Thyroid-stimulating hormone

Thyrotrophin-stimulating hormone (also known as TSH or thyrotropin) is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.

Regulation of thyroid hormone levels
TSH stimulates the thyroid gland to secrete the hormones thyroxine (T4) and triiodothyronine (T3). TSH production is controlled by thyrotropin-releasing hormone (TRH), which is manufactured in the hypothalamus and transported to the anterior pituitary gland via the hypothalamo-hypophyseal portal system, where it increases TSH production and release. 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) is nearly identical to that of human chorionic gonadotropin (HCG), luteinizing hormone (LH), follicle-stimulating hormone (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 the following 92-amino acid sequence:
 * The β (beta) subunit (TSHB) is unique to TSH, and therefore determines its receptor specificity. The β chain has a 112-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.

Diagnostic
TSH levels are tested in the blood of patients suspected of suffering from excess (hyperthyroidism), or deficiency (hypothyroidism) of thyroid hormone. In general, a standard reference range for TSH for adults is between 0.4 and 3.0 µIU/mL (equivalent to mIU/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/L. 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 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 over the [following] 20 years, especially if thyroid antibodies were elevated".

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.. The rhTSH is used to treat thyroid cancer.