Thyroid hormone

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'Thyroid Hormone' is an umbrella term referring to Triiodothyronine, T3, and Thyroxine, T4, two Tyrosine-based hormones produced by the Thyroid gland. Their synthesis involves the iodination of two precursors, monoiodothyronine, T1, and Diiodothyronine, T2. Although thyroxine is produced in larger quantities, it must be noted that triiodothyronine is three to eight times more active. Thus, thyroxine is metabolised into triiodothyronine for active use. The thyroid hormones are involved in growth, working synergistically with growth hormone, in cellular metabolism and in bodily thermogenisis.

The level of thyroid hormones carried in the blood plasma must be regulated; over-active thyroid tissue leads to an increase in circulating thyroid hormones, termed hyperthyroidism, the symptoms of which include goitre. The converse, a deficiency of thyroid hormones, or hypothyroidism can have serious acute effects as well as chronic effects, the latter most serious when presented congenitally.



Thyroxine and Triiodothyronine are based on the amino acid tyrosine and which has been iodinated to varying degrees.

Thyroid tissue is composed of distinct functional units called Follicles. These consist of a central Colloid-containing Lumen surrounded by a thin epithelium of follicular cells [1]. The follicular cells produce a glycoprotein, Thyroglobulin, which is rich in tyrosine residues. This is exocytosed into the colloid where it is stored. Tyrosine residues of thyroglobulin are iodinated to produce monoiodothyronine and diiodothyronine, the precursors to the thyroid hormones, catalysed by the enzyme Thyroperoxidase [2]. The iodine is provided via the Na+/-I-Symporter which actively transports Sodium and Iodide ions into the follicular cells from the blood using free energy released from transporting Na+ down its concentration gradient [3]. Monoiodothyronine and diiodothyronine under go a coupling reaction independant of thyroperoxidase in which the active thyroid hormones, thyroxine and triiodothyronine are yielded.

A coupling of monoiodothyronine and diiodothyronine yields triiodothyronine.

A coupling of two diiodothyronine molecules yields thyroxine (tetraiodothyronine).

Upon stimulation from Thyroid-Stimulating Hormone the colloid is pinocytosed into the follicular cell where the thyroglobulin is degraded within the endocytotic vesicles to release the thyroid hormones.

T3 and T4 enter the bloodstream and is bound to carrier proteins. Only approximately 0.4% T3 and 0.04% of T4 is circulated in free form. 70% of thyroid hormones are bound with high affinity to Thyroxine-Binding Globulin. 10% of T4 is bound to Thyroxine-Binding Prealbumin which has a tenfold greater affinity for T4 than for T3. Around 15% of thyroid hormones are bound with low affinity to albumin which allows rapid dissociation in the tissues.

Metabolism of T4

Around 100nM of T4 are secreted every day, whereas only 5nM of the more active T3 is secreted. T4 is deiodinated to produce a greater concentration of T3 in ways that both up-regulates and down-regulates the level of thyroid hormone in the blood.

Up-Regulatory processes

1 5'-Deiodinase produces T3 from T4 in the plasma.

2 5'-Deiodinase produces T3 from T4 in the brain and pituitary providing for the CNS.

Down-Regulatory processes

3 5'-Deiodinase produces rT3, an inactive form of T3, thus reducing the effects of active thyroid hormone.

Regulation of Thyroid Hormone release 

The production and secretion of thyroid hormones is controlled by the Hypothalamo-hypophyseal axis.

The Hypothalamus secretes Thyrotrophin-Releasing Hormone into the medial eminence which drains into the hypophyseal portal system. This carries the TRH to the adenohypophysis, or anterior pituitary gland where it acts on thyrotrophs which secrete Thyroid-Stimulating Hormone.

Effects of Thyroid-Stimulating Hormone

Effects of Thyroid Hormone


Hyperthyroidism is the over-production of thyroid hormones caused by hyperactive thyroid tissue. This brings about a consequent over-stimulation of target cells, Many symptoms are brought about due to an increase in cellular metabolism. It is characterised by a decrease in Thyroid-Stimulating Hormone in the blood.

