Levothyroxine: a medicine for an underactive thyroid (hypothyroidism)

1. About levothyroxine

Levothyroxine is a medicine used to treat an underactive thyroid gland (hypothyroidism).

The thyroid gland makes thyroid hormones which help to control energy levels and growth. Levothyroxine is taken to replace the missing thyroid hormone thyroxine.

Levothyroxine is only available on prescription. It comes as tablets or as a liquid that you swallow.

2. Key facts

• Levothyroxine is a synthetic version of a hormone called thyroxine. It replaces thyroxine if your thyroid gland cannot produce it and prevents the symptoms of hypothyroidism.
• Levothyroxine starts working straight away, but it may be several weeks before your symptoms start to improve.
• The most common side effects of levothyroxine are caused by taking a bigger dose than you need. Your doctor can lower your dose to help reduce any side effects.
• Before you start taking levothyroxine, your doctor will do a blood test. Once you start taking the medicine you’ll have regular blood tests to see how well it’s working.
• Levothyroxine doses need to be carefully monitored during pregnancy. If you’re planning to become pregnant or think you may be pregnant, it’s important to talk to your doctor to get the right care for you and your baby.

3. Who can and cannot take levothyroxine

Levothyroxine can be taken by most adults and children. However, it’s not suitable for some people.

Check with your doctor before taking levothyroxine if you:

• have ever had an allergic reaction to levothyroxine or any other medicine
• you have an overactive thyroid that produces too much thyroid hormone (thyrotoxicosis)
• have a health problem that affects your adrenal glands (your doctor will be able to tell you if you’re not sure)
• have a heart problem including angina, heart disease or heart failure
• have high blood pressure
• have ever had a heart attack
• have diabetes – the dose of your diabetes medicine may need to change because levothyroxine can raise blood sugar levels

4.

How and when to take levothyroxine

Take levothyroxine once a day in the morning, ideally at least 30 minutes before having breakfast or a drink containing caffeine, like tea or coffee.

Food and caffeinated drinks can both stop your body taking in levothyroxine properly so it does not work as well.

If you stop taking levothyroxine, your symptoms are likely to come back.

Dosage and strength

The dose of levothyroxine varies from person to person.

You may need to take several different tablets to make up your dose. Your doctor will tell you how many tablets to take each day.

Levothyroxine comes in 12.5 microgram, 25 microgram, 50 microgram, 75 microgram and 100 microgram tablets.

If you’re taking levothyroxine as a liquid, 5ml can have 25 micrograms, 50 micrograms, 100 micrograms or 125micrograms in it.

Although starting doses are usually the same, the dose of levothyroxine you end up taking, or how quickly the dose is increased, depends on your symptoms, hormone levels, age and whether you have any other health problems.

Adults usually start with a dose between 50 micrograms and 100 micrograms taken once a day. This may be increased gradually over a few weeks to between 100 micrograms and 200 micrograms taken once a day.

Some people, such as over-50s or people with heart disease, may start on a lower dose.

How to take levothyroxine

Swallow the tablets whole with a drink of water.

Levothyroxine is available as a liquid for children and people who find it difficult to swallow tablets. It’s available in different strengths.

If you or your child are taking levothyroxine as a liquid, it will usually come with a plastic syringe or spoon to help you measure out the right dose.

If you do not have a syringe or measuring spoon, ask your pharmacist for one. Do not use a kitchen teaspoon as it will not give the right amount.

If you forget to take it

If you forget to take a dose, take it as soon as you remember, unless it’s almost time for your next dose. In this case just skip the forgotten dose and take the next one at the usual time.

Do not take 2 doses together to make up for a missed dose.

If you often forget doses, it may help to set an alarm to remind you. You could also ask your pharmacist for advice on other ways to help you remember to take your medicine.

If you take too much

Taking more than your prescribed dose of levothyroxine can give you symptoms such as a racing heartbeat (palpitations).

Urgent advice: Contact 111 for advice now if:

• you take more than 1 extra dose of levothyroxine

Go to 111. nhs.uk or call 111

Immediate action required: Call 999 if:

• you get chest pains – these may not happen immediately, it can be several days before they begin

Having regular blood tests

Your doctor will do regular blood tests to check the levels of thyroid hormones in your body before and after starting levothyroxine.

These will allow your doctor to adjust the dose to suit you.

At the start of treatment you can expect to have blood tests quite often but once your hormone levels are stable and your symptoms are under control, your levels will usually be checked once a year.

