Thyroid function tests
Thyroid function tests is a collective term for blood tests used to check the function of the thyroid.
TFTs may be requested if a patient is thought to suffer from hyperthyroidism or hypothyroidism, or to monitor the effectiveness of either thyroid-suppression or hormone replacement therapy. It is also requested routinely in conditions linked to thyroid disease, such as atrial fibrillation and anxiety disorder.
A TFT panel typically includes thyroid hormones such as thyroid-stimulating hormone and thyroxine, and triiodothyronine depending on local laboratory policy.
Thyroid-stimulating hormone
is generally increased in hypothyroidism and decreased in hyperthyroidism, making it the most important test for early detection of both of these conditions. The result of this assay is suggestive of the presence and cause of thyroid disease, since a measurement of elevated TSH generally indicates hypothyroidism, while a measurement of low TSH generally indicates hyperthyroidism. However, when TSH is measured by itself, it can yield misleading results, so additional thyroid function tests must be compared with the result of this test for accurate diagnosis.TSH is produced in the pituitary gland. The production of TSH is controlled by thyrotropin-releasing hormone, which is produced in the hypothalamus. TSH levels may be suppressed by excess free T3 or free T4 in the blood.
History
First-generation TSH assays were done by radioimmunoassay and were introduced in 1965. There were variations and improvements upon TSH radioimmunoassay, but their use declined as a new immunometric assay technique became available in the middle of the 1980s. The new techniques were more accurate, leading to the second, third, and even fourth generations of TSH assay, with each generation possessing ten times greater functional sensitivity than the last. Third generation immunometric assay methods are typically automated. Fourth generation TSH immunometric assay has been developed for use in research.Current status
Third generation TSH assay is the current requirement for modern standards of care. At present, TSH testing in the United States is typically carried out with automated platforms using advanced forms of immunometric assay. Nonetheless, there is currently no international standard for measurement of thyroid-stimulating hormone.Interpretation
Accurate interpretation takes a variety of factors into account, such as the thyroid hormones i.e. thyroxine and triiodothyronine, current medical status, certain medications like propylthiouracil, temporal effects including circadian rhythm and hysteresis, and other past medical history.Thyroid hormones
Total thyroxine
Total thyroxine is rarely measured, having been largely superseded by free thyroxine tests. Total thyroxine is generally elevated in hyperthyroidism and decreased in hypothyroidism. It is usually slightly elevated in pregnancy secondary to increased levels of thyroid binding globulin.Total T4 is measured to see the bound and unbound levels of T4. The total T4 is less useful in cases where there could be protein abnormalities. The total T4 is less accurate due to the large amount of T4 that is bound. The total T3 is measured in clinical practice since the T3 has decreased amount that is bound as compared to T4.
Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:
Free thyroxine
Free thyroxine is generally elevated in hyperthyroidism and decreased in hypothyroidism.Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:
Total triiodothyronine
Total triiodothyronine is rarely measured, having been largely superseded by free T3 tests. Total T3 is generally elevated in hyperthyroidism and decreased in hypothyroidism.Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:
Free triiodothyronine
Free triiodothyronine is generally elevated in hyperthyroidism and decreased in hypothyroidism.Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:
Carrier proteins
Thyroxine-binding globulin
An increased thyroxine-binding globulin results in an increased total thyroxine and total triiodothyronine without an actual increase in hormonal activity of thyroid hormones.Reference ranges:
Thyroglobulin
Reference ranges:Other binding hormones
- Transthyretin
- Albumin
Protein binding function
Thyroid hormone uptake
Thyroid hormone uptake is a measure of the unbound thyroxine binding globulins in the blood, that is, the TBG that is unsaturated with thyroid hormone. Unsaturated TBG increases with decreased levels of thyroid hormones. It is not directly related to triiodothyronine, despite the name T3 uptake.Reference ranges:
Other protein binding tests
- Thyroid Hormone Binding Ratio
- Thyroxine-binding index
Mixed parameters
Free thyroxine index
The Free Thyroxine Index is obtained by multiplying the total T4 with T3 uptake. FTI is considered to be a more reliable indicator of thyroid status in the presence of abnormalities in plasma protein binding. This test is rarely used now that reliable free thyroxine and free triiodothyronine assays are routinely available.FTI is elevated in hyperthyroidism and decreased in hypothyroidism.
