TSH
Thyroid-stimulating hormone (also known as TSH or thyrotropin) is a hormone synthesized and secreted by thyrotrope 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 (T4) and triiodothyronine (T3). TSH production is controlled by a Thyrotropin Releasing Hormone, (TRH), which is manufactured in the hypothalamus and transpored to the pituitary gland, 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 have an additional 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: Low T3 or T4 leads to high TSH, while high T3 and T4 leads to lowering of TSH.
Subunits of TSH
TSH consists of two subunits, the alpha and the beta subunit. The α (alpha) subunit is identical to that of human chorionic gonadotropin (HCG), luteinising hormone (LH), follicle-stimulating hormone (FSH). The β (beta) subunit 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.
Genetics
The alpha chain is located on chromosome 6q12-21. The beta chain is located on chromosome 1p13.
Diagnostic use
TSH levels are tested in the blood of patients suspected of suffering from excess (hyperthyroidism), or deficiency (hypothyroidism) of thyroid homone. Generally, a normal range for TSH is between 0.3 and 3.0 mIU/mL, but the interpretation depends also on what the blood levels of thyriod hormones (T3 and T4) are.
Primarily Abnormal Pituitary Function
Higher than normal levels of TSH combined with high levels of thyroid hormone (T3 and T4) may indicate disfunction of the hypothalamus and pituitary gland. In these case, a high TSH is often produced by a benign tumor of the pituitary (adenoma). Conversely, low levels of TSH, while blood levels of T3 and T4 are also low, indicates abnormally low function of the pituitary, known as hypopituitarism.
Primarily Abnormal Thyroid function
On the other hand, due to the negative feedback described above, abnormally high levels of Thyroid hormone, due to overproduction in the thyroid, results in low TSH levels. This occurs in diseases such as hyperthyroidism or Grave's disease. Conversely, an underproduction of T3 and T4 caused by diseases such as congenital hypothyroidism (cretinism), hypothyroidism or thyroid hormone resistance, gives rise to an increase in the measured TSH.
Clearly both TSH and T3 and T4 should be measured to ascertain where a specific thyroid disfunction 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.
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