You may need blood tests more often if you:

• are pregnant
• start or stop a medicine that can affect the way levothyroxine works
• have any symptoms that could mean your dose is not quite right

5.

Side effects

Like all medicines, levothyroxine can cause side effects, although not everyone gets them. Once you are on the right dose of levothyroxine, side effects should go away.

Talk to your doctor or pharmacist if you have switched to a different brand of levothyroxine and start to get:

• symptoms of an underactive thyroid including feeling tired, weight gain or feeling depressed
• symptoms of an overactive thyroid (similar to the common side effects below)

You may be sensitive to the new brand of levothyroxine you have been prescribed and may need to stay on the one you were taking before.

Common side effects

The common side effects of levothyroxine usually happen because the dose you’re taking is more than you need. These side effects usually go away after you go on to a lower dose of levothyroxine or stop treatment.

Common side effects are the same as the symptoms of an overactive thyroid. There are things you can do to help cope with them.

Feeling sick (nausea)

Stick to simple meals and do not eat rich or spicy food.

Being sick (vomiting)

If you’re being sick try to take small, frequent sips of fluids, such as water or squash, to prevent dehydration. Speak to a pharmacist if you have signs of dehydration, such as peeing less than usual or having dark, strong-smelling pee. If you are vomiting due to a stomach bug or illness, tell your doctor. Do not take any other medicines to treat vomiting without speaking to a pharmacist or doctor first.

If you take contraceptive pills and you’re being sick, your contraception may not protect you from pregnancy. Check the pill packet for advice.

Diarrhoea

Drink plenty of water to prevent dehydration. Speak to a pharmacist if you have signs of dehydration, such as peeing less than usual or having dark, strong-smelling pee. If you get severe diarrhoea from a stomach bug or illness, tell your doctor. Do not take any other medicines to treat diarrhoea without speaking to a pharmacist or doctor first.

If you take contraceptive pills and you have severe diarrhoea for over 24 hours, your contraception may not protect you from pregnancy. Check the pill packet for advice.

Headaches

Make sure you rest and drink plenty of fluids. Do not drink too much alcohol. Ask your pharmacist to recommend a painkiller. Talk to your doctor if they last longer than a week or are severe.

Feeling restless or excitable, or problems sleeping

These symptoms should improve as your body gets used to levothyroxine. If it does not go away, or if it’s causing you problems, contact your doctor.

Flushing or sweating

Try cutting down on coffee, tea and alcohol. It might help to keep the room cool and use a fan. You could also spray your face with cool water or sip cold or iced drinks. If it does not go away, contact your doctor as they may need to review your dose .

Muscle cramps

If you get unusual muscle aches, which is not from exercise or hard work, talk to your doctor. You may need a blood test to find the cause.

Shaking, usually of the hands

Talk to your doctor as you may need to have your dose reduced.

Talk to your doctor or pharmacist if these side effects bother you or do not go away.

Serious side effects

It happens rarely, but some people may have serious side effects when taking levothyroxine.

Tell your doctor or contact 111 now if:

• you get fast or irregular heartbeats (palpitations)

Go to 111. nhs.uk or call 111

Immediate action required: Call 999 now if:

Serious allergic reaction

In rare cases, it’s possible to have a serious allergic reaction (anaphylaxis) to levothyroxine.

Immediate action required: Call 999 or go to A&E now if:

• you get a skin rash that may include itchy, red, swollen, blistered or peeling skin
• you’re wheezing
• you get tightness in the chest or throat
• you have trouble breathing or talking
• your mouth, face, lips, tongue or throat start swelling

You could be having a serious allergic reaction and may need immediate treatment in hospital.

These are not all the side effects of levothyroxine. For a full list see the leaflet inside your medicines packet.

Information:

You can report any suspected side effect using the Yellow Card safety scheme.

Visit Yellow Card for further information.

6. Pregnancy and breastfeeding

Levothyroxine and pregnancy

Levothyroxine is safe to take in pregnancy.

It’s important to carry on taking levothyroxine throughout your pregnancy. Having too low or too high levels of thyroid hormone in pregnancy can cause problems for you and your baby.

You’ll need to have regular blood tests during pregnancy to make sure you’re on the right dose of levothyroxine. Your doctor may need to increase your dose of levothyroxine while you’re pregnant.

Levothyroxine and breastfeeding

It’s OK to breastfeed while you’re on levothyroxine. Thyroid hormones are a normal part of breast milk. When taken as a supplement they only pass into breast milk in tiny amounts that are too small to affect your baby.

