Thyroid Hormone

The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. 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).

Circulation and Transport

Plasma Transport 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.

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

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.

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[3]. Some research[4] 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.

Thyroxine is believed to be 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.

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

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