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Thyroid-stimulating hormone, alpha (Glycoprotein hormones, alpha polypeptide)
Identifiers
Symbol CGA
Alt. symbols HCG, GPHa, GPHA1
Entrez 1081
HUGO 1885
OMIM 118850
RefSeq NM_000735
UniProt P01215
Other data
Locus Chr. 6 q14-q21
Thyroid-stimulating hormone, beta
Identifiers
Symbol TSHB
Entrez 7252
HUGO 12372
OMIM 188540
RefSeq NM_000549
UniProt P01222
Other data
Locus Chr. 1 p13

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.[1]

Contents

Physiology

The system of the thyroid hormones T3 and T4.[2]
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Controlling thyroid hormone levels

TSH stimulates the thyroid gland to secrete the hormones thyroxine (T4) and triiodothyronine (T3).[3] TSH production is controlled by thyrotropin-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 (T3 and T4) in the blood have an effect on the pituitary release of TSH; when the levels of T3 and T4 are low, the production of TSH is increased, and conversely, when levels of T3 and T4 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 TSH receptor

The TSH receptor is found mainly on thyroid follicular cells.[4] Stimulation of the receptor increases T3 and T4 production and secretion.

Stimulating antibodies to this receptor mimic TSH and cause 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 standard reference range for TSH for adults is between 0.4 and 5.0 µIU/mL (equivalent to mIU/L), but values vary slightly among labs. The therapeutic target range TSH level for patients on treatment ranges between 0.3 to 3.0 mIU/L.[5] The interpretation depends also on what the blood levels of thyroid hormones (T3 and T4) are.

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 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.[6]

The NACB also stated that it expected the normal (95%) 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".[7]

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

Clearly, both TSH and T3 and T4 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 (T3 and T4) 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 T4.[1]

Therapeutic use

A drug, recombinant human TSH (rhTSH), called Thyrogen, is manufactured by Genzyme Corp. in Cambridge, Massachusetts. The rhTSH is used in patients with thyroid cancer which is related to tumoral factors.

References

  1. ^ 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.  
  2. ^ References used in image are found in image article in Commons:Commons:File:Thyroid_system.png#References.
  3. ^ Physiology at MCG 5/5ch5/s5ch5_4
  4. ^ Parmentier M, Libert F, Maenhaut C, et al. (December 1989). "Molecular cloning of the thyrotropin receptor". Science (journal) 246 (4937): 1620–2. doi:10.1126/science.2556796. PMID 2556796.  
  5. ^ Campbell B (2006-01-10). "Thyroid Imbalance? Target Your Numbers". Press release. American Association of Clinical Endocrinologists. http://www.aace.com/newsroom/press/2006/index.php?r=20060110. Retrieved 2009-07-09.  
  6. ^ Demers, Laurence M.; Carole A. Spencer (2002). "LMPG: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease". National Academy of Clinical Biochemistry (USA). http://www.aacc.org/members/nacb/Archive/LMPG/ThyroidDisease/Pages/default.aspx. Retrieved 2010-01-05.   - see Section 2. Pre-analytic factors
  7. ^ Demers, Laurence M.; Carole A. Spencer (2002). "LMPG: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease". National Academy of Clinical Biochemistry (USA). http://www.aacc.org/members/nacb/Archive/LMPG/ThyroidDisease/Pages/default.aspx. Retrieved 2010-01-05.   - see Section 3.C.Thyrotropin/ Thyroid Stimulating Hormone (TSH) measurement

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