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Levothyroxine

Pharmacological group: thyroid hormones; synthetic natural thyroid hormones.

Pharmacological action: treatment of hypothyroidism.

IUPAC name: (S) -2-amino-3- [4- (4-hydroxy-3,5-diiodophenoxy) -3,5-diiodophenyl] propanoic acid

Other names: 3,5,3 ', 5'- tetradiodo-L-thyronin

Bioavailability ~ 100%

Application: oral, intravenous

Metabolism: mainly in the liver, kidneys, brain and muscles

Half-life period: approx. 7 days (for hyperthyroidism 3-4 days, for hypothyroidism 9-10 days)

Excretion: with feces and urine

Legal Status: Prescription only

Molecular formula: C15H11I4NO4

Molar mass: 776.87 g mol-1

Melting point: 231-233 ° C

Solubility in water: slightly soluble substance (0105 mg · l -1 at 25 ° С).

Description

Levothyroxine sodium is a synthetic form of the natural thyroid hormone tetraiodothyronine (T-4). Thyroid hormones are responsible for regulating the metabolic rate in the body, and play a vital role in the absorption of proteins, fats and carbohydrates. Levothyroxine sodium is used in medicine to treat hypothyroidism, a disease characterized by insufficient levels of natural thyroid hormone production. The disease has a number of symptoms, including energy loss, lethargy, weight gain, hair loss and changes in skin texture. Levothyroxine sodium is considered a slow-acting drug, and it may take 4-6 weeks to achieve full therapeutic effects. The drug is the most commonly prescribed treatment for the thyroid gland in the world, and is considered the standard treatment for most cases of hypothyroidism. The action of levothyroxine sodium is very close to that of the popular thyroid drug Cytomel (liothyronine sodium). Cytomel has a slightly different structure, and is a synthetic form of the thyroid hormone triiodothyronine (T-3). In the body of a healthy person, there are sufficient levels of thyroid hormones T-3 and T-4. T-3 is considered the main active form of thyroid hormone, while T4 serves mainly as a reserve for T3, showing most of its metabolic activity through transformation in peripheral tissues to T3. It is estimated that T3 has about four times more efficacy than T-4 in comparing milligrams per milligram. In addition, Cytomel is considered a more effective form of the drug for the treatment of the thyroid gland, both in its activity and in terms of side effects. Levothyroxine sodium is used by many athletes and bodybuilders for its ability to stimulate metabolism and support the breakdown of body fat reserves. The drug is usually taken with calorie restriction ("drying"), when the user is interested in losing fat or increasing muscle relief. It is assumed that the use of thyroid drugs may contribute to fat loss with a higher level of calorie intake than would be possible without the use of such drugs. Anabolic steroids are commonly used with these hormones, and many believe that the improved metabolism caused by these drugs can produce a rapid increase in muscle mass. However, the effectiveness of the drug in this regard has not yet been proven.

Medical use of thyroxine

T4 is usually used to treat hypothyroidism. Due to its ability to reduce the level of thyroid-stimulating hormone (TSH), a hormone that, presumably, causes the development of goiter, the drug can also be used to treat goiter.

Story

Levothyroxine sodium is the first commercial synthetic drug for the treatment of the thyroid gland in the United States, which was first marketed in 1955 under the name Synthroid from Flint Laboratory. The drug has a long history of therapeutic use in the United States and internationally, and for decades has been the most widely used drug for the treatment of hypothyroidism. The figures show that the Synthroid brand provided 85% of total sales of levothyroxine and annual revenues from the sale of the drug are $ 600 million. In the community of bodybuilders and athletes, however, the faster and more powerful drug Cytomel (liothyrosine sodium) is more popular. Since Synthroid is considered a weaker delayed drug, you have to take it longer to achieve similar results. The brand itself Synthroid has a long and complex history. A few years after its creation, Synthroid gained a monopoly in the market for levothyroxine sodium. In the 1980s, however, levothyroxine sodium generics began to appear. In response, in 1986, Flint funds research at the University of California. This was done to demonstrate that Synthroid has a higher therapeutic value than its generics. The study was completed in 1990, and, in fact, proved that generic drugs have equal effectiveness with Synthroid. The contract was a clause that for the publication of this study, you must obtain an approval from the company Flint. Began litigation for the publication. Even after Flint's lab was sold to Boots, which was then sold to Knoll, the publication of the study was constantly postponed. Ultimately, the study was published in 1997. This was followed by a collective action claiming that the lack of information forced consumers to overpay 2-3 times only for the brand of the drug. In the end, Knoll agreed to pay $ 135,000,000.

