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Thyroid-stimulating hormone

Thyroid-stimulating hormone

Overview
Thyrotrophin-stimulating hormone (also known as TSH or thyrotropin) is a peptide hormone
Peptide hormone
Peptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.Like other proteins, peptide hormones are synthesized in cells from amino acids according to an mRNA template, which is itself synthesized from a DNA template inside the...

 synthesized and secreted by thyrotrope
Thyrotrope
Thyrotropes are endocrine cells in the anterior pituitary which produce thyroid stimulating hormone in response to thyrotropin releasing hormone .Thyrotropes appear basophilic in histological preparations....

 cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.



TSH stimulates the thyroid gland to secrete the hormones thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...

 (T4) and triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate....

 (T3). TSH production is controlled by thyrotropin-releasing hormone
Thyrotropin-releasing hormone
Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...

 (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...

 and transported to the anterior pituitary gland via the hypothalamo-hypophyseal portal system, where it increases TSH production and release.
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Encyclopedia
Thyrotrophin-stimulating hormone (also known as TSH or thyrotropin) is a peptide hormone
Peptide hormone
Peptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.Like other proteins, peptide hormones are synthesized in cells from amino acids according to an mRNA template, which is itself synthesized from a DNA template inside the...

 synthesized and secreted by thyrotrope
Thyrotrope
Thyrotropes are endocrine cells in the anterior pituitary which produce thyroid stimulating hormone in response to thyrotropin releasing hormone .Thyrotropes appear basophilic in histological preparations....

 cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.

Physiology



Regulation of thyroid hormone levels


TSH stimulates the thyroid gland to secrete the hormones thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...

 (T4) and triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate....

 (T3). TSH production is controlled by thyrotropin-releasing hormone
Thyrotropin-releasing hormone
Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...

 (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...

 and transported to the anterior pituitary gland via the hypothalamo-hypophyseal portal system, 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.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 has an effect on the pituitary release of TSH; when the levels of T3 and T4 are low, the production of TSH is increased, and, on the converse, when levels of T3 and T4 are high, TSH production is decreased. This effect creates a regulatory negative feedback loop.

Subunits


TSH is a glycoprotein and consists of two subunits, the alpha and the beta subunit.
  • The α (alpha) subunit (i.e., chorionic gonadotropin alpha
    Chorionic gonadotropin alpha
    Glycoprotein hormones alpha chain is a protein that in humans is encoded by the CGA gene.-Further reading:...

    ) is nearly identical to that of human chorionic gonadotropin
    Human chorionic gonadotropin
    Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...

     (HCG), luteinizing hormone
    Luteinizing hormone
    Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...

     (LH), follicle-stimulating hormone
    Follicle-stimulating hormone
    Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...

     (FSH). The α subunit is thought to be the effector region responsible for stimulation of adenylate cyclase (involved the generation of cAMP). The α chain has a 92-amino acid sequence
  • The β (beta) subunit (TSHB
    TSHB
    Thyroid stimulating hormone, beta also known as TSHB is a protein which in humans is encoded by the TSHB gene.- Function :Thyrotropin-stimulating hormone is a noncovalently linked glycoprotein heterodimer and is part of a family of pituitary hormones containing a common alpha subunit and a unique...

    ) is unique to TSH, and therefore determines its receptor specificity. The β chain has a 118-amino acid sequence.

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 and cause Graves' disease
Graves-Basedow disease
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

.

Diagnostic



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 causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

), or deficiency (hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

) of thyroid hormone. In general, a standard reference range for TSH for adults is between 0.4 and 3.0 µIU
International unit
In pharmacology, the International Unit is a unit of measurement for the amount of a substance, based on biological activity or effect. It is abbreviated as IU, as UI , or as IE...

/mL (equivalent to m
Milli
Milli is a prefix in the metric system denoting a factor of one thousandth . Adopted in 1795, the prefix comes from the Latin mille, meaning one thousand ....

IU/L), but values vary slightly among labs. The therapeutic target range TSH level for patients on treatment ranges between 0.3 to 3.0 μIU/mL. 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
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

 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.

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
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

 over the [following] 20 years, especially if thyroid antibodies were elevated".
! Source of pathology >
TSH level Thyroid hormone level >-
| Hypothalamus/pituitary
High High adenoma
Adenoma
An adenoma is a benign tumor of glandular origin. Adenomas can grow from many organs including the colon, adrenal glands, pituitary gland, thyroid, prostate, etc. Although these growths are benign, over time they may progress to become malignant, at which point they are called adenocarcinomas...

) 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.-Causes:...


>-
| 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 causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

 or Graves' disease
Graves' disease
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...


>-
| 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. If untreated for several months after birth, severe congenital hypothyroidism...

 (cretinism), hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

 or Hashimoto's thyroiditis
Hashimoto's thyroiditis
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune 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.

Therapeutic


A synthetic drug called recombinant human TSH alpha (rhTSHα or simply rhTSH, (trade name Thyrogen), is manufactured by Genzyme Corp.
Genzyme
Genzyme Corporation is a fully owned subsidiary of Sanofi-Aventis. Before its acquisition, Genzyme was an American biotechnology company based in Cambridge, Massachusetts. In 2010, Genzyme was the world’s third-largest biotechnology company, employing more than 11,000 people around the world...

. The rhTSH is used to treat thyroid cancer
Thyroid cancer
Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm , such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected...

.