Thyroid-stimulating hormone

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

TSH stimulates the thyroid gland to secrete the hormones thyroxine (T₄) and triiodothyronine(T₃).^[3] TSH production is controlled by thyrotropin-releasing hormone (TRH), which is manufactured in the hypothalamus and transported to the anterior pituitary gland via thehypothalamo-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.

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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:

NH₂ – Ala – Pro – Asp – Val – Gln – Asp – Cys – Pro – Glu – Cys – Thr – Leu – Gln – Glu – Asn – Pro – Phe – Phe – Ser – Gln – Pro – Gly – Ala – Pro – Ile – Leu – Gln – Cys – Met – Gly – Cys – Cys – Phe – Ser – Arg – Ala – Tyr – Pro – Thr – Pro – Leu – Arg – Ser – Lys – Lys – Thr – Met – Leu – Val – Gln – Lys – Asn – Val – Thr – Ser – Glu – Ser – Thr – Cys – Cys – Val – Ala – Lys – Ser – Tyr – Asn – Arg – Val – Thr – Val – Met – Gly – Gly – Phe – Lys – Val – Glu – Asn – His – Thr – Ala – Cys – His – Cys – Ser – Thr – Cys – Tyr – Tyr – His – Lys – Ser – OH

§ The β (beta) subunit (TSHB) is unique to TSH, and therefore determines its receptor specificity. The β chain has the following 112-amino acid sequence:

NH₂ – Phe – Cys – Ile – Pro – Thr – Glu – Tyr – Thr – Met – His – Ile – Glu – Arg – Arg – Glu – Cys – Ala – Tyr – Cys – Leu – Thr – Ile – Asn – Thr – Thr – Ile – Cys – Ala – Gly – Tyr – Cys – Met – Thr – Arg – Asp – Ile – Asn – Gly – Lys – Leu – Phe – Leu – Pro – Lys – Tyr – Ala – Leu – Ser – Gln – Asp – Val – Cys – Thr – Tyr – Arg – Asp – Phe – Ile – Tyr – Arg – Thr – Val – Glu – Ile – Pro – Gly – Cys – Pro – Leu – His – Val – Ala – Pro – Tyr – Phe – Ser – Tyr – Pro – Val – Ala – Leu – Ser – Cys – Lys – Cys – Gly – Lys – Cys – Asn – Thr – Asp – Tyr – Ser – Asp – Cys – Ile – His – Glu – Ala – Leu – Lys – Thr – Asn – Tyr – Cys – Thr – Lys – Pro – Gln – Lys – Ser – Tyr – OH

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The TSH receptor

The TSH receptor is found mainly on thyroid follicular cells.^[4] Stimulation of the receptor increases T₃ and T₄ production and secretion.

Stimulating antibodies to this receptor mimic TSH and cause Graves' disease.

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Applications

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Diagnostic

Further information: Thyroid function tests

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 5.0 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.^[5] 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.^[6]

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".^[7]

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 Graves' disease
Thyroid	High	Low	Congenital hypothyroidism (cretinism), hypothyroidism or Hashimoto's thyroiditis

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.^[1]

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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.^[8]

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