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.
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 affect 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.
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.
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.
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.
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.
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.
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.