Thyrotropin

from Wikipedia, the free encyclopedia
Thyrotropin, beta subunit
Properties of human protein
Mass / length primary structure 92 + 112 = 204 amino acids (α + β)
Secondary to quaternary structure TSH = TSH-α + TSH-β
Precursor (118 amino acids)
Identifier
Gene name TSHB
External IDs
Drug information
ATC code H01 AB01 V04 CJ01
DrugBank DB00024
Drug class hormone
Occurrence
Homology family LH-beta
Parent taxon Vertebrates

Thyrotropin (also thyrotropin ) is also thyroid stimulating hormone ( TTH ) or thyroid-stimulating hormone ( TSH called). Thyrotropin is a hormone that is produced and secreted in the basophilic cells of the anterior pituitary gland and has a stimulating effect on growth, iodine uptake and hormone production in the thyroid gland . The TSH production of the thyrotropic cells of the anterior pituitary gland is regulated on the one hand by the thyroid gland via the concentration of thyroid hormones (negative feedback ), the other from the hypothalamus , a specific diencephalon -Areal.

structure

The glycoprotein TSH consists of two subunits, the α subunit ( TSH-α ) with 92 amino acids and the β subunit (TSH-β) with 112 amino acids. The β subunit is specific for TSH. The α subunit contains three fewer N-terminal amino acids than the alpha subunit in the hormones human chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In addition, the alpha subunit contains five disulfide bridges and two separate carbohydrate components.

physiology

The thyrotropic control loop or the hypothalamic-pituitary-thyroid axis (simplified representation). The end products T 4 and T 3 inhibit both TRH and TSH formation.

With the help of the releasing hormone thyreoliberin (TRH), which is produced in the hypothalamus, a specific brain area, and then reaches the anterior pituitary lobe through a special portal vascular system, the hypothalamus stimulates the production and release of TSH from the thyrotropic cells. TSH reaches the thyroid via the bloodstream and causes the thyroid cells to accelerate division, increase iodine uptake and increase the formation of the iodine-containing thyroid hormones thyroxine (T 4 ) and triiodothyronine (T 3 ); In addition, it promotes the conversion of T 4 into the more effective T 3 in the periphery . Conversely, the thyroid hormones inhibit the production and release of TRH from the hypothalamus and TSH from the anterior pituitary through negative feedback within the framework of the thyrotropic control loop . In this way, constant and demand-adapted blood concentrations of thyroid hormones are achieved.

TSH deficiency, TSH overproduction

If TSH is missing or cannot be produced sufficiently, the thyroid gland no longer has any incentive to grow, absorb iodine and produce thyroid hormones, so that it becomes smaller and smaller and wither away. The result is a so-called pituitary hypothyroidism (secondary hypothyroidism).

For example, if the pituitary gland produces too much TSH because of a TSH-producing adenoma , the thyroid gland is constantly stopped to accelerate its growth, increase iodine uptake and increase thyroid hormone production, resulting in an overactive thyroid, which is known as pituitary hyperthyroidism or secondary hyperthyroidism . These secondary thyroid dysfunction due to TSH deficiency or TSH overproduction are extremely rare compared to primary thyroid dysfunction which is caused by a change in the thyroid gland itself.

Disturbances in TRH production and secretion by the hypothalamus or signal transmission in the hypothalamo-pituitary portal vasculature ( Pickardt's syndrome ) can also lead to a TSH deficiency or an excess of TSH and thus to the very rare tertiary hypo- or hyperthyroidism because the hypothalamus controls the TSH production in the anterior pituitary via the TRH .

Autoantibodies

Immunoglobulins , which are produced by the immune system in autoimmune Graves' disease and autoimmune Hashimoto's thyroiditis , can cause changes in hormone production in the thyroid. The antibodies of Graves disease, the so-called TSH receptor antibodies (TRAK) of the IgG type, block the TSH receptors of the thyroid gland and independently and unregulated stimulate the growth, iodine uptake and hormone production of the thyroid gland. A hyperthyroidism is the result. The antibodies in Hashimoto's thyroiditis destroy the thyroid tissue, causing the thyroid to decrease in size and function, which can lead to hypothyroidism .

Normal values ​​in the blood serum

  • Healthy adults in general: 0.4 - 4.5 mU / l
  • Pregnancy - 1st third: 0.4 - 2.5 mU / l
  • Pregnancy - 2nd third: 0.4-3.0 mU / l
  • Pregnancy - 3rd trimester: 0.4-3.5 mU / l

The values ​​are general guide values ​​from the guidelines of relevant medical specialist societies. In practice, the reference values ​​of the testing laboratory should also be observed - but only if they have been scientifically and comprehensibly justified beforehand.

