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Levothyroxine, also known as -thyroxine, is a synthetic form of the thyroid hormone thyroxine (T<sub>4</sub>).

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Levothyroxine was first made in 1927. It is on the World Health Organization's List of Essential Medicines. Levothyroxine is available as a generic medication.

Medical uses

Levothyroxine is typically used to treat hypothyroidism, and is the treatment of choice for people with hypothyroidism who often require lifelong thyroid hormone therapy.

It may also be used to treat goiter via its ability to lower thyroid-stimulating hormone (TSH), which is considered goiter-inducing. Levothyroxine is also used as interventional therapy in people with nodular thyroid disease or thyroid cancer to suppress TSH secretion. A subset of people with hypothyroidism treated with an appropriate dose of levothyroxine will describe continuing symptoms despite TSH levels in the normal range. Annual or semiannual clinical evaluations and TSH monitoring are appropriate after dosing has been established. Levothyroxine is taken on an empty stomach about half an hour to an hour before meals. Doses of levothyroxine that normalize serum TSH may not normalize abnormal levels of LDL cholesterol and total cholesterol.

Poor compliance in taking the medicine is the most common cause of elevated TSH levels in people receiving appropriate doses of levothyroxine. Since thyroid hormone increases the heart's oxygen demand by increasing heart rate and contractility, starting at higher doses may cause an acute coronary syndrome or an abnormal heart rhythm. According to the U.S. Food and Drug Administration pregnancy categories, levothyroxine has been assigned category A.

Too high a dose of levothyroxine causes hyperthyroidism. Overdose can result in heart palpitations, abdominal pain, nausea, anxiousness, confusion, agitation, insomnia, weight loss, and increased appetite.

Interactions

Many foods and other substances can interfere with the absorption of thyroxine. Substances that reduce absorption are aluminium- and magnesium-containing antacids, simethicone, sucralfate, cholestyramine, colestipol, and polystyrene sulfonate. Sevelamer with calcium carbonate may decrease the bioavailability of levothyroxine. Grapefruit juice may delay the absorption of levothyroxine, but based on a study of 10 healthy people aged 20–30 (eight men, two women), it may not have a significant effect on bioavailability in young adults. A study of eight women suggested that coffee may interfere with the intestinal absorption of levothyroxine, though at a level less than eating bran. Certain other substances can cause adverse effects that may be severe. Combination of levothyroxine with ketamine may cause hypertension and tachycardia; and tricyclic and tetracyclic antidepressants increase its toxicity. Soy, <!-- humans should not eat CSM - toxic cottonseed meal, --> walnuts, fiber, calcium supplements, and iron supplements can also adversely affect absorption.

To minimize interactions, a manufacturer of levothyroxine recommends after taking it, waiting 30 minutes to one hour before eating or drinking anything that is not water. They further recommend taking it in the morning on an empty stomach.

Chemistry

Levothyroxine is a synthetic form of thyroxine (T<sub>4</sub>), which is secreted by the thyroid gland. Levothyroxine and thyroxine are chemically identical: natural thyroxine is also in the "levo" chiral form, the difference is only in terminological preference. T<sub>4</sub> is biosynthesized from tyrosine. Approximately 5% of the US population suffers from over- or underproduction of T and T. See for more information on its biosynthesis.

Industrially, levothyroxine is made by chemical synthesis. Tyrosine is a common starting material. The produced hormone is incorporated into drugs as its sodium salt, levothyroxine sodium. Solid drugs such as tablets contain the pentahydrate form of the salt.

Dextrothyroxine is the mirror form of levothyroxine with the opposite, non-natural chirality.

Mechanism of action

T is a ‌a precursor to the hormone T. While T is a tetraiodide, T is a triiodide known as triiodothyronine. The selenoenzyme iodothyronine deiodinase mediates the T→T conversion. T-thyroxine is a unique example of an iodine compound essential for human health. T binds to thyroid receptor proteins in the cell nucleus and causes metabolic effects through the control of DNA transcription and protein synthesis. In addition to deiodination, thyroid hormones are also excreted through the kidneys and metabolized through conjugation and glucuronidation and excreted directly into the bile and the gut, where they undergo enterohepatic recirculation. The hormone was synthesized in 1927 by British chemists Charles Robert Harington and George Barger.

Society and culture

Economics

thumb|right|A 30 tablet [[blister pack package of generic Euthyrox (levothyroxine) manufactured by Merck KGaA and marketed by Provell Pharmaceuticals in the US]]

, levothyroxine was the second-most commonly prescribed medication in the US, with 23.8&nbsp;million prescriptions filled each year.

In 2023, it was the third most commonly prescribed medication in the United States, with more than 80million prescriptions. Furthermore, it is available as both brand-name and generic products.

References

  • Levothyroxine pronunciation guide – audio, phonetic spelling, and syllable breakdown