Chemical structure of thyroxine
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Liothyronine

The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are tyrosine-based hormones produced by the thyroid gland. An important component in the synthesis is iodine. The major form of thyroid hormone in the blood is thyroxine (T4). This is converted to the active T3 within cells by deiodinases. These are further processed by decarboxylation and deiodination to produce iodothyronamine (T1a) and thyronamine (T0a). more...

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Circulation

Most of the thyroid hormone circulating in the blood is bound to transport proteins :

  • Thyroxine-binding globulin (TBG)
  • Thyroid-binding prealbumin (TBPA) - this protein is also responsible for the transport of retinol, and so now has the preferred name of transthyretin (TTR)
  • albumin.

Only a very small fraction of the circulating hormone is free (unbound) - T4 0.03% and T3 0.3%. This free fraction is biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value. These values are referred to as fT4 and fT3. Another critical diagnostic tool is the amount of thyroid-stimulating hormone that is present. 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.

Function

The thyronines act on the body to increase the basal metabolic rate, affect protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline).The thyroid hormones are essential to proper development and differentiation of all cells of the human body. To various extents, they regulate protein, fat and carbohydrate metabolism. But they have their most pronounced effects on how human cells use energetic compounds. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.

The thyronamines function via some unknown mechanism to inhbit neuronal activity; this plays an important role in the hibernation cycles of mammals. One effect of administering the thyronamines is a severe drop in body temperature.

Related diseases

Both excess and deficiency of thyroxine can cause disorders.

  • Thyrotoxicosis or hyperthyroidism 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.
  • Hypothyroidism is the case where there is a deficiency of thyroxine.

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 form, is a stereoisomer of physiological thyroxine, which is metabolised more slowly and hence usually only needs once-daily administration.

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.

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Drug Update: Hypothyroidism
From OB/GYN News, 7/1/01 by Mitchel L. Zoler

Ask 100 endocrinologists what they prescribe for hypothyroidism and you'll generally get the same answer: levothyroxine--synthetic thyroxine, or [T.sub.4].

Experts say synthetic [T.sub.4] therapy most closely mimics the effects of a healthy thyroid gland. Its long half-life keeps the bioavailability of the drug on a much more even keel, compared with the roller-coaster effect of synthetic triiodothyronine, or [T.sub.3], which has a much shorter half-life.

In the last decade, the real advances in managing hypothyroidism haven't been about new therapies but instead about the use of more sensitive thyroid-stimulating hormone (TSH) tests and a better understanding of how to interpret the clinical relevance of their results.

Guidelines from the American Association of Clinical Endocrinologists (AACE) advise against using combinations of thyroid hormones, yet lately endocrinologists have received a steady stream of patients who, armed with information from the Internet, are interested in a combination of [T.sub.3] and [T.sub.4]. In 1999, the results of a controversial study suggested that the combination eased the psychological symptoms of patients with comorbid depression. But at least some experts say that the evidence was too subjective and that it is far too soon to prescribe the combination without further study.

Levothyroxine is the preferred agent to use during pregnancy, but hormone levels must be closely monitored throughout gestation. In nonpregnant patients, follow-up TSH testing is generally done 6 months after a normal hormone level is attained. If that result is normal, patients can be retested after 12 months. During pregnancy, however, follow-up testing should be done every 6 weeks.

Starting dosages of thyroid hormone should be low in the elderly.

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COPYRIGHT 2001 International Medical News Group
COPYRIGHT 2001 Gale Group

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