The upper value of the TSH normal range increases steadily with age in adults, namely - according to an analysis of an extensive data collection in the USA - between the age groups 20–29 and 80+ from 3.5 to 7.5 mU / l.

The TSH value is determined by analyzing the serum. In the primary hypothyroidism it is increased. In the case of primary hyperthyroidism , it is reduced.

TSH levels below 0.1 mU / l

This finding is not uncommon, even in people who are actually symptom-free. A lowered TSH level can have several causes:

  1. You take thyroid hormones. Then the pituitary gland receives the message that there are already enough or even too many thyroid hormones in the blood, and the pituitary gland slows down its TSH production. In this case, the dose of the hormones to be taken should be adjusted, except when this dose is urgently needed for well-being (especially in therapy with the addition of T 3 and normal free T 3 ).
  2. TSH is low, but free T 3 and free T 4 are normal. An overactive thyroid gland may or may not be present here.
  3. TSH is decreased, free T 3 and free T 4 are increased. There is an overactive thyroid gland ( hyperthyroidism ).
  4. Very rarely, a lowered TSH level can also be due to a true TSH deficiency in the pituitary gland. Free T 3 and free T 4 are usually also reduced.

In the case of the last three constellations, further diagnostics (e.g. thyroid sonography, scintigraphy , laboratory examination for TRAK ) and, if necessary, appropriate therapy are necessary.

Other influencing criteria on the TSH value

Medicines and also endogenous influences can influence the TSH value.

Medication

TSH secretion is lowered by:

  • Dopamine and dopamine agonists (L-dopa, bromocriptine, lisuride, apomorphine)
  • Serotonin antagonists (metergoline)
  • Somatostatin, octreotide
  • Morphine and morphine derivatives
  • Glucocorticoids
  • Heparin
  • L-thyroxine

TSH secretion is increased by:

Chronobiology:

For the clinical interpretation of laboratory results it is important to take into account that TSH is released ( secreted ) in phases ( pulsatile ) so that the serum concentrations are subject to circadian and ultradian rhythms.

endogenous influences:

  • Malnutrition
  • Disorder of the adrenal function
  • increased histamine

TRH test

The TRH stimulation test can be used to check whether TSH can be stimulated in the pituitary gland: TRH stimulates TSH production to an excessive or reduced extent.

history

  • 1929 Thyrotropin is discovered by Max Aron and Leon Loeb .
  • 1932 Isolation of thyrotropin by Karl Junkmann and Walter Schoeller .
  • In 1965 a first radioimmunoassay for TSH is described by Odell.
  • 1971 Bovine TSH was first sequenced in 1971, followed by human TSH in 1977.
  • Recombinant (human) TSH ( rhTSH or rTSH ), which is used in the therapy and aftercare of thyroid cancer , has existed since the end of the 20th century .

literature

Guidelines

  • O. Okosieme, J. Gilbert, P. Abraham, K. Boelaert, C. Dayan, M. Gurnell, G. Leese, C. McCabe, P. Perros, V. Smith, G. Williams, M. Vanderpump: Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee. In: Clinical endocrinology. Volume 84, No. 6, 2016, pp. 799-808, doi: 10.1111 / cen.12824 . PMID 26010808 , (Review), PDF (accessed March 21, 2016).
  • JR Garber, RH Cobin, H. Gharib, JV Hennessey, I. Klein, JI Mechanick, R. Pessah-Pollack, PA Singer, KA Woeber: Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. In: Thyroid: official journal of the American Thyroid Association. Volume 22, number 12, December 2012, pp. 1200-1235, doi: 10.1089 / thy.2012.0205 . PMID 22954017 , (free full text).
  • Association of Clinical Biochemistry, British Thyroid Association and British Thyroid Foundation: UK guidelines for the use of thyroid function tests (2006). PDF (accessed on March 21, 2016).
  • DEGAM guideline no. 18: Increased TSH levels in the general practitioner's practice. 2016, (PDF)

Information for patients and relatives

  • American Thyroid Association (ATA): Hypothyroidism - A Booklet for Patients and their Families. 2013. ( PDF ; accessed on March 21, 2016)
  • DEGAM patient information "Increased TSH value in the family doctor's practice", 2016, PDF (accessed on December 6, 2017).