If you’re breastfeeding, it’s important that you continue to take levothyroxine, as this is replacing what your body would normally be making. Your body needs good levels of thyroid hormones to make enough breast milk for your baby.

If you notice that your baby is not feeding as well as usual, or if you have any other concerns about your baby, talk to your midwife, health visitor, pharmacist or doctor as soon as possible.

Non-urgent advice: Tell your doctor if you’re:

• trying to get pregnant
• pregnant
• breastfeeding

7. Cautions with other medicines

Some medicines can affect thyroid hormones, so the dose of levothyroxine may need to be changed. They include:

• epilepsy medicines like carbamazepine and phenytoin
• rifampicin
• amiodarone
• oestrogens – such as in combined contraceptive pills or hormone replacement therapy (HRT)

Levothyroxine can affect how other medicines work, so their doses may need to be changed. These medicines include:

• medicines for diabetes – either insulin or tablets
• warfarin, used to prevent blood blots

Some medicines should not be taken at the same time of day as levothyroxine as they can reduce the amount of levothyroxine your body takes in, including:

• antacids
• calcium salts
• iron salts
• orlistat, a medicine used for weight loss
• sucralfate, a medicine used to treat stomach ulcers
• some cholesterol-lowering medicines such as colestyramine, colestipol or colesevelem

Find out more from the information leaflets that come with the medicines. Or get your pharmacist’s advice on how much time to leave between taking these medicines and taking levothyroxine.

Mixing levothyroxine with herbal remedies and supplements

There’s very little information about taking herbal remedies and supplements with levothyroxine.

However, biotin supplements can affect the accuracy of thyroid function tests. Do not take biotin without talking to your doctor.

Kelp (a type of seaweed) can contain high levels of iodine, which sometimes makes an underactive thyroid worse. Do not take supplements containing kelp if you’re taking levothyroxine.

Important:
Medicine safety

Tell your doctor or pharmacist if you’re taking any other medicines, including herbal medicines, vitamins or supplements.

8. Common questions about levothyroxine

How does levothyroxine work?

The thyroid gland in your neck makes a hormone called thyroxine. Thyroxine controls how much energy your body uses (the metabolic rate). It’s also involved in digestion, how your heart and muscles work, brain development and bone health.

When the thyroid gland does not make enough thyroxine (called hypothyroidism), many of the body’s functions slow down. Some of the most common symptoms of an underactive thyroid gland are:

• tiredness
• feeling cold
• difficulty concentrating
• weight gain
• feeling depressed

Levothyroxine is a synthetic version of thyroxine. You take levothyroxine tablets to replace the thyroxine that your thyroid gland cannot produce and prevent the symptoms of hypothyroidism.

How long does levothyroxine take to work?

Levothyroxine starts working straight away, but it may be several weeks before your symptoms start to improve and you feel any different.

How long will I take levothyroxine for?

Treatment with levothyroxine is usually lifelong. If you stop taking levothyroxine your symptoms are likely to come back.

Are there any long term side effects?

Yes, it’s safe to take levothyroxine for a long time, even many years. However, high doses of levothyroxine over a long time can sometimes cause weakening of the bones (osteoporosis).

This should not happen if you are on the right dose. It’s important to have regular blood tests to make sure your dose is not too high.

Will it affect my fertility?

There’s no evidence to suggest that taking levothyroxine reduces fertility in either men or women.

However, speak to a pharmacist or your doctor if you’re trying to get pregnant as they may want to review your treatment.

Can I drink alcohol with it?

Yes, you can drink alcohol while taking levothyroxine. Alcohol does not affect how this medicine works.

However, if you have side effects such as headaches, flushing or sweating with levothyroxine, alcohol may make these worse.

Will it make me lose weight?

One of the symptoms of an underactive thyroid gland is weight gain. So, once you start taking levothyroxine, you may lose weight as your body’s hormones rebalance. Losing weight can also be a sign that your dose of levothyroxine is too high.

Once your thyroid hormone levels have returned to normal, your tendency to gain or lose weight is the same as for people who do not have thyroid problems.

Can I drive or ride a bike with it?

Yes, levothyroxine does not affect your ability to drive or ride a bike.

Is there any food or drink I need to avoid?

