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Thyroid-stimulating hormone
 
 
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Thyroid-stimulating hormone (also known as TSH or thyrotropin) is a peptide hormone
Peptide hormone

Peptide hormones are a class of peptide that are secreted into the blood stream and have endocrine functions in living animals. Peptide hormones are increasingly being identified in plants with important roles in cell-to-cell communication and plant defence....
 synthesized and secreted by thyrotrope
Thyrotrope

Thyrotropes are cells in the anterior pituitary which produce thyroid stimulating hormone....
 cells in the anterior pituitary gland which regulates the endocrine function of the thyroid gland.

stimulates the thyroid gland to secrete the hormones thyroxine
Thyroxine

Thyroxine, or 3,5,3',5'-tetra?iodothyronine , a form of thyroid hormones is the major hormone secreted by the follicular cells of the thyroid gland....
 (T4) and triiodothyronine
Triiodothyronine

Triiodothyronine, carbonhydrogeniodinenitrogenoxygen, also known as T3, is a thyroid hormone.Thyroid-stimulating hormone activates the production of thyroxine and T3....
 (T3).






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Thyroid-stimulating hormone (also known as TSH or thyrotropin) is a peptide hormone
Peptide hormone

Peptide hormones are a class of peptide that are secreted into the blood stream and have endocrine functions in living animals. Peptide hormones are increasingly being identified in plants with important roles in cell-to-cell communication and plant defence....
 synthesized and secreted by thyrotrope
Thyrotrope

Thyrotropes are cells in the anterior pituitary which produce thyroid stimulating hormone....
 cells in the anterior pituitary gland which regulates the endocrine function of the thyroid gland.

Physiology


Controlling the rate of release

TSH stimulates the thyroid gland to secrete the hormones thyroxine
Thyroxine

Thyroxine, or 3,5,3',5'-tetra?iodothyronine , a form of thyroid hormones is the major hormone secreted by the follicular cells of the thyroid gland....
 (T4) and triiodothyronine
Triiodothyronine

Triiodothyronine, carbonhydrogeniodinenitrogenoxygen, also known as T3, is a thyroid hormone.Thyroid-stimulating hormone activates the production of thyroxine and T3....
 (T3). TSH production is controlled by a Thyrotropin Releasing Hormone, (TRH), which is manufactured in the hypothalamus
Hypothalamus

The hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
 and transported to the anterior pituitary gland via the superior hypophyseal artery, where it increases TSH production and release. Somatostatin
Somatostatin

Somatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones....
 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 a (alpha) subunit (i.e., chorionic gonadotropin alpha
    Chorionic gonadotropin alpha

    Glycoprotein hormones, alpha polypeptide, also known as CGA, is a human gene.ReferencesFurther reading...
    ) is identical to that of human chorionic gonadotropin
    Human chorionic gonadotropin

    Human chorionic gonadotropin is a glycoprotein hormone produced in pregnancy that is made by the the developing embryo soon after Conception and later by the syncytiotrophoblast ....
     (HCG), luteinizing hormone
    Luteinizing hormone

    Luteinizing hormone is a hormone produced by the anterior pituitary gland.* In the female, an acute rise of LH ? the LH surge ? triggers ovulation....
     (LH), follicle-stimulating hormone
    Follicle-stimulating hormone

    Follicle-stimulating hormone is a hormone synthesized and secreted by gonadotropes in the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the human body....
     (FSH).
  • The ß (beta) subunit (TSHB
    TSHB

    Thyroid stimulating hormone, beta also known as TSHB is a protein which in humans is encoded by the TSHB gene....
    ) is unique to TSH, and therefore determines its function.


The TSH receptor

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

Stimulating antibodies to this receptor mimic TSH action and are found in Graves' disease
Graves-Basedow disease

Graves' disease is a thyroid disorder characterized by Goitre, exophthalmos, "orange-peel" skin, and hyperthyroidism. It is caused by an antibody-mediated auto-immune reaction, but the trigger for this reaction is still unknown....
.

