Thyroid hormone: Wikis

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thyroxine (T4)
Thyroxine, T4
Triiodothyronine, T3

The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are tyrosine-based hormones produced by the thyroid gland. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half life than T3. The ratio of T4 to T3 released in the blood is roughly 20 to 1. Thyroxine is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases (5'-iodinase). These are further processed by decarboxylation and deiodination to produce iodothyronamine (T1a) and thyronamine (T0a).

Contents

Circulation

Most of the thyroid hormone circulating in the blood is bound to transport proteins. Only a very small fraction of the circulating hormone is free (unbound) and biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value.

When thyroid hormone is bound, it is not active, so the amount of free T3/T4 is what is important. For this reason, measuring total thyroxine in the blood can be misleading.

Type Percent
bound to thyroxine-binding globulin (TBG) 70%
bound to transthyretin or "thyroxine-binding prealbumin" (TTR or TBPA) 10-15%
paraalbumin 15-20%
unbound T4 (fT4) 0.03%
unbound T3 (fT3) 0.3%

T3 and T4 cross the cell membrane easily as they are lipophilic molecules, and function via a well-studied set of nuclear receptors in the nucleus of the cell, the thyroid hormone receptors.

T1a and T0a are positively charged and do not cross the membrane; they are believed to function via the trace amine-associated receptor TAAR1 (TAR1, TA1), a G-protein-coupled receptor located in the cell membrane.

Another critical diagnostic tool is measurement of the amount of thyroid-stimulating hormone (TSH) that is present.

Function

The thyroid system of the thyroid hormones T3 and T4.[1]

The thyronines act on nearly every cell in the body. They act to increase the basal metabolic rate, affect protein synthesis, help regulate long bone growth (synergy with growth hormone), neuronal maturation and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.

Thyroid hormone leads to heat generation in humans. However, the thyronamines function via some unknown mechanism to inhibit neuronal activity; this plays an important role in the hibernation cycles of mammals and the moulting behaviour of birds. One effect of administering the thyronamines is a severe drop in body temperature.

Related diseases

Both excess and deficiency of thyroxine can cause disorders.

  • Hyperthyroidism (an example is Graves Disease) is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 2% of women and 0.2% of men. Thyrotoxicosis is often used interchangeably with hyperthyroidism, but there are subtle differences. Although thyrotoxicosis also refers to an increase in circulating thyroid hormones, it can be caused by the intake of thyroxine tablets or by an over-active thyroid, whereas hyperthyroidism refers solely to an over-active thyroid.
  • Hypothyroidism (an example is Hashimoto's thyroiditis) is the case where there is a deficiency of thyroxine, triiodiothyronine, or both.
  • Clinical depression can sometimes be caused by hypothyroidism[2]. Some research[3] has shown that T3 is found in the junctions of synapses, and regulates the amounts and activity of serotonin, norepinephrine, and Gamma-aminobutyric acid (GABA) in the brain.

Medical use of thyroid hormones

Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidism). They are both absorbed well by the gut, so can be given orally. Levothyroxine, the most commonly used synthetic thyroxine form, is a stereoisomer of physiological thyroxine (t4 only), which is metabolised more slowly and hence usually only needs once-daily administration. Natural desiccated thyroid hormones, also under the commercial name Armour Thyroid, is derived from pig thyroid glands, it is a "natural" hypothyroid treatment containing 20% T3 and traces of T2, T1 and calcitonin. Also available are synthetic combinations of T3/T4 in different ratios (such as Thyrolar) and pure-T3 medications (Cytomel). Levothyroxine is usually the first course of treatment tried. Some patients feel they do better on Armour thyroid, though not all doctors like to work with it, as some believe it is harder to regulate. This is not supported by the evidence.

Thyronamines have no medical usages yet, though their use has been proposed for controlled induction of hypothermia which causes the brain to enter a protective cycle, useful in preventing damage during ischemic shock.

Synthetic thyroxine was first successfully produced by Charles Robert Harington and George Barger in 1926.

Production of the thyroid hormones

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Central

Thyroid hormones (T4 and T3) are produced by the follicular cells of the thyroid gland and are regulated by TSH made by the thyrotrophs of the anterior pituitary gland. Because the effects of T4 in vivo are mediated via T3 (T4 is converted to T3 in target tissues; T3 is 3- to 5- fold more active than T4).

Thyroxine (3,5,3',5'-tetraiodothyronine) is produced by follicular cells of the thyroid gland. It is produced as the precursor thyroglobulin (this is not the same as TBG), which is cleaved by enzymes to produce active T4.

Thyroxine is produced by attaching iodine atoms to the ring structures of tyrosine molecules. Thyroxine (T4) contains four iodine atoms. Triiodothyronine (T3) is identical to T4, but it has one less iodine atom per molecule.

Iodide is actively absorbed from the bloodstream by a process called iodide trapping. In this process, sodium is cotransported with iodide from the basolateral side of the membrane into the cell and then concentrated in the thyroid follicles to about thirty times its concentration in the blood. Via a reaction with the enzyme thyroperoxidase, iodine is bound to tyrosine residues in the thyroglobulin molecules, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). Linking two moieties of DIT produces thyroxine. Combining one particle of MIT and one particle of DIT produces triiodothyronine.

  • DIT + MIT → r-T3 (biologically inactive)
  • MIT + DIT → triiodothyronine (usually referred to as T3)
  • DIT + DIT → thyroxine (referred to as T4)

Proteases digest iodinated thyroglobulin, releasing the hormones T4 and T3, the biologically active agents central to metabolic regulation.