As shipped

Levothyroxine sodium is most often supplied in the form of oral tablets of 25, 50, 75, 100, 125, 150, 200 and 300 micrograms.

Structural characteristics

Levothyroxine sodium is a synthetic form of the thyroid hormone T4. It has the chemical designation L-3, 3 ', 5.5' tetraiodothyronine sodium salt.

Warnings

The FDA requires that all prescription lyothyronine sodium in the United States contain the following warning in the black box: "Thyroid hormones, including levothyroxine sodium, alone or in combination with other therapeutic drugs, should not be used to treat obesity or weight loss. In euthyroid patients, doses in the range of daily hormonal needs are not effective for weight loss. Taking larger doses can lead to serious and even life-threatening manifestations of toxicity, especially in combination with sympathomimetic amines (anorexia drugs). "

Drug interactions of thyroxine

Some products and other substances may also affect the absorption of thyroxin replacement. Patients should avoid taking calcium and iron for 4 hours, as well as soy products for 3 hours after using the drug, as this may reduce the absorption of the drug. Grapefruit juice may delay absorption of Levothyroxine, but it does not significantly affect the bioavailability of the substance. Other substances that reduce the absorption of L-Thyroxine include antacids containing aluminum and [[magnesium | magnesium]], simethicone or sucralfate, cholestyramine, colestipol, Kayexalate. A study involving eight women showed that coffee may also have an effect on intestinal absorption of levothyroxine, although to a lesser extent than bran. Different substances can cause other side effects that can be very serious. Ketamine can lead to the development of hypertension and tachycardia, and tricyclic and tetracyclic antidepressants can increase the toxicity of the substance. On the other hand, lithium can cause hyperthyroidism (but more often hypothyroidism), affecting the iodine metabolism in the thyroid gland itself and, therefore, inhibiting synthetic levothyroxine.

Side effects

Side effects are usually associated with an overdose, and may include headache, irritability, nervousness, sweating, irregular heartbeat, increased intestinal motility, or menstrual disorders. Overdosing can also cause shock, as well as aggravate or cause angina pectoris or congestive heart failure. Chronic overdose of levothyroxine sodium causes symptoms usually associated with hyperthyroidism or overproduction of natural thyroid hormones in the body. If such side effects occur, you should immediately reduce the dosage or stop taking levothyroxine sodium at all. Acute overdose can be life threatening.

Application

For the treatment of hypothyroidism from mild to moderate, the average replacement dose of levothyroxine sodium is about 1.7 mcg / kg / day, that is, 100-125 mcg / day for an adult weighing 154 pounds. At the beginning of therapy, a full therapeutic dose can also be applied, provided that the patient has no other diseases. It should be noted that, due to the long half-life of levothyroxine, the peak therapeutic effect with this dosage is reached after 4-6 weeks of use. When using (not for its intended purpose) to speed up the process of fat loss in bodybuilders and athletes, so that the body has enough time to adapt to changing levels of thyroid hormones, the dosage is usually increased gradually. The drug usually starts with a low dose of 25-50 mcg, and gradually increases this amount by 25-50 mcg every day or two. The final dosage is usually in the range of 100-150 mcg, and rarely exceeds 250 mcg. It is important to remember that preparations for the thyroid gland are very powerful drugs and have significant potential for side effects. For caution, it is not recommended to use levothyroxine sodium in high doses and for more than eight weeks. In addition, at the end of each cycle it is usually recommended to also gradually reduce the dosage. Usually, this dosage is reduced by 25 MB every second or third day. This is done to avoid sudden changes in hormone levels, which, otherwise, can cause side effects. It should be noted that, due to the slow action of levothyroxine sodium, complete elimination of the drug from the body may take several weeks or longer.

Analogs L-thyroxine

Common brand names for Levothyroxine include: Eltroxin, Euthyrox, Letrox, Levaxin, L-thyroxine, Thyrax and Thyrax Duotab in Europe; Thyrox in South Asia; Eutirox, Levoxyl, Synthroid and Tirosint in North and South America, Thyrin, Thyrolar in Bangladesh. There are also numerous generic versions of the drug.

Availability

Although levothyroxine sodium is produced in fairly large quantities, it is not as common on the black market as the more powerful preparation for the thyroid gland Cytomel® (Cytomel). Counterfeit drugs are rare.

How to take levothyroxine daily or weekly?