Web links

Individual evidence

  1. ↑ UniProt P01222
  2. ↑ O. Okosieme, J. Gilbert, P. Abraham, K. Boelaert, C. Dayan, M. Gurnell, G. Leese, C. McCabe, P. Perros, V. Smith, G. Williams, M. Vanderpump: Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee. In: Clinical endocrinology. Volume 84, No. 6, 2016, pp. 799-808, doi: 10.1111 / cen.12824 . PMID 26010808 , (Review), PDF (accessed March 21, 2016).
  3. ↑ JR Garber, RH Cobin, H. Gharib, JV Hennessey, I. Klein, JI Mechanick, R. Pessah-Pollack, PA Singer, KA Woeber: Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. In: Thyroid: official journal of the American Thyroid Association. Volume 22, number 12, December 2012, pp. 1200-1235, doi: 10.1089 / thy.2012.0205 . PMID 22954017 , (free full text).
  4. ^ Association of Clinical Biochemistry, British Thyroid Association and British Thyroid Foundation: UK guidelines for the use of thyroid function tests (2006). ( PDF ; accessed on March 21, 2016)
  5. ↑ DEGAM guideline No. 18: Increased TSH value in the family doctor's practice , 2016, (PDF) , p. 7.
  6. ↑ MI Surks, JG Hollowell: Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. In: The Journal of clinical endocrinology and metabolism. Volume 92, Number 12, December 2007, pp. 4575-4582, doi: 10.1210 / jc.2007-1499 . PMID 17911171 (free full text).
  7. ↑ N. Aggarwal, S. Razvi: Thyroid and aging or the aging thyroid? An evidence-based analysis of the literature. In: Journal of thyroid research. Volume 2013, p. 481287, doi: 10.1155 / 2013/481287 . PMID 24106641 , PMC 3782841 (free full text) (review).
  8. ↑ JV Hennessey, R. Espaillat: Diagnosis and Management of Subclinical Hypothyroidism in Elderly Adults: A Review of the Literature. In: Journal of the American Geriatrics Society. Volume 63, number 8, August 2015, pp. 1663–1673, doi: 10.1111 / jgs.13532 . PMID 26200184 (Review) ( free full text: PDF ).
  9. ↑ L. Grasso, L. Bartalena, C. Mammoli, E. Martino, AC Kessler, A. Pinchera: Serum TSH measurements by a sensitive enzyme immunoassay discriminate euthyroid from hyperthyroid subjects and avoid the need for TRH test during suppressive therapy with L- thyroxine. In: Clin Biochem. 20 (3), Jun 1987, pp. 197-200. PMID 3115625
  10. ↑ Labor Lexicon - specialist knowledge for everyone
  11. ^ Greenspan SL, Klibanski A., Schoenfeld D., Ridgway EC: Pulsatile secretion of thyrotropin in man . In: The Journal of clinical endocrinology and metabolism . tape 63 , no. 3 , September 1986, pp. 661-668 , PMID 3734036 .
  12. ↑ G. Brabant, K. Prank, U. Ranft, T. Schuermeyer, TO Wagner, H. Hauser, B. Kummer, H. Feistner, RD Hesch, A. von zur Mühlen: Physiological regulation of circadian and pulsatile thyrotropin secretion in normal man and woman . In: The Journal of clinical endocrinology and metabolism . tape 70 , no. 2 , February 1990, p. 403-409 , PMID 2105332 .
  13. ↑ MH Samuels, JD Veldhuis, P. Henry, EC Ridgway: Pathophysiology of pulsatile and copulsatile release of thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and alpha-subunit. In: The Journal of clinical endocrinology and metabolism . tape 71 , no. 2 , August 1990, p. 425-432 , PMID 1696277 .
  14. ^ Rudolf Hoermann, John EM Midgley, Rolf Larisch, Johannes W. Dietrich: Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment . In: Frontiers in Endocrinology . tape 6 , November 20, 2015, p. 177 , doi : 10.3389 / fendo.2015.00177 , PMID 26635726 .
  15. ↑ A. Falus, K. Meretey: Histamine: an early messenger in inflammatory and immune reactions. In: Immunology today. Vol. 13, No. 5, 1992, pp. 154-156.
  16. ↑ K. Junkmann, W. Schöller: About the thyreotrope hormone of the anterior pituitary lobe. In: Clinical weekly. Volume 11, (July) 1932, p. 1176 f. ( doi: 10.1007 / BF01766365 ).
  17. ↑ WD Odell et al: Radioimmunoassay of thyrotropin in human serum. In: J. Clin. Endocrinol. Metab. Volume 5 1965, pp. 1179-1188. PMID 4157804 .
  18. ↑ TH Liao, JG Pierce: The Primary Structure of Bovine Thyrotropin II. The linear amino acid sequences of the reduced, S-Carboxymethyl α and β chains. In: J. Biol. Chem. 246, 1971, pp. 850-865.
  19. ↑ MR Sairam, CH Li: Human pituitary thyrotropin. The primary structure of the alpha and beta subunits . In: Can. J. Biochem. tape 55 , no. 7 July 1977, p. 755-760 , PMID 890569 .