Thyroid function tests

Routinely three hormones are often measured namely Thyroxine, tri-iodothyronine and Thyroid Stimulating Hormone (TSH).

Thyroxine is found in the blood in two forms i.e. bound to proteins and free of protein binding.The free component is the active form of the hormone and comprises only 0.03% of the circulating total T4. Some laboratories still measure total thyroxine which comprises both the bound and free forms. The trouble with this is that the level of total thyroxine very much depends on the amount bound to proteins and therefore the level of binding proteins in the blood. The major protein binding thyroxine is called Thyroid Binding Protein (TBG). TBG can be low in some patients due to an inherited but seemingly harmless deficiency. In these patients total thyroxine is low but the free and active component is normal. Medicines such as the contraceptive pill and life events such as pregnancy can also alter binding proteins giving spuriously high levels of total thyroxine.

For these reasons most laboratories have now introduced the measurement of free thyroxine and this is what we measure.

There are two assays available, one measures total T3 and the other free T3. The total T3 comprises of both protein bound and free T3. The free component is the active form and comprises 0.3% of total circulating T3. Gradually laboratories are moving over to free T3 measurements as more reliable free T3 assays become available.T3 is the biologically active thyroid hormone, possessing 5 times the metabolic power of T4. In man some 80% of T3 is produced from T4 by conversion in liver and kidney. Therefore little is produced in the thyroid itself. The conversion of T4 to T3 can depend on a number of situations such as chronic illness or surgical stress which cause a fall in T4 to T3 conversion (called low T3 syndrome). Starvation also alters T4 to T3 conversion with a fall in T3 as the body tries to reduce its metabolism to conserve energy.

T3 alters the metabolism of the body. It alters protein manufacture, cellular activity and is essential for growth and well being. Without T3 the patient develops hypothyroidism. Too much and the patient develops an overactive thyroid called thyrotoxicosis.

TSH

TSH is released by the pituitary gland and circulates in the blood stream to the thyroid where it controls release of the thyroid hormones T4 and T3. TSH release is very sensitive to alterations in the blood thyroid hormones, with small decreases augmenting TSH secretion and small increases reducing release. Therefore in hypothyroidism, TSH is raised above normal reference ranges whereas in thyotoxicosis TSH is suppressed into the undetectable range. In thyrotoxicosis the thyroid automatically manufactures too much T4 and T3 without the need for TSH to switch on. As TSH is so sensitive to changes in thyroid hormone levels it is used as the number one test for screening for thyroid disease. If the laboratories notice a raised TSH then automatically T4 is measured. If the laboratories notice a suppressed TSH then T4 and T3 are measured. Why both? Because there are some patients whose thyroid oversecrete only T3 called T3 Toxicosis and both hormones need to be measured to detect this form of thyrotoxicosis; it is usually seen in those who have had previously a thyroidectomy or radioactive iodine for thyrotoxicosis in the past.

T4, T3 and TSH are compared to what is known as the reference range. These are the values which one might expect to see in a normal population who are healthy. Most healthy people have results which lie within the range, and if they do not then investigations are required. However a reference range can vary slightly from one hospital to another, possibly due to various factors such as iodine content in the diet etc. Therefore the specialist has to be aware that not all patients fit into the reference range and borderline levels still within the range can actually be indicative of borderline disease. This is where the TRH test can be useful to sort out normal from abnormal.

When the level of TSH is borderline low or high sometimes the specialist will request a TRH test. This a hormone released by the brain (hypothalamus) which controls the pituitary release of TSH. By using this simple test the specialist can tell whether a patient has in reality an overactive, normal or underactive thyroid

These are circulating antibodies to various thyroid gland components and indicate something may be amiss when the body is directing the immune response against itself, a so called "autoimmune" phenomenon.. The major antibody measured is thyroid microsomal antibody  another antibody now less often measured is thyroglobulin antibody. What do these indicate? Possible disease of the thyroid and the need for thyroid hormone surveillance. Why? Because a certain low number of patients with thyroid antibodies develop hypothyroidism over years if not decades.

A third antibody commonly measured is TRAB i.e. Thyroid Receptor Activating Antibody, which is raised in some forms of thyrotoxicosis and is the cause of the disease. Obviously if TRAB remains elevated then the disease process is still active.

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Ó NHS Tayside; 2006; version 1.0

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