Diagnostic use

TSH levels are tested in the blood of patients suspected of suffering from excess (hyperthyroidism
Hyperthyroidism

Hyperthyroidism is the term for overactive tissue within the thyroid gland,resulting in overproduction and thus an excess of circulating free thyroid hormones: thyroxine , triiodothyronine , or both....
), or deficiency (hypothyroidism
Hypothyroidism

Hypothyroidism is the disease state in humans and in animals caused by insufficient production of thyroid hormone by the thyroid gland. Cretinism is a form of hypothyroidism found in infants....
) of thyroid hormone. Generally, a normal range for TSH for adults is between 0.4 and 5.0 u
Micro

The term micro is a SI prefix in the SI and other systems of Units of measurements denoting a factor of 10−6 .Confirmed in 1960, the prefix comes from the Ancient Greek , meaning "small"....
IU
International unit

In pharmacology, the International Unit is a unit of measurement for the amount of a substance, based on measured biological activity or effect....
/mL (equivalent to m
Milli

milli is a SI prefix in the SI and other systems of Units of measurements denoting a factor of 10-3, or 1/1,000 .Adopted in 1795, the prefix comes from the Latin mille, meaning one thousand ....
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.. The interpretation depends also on what the blood levels of thyroid hormones (T3 and T4) are. The National Health Service
National Health Service

The National Health Service is the name commonly used to refer to the four publicly funded healthcare systems of the United Kingdom, collectively or individually, although only the health service in England uses the name 'National Health Service' without further qualification....
 in the UK considers a "normal" range to be more like 0.1 to 5.0 uIU/mL.

TSH levels for children normally start out much higher. In 2002, the National Academy of Clinical Biochemistry (NACB) in the United States
United States

The United States of America is a Federal government constitutional republic comprising U.S. state and a federal district. The country is situated mostly in central North America, where its Contiguous United States and Washington, D.C., the Capital districts and territories, lie between the Pacific Ocean and Atlantic Oceans, Borders of the U...
 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.

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
Hypothyroidism

Hypothyroidism is the disease state in humans and in animals caused by insufficient production of thyroid hormone by the thyroid gland. Cretinism is a form of hypothyroidism found in infants....
 over the [following] 20 years, especially if thyroid antibodies were elevated".

Source of pathology TSH level thyroid hormone level Disease causing conditions >- | hypothalamus/pituitary high high benign tumor of the pituitary (adenoma
Adenoma

An adenoma is a collection of growths of glandular origin. Adenomas can grow from many organs including the colon , adrenal, pituitary, thyroid, etc....
) or thyroid hormone resistance
Thyroid hormone resistance

Thyroid hormone resistance describes a rare syndrome where the thyroid hormone levels are elevated but the thyroid stimulating hormone level is not suppressed, or not completely suppressed as would be expected....
 |- | hypothalamus/pituitary 		low low hypopituitarism
Hypopituitarism

Hypopituitarism is the decreased secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain....
 |- | thyroid 		low high hyperthyroidism
Hyperthyroidism

Hyperthyroidism is the term for overactive tissue within the thyroid gland,resulting in overproduction and thus an excess of circulating free thyroid hormones: thyroxine , triiodothyronine , or both....
 or Grave's disease |- | thyroid 		high low congenital hypothyroidism
Congenital hypothyroidism

Congenital hypothyroidism is a condition of thyroid hormone deficiency present at birth. Approximately 1 in 4000 newborn infants has a severe deficiency of thyroid function, while even more have mild or partial degrees....
 (cretinism), hypothyroidism
Hypothyroidism

Hypothyroidism is the disease state in humans and in animals caused by insufficient production of thyroid hormone by the thyroid gland. Cretinism is a form of hypothyroidism found in infants....


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.

Therapeutic use

A drug, recombinant human TSH (rhTSH), called Thyrogen, is manufactured by Genzyme Corp.
Genzyme

Genzyme Corporation is a biotechnology company based in Cambridge, Massachusetts. Genzyme is the world?s third largest biotechnology company employing over 9,000 people around the world....
 in Cambridge, Massachusetts. The rhTSH is used in patients with thyroid cancer which is related to tumoral factors.

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