long half life of thyroid medication is Cytomel - a thyroid pill with a half life of only forty-eight hours. Therefore it is possible to change a person's thyroid replacement to Cytomel for one month to allow time for his regular pills to clear the body. Cytomel is then stopped for ten days (five half lives) and the appropriate test can then be done. Usually patients, even those who have no remaining thyroid function, tolerate being off thyroid replacement only ten days quite well.

Thyroid Function Tests

TSH (Thyroid Stimulation Hormone) 

Specimen Required: 2 mL blood. Plain tube 
Minimum Referred Volume: 0.4 mL serum 
Reference Interval: 0.3 - 4.0 mU/L 
Imprecision: ? 5% 
Turnaround Time: 1 day 

How the Test is Performed: 
Adult or child: 
Blood is drawn from a vein ( venipuncture ), usually from the inside of the elbow or the back of the hand. The puncture site is cleaned with antiseptic, and a tourniquet (an elastic band) or blood pressure cuff is placed around the upper arm to apply pressure and restrict blood flow through the vein. This causes veins below the tourniquet to distend (fill with blood). A needle is inserted into the vein, and the blood is collected in an air-tight vial or a syringe. During the procedure, the tourniquet is removed to restore circulation. Once the blood has been collected, the needle is removed, and the puncture site is covered to stop any bleeding . 

Infant or young child: 
The area is cleansed with antiseptic and punctured with a sharp needle or a lancet. The blood may be collected in a pipette (small glass tube), on a slide, onto a test strip, or into a small container. Cotton or a bandage may be applied to the puncture site if there is any continued bleeding. 



Why this Test is Performed: 
TSH is measured to differentiate primary versus secondary hyperthyroidism or hypothyroidism . Primary hypothyroidism , for example, results from decreased production of T3 and T4 by the thyroid gland in spite of normal or increased stimulation by TSH. Secondary hypothyroidism results from decreased production of T3 and T4 as a result of decreased secretion of TSH from the pituitary gland. 

TSH is secreted by the pituitary and stimulates secretion of T4 and T3 from the thyroid gland. TSH is, itself, stimulated by TRH, which is released by the hypothalamus . T3 and T4 feedback inhibit the release of both TSH and TRH in normal people. 

Normal Values: 
0.2 to 4.7 mcU/ml 

Note: mcU/ml = microunits per milliliter 

Abnormal Results: 
Greater-than-normal levels may indicate: 

congenital hypothyroidism (cretinism) 
hypothyroidism; primary 
hypothyroidism; secondary 
thyroiditis 
Lower-than-normal levels may indicate: 

hyperthyroidism 
hypopituitarism 
Additional conditions under which the test may be performed: 

colloid nodular goiter 
delirium 
dementia 
drug-induced hypothyroidism 
goiter 
graves' disease 
multiple endocrine neoplasia (MEN) I 
subacute thyroiditis 
thyrotoxic periodic paralysis 
toxic nodular goiter 


Special Considerations: 
Drugs that can increase TSH measurements include antithyroid medications, lithium, and potassium iodide. 

Drugs that can decrease TSH measurements include aspirin, dopamine , heparin, and corticosteroids. 

Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. 





TRH-Stimulation Testing
[Q&As are placed in reverse chronological order. In other words,
the latest Q&As come first. Earlier ones are further down the page.]

Date: April 12, 2000

Question: Mary Shomon recommended your website for information on problems with the conversion of thyroid hormone. I have most of the symptoms on a checklist for hypothyroidism. Interestingly, two doctors told me that some of my symptoms are fibromyalgia, but they don’t know the cause of my other symptoms. To me, all the symptoms could be hypothyroidism or the problem converting T4 to T3 that Dr. Dennis Wilson writes about. Hypothyroidism is common in my family. However, my doctor has ordered TSH and T4 levels twice, and both times the levels were normal. Since my lab tests are normal, does this mean my "hypothyroid"symptoms are caused by a conversion problem? 

