Thyroid-stimulating hormone 330361 226109935 2008-07-16T21:28:32Z Boghog2 2428506 [[WP:UNDO|Undid]] revision 226103556 by [[Special:Contributions/118.94.91.129|118.94.91.129]] ([[User talk:118.94.91.129|talk]]): What are the bad effects of increased TSH? Perhaps hypothyroidism? {{protein | Name = [[Chorionic gonadotropin alpha|Thyroid-stimulating hormone, alpha]] (Glycoprotein hormones, alpha polypeptide) | caption = | image = | width = | HGNCid = 1885 | Symbol = [[Chorionic gonadotropin alpha|CGA]] | AltSymbols = HCG, GPHa, GPHA1 | EntrezGene = 1081 | OMIM = 118850 | RefSeq = NM_000735 | UniProt = P01215 | PDB = | ECnumber = | Chromosome = 6 | Arm = q | Band = 14 | LocusSupplementaryData = -q21 }} {{Protein |Name=Thyroid-stimulating hormone, beta |image= |caption= |Symbol=TSHB |AltSymbols= |HGNCid=12372 |Chromosome=1 |Arm=p |Band=13 |LocusSupplementaryData= |ECnumber= |OMIM=188540 |EntrezGene=7252 |RefSeq=NM_000549 |UniProt=P01222 |PDB= }} '''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 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== ===Controlling the rate of release=== TSH stimulates the thyroid gland to secrete the hormones [[thyroxine]] (T<sub>4</sub>) and [[triiodothyronine]] (T<sub>3</sub>).<ref>{{GeorgiaPhysiology|5/5ch5/s5ch5_4}}</ref> TSH production is controlled by a Thyrotrophin Releasing Hormone, ([[TRH]]), which is manufactured in the [[hypothalamus]] and transported to the [[anterior pituitary gland]] via the [[superior hypophyseal artery]], 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 level of thyroid hormones (T<sub>3</sub> and T<sub>4</sub>) in the blood have an additional effect on the pituitary release of TSH; When the levels of T<sub>3</sub> and T<sub>4</sub> are low, the production of TSH is increased, and conversely, when levels of T<sub>3</sub> and T<sub>4</sub> are high, then TSH production is decreased. This effect creates a regulatory negative [[feedback loop]]. ===Subunits of TSH=== TSH is a glycoprotein and consists of two subunits, the ''alpha'' and the ''beta'' subunit. * The [[Alpha subunit of glycoprotein hormones|α (''alpha'') subunit]] (i.e., [[chorionic gonadotropin alpha]]) is identical to that of [[human chorionic gonadotropin]] (HCG), [[luteinizing hormone]] (LH), [[follicle-stimulating hormone]] (FSH). * The β (''beta'') subunit is unique to TSH, and therefore determines its function. ===The TSH receptor=== The [[TSH receptor]] is found mainly on thyroid [[follicular cells]]<ref>Parmentier M, Libert F, Maenhaut C, Lefort A, Gérard C, Perret J, Van Sande J, Dumont JE and Vassart G., Molecular cloning of the thyrotropin receptor, Science 246 (1989), 1620-1622</ref>. Stimulation of the receptor increases T<sub>3</sub> and T<sub>4</sub> production and secretion. Stimulating antibodies to this receptor mimic TSH action and are found in [[Graves-Basedow disease|Graves' disease]]. ==Diagnostic use== TSH levels are tested in the blood of patients suspected of suffering from excess ([[hyperthyroidism]]), or deficiency ([[hypothyroidism]]) of thyroid hormone. Generally, a normal range for TSH for adults is between 0.4 and 5.0 [[Micro-|u]][[international unit|IU]]/mL (equivalent to [[milli|m]]IU/L), but values vary slightly among labs. The optimal goal TSH level for patients on treatment ranges between 0.3 to 3.0 mIU/L.<ref>[http://www.aace.com/newsroom/press/2006/index.php?r=20060110 American Association of Clinical Endocrinologists<!-- Bot generated title -->]</ref>. The interpretation depends also on what the blood levels of thyroid hormones (T<sub>3</sub> and T<sub>4</sub>) are. The [[National Health Service]] in the UK considers a "normal" range to be more like 0.1 to 5.0 uIU/mL.