Common symptoms
Graves' Disease

Graves' Disease is autoimmune hyperthyroidism resulting when auto-antibodies bind to the Thyroid-Stimulating Hormone receptors resulting in increased presentation of typical TSH effects. Graves' Disease is normally characterised by the accompanying opthalmopathy and goitre.

Graves' Opthalmopathy is caused by auto-antibodies attacking adipose tissue around the eyes, bringing about edema, erythema, characteristic proptosis and in severe cases, lagopthalamos. Studies have been carried out which have shown that Selenium supplementation is beneficial in reducing exopthalmus in patients. [5]

Goitre is brought about by the hypertrophy caused by stimulation of TSG receptors [6].


There are several possible treatments depending on the severity of the symptoms.

Surgical methods are often used to relieve the discomfort of the opthalmopathy associated with Graves' disease and to reduce the anterior neck swelling if it begins to inhibit swallowing and breathing. Thyroidectomy can also be carried out on the thyroid to reduce thyroid hormone production to a normal level.

Radioactive Iodine, usually with isotope 131I, can be administered to destroy thyroid cells and reduce the size of the thyroid gland [7]. However, in most cases the patient will be required to take thyroid replacement hormone post-treatment.


Hypothyroidism is caused by under-active thyroid tissue resulting in a deficiency in thyroxine and triiodothyronine. Many symptoms are associated with a decrease in metabolic rate.


Cretinism is a form of congenital hypothyroidism caused by untreated deficiency of iodine in the maternal blood supply during gestational development or problems in thyroid development. This leads to stunted growth and mental impairment that cannot be reversed.

Congenital hypothyroidism does not manifest itself at birth. Screening for elevated TSH and decreased T3 and T4 is therefore very important in diagnosing and treating neonates before development is severely impaired.

An elongated gestation period (above forty-two weeks), jaundice or hyperpigmentation, a hoarse cry and lethargy may be tell-tale signs in neonates [8].


The aim of treatment is to raise thyroxine blood levels and this is achieved by administering tablets of levothyroxine, the laevatory enantiomer of thyroxine. In adults, the dose s dependant on the severity of the hypothyroidism [9].

In children, T4 levels are to be normalised within two weeks of birth and maintained in the upper range of normal for the first year of life. Evaluation and follow-up treatment can be arranged over the next three years to ensure correct development continues. If treated quickly enough, children can avoid any sort of mental impairment and will continue to develop normally, cognatively and neurologically [10].


  1. Hadley, M. E (2000) Endocrinology 5th Edition, Upper Saddle River, Prentice Hall
  2. Ruf, J., Carayon, P. (2006). "Structural and functional aspects of thyroid peroxidase." Archives of Biochemistry and Biophysics 445: 2; 269-277
  3. Li, C.C., Ho, T.Y., Kao, C.H., Wu, S.L., Liang, J.A., Hsaing, C.Y. (2010). "Conserved charged amino acid residues in the extracellular region of sodium/iodide symporter are critical for iodide transport activity.", Journal of Biomedical Science, 17: 89
  4. Bielecka-Dabrowa, A., Mikhailidis, D.P., Rysz, J., Banach, M. (2009). "The mechanisms of atrial fibrillation in hyperthyroidism.", Thyroid Research 2:4
  6. Van den Berghe, G. (2008). Acute Endocrinology, Springer; Chapter 1: Thyrotoxicology
  7. NHS (2010). "Treating overactive thyroid" available at, accessed 9.1.11
  8. Rastogi, M.V., LaFranchi, S.H. (2010). "Congenital hypothyroidism", Orphanet Journal of Rare Diseases, 5:17
  9. NHS, (2010). "Treating underactive thyroid", available at, accessed 9.1.11
  10. Rose, S.R., Brown, R.S., Wilkins, L., (2006). "Update of Newborn Screening and Therapy for Congenital Hypothyroidism.", Official Journal of the American Academy for Pediatrics 117:6 2290-2303
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