Thyroid-stimulating hormone

Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid.[1][2]

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.[4]

Applications

locussupplementarydata	-q21

Diagnostics

Reference ranges for TSH may vary slightly, depending on the method of analysis, and do not necessarily equate to cut-offs for diagnosing thyroid dysfunction. In the UK, guidelines issued by the Association for Clinical Biochemistry suggest a reference range of 0.4–4.0 μIU/mL (or mIU/L).[15] The 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]

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.

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 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.

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

Heterophile antibodies (which include human anti-mouse antibodies (HAMA) and Rheumatoid Factor (RF)), which bind weakly to the test assay's animal antibodies, causing a higher (or less commonly lower) TSH result than the actual true TSH level.[21][22] Although the standard lab assay panels are designed to remove moderate levels of heterophilic antibodies, these fail to remove higher antibody levels. "Dr. Baumann [from Mayo Clinic] and her colleagues found that 4.4 percent of the hundreds of samples she tested were affected by heterophile antibodies.........The hallmark of this condition is a discrepancy between TSH value and free T4 value, and most important between laboratory values and patient's conditions. Endocrinologists, in particular, should be on alert for this."
Macro-TSH - endogenous antibodies bind to TSH reducing its activity, so the pituitary gland would need to produce more TSH to obtain the same overall level of TSH activity.[23]
TSH Isomers - natural variations of the TSH molecule, which have lower activity, so the pituitary gland would need to produce more TSH to obtain the same overall level of TSH activity.[24]

Diagnosis of disease

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 and 3.0 μIU/mL.[18]

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

Difficulties with interpretation of TSH measurement

Heterophile antibodies (which include human anti-mouse antibodies (HAMA) and Rheumatoid Factor (RF)), which bind weakly to the test assay's animal antibodies, causing a higher (or less commonly lower) TSH result than the actual true TSH level.[21][22] Although the standard lab assay panels are designed to remove moderate levels of heterophilic antibodies, these fail to remove higher antibody levels. "Dr. Baumann [from Mayo Clinic] and her colleagues found that 4.4 percent of the hundreds of samples she tested were affected by heterophile antibodies.........The hallmark of this condition is a discrepancy between TSH value and free T4 value, and most important between laboratory values and patient's conditions. Endocrinologists, in particular, should be on alert for this."
Macro-TSH - endogenous antibodies bind to TSH reducing its activity, so the pituitary gland would need to produce more TSH to obtain the same overall level of TSH activity.[23]
TSH Isomers - natural variations of the TSH molecule, which have lower activity, so the pituitary gland would need to produce more TSH to obtain the same overall level of TSH activity.[24]

Therapeutic

Synthetic recombinant human TSH alpha (rhTSHα or simply rhTSH) or thyrotropin alfa (INN) is manufactured by Genzyme Corp under the trade name Thyrogen.[29][30] It is used to manipulate endocrine function of thyroid-derived cells, as part of the diagnosis and treatment of thyroid cancer.[31][32]

A Cochrane review compared treatments using recombinant human thyrotropin-aided radioactive iodine to radioactive iodine alone.[33] In this review it was found that the recombinant human thyrotropin-aided radioactive iodine appeared to lead to a greater reduction in thyroid volume at the increased risk of hypothyroidism.[33]

References

The American Heritage Dictionary of the English Language, Fourth Edition Houghton Mifflin Company, 2006^

Widmann's Clinical Interpretation of Laboratory Tests, 11th ed. F.A. Davis Company, 2000^

References used in image are found in image article in Commons:.^

Merck Manual of Diagnosis and Therapy, Thyroid gland disorders.^

Thyrotropin isoforms: implications for thyrotropin analysis and clinical practice Thyroid, Mar 2014^

Pulsatile secretion of thyrotropin in man The Journal of Clinical Endocrinology and Metabolism, Sep 1986^

Physiological regulation of circadian and pulsatile thyrotropin secretion in normal man and woman The Journal of Clinical Endocrinology and Metabolism, Feb 1990^

Pathophysiology of pulsatile and copulsatile release of thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and alpha-subunit The Journal of Clinical Endocrinology and Metabolism, Aug 1990^

Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment Frontiers in Endocrinology, 20 November 2015^

Thyroid-stimulating hormone (TSH)-directed induction of the CREM gene in the thyroid gland participates in the long-term desensitization of the TSH receptor Proceedings of the National Academy of Sciences of the United States of America, Oct 1995^

The expression of the thyroid-stimulating hormone (TSH) receptor and the cAMP-dependent protein kinase RII beta regulatory subunit confers TSH-cAMP-dependent growth to mouse fibroblasts The Journal of Biological Chemistry, Oct 2003^

Molecular cloning of the thyrotropin receptor Science, Dec 1989^

Medical Physiology Elsevier Saunders, 2012^

Thyroid function during pregnancy Clinical Chemistry, Dec 1999^

Use of thyroid function tests: guidelines development group. UK Guidelines for the Use of Thyroid Function Tests 1 June 2008, retrieved 30 April 2018^

Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease Thyroid, Jan 2003, retrieved 5 January 2010^

American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism Endocrine Practice, 2002, retrieved 8 August 2015^

Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study The Lancet Diabetes & Endocrinology, Oct 2015^

Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism The Journal of Clinical Endocrinology and Metabolism, 2007^

When lab tests lie ... heterophile antibodies Australian Family Physician, June 2014^

Serum sample containing endogenous antibodies interfering with multiple hormone immunoassays. Laboratory strategies to detect interference Practical Laboratory Medicine, April 2016^

Variability in the detection of macro TSH in different immunoassay systems European Journal of Endocrinology, Jan 2016^

Variable biological activity of thyroid-stimulating hormone European Journal of Endocrinology, Oct 1994^

Immunoreactive and bioactive isoforms of human thyrotropin Endocrinology, Jun 1991^

Time for a reassessment of the treatment of hypothyroidism BMC Endocrine Disorders, April 2019^

Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency Endocrine Connections, December 2015^

Thyrogen EPAR European Medicines Agency (EMA), 9 March 2000, retrieved 14 August 2024^

Drug Approval Package: Thyrogen (Thyrotropin Alfa) NDA# 20-898 U.S. Food and Drug Administration (FDA), 10 September 2001, retrieved 13 March 2020^

Drugs@FDA: FDA-Approved Drugs U.S. Food and Drug Administration (FDA), retrieved 13 March 2020^

The use of recombinant human thyrotropin (Thyrogen) in the diagnosis and treatment of thyroid cancer Hormones, 2003^

Thyrogen- thyrotropin alfa injection, powder, for solution Thyrogen- thyrotropin alfa kit DailyMed, 1 October 2018, retrieved 13 March 2020^

Recombinant human thyrotropin (rhTSH)-aided radioiodine treatment for non-toxic multinodular goitre The Cochrane Database of Systematic Reviews, December 2021^

Historical note: many steps led to the 'discovery' of thyroid-stimulating hormone European Thyroid Journal, June 2014^

The preparation of a purified thyrotropic hormone by chemical precipitation The Biochemical Journal, June 1937^

band
hgncid	1885
symbol	CGA
altsymbols	HCG, GPHa, GPHA1
entrezgene	1081
omim	118850
refseq	NM_000735
uniprot	P01215
chromosome	6
arm	q

Thyroid-stimulating hormone

Physiology

Hormone levels

Subunits

The TSH receptor

Applications

Diagnostics

Diagnosis of disease

Monitoring

Difficulties with interpretation of TSH measurement

Diagnosis of disease

Monitoring

Difficulties with interpretation of TSH measurement

Therapeutic

History

External links

References