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'''Thyroid-stimulating hormone''' (also known as '''TSH''' or '''thyrotropin''') is a [[peptide hormone]] synthesized and secreted by [[thyrotrope]] cells in the [[anterior pituitary gland]], which regulates the endocrine function of the [[thyroid gland]].<ref>{{cite book|title= The American Heritage Dictionary of the English Language, Fourth Edition|year= 2006|publisher= Houghton Mifflin Company|isbn= 0-395-82517-2}}</ref><ref name="Sacher">{{cite book |last= Sacher|first= Ronald|coauthors= Richard A. McPherson|title= Wildmann's Clinical Interpretation of Laboratory Tests, 11th ed.|year= 2000|publisher= F.A. Davis Company|isbn= 0-8036-0270-7}}</ref>
'''Thyroid-stimulating hormone''' (also known as '''TSH''' or '''thyrotropin''') is a [[glycoprotein hormone]] synthesized and secreted by [[thyrotrope]] cells in the [[anterior pituitary gland]], which regulates the endocrine function of the [[thyroid gland]].<ref>{{cite book|title= The American Heritage Dictionary of the English Language, Fourth Edition|year= 2006|publisher= Houghton Mifflin Company|isbn= 0-395-82517-2}}</ref><ref name="Sacher">{{cite book |last= Sacher|first= Ronald|coauthors= Richard A. McPherson|title= Wildmann's Clinical Interpretation of Laboratory Tests, 11th ed.|year= 2000|publisher= F.A. Davis Company|isbn= 0-8036-0270-7}}</ref>


== Physiology ==
== Physiology ==

Revision as of 17:49, 2 May 2012

Thyroid-stimulating hormone, alpha
Identifiers
SymbolCGA
Alt. symbolsHCG, GPHa, GPHA1
NCBI gene1081
HGNC1885
OMIM118850
RefSeqNM_000735
UniProtP01215
Other data
LocusChr. 6 q14-q21
Search for
StructuresSwiss-model
DomainsInterPro
Thyroid-stimulating hormone, beta
Identifiers
SymbolTSHB
NCBI gene7252
HGNC12372
OMIM188540
RefSeqNM_000549
UniProtP01222
Other data
LocusChr. 1 p13
Search for
StructuresSwiss-model
DomainsInterPro

Thyroid-stimulating hormone (also known as TSH or thyrotropin) is a glycoprotein hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.[1][2]

Physiology

The system of the thyroid hormones T3 and T4.[3]

Regulation of thyroid hormone levels

TSH stimulates the thyroid gland to secrete the hormones thyroxine (T4) and triiodothyronine (T3).[4] TSH production is controlled by thyrotropin-releasing hormone (TRH), which is manufactured in the hypothalamus and transported to the anterior pituitary gland via the hypothalamo-hypophyseal portal system, where it increases TSH production and release. 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

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

The TSH receptor

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

Diagnostics

Further information: Thyroid function tests

In adults, a standard reference range is between 0.4 and 3.0 µIU/mL (equivalent to mIU/L), but values vary slightly among labs. 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 normal 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, 0.4–4.0 µIU/mL.[8]: Section 2 

Diagnosis of disease

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 pathology TSH level Thyroid hormone level Disease causing conditions
Hypothalamus/pituitary High High Benign tumor of the pituitary (adenoma) or thyroid hormone resistance
Hypothalamus/pituitary Low Low Hypopituitarism
Thyroid Low High Hyperthyroidism or Graves' disease
Thyroid High Low Congenital hypothyroidism (cretinism), hypothyroidism or 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.[2]

Monitoring

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

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

  1. ^ The American Heritage Dictionary of the English Language, Fourth Edition. Houghton Mifflin Company. 2006. ISBN 0-395-82517-2.
  2. ^ a b Sacher, Ronald (2000). Wildmann's Clinical Interpretation of Laboratory Tests, 11th ed. F.A. Davis Company. ISBN 0-8036-0270-7. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  3. ^ References used in image are found in image article in Commons:Commons:File:Thyroid_system.png#References.
  4. ^ Template:GeorgiaPhysiology
  5. ^ Parmentier M, Libert F, Maenhaut C, Lefort A, Gérard C, Perret J, Van Sande J, Dumont JE, Vassart G (1989). "Molecular cloning of the thyrotropin receptor". Science. 246 (4937): 1620–2. doi:10.1126/science.2556796. PMID 2556796. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Fantz CR, Dagogo-Jack S, Ladenson JH, Gronowski AM (1999). "Thyroid function during pregnancy". Clin. Chem. 45 (12): 2250–8. PMID 10585360. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  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. ^ a b 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 (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Baskin; et al. (2002). "AACE Medical Guidelines for Clinical Practice for Evaluation and Treatment of Hyperthyroidism and Hypothyroidism" (PDF). American Association of Clinical Endocrinologists. pp. 462, 465. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help); Explicit use of et al. in: |author= (help)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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