Peripheral

Thyroxine is supposedly a prohormone and a reservoir for the most active and main thyroid hormone T3. T4 is converted as required in the tissues by iodothyronine deiodinase. Deficiency of deiodinase can mimic an iodine deficiency. T3 is more active than T4 and is the final form of the hormone, though it is present in less quantity than T4.

Effect of iodine deficiency on thyroid hormone synthesis

If there is a deficiency of dietary iodine, the thyroid will not be able to make thyroid hormone. The lack of thyroid hormone will lead to decreased negative feedback on the pituitary, leading to increased production of thyroid stimulating hormone, which causes the thyroid to enlarge (goiter)endemic colloid goiter. This has the effect of increasing the thyroid's ability to trap more iodide, compensating for the iodine deficiency and allowing it to produce adequate amounts of thyroid hormone.

Anti-thyroid drugs

Iodine uptake against a concentration gradient is mediated by a sodium-iodine symporter and is linked to a sodium-potassium ATPase. Perchlorate and thiocyanate are drugs that can compete with iodine at this point. Compounds such as goitrin can reduce thyroid hormone production by interfering with iodine oxidation.[4]

Effects of thyroxine

  • Increases cardiac output
  • Increases heart rate
  • Increases ventilation rate
  • Increases basal metabolic rate
  • Potentiates the effects of catecholamines (i.e increases sympathetic activity)
  • Potentiates brain development
  • Thickens endometrium in females

Treatment

Today most patients (at least in industrialized countries) are treated with levothyroxine, or a similar synthetic thyroid hormone[5][6][7 ]. However, natural thyroid hormone supplements from the dried thyroids of animals are still available[7 ]. Natural thyroid hormones have become less popular, mostly because the concentration of thyroid hormones in the thyroids of animals before they were slaughtered naturally varies somewhat[7 ]. However, some people are afraid of rare allergic reactions to synthetic pharmaceuticals, and some patients & doctors just prefer natural treatments. For these people, natural thyroid treatments hormones are still available[7 ][8 ][9][10][11 ]. Some natural thyroid hormone brands are F.D.A. approved, but some are not[12 ][13 ][14 ]. Thyroid hormones are generally well tolerated[6]. Thyroid hormones are usually not dangerous for pregnant women or nursing mothers, but should be given a doctor's supervision. In fact, if a woman who is hypothyroid is left untreated, her baby is at a higher risk for birth defects. When pregnant, a woman with a low functioning thyroid will also need to increase her dosage of thyroid hormone.[6]. One exception is that thyroid hormones may aggravate heart conditions, especially in older patients; therefore, doctors may start these patients on a lower dose & work up to avoid risk of heartattack[7 ].

Herbs

There are no herbs (plant chemicals) that contain thyroid hormone[8 ][15]. Therefore, while there are some herbs that may provide some help for a sluggish thyroid (i.e. if the thyroid is producing a low amount of thyroid hormone, but has not stopped completely)[16 ], myxedema requires treatment with synthetic or desiccated natural thyroid hormones[15][17 ].

See also

References

  1. ^ References used in image are found in image article in Commons:Commons:File:Thyroid_system.png#References.
  2. ^ Kirkegaard C, Faber J (1998). "The role of thyroid hormones in depression". Eur J Endocrinol 138 (1): 1–9. doi:10.1530/eje.0.1380001. PMID 9461307.  
  3. ^ Dratman M, Gordon J (1996). "Thyroid hormones as neurotransmitters". Thyroid 6 (6): 639–47. doi:10.1089/thy.1996.6.639. PMID 9001201.  
  4. ^ Spiegel C, Bestetti GE, Rossi GL, Blum JW (September 1993). "Normal circulating triiodothyronine concentrations are maintained despite severe hypothyroidism in growing pigs fed rapeseed presscake meal". J. Nutr. 123 (9): 1554–61. PMID 8360780. http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=8360780.  
  5. ^ Robert Lloyd Segal, MD Endocrinologist
  6. ^ a b c "prefered thyroid hormone -- Levothyroxine Sodium (Synthroid, Levoxyl, Levothroid, Unithroid)", Retrieved on 2009-3-27
  7. ^ a b c d e "Hypothyroidism Causes, Symptoms, Diagnosis, Treatment Information Produced by Medical Doctors", Retrieved on 2009-3-27
  8. ^ a b "Consequences of Not Taking Thyroid Medications - Implications of Failing to Take Prescription Thyroid Drugs", Retrieved on 2009-3-27
  9. ^ "Armour Thyroid", Retrieved on 4-1-2009
  10. ^ "Nature-Throid", Retrieved on 4-1-2009
  11. ^ "Armour Thyroid Shortages Worsening: What Can Thyroid Patients Do?", Retrieved on 2009-3-27
  12. ^ "Thyroid Information", Retrieved on 2009-3-27
  13. ^ "Desiccated thyroid in a nutritional supplement | Journal of Family Practice | Find Articles at BNET", Retrieved on 2009-3-27
  14. ^ "Nature-Throid", Retrieved on 4-1-2009
  15. ^ a b "Thyroid Disease: A Natural/Herbal Perspective -- Interview with Shasta Tierra-Tayam, L.Ac", Retrieved on 2009-3-27
  16. ^ “WikiAnswers - Is there are natural herb to take for a sluggish thyroid”, Retrieved on 2009-3-27
  17. ^ "Hypothyroidism Causes, Symptoms, Diagnosis, Treatment Information Produced by Medical Doctors", Retrieved on 2009-3-27

External links

Thyroid hormone treatment in thyroid disease


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