Thyroid hormone

2016-10-17T14:10:36Z

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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|iodination]] of two precursors, [[Monoiodothyronine|monoiodothyronine]], T1, and [[Diiodothyronine]], T2. Although thyroxine is produced in larger quantities, it must be noted that [[Triiodothyronine|triiodothyronine]] is three to eight times more active. Thus, [[Thyroxine|thyroxine]] is metabolised into [[Triiodothyronine|triiodothyronine]] for active use. The thyroid hormones are involved in growth, working synergistically with [[Growth hormone|growth hormone]], in cellular [[Metabolism|metabolism]] and in bodily [[Thermogenisis|thermogenisis]].

The level of thyroid hormones carried in the [[Blood|blood]] plasma must be regulated; over-active thyroid tissue leads to an increase in circulating thyroid [https://teaching.ncl.ac.uk/bms/wiki/index.php/Hormone hormones], termed [[Hyperthyroidism|hyperthyroidism]], the symptoms of which include [[Goitre|goitre]]. The converse, a deficiency of thyroid hormones, or [[Hypothyroidism|hypothyroidism]] can have serious acute effects as well as chronic effects, the latter most serious when presented congenitally.

=== Synthesis ===

[[Thyroxine|Thyroxine]] and [[Triiodothyronine|Triiodothyronine]] are based on the [[Amino acid|amino acid]] [[Tyrosine|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|epithelium]] of follicular cells <ref>Hadley, M. E (2000) Endocrinology 5th Edition, Upper Saddle River, Prentice Hall</ref>. The follicular cells produce a [[Glycoproteins|glycoprotein]], [[Thyroglobulin]], which is rich in tyrosine residues. This is [[Exocytosis|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]] <ref>Ruf, J., Carayon, P. (2006). "Structural and functional aspects of thyroid peroxidase." Archives of Biochemistry and Biophysics 445: 2; 269-277</ref>. The [[Iodine|iodine]] is provided via the [[Sodium-Iodide Symporter|Na+/-I-Symporter which]] actively transports [[Sodium|Sodium]] and Iodide ions into the follicular cells from the blood using free energy released from transporting Na+ down its concentration gradient <ref>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</ref>. 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|Thyroid-Stimulating Hormone]] the colloid is [[Pinocytosis|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|medial eminence]] which drains into the [[Hypophyseal portal system|hypophyseal portal system]]. This carries the TRH to the adenohypophysis, or [[Anterior pituitary gland|anterior pituitary gland where]] it acts on [[Thyrotroph|thyrotrophs]] which secrete [[Thyroid stimulating hormone|Thyroid-Stimulating Hormone]].

===== Effects of Thyroid-Stimulating Hormone =====

*Upregulation of [[Thyroglobulin|thyroglobulin]] gene transcription
*Upregulation of [[Thyroperoxidase|thyroperoxidase]] gene transcription
*Binds to receptors on Na+/I- Symporter causing it to open, thus increasing uptake of iodine into follicular cells
*Increases rate of pinocytosis of colloid
*Increases lysosomal activity to degrade incoming colloid and release thyroid hormones
*Increases thyroid cell size

=== Effects of Thyroid Hormone ===

*Increased protein synthesis
*Increased cellular metabolism, particularly of [[Lipid|fats]] and [[Carbohydrate|carbohydrates]]
*Thermatogenesis
*Increased cardiac output through increased gene transcription of Ca2+-ATPase, thus causing increased muscle contraction <ref>Bielecka-Dabrowa, A., Mikhailidis, D.P., Rysz, J., Banach, M. (2009). "The mechanisms of atrial fibrillation in hyperthyroidism.", Thyroid Research 2:4</ref>
*Increased oxygenation of blood due to a higher rate of breathing
*Works synergistically with growth hormone to encourage normal growth in early development

=== Hyperthyroidism ===

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 =====

*Weight loss due to increased [[Lypolysis|lypolysis]]
*Gain in appetite due to increased metabolism of food
*Intolerance of heat due to increased calorigenesis
*Sweating
*Warm, moist skin
*Tachycardia
*Arrhythmia

===== Graves' Disease =====

Graves' Disease is autoimmune [[Hyperthyroidism|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. <ref>http://www.nejm.org/doi/full/10.1056/NEJMoa1012985</ref>

Goitre is brought about by the hypertrophy caused by stimulation of TSG receptors <ref>Van den Berghe, G. (2008). Acute Endocrinology, Springer; Chapter 1: Thyrotoxicology</ref>.

==== Treatment ====

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 <ref name="null">NHS (2010). "Treating overactive thyroid" available at http://www.nhs.uk/Conditions/Thyroid-over-active/Pages/Treatment.aspx, accessed 9.1.11</ref>. However, in most cases the patient will be required to take thyroid replacement hormone post-treatment.

=== Hypothyroidism ===

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.

===== Symptoms =====

*Weight gain due to decreased lipolysis
*Puffy hands and feet
*Easily fatigued due to decreased glucose metabolism
*Intolerance of cold due to decreased calorigenesis
*Hard, dry, rough skin
*Drooping eyelids
*Possible mental impairment

===== Cretinism =====

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 <ref>Rastogi, M.V., LaFranchi, S.H. (2010). "Congenital hypothyroidism", Orphanet Journal of Rare Diseases, 5:17</ref>.

===== Treatment =====

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 <ref>NHS, (2010). "Treating underactive thyroid", available at http://www.nhs.uk/Conditions/Thyroid-under-active/Pages/Treatment.aspx, accessed 9.1.11</ref>.

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 <ref>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</ref>.

=== References ===

<references />

Density

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Density (D or ρ = Greek letter roh )can be defined [[Mass|mass ]]per unit of volume.<ref>wikipedia-density-https://en.wikipedia.org/wiki/Density</ref>

Equation: ρ= m/V SI UNITS = kg/m^3 Many liquids have different densities; we can use this to separate or identify specific liquids. This also explains why [[Water|water and]] oil are immiscible.

= =

= '''References''' <references /> =

Density

2015-11-17T00:02:24Z

150072090:

Density (D or ρ = Greek letter roh )can be defined [[Mass|mass ]]per unit of volume.<ref>Wikepedia-density-https://en.wikipedia.org/wiki/Density</ref>

Equation: ρ= m/V SI UNITS = kg/m^3 Many liquids have different densities; we can use this to separate or identify specific liquids. This also explains why [[Water|water and]] oil are immiscible.

= =

= '''References''' <references /> =

Density

2015-11-17T00:01:07Z

150072090: Created page with "Density (D or ρ = Greek letter roh )can be defined mass per unit of volume.<ref>Wikepedia - Density -h..."

Density (D or ρ = Greek letter roh )can be defined [[Mass|mass ]]per unit of volume.<ref>Wikepedia - Density -https://en.wikipedia.org/wiki/Density#/media/File:Artsy_density_column.png</ref>

Equation: ρ= m/V SI UNITS = kg/m^3 Many liquids have different densities; we can use this to separate or identify specific liquids. This also explains why [[Water|water ]]and oil are immiscible.

= =

= '''References''' [[Image:]]<references /> =

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Thyroid hormone

Density

Density

Density