The drug levothyroxine (Synthroid, Levoxyl and others) has long been used to treat hypothyroidism. In order for the tablets to be properly absorbed, it takes time, so usually patients are recommended to take them daily for an hour - half an hour before breakfast. But such a regimen for some people may be inconvenient and not always respected.

A new study suggests that the weekly dosage appears to be working. Indian scientists presented the results of the study at the annual meeting of the American Association of Clinical Endocrinologists 2016 in Orlando.

"Replacing L-thyroxin once a week was well tolerated and there were no signs of acute toxicity or symptoms of hypothyroidism," according to researchers Satish Wasoori and Manoj Naik, MD, from Park Hospital in Gurgaon, India.

New research echoes some of the findings of previous studies.

American endocrinologists, who reviewed the results, said that in general, they still prefer daily dosage.

In the new study, 40 women participated, aged 25 to 55 years with a diagnosis of hypothyroidism, which they had for at least five years, and they were on a daily dose of levothyroxine. They were divided into two groups. One group included women who had a normal level of thyroid stimulating hormone (TSH) at the beginning of the study; in another group - whose level was above the normal range (elevated TSH level indicates an insufficiently active thyroid gland).

In both groups of women, for six months, once a week, they took a dose of levothyroxine seven times their daily dose. In the 1st group, with a TSH level close to ideal at the beginning of the study, the normal functioning of the thyroid gland was maintained for 6 months. In the second group, 16 out of 20 also had normal functioning for 16 weeks. By the age of six months, the rates had reached 18. Two did not achieve normal thyroid function, possibly due to diabetes and obesity, the researchers said.

The researchers claim that the weekly regimen is effective and safe, making it a possible alternative to daily therapy. They also came to the conclusion that the weekly schedule, "can be considered as the first line of therapy when working with young and middle-aged women, faced with impaired absorption due to early breakfast. They should take a weekly dose on an empty stomach, and skip the remaining six days."

Opinions of experts (discussion)

Not everyone supports this idea.

"There is no doubt that daily therapy is preferable to weekly therapy," says Jacqueline Jonklaas, MD, assistant professor of endocrinology at Georgetown University Medical Center, Washington, DC. "What for? The "half-life" of the thyroid hormone (how long it stays in your system) means that if you give it daily there are minimal highs and lows (highs and lows) of its blood level, "she says. "However, if you give a large dose once a week, you will get large fluctuations. This means that the patient may have symptoms of too much thyroid hormone immediately after the dose and symptoms of too little before the next dose. This is not an ideal at all. High levels can potentially be associated with risks such as fast or irregular heartbeat."

In her opinion, "the only patient who can be considered for weekly therapy is one who cannot reach normal levels on daily therapy." This is usually due to non-compliance with daily medication, she says. "Therefore, weekly therapy is only a compromise when normal levels simply cannot be achieved on daily therapy."

Numerous studies have reviewed weekly dosage for several years, says Matthew Freeby, MD, director of the UCLA Diabetes Center in Santa Monica. While the study as a whole showed that patients were fine, he would not recommend it for people with heart disease.

Recalling the daily dose is easy, says Dr. Neydo, MD, if the patient holds the medicine next to the bed. "As soon as I woke up, I immediately accepted it. Then you can go in for the usual morning procedures before breakfast while the medicine is absorbed."

For most patients, there is not even a problem to remember the daily dose, says Dr. Jonklaas, adding that the medicine can be taken both morning and evening. "Patients can put their thyroid hormone on a bedside table, next to a toothbrush, use a pill container, set a signal on an iPhone and so on ... I think working on finding a suitable schedule that you could stick to is much preferable to weekly therapy. I am also concerned that this is not suitable for women of childbearing age. I don’t think that thyroid hormone surges will be favorable during pregnancy."

If the problem is the problem of absorption, she says, you need to treat what causes the bad absorption.

Current guidelines issued by the American Thyroid Association say that weekly dosage can be considered if the patient has problems with adherence to treatment.

Thyroid gland: 12 signs that you should go to the doctor

Tired of your own fatigue? Your weight increases, and the image of the food remained the same? Do you often feel chills? Do you have hair loss, sweating? Often feel anxiety, explode on trifles?

All the fault may be dysfunction of the thyroid gland.

Hypothyroidism is a general condition of the body caused by a deficiency of thyroid hormones, which is more common in women. It is difficult to diagnose it, since the disease is almost asymptomatic. Often, when we feel drowsiness, lethargy, pain in the joints, we blame everything on avitaminosis or overwork.