There are some foods and drinks that do not mix well with levothyroxine:

• drinks containing caffeine, like coffee, tea and some fizzy drinks, can reduce the amount of levothyroxine your body takes in. Leave at least 30 minutes after taking levothyroxine before you drink them.
• calcium-rich foods, such as milk, cheese, yoghurt and broccoli, can reduce the amount of levothyroxine your body takes in. Leave at least 4 hours between taking levothyroxine and eating calcium-rich foods.
• soya in food and supplements may stop levothyroxine working properly. If you regularly eat soya or take soya supplements your doctor might need to do extra blood tests to make sure you’re getting enough levothyroxine.
• kelp (a type of seaweed) can contain high levels of iodine, which sometimes makes an underactive thyroid worse. Do not take supplements containing kelp if you’re taking levothyroxine.

Can I get thyroid medicines for free?

If you have an underactive thyroid, you’re entitled to free prescriptions for all of your medicines (not just your levothyroxine). To claim your free prescriptions you’ll need to have a medical exemption certificate.

The application form for the medical exemption certificate is called FP92A. You can get this from your doctor’s surgery. You will need to fill in the form, then your doctor will sign it and send it off.

Will it affect my contraception?

Levothyroxine does not affect any types of contraception, including the combined pill or emergency contraception.

However, the combined pill contains oestrogen which can reduce the amount of levothyroxine in your body.

Speak to your doctor if you start or stop taking the Pill as your dose of levothyroxine may need to change.

If levothyroxine makes you sick (vomit) or you have severe diarrhoea for over 24 hours while you’re taking levothyroxine, your contraceptive pills may not protect you from pregnancy.

If this happens, follow the instructions in the leaflet that comes with your contraceptive pills.

Find out more about what to do if you’re on the pill and you’re being sick or you have diarrhoea.

Will I lose my hair?

It’s having an underactive thyroid that causes hair loss – not treatment with levothyroxine.

Because the natural hair growth cycle takes several months, hair loss related to thyroid disease might only be seen months after the condition has begun. If treatment with levothyroxine has already started, it may seem like the medicine – rather than the underlying illness – is causing the hair loss.

Hair usually regrows after treatment with levothyroxine, but it may take many months.

What Your Pharmacist Wants You to Know About Hypothyroidism Medication

To get the most from your hypothyroidism treatment, you need to take your medication correctly — that’s where your pharmacist comes in.

By Julie H. CaseMedically Reviewed by Rosalyn Carson-DeWitt, MD

Reviewed: February 1, 2018

Medically Reviewed

Thinkstock

For many people with hypothyroidism, levothyroxine — the most common form of synthetic thyroid hormone medication — can help restore hormone levels and alleviate symptoms. Continued regular use of the medication is essential, however, even when thyroid hormone levels are restored.

While a doctor may be the one who diagnoses your hypothyroidism and prescribes medication, when it comes to managing your treatment regimen, your pharmacist can be a valuable member of your care team and can offer essential advice about medication maintenance.

In addition, pharmacists can inform you of potential drug interactions, instruct you on when to take your daily dose, offer insight on what to expect from treatment, and advise you on how to manage life changes like weight gain or loss.

These are the top seven things pharmacists want you to know about hypothyroidism medication:

Getting better takes time. The medication used to treat hypothyroidism is long acting, so in the beginning, it may take weeks before you experience improvement. When you start levothyroxine you won’t feel better the next day. You may not feel better in two weeks. But symptoms should start disappearing within a month. After six weeks of treatment, you should be almost completely free of symptoms, assuming you’re at the right medication level. If not, you may have to work with your doctor for a while on adjusting your dosage to get it just right.

Generally, hypothyroidism is the type of condition that won’t change from one day to the next but over weeks. A test for thyroid-stimulating hormone (TSH) that identifies thyroxine (T4) and triiodothyronine (T3) levels in the blood is important for diagnosis and for treatment, but changes in medication can take a long time — about six weeks — to be reflected in test results.

“We can certainly change medication levels, but we have to wait six weeks every time we make a change with a dose or have a new medication interaction,” says Rachael W. Duncan, PharmD, BCPS, an emergency medicine clinical pharmacist at Swedish Medical Center in Englewood, Colorado.

Even if you feel your symptoms are under control, the American Thyroid Association (ATA) says you should have your TSH levels tested periodically so your medication can be adjusted if needed.

If you miss a dose, it’s not the end of the world. Even if you miss a dose of your medication, you’re unlikely to have a bad day. Because this type of medication builds up in your system, missing a dose isn’t a huge deal. But remember that the best way to manage hypothyroidism is to take your medication regularly and consistently. You should take your medication at the same time and in the same way every day. If you do miss a dose, the ATA says to take the missed dose as soon as possible, or to take two pills the following day — one in the morning and one in the evening. And never stop taking your medication without talking to your doctor.