Dr. Lowe: No—the clinical picture you describe (normal TSH and T4 levels in someone with hypothyroid-like symptoms) does not necessarily point to a problem in converting T4 to T3. In fact, it is highly unlikely that impaired conversion is the problem. Instead, you may be hypothyroid despite normal TSH and T4 test results. Bear in mind the definition of hypothyroidism: lower-than-normal blood levels of thyroid hormone due to an underactive thyroid gland. Our TSH and thyroid hormone levels vary during the day and from day-to-day during the week. It’s possible that when you were tested, your TSH and T4 levels were within the normal range, but that the levels are abnormal at other times. As a result, on average, your tissue may have too little stimulation by thyroid hormone. Also, recent evidence suggests that the so-called "normal" ranges may be too wide. As a result, some people’s doctors may believe their test results are normal when in fact the patients are hypothyroid. 

In addition, you might have central hypothyroidism. In central hypothyroidism, the thyroid gland is underactive. As a result, the blood level of thyroid hormone is too low, at least part of the time. But the cause of the underactive thyroid gland and low thyroid hormone level is not an abnormality of the thyroid gland. Instead, the cause is a dysfunction of the pituitary gland or hypothalamus. When a patient’s standard thyroid test results are normal, the doctor should always consider the possibility of central hypothyroidism. The best way to test for this form of hypothyroidism is the TRH stimulation test. With this test, we identify many patients who’re hypothyroid, although their standard thyroid test results are normal. 

Some patients do have impaired conversion of T4 to T3. However, the available scientific evidence suggests that at the longest, impaired conversion lasts only a few weeks. I know of no scientific evidence supporting Dr. Dennis Wilson’s speculation that some patients have chronically impaired conversion of T4 to T3. When patients have impaired T4 to T3 conversion, they also have a predictable pattern of lab test results. However, despite extensive testing, one other researcher and I have never found this predictable lab test pattern in fibromyalgia outpatients. 

Date: April 15, 1998

Question—Part 1: I am a 44-year old male diagnosed with fibromyalgia four years ago. About two years ago my chiropractor brought to my attention your work relating hypothyroidism with fibromyalgia. My family doctor was curious so he ordered T4 and TSH tests which both come back normal, but both at the very low-normal end (T4 = 0.70; TSH = 0.44). I took the tests to an internist who dismissed my thyroid tests as normal. At my insistence, he referred me to an endocrinologist who was curious about your work, but he also thought my thyroid tests were normal. He did order the TRH and CRH stimulation tests, which both came out "normal." However, my TSH during the TRH test only reached a maximum of 6.8. Isn't this a "blunted" response?

Dr. Lowe: Yes, your TSH response of 6.8 ตIU/mL was blunted. (The range of normal for the TSH level 30 minutes following a TRH injection is 8.5-to-20.0 ตIU/mL above the baseline TSH value.) My conclusion, however, isn't based only on the result of your TRH stimulation test. Both your T4 and baseline TSH levels were low (and in later testing, your T3 was also low). It is abnormal for your TSH level also to be low when your T4 and T3 levels are low. Normally, the TSH level is inversely related to the T4 and T3 levels: When the T4 and T3 levels are low, a "normal" anterior pituitary gland increases its output of TSH.

That your TSH level was low despite your low T4 and T3 levels suggests that your pituitary gland is not able to synthesize and secrete normal amounts of TSH. This was confirmed by your TRH stimulation test. TRH, a hormone secreted by the hypothalamus, stimulates your pituitary gland to secrete TSH. When the T4 level is low, an injection of TRH causes a normal pituitary gland to secrete an unusually large amount of TSH—an amount that exceeds the upper normal level of 20.0 ตIU/mL. The failure of your pituitary gland to secrete this increased amount in response to the TRH injection supports the hypothesis that your pituitary gland is not able to synthesize and secrete normal amounts of TSH. It is highly probable that your low T4, T3, and baseline TSH levels were all a result of a pituitary abnormality. That you were hypothyroid is indicated by your symptoms and your positive response to exogenous T4 and T3 (see below). The appropriate diagnosis, as your endocrinologist later concluded, is central (more specifically, pituitary) hypothyroidism.