Thyroid-stimulating hormone

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Thyroid-stimulating hormone, alpha
Identifiers
SymbolCGA
Alt. symbolsHCG, GPHa, GPHA1
Entrez1081
HUGO1885
OMIM118850
RefSeqNM_000735
UniProtP01215
Other data
LocusChr. 6 q14-q21
 
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Thyroid-stimulating hormone, alpha
Identifiers
SymbolCGA
Alt. symbolsHCG, GPHa, GPHA1
Entrez1081
HUGO1885
OMIM118850
RefSeqNM_000735
UniProtP01215
Other data
LocusChr. 6 q14-q21
Thyroid-stimulating hormone, beta
Identifiers
SymbolTSHB
Entrez7252
HUGO12372
OMIM188540
RefSeqNM_000549
UniProtP01222
Other data
LocusChr. 1 p13

Thyroid-stimulating hormone (also known as thyrotropin, TSH, or hTSH for human TSH) is a hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body.[1] It is a glycoprotein hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.[2][3]

Physiology[edit]

The system of the thyroid hormones T3 and T4.[4]

Regulation of thyroid hormone levels[edit]

TSH stimulates the thyroid gland to secrete the hormone thyroxine (T4), which has only a slight effect on metabolism. T4 is converted to triiodothyronine (T3), which is the active hormone that stimulates metabolism. About 80% of this conversion is in the liver and other organs, and 20% in the thyroid itself.[1]

The hypothalamus, in the base of the brain, produces thyrotropin-releasing hormone (TRH). TRH stimulates the pituitary gland to produce TSH.

Somatostatin is also produced by the hypothalamus, and has an opposite effect on the pituitary production of TSH, decreasing or inhibiting its release.

The concentration of thyroid hormones (T3 and T4) in the blood regulates the pituitary release of TSH; when T3 and T4 concentrations are low, the production of TSH is increased, and, conversely, when T3 and T4 concentrations are high, TSH production is decreased. This is an example of a negative feedback loop.

Subunits[edit]

TSH is a glycoprotein and consists of two subunits, the alpha and the beta subunit.

It is secreted throughout life but particularly reaches high levels during the periods of rapid growth and development.

The TSH receptor[edit]

The TSH receptor is found mainly on thyroid follicular cells.[5] Stimulation of the receptor increases T3 and T4 production and secretion. Stimulating antibodies to this receptor mimic TSH and cause Graves' disease. In addition, hCG shows some cross-reactivity to the TSH receptor and therefore can stimulate production of thyroid hormones. In pregnancy, prolonged high concentrations of hCG can produce a transient condition termed gestational hyperthyroidism.[6]

Applications[edit]

Diagnostics[edit]

Reference ranges for TSH may vary slightly, depending on the method of analysis, and do not necessarily equate to cut-offs for diagnosing thyroid dysfunction. In the UK, guidelines issued by the Association for Clinical Biochemistry suggest a reference range of 0.4-4.5 mIU/L.[7] The National Academy of Clinical Biochemistry (NACB) stated that it expected the reference range for adults to be reduced to 0.4–2.5 µIU/mL, because research had shown that adults with an initially measured TSH level of over 2.0 µIU/mL had "an increased odds ratio of developing hypothyroidism over the [following] 20 years, especially if thyroid antibodies were elevated".[8]

TSH concentrations in children are normally higher than in adults. In 2002, the NACB recommended age-related reference limits starting from about 1.3 to 19 µIU/mL for normal-term infants at birth, dropping to 0.6–10 µIU/mL at 10 weeks old, 0.4–7.0 µIU/mL at 14 months and gradually dropping during childhood and puberty to adult levels, 0.3 µIU/mL - 3.0 µIU/mL.[9]:Section 2

Diagnosis of disease[edit]

TSH concentrations are measured as part of a thyroid function test in patients suspected of having an excess (hyperthyroidism) or deficiency (hypothyroidism) of thyroid hormones. Interpretation of the results depends on both the TSH and T4 concentrations. In some situations measurement of T3 may also be useful.

Source of pathologyTSH levelThyroid hormone levelDisease causing conditions
Hypothalamus/pituitaryHighHighBenign tumor of the pituitary (adenoma) or thyroid hormone resistance
Hypothalamus/pituitaryLowLowSecondary Hypothyroidism
ThyroidLowHighPrimary Hyperthyroidism i.e. Graves' disease
ThyroidHighLowCongenital hypothyroidism (cretinism), Primary hypothyroidism i.e. Hashimoto's thyroiditis

A TSH assay is now also the recommended screening tool for thyroid disease. Recent advances in increasing the sensitivity of the TSH assay make it a better screening tool than free T4.[3]

Monitoring[edit]

The therapeutic target range TSH level for patients on treatment ranges between 0.3 to 3.0 μIU/mL.[9]

For hypothyroid patients on thyroxine, measurement of TSH alone is generally considered sufficient. An increase in TSH above the normal range indicates under-replacement or poor compliance with therapy. A significant reduction in TSH suggests over-treatment. In both cases, a change in dose may be required.

For hyperthyroid patients, both TSH and T4 are usually monitored.

Therapeutic[edit]

A synthetic drug called recombinant human TSH alpha (rhTSHα or simply rhTSH, (trade name Thyrogen), is manufactured by Genzyme Corp. The rhTSH is used to treat thyroid cancer.[10]

References[edit]

  1. ^ a b Merck Manual of Diagnosis and Therapy, Thyroid gland disorders.
  2. ^ The American Heritage Dictionary of the English Language, Fourth Edition. Houghton Mifflin Company. 2006. ISBN 0-395-82517-2. 
  3. ^ a b Sacher, Ronald; Richard A. McPherson (2000). Wildmann's Clinical Interpretation of Laboratory Tests, 11th ed. F.A. Davis Company. ISBN 0-8036-0270-7. 
  4. ^ References used in image are found in image article in Commons:Commons:File:Thyroid system.png#References.
  5. ^ Parmentier M, Libert F, Maenhaut C, Lefort A, Gérard C, Perret J, Van Sande J, Dumont JE, Vassart G (December 1989). "Molecular cloning of the thyrotropin receptor". Science 246 (4937): 1620–2. doi:10.1126/science.2556796. PMID 2556796. 
  6. ^ Fantz CR, Dagogo-Jack S, Ladenson JH, Gronowski AM (December 1999). "Thyroid function during pregnancy". Clin. Chem. 45 (12): 2250–8. PMID 10585360. 
  7. ^ Use of thyroid function tests: guidelines development group (2006-06-01). "UK Guidelines for the Use of Thyroid Function Tests" (pdf). Retrieved 2012-02-02. 
  8. ^ Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruf J, Smyth PP, Spencer CA, Stockigt JR (January 2003). "Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease". Thyroid 13 (1): 3–126. doi:10.1089/105072503321086962. PMID 12625976. 
  9. ^ a b Baskin et al. (2002). "AACE Medical Guidelines for Clinical Practice for Evaluation and Treatment of Hyperthyroidism and Hypothyroidism". American Association of Clinical Endocrinologists. pp. 462, 465. 
  10. ^ Duntas LH, Tsakalakos N, Grab-Duntas B, Kalarritou M, Papadodima E (2003). "The use of recombinant human thyrotropin (Thyrogen) in the diagnosis and treatment of thyroid cancer". Hormones (Athens) 2 (3): 169–74. PMID 17003018. 

External links[edit]