Always take your medication on an empty stomach. Food and other medications can bind to levothyroxine and prevent its absorption, meaning that you may not get the full dose of your medication. So avoid eating or taking any other medications within an hour of taking your daily dose of thyroid replacement hormone. You should take your medication with a glass of water, however.

An easy way to ensure you’re taking your medication on an empty stomach is to take it first thing in the morning and to wait an hour before eating. But for those who want to eat within an hour of rising, this approach may not work. Taking your daily pill at bedtime may be an adequate adjustment, so long as you’re not an evening snacker.

Don’t take your medication with multivitamins, antacids, or iron supplements. Just as food can, antacids and iron supplements can bind with your hypothyroidism medication and prevent its absorption. Build a time buffer between taking your thyroid medication and taking any other medications, as well as any antacids, multivitamins, or other supplements, like iron.

Discuss any treatment changes with your pharmacist. While your pharmacist should have access to your medication profile, it doesn’t hurt to discuss medication changes — for hypothyroidism or another condition — with him or her. Some medications are processed by the same enzyme in the liver as levothyroxine — this could interfere enough with your thyroid medication to require dosage adjustments.

You should also discuss any potential changes to the brand of thyroid medication that you take. The ATA says that you should not switch from one brand of thyroid medication to another, from your brand to a generic, or from one generic to another without talking to your doctor first. This is because there may be variation in hormone content among thyroid medications.

Hormones matter, and so could weight changes. Hypothyroidism is five to eight times as likely to occur in women as men, according to the ATA. And some life changes that women experience — like pregnancy — can require a dose change.

What’s more, if you gain weight, you might need a higher dose; similarly, if you lose weight, you might need a lower dose. While your pharmacist can’t prescribe a new dose of medication, a discussion of how certain life changes can affect your treatment can be informative.

Managing hypothyroidism is a lifelong commitment, so it’s important to stick with your medication. “Just because you’re feeling better doesn’t mean you should stop taking your medication,” says Duncan. “You’re feeling better because you’re taking your medication.” If you stop taking your medication, symptoms such as lethargy, coldness, and weight gain are sure to return.

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Treatment with levothyroxine. Why jumps TTG?

Primary hypothyroidism is a pathology of the thyroid gland, in which the production of hormones decreases. It is considered a favorable endocrine disease, provided that an adequate dose of levothyroxine is taken, the selection of which takes 2-6 months.

Sometimes, after reaching the required dosage, at the next control, a low or high level of thyroid-stimulating hormone (TSH) is detected.

7 Reasons for Fluctuating TSH Levels

1. Non-compliance with the regimen of taking the drug: regular skips or a small gap between taking the pill and eating.

• Tip . Take levothyroxine in the morning, on an empty stomach, at least 30-40 minutes in advance, optimally 60 minutes before meals.

2. Use of levothyroxine from different manufacturers. Drugs differ in bioavailability, so the same dose of a drug with the same name, but of different production, may be insufficient or excessive.

• Tip. If, for example, you took L-thyroxine Berlin-Chemie for a long time and switched to Eutirox, do an additional TSH check after 2 months.

3. Simultaneous administration with calcium, iron, aluminum preparations leads to a decrease in the absorption of levothyroxine, so the effective concentration of the substance is less than necessary.

• Council. If there is a need to take medications that can affect the absorption of thyroxine, it is worth making an interval between tablets of at least 4 hours, it is better to drink levothyroxine in the morning, and other medications in the afternoon or evening.

4. Taking products that impair the absorption of levothyroxine: coffee, grapefruit, soy products, papaya.

5. Concomitant gastrointestinal diseases: Helicobacter pylori infection, lactose intolerance, bacterial overgrowth syndrome, giardiasis, celiac disease, atrophic gastritis. All these diseases reduce the absorption of thyroxin.
6. Taking drugs that affect the synthesis of proteins that carry thyroxin: estrogens, tamoxifen, androgens, large doses of glucocorticosteroids, antiepileptic drugs, rifampicin, some antidepressants. These drugs also help to reduce the current concentration of the hormone in the human body.
7. Concomitant adrenal insufficiency. The combination of autoimmune damage to the adrenal glands and the thyroid gland occurs in autoimmune polyglandular syndrome type 2. The disease is rare, affecting one to two people out of 100,000. Women are affected 3 times more often than men.

• Tip. Suspect adrenal insufficiency with unclear weight loss, nausea, low blood pressure, low blood sugar, darkening of the skin or skin folds. If in doubt, consult a doctor before the appointed time.