Thyroid hormones affect the work of absolutely all organs, so it is important to identify the problem in a timely manner and begin treatment by an endocrinologist.

Symptoms of thyroid disease

1. Depression and depression
Insufficient production of thyroid hormones often causes depression, apathy and depression due to the fact that these hormones are directly related to the production of serotonin in the brain.

At the same time, an excess of thyroid hormones makes us aggressive, irritable and anxious.

2. Constipation
One of the most common symptoms of hypothyroidism. Malfunctions of the thyroid gland lead to indigestion and constipation. Patients also complain of belching and heaviness in the stomach.

3. Drowsiness
A person with hypothyroidism can sleep 12 hours a day for several days in a row, but still feel tired. Constant morning lethargy and drowsiness are very disturbing signals.

4. Hair loss and dry skin
Due to the slow metabolism caused by hormonal imbalances, hair and skin do not receive adequate nutrition. This leads to a deterioration of their condition. Dull eyes, pale skin with a yellowish tinge - a portrait of a patient with hypothyroidism.

5. Unreasonable weight gain
A sudden increase in weight without any reason is a very important symptom. At the same time, all efforts to reduce body weight are unsuccessful.

6. Decreased libido
Insufficient thyroid function also affects hormone production, which is responsible for sexual desire.

7. Muscle pain, convulsions
A small amount of thyroid hormones can damage nerves, which send signals from the brain to the rest of the body. For this reason, there are various kinds of muscle spasms and cramps, numbness of the limbs.

8. Heart rhythm disorder
Failures of heart rhythm, its slowing or increasing, as well as pain in the heart area may indicate a lack of thyroid hormones.

9. Absent-mindedness
Malfunctions of the thyroid gland lead to a decrease in memory and performance. It becomes difficult for a person to perceive new information. Often, women attribute this symptom to natural forgetfulness, although as soon as they begin to treat the thyroid gland, clarity of thought returns.

10. Reducing blood pressure
Low blood pressure in the complex with lethargy, drowsiness and absent-mindedness is a weighty reason to see a doctor.

11. Edema
Thickening of the tongue, side marks on it from the teeth, swelling of the face and extremities, in which there is no pressure hole, are clear signs of hypothyroidism.

12. Neck discomfort
The patient may feel a lump in the throat, discomfort in the neck, and even unusual wheeze may appear. An increase in gland size is a symptom for an immediate visit to an endocrinologist.

Pay due attention to the signals that the body gives you to maintain health for many years. Sometimes ordinary muscle pain can indicate a serious illness!

Nodular goiter (thyroid goiter): causes of the disease, main symptoms, treatment and prevention

The general concept that includes thyroid neoplasms, determined by touch or using instrumental methods

Causes of nodular goiter

The true reason for the development of this pathology remains unknown, there is an opinion that the main factor of influence is the genetic factor. The provoking factors for the development of nodular goiter are iodine deficiency, the formation of a cyst of the thyroid gland (small hemorrhages in the thyroid gland, an increase in gland cells).

Symptoms of nodular goiter

Most often, patients have no complaints. However, as the process progresses, they may be disturbed by the feeling of squeezing of the respiratory tract and esophagus, respiratory function and swallowing may be disturbed, hoarseness, pain in the thyroid gland, the appearance of a cosmetic defect in the neck, an increase in the neck, a nodular formation in the neck.

Diagnosis of nodular goiter

The analysis of the history of life and patient complaints, conducted a general examination. From laboratory methods: determination of the level of TSH, the content of free thyroxine and triiodothyronine in the blood, the determination of histochemical markers. From instrumental methods: ultrasound of the thyroid gland, thyroid scintigraphy for the diagnosis of tumor processes, fine-needle biopsy of the thyroid gland, x-ray examination of the chest.

Treatment of nodular goiter

Patients with small goiter, need dynamic observation, conducting an annual assessment of the function of the organ, determining the size of the nodules under ultrasound control. Slow growth of a neoplasm is usually noted in most cases of goiter, nor is it indicative of the malignancy of the nodular formation.

During the treatment of nodular goiter, thyroid hormone therapy is applied to those patients who underwent the removal of the thyroid gland. With diffuse colloid goiter, you must use iodine preparations. With a large amount of goiter, applied surgical treatment or radiation therapy.

Prevention of nodular goiter

Since there is a danger of reborn nodes in the thyroid gland into malignant, due attention should be paid to preventing the development of this pathology. In order to prevent, it is recommended to take iodine preparations, special diet food, rich in seafood.