{{Fact|date=April 2007}} TSH levels for children normally start out much higher. In [[2002]], the [[National Academy of Clinical Biochemistry]] (NACB) in the [[United States]] recommended age-related reference limits starting from about 1.3-19 uIU/mL for normal term infants at birth, dropping to 0.6-10 uIU/mL at 10 weeks old, 0.4-7.0 uIU/mL at 14 months and gradually dropping during childhood and puberty to adult levels, 0.4-4.0 uIU/mL.<ref>{{cite web| last =Demers| first =Laurence M.| authorlink =| coauthors =Carole A. Spencer| title = LMPG: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease| work =| publisher =[[National Academy of Clinical Biochemistry]] (USA)| date =2002| url =http://www.nacb.org/lmpg/thyroid_LMPG_PDF.stm |format =| doi =| accessdate =2007-04-13 }} - see ''Section 2. Pre-analytic factors''</ref> The NACB also stated that it expected the normal (95%) range for adults to be reduced to 0.4-2.5 uIU/mL, because research had shown that adults with an initially measured TSH level of over 2.0 uIU/mL had "an increased odds ratio of developing [[hypothyroidism]] over the [following] 20 years, especially if thyroid antibodies were elevated".<ref>{{cite web| last =Demers| first =Laurence M.| authorlink =| coauthors =Carole A. Spencer| title = LMPG: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease| work =| publisher =[[National Academy of Clinical Biochemistry]] (USA)| date =2002| url =http://www.nacb.org/lmpg/thyroid_LMPG_PDF.stm |format =| doi =| accessdate =2007-04-13 }} - see ''Section 3.C.Thyrotropin/ Thyroid Stimulating Hormone (TSH) measurement</ref> {| class="wikitable" | '''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 [[Grave's disease]] |- | thyroid || high || low || [[congenital hypothyroidism]] (cretinism), [[hypothyroidism]] |} Clearly, both TSH and T<sub>3</sub> and T<sub>4</sub> should be measured to ascertain where a specific thyroid dysfunction is caused by primary pituitary or by a primary thyroid disease. If both are up (or down) then the problem is probably in the pituitary. If the one component (TSH) is up, and the other (T<sub>3</sub> and T<sub>4</sub>) is down, then the disease is probably in the thyroid itself. The same holds for a low TSH, high T3 and T4 finding. 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 T<sub>4</sub>.<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> ==Therapeutic use== A drug, recombinant human TSH (rhTSH), called Thyrogen, is manufactured by [[Genzyme|Genzyme Corp.]] in Cambridge, Massachusetts. The rhTSH is used in patients with thyroid cancer which is related to tumoral factors. ==Footnotes== <references/> ==External links== * {{MedlinePlus|003684}} * {{MeshName|Thyrotropin}} {{Hormones}} [[Category:Glycoproteins]] [[Category:Peptide hormones]] [[Category:Anterior pituitary hormones]] [[Category:HPT axis]] [[bs:Tireostimulišući hormon]] [[cs:Thyreotropní hormon]] [[da:TSH]] [[de:Thyreotropin]] [[dv:ތައިރޮއިޑް ސްޓިމިއުލޭޓިންގ ހޯރމޯން]] [[es:Tirotropina]] [[fr:Thyréostimuline]] [[id:Hormon Tirotrop]] [[it:Ormone tireostimolante]] [[he:תירוטרופין]] [[lt:Tireotropinas]] [[hu:Thyreoidea-stimuláló hormon]] [[mk:Тиреотропин]] [[nl:Thyroïdstimulerend hormoon]] [[ja:甲状腺刺激ホルモン]] [[no:Tyroideastimulerende hormon]] [[pl:Hormon tyreotropowy]] [[pt:Hormônio estimulante da tiróide]] [[ru:Тиреотропный гормон]] [[sk:Tyreotropín]] [[sr:Тиреостимулишући хормон]] [[fi:Tyreotropiini]] [[sv:Tyreoideastimulerande hormon]]