Regularly monitor the level of TSH in the blood while taking levothyroxine:

• after changing the dose of levothyroxine – after 1.5-2 months,

• upon reaching the target level of TSH and compensation of hypothyroidism – every 6-12 months.

Information for you was prepared by:

Grechkina Alla Pavlovna, endocrinologist. Conducts a reception in the building of the clinic on Ozerkovskaya.




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do we all know about him? uMEDp

Levothyroxine is the gold standard for hypothyroidism replacement therapy. At the same time, in some cases, taking levothyroxine does not lead to compensation for the disease due to impaired absorption of the drug. Various factors can prevent adequate absorption of levothyroxine, including primary or secondary lactase deficiency. The use of the lactose-free form of levothyroxine reduces the need for the drug, levels the lability of hormonal parameters and, as a result, significantly improves the quality of life of patients.

Thyroid diseases occupy the second place in the structure of endocrine pathology. And this primarily applies to hypothyroidism. Hypothyroidism is a condition caused by a long-term, persistent deficiency of thyroid hormones. According to the literature, at present, the prevalence in the general population of overt hypothyroidism is 0.2-2%, and subclinical – 10-12% [1]. In women, this disease occurs 6 times more often than in men [2].

Since about 10 million people today require replacement therapy with levothyroxine, a doctor of any profile should know the basics of treating hypothyroidism, as well as take into account the individual characteristics of the patient when choosing a drug for replacement therapy.

Levothyroxine replacement therapy

Levothyroxine is the gold standard for hypothyroidism replacement therapy. The thyroid gland practically does not perform other functions, except for secretory. The synthesis of thyroid hormones is not associated with the circadian rhythm. Therefore, a single daily dose of levothyroxine in a dose that compensates for the deficiency of the hormone allows you to maintain normal thyroid function.

Preparations of synthetic levothyroxine appeared in the 50s. last century. There is a sufficient number of studies confirming that levothyroxine is the best of the existing agents for the treatment of hypothyroidism [3]. Nevertheless, new studies on the effectiveness of levothyroxine replacement therapy are emerging, expanding the possibilities of its use.

One of the latest cross-sectional studies conducted in Pakistan was on the detection of hypothyroidism in newborns. The criterion is the level of thyroid-stimulating hormone (TSH). If hypothyroidism was detected, treatment with levothyroxine was prescribed. Of 550 newborns, 4 (0.8%) had an elevated TSH level. Congenital hypothyroidism had a statistically significant relationship with hypothyroidism in the mother (p = 0.0001) and her intake of levothyroxine during pregnancy (p = 0.013) [4].

A population-based study in the Netherlands has shown an association between patient age and decreased thyroid function. From 2002 to 2003, 5816 people of different ages without previously identified thyroid diseases took part in it. The mortality rate among older people with a TSH level of 3.0–4.0 mIU/L was significantly higher than in patients with a TSH level in the middle range of 1.0–2.0 mIU/L (RR 1.8 (95% CI 1.0–3.1)). The authors suggested that there is a potential possibility of prescribing levothyroxine replacement therapy to such patients [5].

A meta-analysis conducted in Kuwait showed that suppressive therapy with levothyroxine of solitary thyroid nodules reduces the size of the nodules by 2 times and reduces the risk of cancer by 50%. Thus, it was proposed to consider this type of treatment as an alternative for patients receiving levothyroxine, but on the condition that the risk of side effects in such patients would be minimal [6]. However, the clinical efficacy and safety of such therapy is still controversial.

At present, it can be said with certainty that the indication for the use of levothyroxine is not only hypothyroidism of various origins (including during pregnancy, lactation, and also when planning a pregnancy [7]), but also mixed goiter. The drug is prescribed as part of the complex therapy of diffuse toxic goiter (after reaching the euthyroid state), euthyroid hyperplasia of the thyroid gland, for the prevention of relapses after surgical treatment of nodular and malignant neoplasms of the thyroid gland, with cretinism. Levothyroxine is also recommended for use in a thyroid suppression test.

The half-life of levothyroxine is quite long – 6-7 days. About 15% is excreted by the kidneys and with bile (unchanged and in the form of conjugates). The bioavailability of the drug when taken orally is quite high. After taking levothyroxine from the gastrointestinal tract (GIT), from 48 to 79% of the drug is absorbed. Reception on an empty stomach increases the absorption of the active substance. The maximum plasma concentration is reached after about 6 hours. Plasma protein binding (thyroxine-binding globulin, prealbumin and albumin) is 99%. The volume of distribution is 0.5 l/kg. Distribution occurs mainly in the liver, brain and muscles. In various tissues, monodeiodination occurs (approximately 80% of levothyroxine sodium) with the formation of triiodothyronine and inactive products. A small amount of the active substance undergoes deamination and decarboxylation with the formation of tetraiodothyroacetic acid, as well as conjugation with sulfuric and glucuronic acids (in the liver).