Structure parameters
Derived structure parameters that describe constant properties of the overall feedback control system may add useful information for special purposes, e.g. in diagnosis of nonthyroidal illness syndrome or central hypothyroidism.Secretory capacity (''GT'')
is the maximum stimulated amount of thyroxine the thyroid can produce in one second. GT is elevated in hyperthyroidism and reduced in hypothyroidism.GT is calculated with
or
K41: Dissociation constant T4-TBG
K42: Dissociation constant T4-TBPA
DT: EC50 for TSH
Sum activity of peripheral deiodinases (''GD'')
The sum activity of peripheral deiodinases is reduced in nonthyroidal illness with hypodeiodination.GD is obtained with
or
KM1: Dissociation constant of type-1-deiodinase
K30: Dissociation constant T3-TBG
TSH index
helps to determine thyrotropic function of anterior pituitary on a quantitative level. It is reduced in thyrotropic insufficiency and in certain cases of non-thyroidal illness syndrome.It is calculated with
Additionally, a standardized form of TSH index may be calculated with
TTSI
The Thyrotroph Thyroid Hormone Sensitivity Index was developed to enable fast screening for resistance to thyroid hormone. Somewhat similar to the TSH Index it is calculated from equilibrium values for TSH and FT4, however with a different equation.TFQI
The Thyroid Feedback Quantile-based Index is another parameter for thyrotopic pituitary function. It was defined to be more robust to distorted data than JTI and TTSI. It is calculated withfrom quantiles of FT4 and TSH concentration. Per definition the TFQI has a mean of 0 and a standard deviation of 0.37 in a reference population. Higher values of TFQI are associated with obesity, metabolic syndrome, diabetes, and diabetes-related mortality.
Effects of drugs
Drugs can profoundly affect thyroid function tests. Listed below is a selection of important effects.Cause | Drug | Effect on hormone concentrations | Effect on structure parameters |
Inhibited TSH secretion | Dopamine, L-DOPA, glucocorticoids, somatostatin | ↓T4; ↓T3; ↓TSH | ↔SPINA-GT; ↓JTI |
Inhibited synthesis or release of thyroid hormone | Iodine, lithium | ↓T4; ↓T3; ↑TSH | ↓SPINA-GT; ↔JTI |
Inhibited conversion of T4 to T3 | Amiodarone, glucocorticoids, propranolol, propylthiouracil, radiographic contrast agents | ↓T3; ↑rT3; ↓, ↔, ↑T4 and fT4; ↔, ↑TSH | ↓SPINA-GD |
Inhibited binding of T4/T3 to serum proteins | Salicylates, phenytoin, carbamazepine, furosemide, nonsteroidal anti-inflammatory agents, heparin | ↓T4; ↓T3; ↓fT4E, ↔, ↑fT4; ↔TSH | ↓T4/fT4 ratio |
Stimulated metabolism of iodothyronines | Phenobarbital, phenytoin, carbamazepine, rifampicin | ↓T4; ↓fT4; ↔TSH | |
Inhibited absorption of ingested T4 | Aluminium hydroxide, ferrous sulfate, cholestyramine, colestipol, iron sucralfate, soybean preparations, kayexalate | ↓T4; ↓fT4; ↑TSH | |
Increase in concentration of T4-binding proteins | Estrogen, clofibrate, opiates, 5-fluorouracil, perphenazine | ↑T4; ↑T3; ↔fT4; ↔TSH | ↔SPINA-GT; ↔SPINA-GD; ↔JTI; ↑T4/fT4 ratio |
Decrease in concentration of T4-binding proteins | Androgens, glucocorticoids | ↓T4; ↓T3; ↔fT4; ↔TSH | ↔SPINA-GT; ↔SPINA-GD; ↔JTI; ↓T4/fT4 ratio |
↓: reduced serum concentration or structure parameter; ↑: increased serum concentration or structure parameter; ↔: no change; TSH: Thyroid-stimulating hormone; T3: Total triiodothyronine; T4: Total thyroxine; fT4: Free thyroxine; fT3: Free triiodothyronine; rT3: Reverse triiodothyronine
CDC laboratory procedure manuals
The Centers for Disease Control and Prevention has published the following laboratory procedure manuals for measuring thyroid-stimulating hormone:- . September 2011. Method: Access 2.
- . September 2011. Method: Access 2.
- . September 2009. Method: Access 2.
- . 2001-2002. Method: Microparticle Enzyme Immunoassay.
- . 1999-2000. Method: Microparticle Enzyme Immunoassay.
Beckman Coulter procedure manuals
- . 2010. Hosted by the University of California, San Francisco.
- http://www.tsh3rdgeneration.com. 2010. Hosted by manufacturer].