Thyroid-stimulating hormone

Source: Wikipedia, the free encyclopedia.
(Redirected from
Thyroid stimulating hormone
)
Chr. 6 q14-q21
Search for
StructuresSwiss-model
DomainsInterPro
Chr. 1 p13
Search for
StructuresSwiss-model
DomainsInterPro

Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a

anterior pituitary gland, which regulates the endocrine function of the thyroid.[2][3]

Physiology

Hormone levels

TSH (with a half-life of about an hour) 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]

TSH is secreted throughout life but particularly reaches high levels during the periods of rapid growth and development, as well as in response to stress.

The hypothalamus, in the base of the brain, produces thyrotropin-releasing hormone (TRH). TRH stimulates the anterior 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.[5] Any inappropriateness of measured values, for instance a low-normal TSH together with a low-normal T4 may signal tertiary (central) disease and a TSH to TRH pathology. Elevated reverse T3 (RT3) together with low-normal TSH and low-normal T3, T4 values, which is regarded as indicative for euthyroid sick syndrome, may also have to be investigated for chronic subacute thyroiditis (SAT) with output of subpotent hormones. Absence of antibodies in patients with diagnoses of an autoimmune thyroid in their past would always be suspicious for development to SAT even in the presence of a normal TSH because there is no known recovery from autoimmunity.

For clinical interpretation of laboratory results it is important to acknowledge that TSH is released in a pulsatile manner[6][7][8] resulting in both circadian and ultradian rhythms of its serum concentrations.[9]

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

sodium-iodide symporter (NIS) on the basolateral membrane of thyroid follicular cells, thereby increasing intracellular concentrations of iodine (iodine trapping). (2) Stimulating iodination of thyroglobulin in the follicular lumen, a precursor protein of thyroid hormone. (3) Stimulating the conjugation of iodinated tyrosine residues. This leads to the formation of thyroxine (T4) and triiodothyronine (T3) that remain attached to the thyroglobulin protein. (4) Increased endocytocis of the iodinated thyroglobulin protein across the apical membrane back into the follicular cell. (5) Stimulation of proteolysis of iodinated thyroglobulin to form free thyroxine (T4) and triiodothyronine (T3). (6) Secretion of thyroxine (T4) and triiodothyronine (T3) across the basolateral membrane of follicular cells to enter the circulation. This occurs by an unknown mechanism.[13]

Stimulating antibodies to the TSH receptor mimic TSH and cause

trophoblastic tumors increasing the production of thyroid hormones.[citation needed
]

Applications

Diagnostics

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".[16]

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, 0.3–3.0 µIU/mL.[17]: 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
Secondary hypothyroidism
or "central" hypothyroidism
Hyperthyroidism Low High Primary hyperthyroidism i.e. Graves' disease
Hypothyroidism High Low Congenital hypothyroidism, 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

The

therapeutic target range TSH level for patients on treatment ranges between 0.3 and 3.0 μIU/mL.[18]

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. A low or low-normal TSH value may also signal pituitary disease in the absence of replacement.[citation needed]

For hyperthyroid patients, both TSH and T4 are usually monitored. In pregnancy, TSH measurements do not seem to be a good marker for the well-known association of maternal thyroid hormone availability with offspring neurocognitive development.[19]

TSH distribution progressively shifts toward higher concentrations with age.[20]

Difficulties with interpretation of TSH measurement

Therapeutic

Synthetic

INN) is manufactured by Genzyme Corp under the trade name Thyrogen.[28][29] It is used to manipulate endocrine function of thyroid-derived cells, as part of the diagnosis and treatment of thyroid cancer.[30][31]

A Cochrane review compared treatments using recombinant human thyrotropin-aided radioactive iodine to radioactive iodine alone.[32] In this review it was found that the recombinant human thyrotropin-aided radioactive iodine appeared to lead to a greater of thyroid volume at the increased risk of hypothyroidism.[32] No conclusive data on changes in quality of life with either treatments were found.[32]

History

In 1916, Bennett M. Allen and Philip E. Smith found that the pituitary contained a thyrotropic substance.[33] The first standardised purification protocol for this thyrotropic hormone was described by Charles George Lambie and Victor Trikojus, working at the University of Sydney in 1937.[34]

References

  1. ^ a b Merck Manual of Diagnosis and Therapy, Thyroid gland disorders.
  2. .
  3. ^ .
  4. ^ References used in image are found in image article in Commons:Commons:File:Thyroid system.png#References.
  5. PMID 24073798
    .
  6. .
  7. .
  8. .
  9. .
  10. .
  11. .
  12. .
  13. .
  14. .
  15. ^ Use of thyroid function tests: guidelines development group (2008-06-01). "UK Guidelines for the Use of Thyroid Function Tests" (Web Page). Retrieved 2018-04-30.
  16. PMID 12625976
    .
  17. PMID 15260011. Archived from the original
    (PDF) on 2015-12-08. Retrieved 2015-08-08.
  18. ^ 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. Archived from the original (PDF) on 2012-09-15. Retrieved 2013-01-30.
  19. PMID 26497402
    .
  20. .
  21. .
  22. .
  23. .
  24. .
  25. .
  26. .
  27. .
  28. ^ "Drug Approval Package: Thyrogen (Thyrotropin Alfa) NDA# 20-898". U.S. Food and Drug Administration (FDA). 10 September 2001. Retrieved 13 March 2020.
  29. ^ "Drugs@FDA: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 13 March 2020.
  30. PMID 17003018
    .
  31. ^ "Thyrogen- thyrotropin alfa injection, powder, for solution Thyrogen- thyrotropin alfa kit". DailyMed. 1 October 2018. Retrieved 13 March 2020.
  32. ^
    PMID 34961921
    .
  33. .
  34. .

External links