The replacement dose of levothyroxine in primary hypothyroidism in adults is determined at the rate of 1.6 µg/kg of the patient’s body weight. With age, the need for the drug sometimes decreases, while the dose of levothyroxine can be reduced to 1 mcg / kg. In overweight patients, the dose is calculated per 1 kg of ideal body weight. Previously, most researchers recommended that the dose be gradually increased to full replacement over 2-4 weeks, while starting with 50 mcg of the drug, increasing the dose by 25 mcg. However, recent evidence suggests that it is safe to start treatment with a full replacement dose in patients without cardiovascular disease and younger than 50 years of age. In the presence of cardiovascular diseases, the initial dose should be 12.5-25 mcg, and then gradually increase.

If hypothyroidism is first diagnosed during pregnancy, levothyroxine is given at a full replacement dose. It should be taken into account that during pregnancy the need for levothyroxine increases significantly and the total replacement dose will be about 2.3 µg/kg [8].

Endocrinologists at the US Children’s National Medical Center (Washington) analyzed the results of treatment of 55 patients with congenital hypothyroidism over 3 years. The patients were divided into three groups depending on the dose of levothyroxine received: the first group – 6–9.9 µg/kg, the second – 10-11.9 µg/kg and the third – 12-15 µg/kg. The criterion for overdose is the level of thyroxin> 16 mcg / dl, free thyroxine> 2.3 ng / dl and TSH 6 mIU / l in a month. The level of thyroid hormones that meets the criteria for conditions such as euthyroidism, hyperthyroidism and thyrotoxicosis, after a month was observed in the first group in 46, 37 and 17% of patients, respectively, in the second – in 30, 55 and 15% of patients, in the third – in 0 , 75 and 25% of patients. The authors concluded that at the time of diagnosis, initial doses of levothyroxine were 10–11.9mcg/kg (TSH level > 100 mIU/L) and 8-10 mcg/kg (TSH level

Causes of decompensated hypothyroidism

Oral levothyroxine at doses that provide hormonal balance is the most convenient form of treatment for hypothyroidism. Nevertheless, one third of patients receiving levothyroxine replacement therapy have decompensated hypothyroidism [10].

O.E. Okosieme et al., after reviewing 58,567 case histories, identified a group of patients with hypothyroidism (n = 1037) treated with levothyroxine in UK hospitals from 2004 to 2009d. Investigators noted that 385 (37.2%) patients did not achieve target TSH levels. An analysis of controlled and cohort studies, as well as systematic reviews published since 1960 and devoted to the problem of uncompensated hypothyroidism, showed that in 50% of cases, levothyroxine replacement therapy does not achieve the target level of TSH [11].

Malabsorption

The fact is that a decrease in the absorption of levothyroxine can be influenced by various factors. The most common cause of failure or resistance to levothyroxine treatment is pseudomalabsorption syndrome.

Already in 2006 M. Muñoz-Torres et al. stated that the cause of resistance to levothyroxine therapy in a 55-year-old patient was a previously undiagnosed lactose intolerance. The researchers suggested that in 7-20% of the adult population, it is lactose intolerance that is the cause of impaired bioavailability of levothyroxine, which, apparently, is associated with the presence of gastrointestinal diseases. According to the authors, this pathology can be corrected with the help of diet [12]. This is confirmed by recent works.

Turkish scientists conducted a study of 83 patients with autoimmune thyroiditis (Hashimoto’s thyroiditis) complicated by hypothyroidism. All patients were taking levothyroxine. The test for lactose intolerance showed its presence in 75.9% of patients. The final analysis included 38 subjects with lactose intolerance (30 patients in euthyroid status and 8 with subclinical hypothyroidism) and 12 subjects without this pathology. Patients with lactose intolerance were on a lactose-free diet. The observation lasted 8 weeks. The results showed a significant decrease in TSH levels in patients with lactose intolerance: in euthyroid patients – from 2.06 ± 1.02 to 1.51 ± 1.1 mU / ml, in patients with subclinical hypothyroidism – from 5.45 ± 0.74 up to 2.25 ± 1.88 mU/ml, respectively (p 0.05). The authors concluded that lactose intolerance is common in patients with autoimmune thyroiditis, and reducing lactose intake reduces TSH levels. Therefore, patients with hypothyroidism who require an increasing dose of levothyroxine and who have unstable TSH levels and are resistant to thyroxine treatment should be examined for lactose intolerance [13].

