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

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

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 with
from 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.
CauseDrugEffect on hormone concentrationsEffect on structure parameters
Inhibited TSH secretionDopamine, L-DOPA, glucocorticoids, somatostatin↓T4; ↓T3; ↓TSH↔SPINA-GT; ↓JTI
Inhibited synthesis or release of thyroid hormoneIodine, 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 proteinsSalicylates, phenytoin, carbamazepine, furosemide, nonsteroidal anti-inflammatory agents, heparin ↓T4; ↓T3; ↓fT4E, ↔, ↑fT4; ↔TSH↓T4/fT4 ratio
Stimulated metabolism of iodothyroninesPhenobarbital, phenytoin, carbamazepine, rifampicin↓T4; ↓fT4; ↔TSH
Inhibited absorption of ingested T4Aluminium hydroxide, ferrous sulfate, cholestyramine, colestipol, iron sucralfate, soybean preparations, kayexalate↓T4; ↓fT4; ↑TSH
Increase in concentration of T4-binding proteinsEstrogen, clofibrate, opiates, 5-fluorouracil, perphenazine↑T4; ↑T3; ↔fT4; ↔TSH↔SPINA-GT; ↔SPINA-GD; ↔JTI; ↑T4/fT4 ratio
Decrease in concentration of T4-binding proteinsAndrogens, 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:
provides the equipment and reagents used in the 2009-2011 CDC manuals, and has published the following manuals for performing the procedure: