Thyroid-stimulating hormone

Thyroid-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.

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 Thyrotrophin Releasing Hormone, (TRH), which is manufactured in the hypothalamus and transported to the anterior pituitary gland via the superior hypophyseal artery, 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.

Subunits of TSH

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 identical to that of human chorionic gonadotropin (HCG), luteinizing 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.

Diagnostic use

TSH levels are tested in the blood of patients suspected of suffering from excess (hyperthyroidism), or deficiency (hypothyroidism) of thyroid hormone. Generally, a normal range for TSH for adults is between 0.4 and 5.0 uIU/mL (equivalent to mIU/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 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 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 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) or thyroid hormone resistance
hypothalamus/pituitary	low	low	hypopituitarism
thyroid	low	high	hyperthyroidism or Grave's disease
thyroid	high	low	congenital hypothyroidism (cretinism), hypothyroidism

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. in Cambridge, Massachusetts. The rhTSH is used in patients with thyroid cancer which is related to tumoral factors.

Footnotes

External links