Evaluation of the efficacy of levothyroxine therapy in patients with lactose intolerance was performed in a study conducted in Rome. It involved 34 patients with autoimmune thyroiditis and hypothyroidism. The work was carried out from 2009 to 2012. A prerequisite for the study was the observance of a lactose-free diet.

In all patients with autoimmune thyroiditis with good lactose tolerance, stabilization of TSH (median TSH – 1.02 mU/l) was achieved with an average dose of levothyroxine 1.31 mcg/kg per day. At the same dose of the drug (1.29mcg/kg per day) in patients with lactose intolerance, only 5 out of 34 patients achieved the target level of TSH (median TSH – 0.83 mU/l). For the remaining 29 patients, the dose of levothyroxine was gradually increased: the target TSH level (median TSH – 1. 21 mU/l) was achieved with an average dose of levothyroxine 1.81 mcg/kg per day (+38%, p

Lactose intolerance is a pathological condition caused by a decrease in the level of lactase. Lactase deficiency is encoded by a single gene (LCT) located on chromosome 2q21. Lactase is an enzyme needed to break down lactose. It has been observed that lactase activity decreases with the transition to an adult type of nutrition. In northern Europeans, lactose intolerance usually develops after the age of 20 [15]. The frequency of constitutional lactase deficiency in the population also depends on ethnicity [16]. Some studies have shown that in the northern regions, lactose intolerance occurs in 35% of the population [17].

Lactase deficiency manifests itself in the form of osmotic diarrhea and increased gas formation in the intestines. The severity of symptoms depends on the level of enzyme production, the characteristics of the intestinal biocenosis, and also on the amount of lactose entering the body.

Eliminating foods containing lactose from the diet (which is not an easy task) can reduce the severity of symptoms or even eliminate this disorder [18].

Lactase deficiency can be primary (hereditary) and secondary (damage to the mucous membrane of the small intestine by infectious agents, toxins, drugs, or as a result of surgical operations on the gastrointestinal tract) [19].

Possible damage to the small intestinal mucosa leading to irreversible lactose intolerance has been described with neomycin and kanamycin, colchicine, aminosalicylic acid, and anticancer agents.

Cases of the onset of clinical symptoms of lactase deficiency in patients treated with drugs containing lactose as an excipient have been described with the use of flutamide, lithium carbonate, tranylcypromine, cromolyn sodium and acyclovir [20].

Therefore, if a hypothyroid patient has confirmed lactose intolerance, either a lactose-free diet or lactose-free levothyroxine should be used.

Another factor preventing adequate absorption of levothyroxine is non-compliance with the drug regimen , for example, a change in the interval between taking the drug and eating. In patients with persistently high TSH levels who require more than 2 mcg/kg of levothyroxine per day, misuse of levothyroxine should first be ruled out and only then they should be examined for the presence of the pathology in question.

Diseases of the gastrointestinal tract . The decrease in bioavailability can be affected by the presence of celiac disease in patients, inflammatory diseases of the gastrointestinal tract and parasitic invasion, bowel resection, as well as atrophic gastritis and Helicobacter pylori infection.

It has been shown that in patients who underwent surgical interventions on the organs of the gastrointestinal tract, the dose of levothyroxine is usually higher than that which ensures the achievement of euthyroidism in normal cases [21].

A gluten-free diet for celiac disease will usually stabilize the dose of levothyroxine, similar to the effect achieved by eliminating H. pylori infection or parasitic infestation. In cases of atrophic gastritis or the development of inflammatory processes in the intestines, the treatment of the disease and the restoration of the normal state of the gastrointestinal tract can increase the absorption of the drug.

The normal metabolism of levothyroxine is interfered with by some foods, dietary fiber and coffee .

Many drugs, such as cholic acid, ferrous sulfate, sucralfate, calcium carbonate, aluminum-containing antacids, phosphate binders, raloxifene, proton pump inhibitors, also adversely affect the absorption of levothyroxine [22].

Decreased activity of the active substance

Various excipients affect the stability of levothyroxine sodium in different ways. The activity of levothyroxine, which includes lactose, decreases faster during storage than the activity of levothyroxine made using dibasic calcium phosphate. Thus, the tablet forms of the drug, which uses lactose as an excipient, cease to meet the requirements of the United States Pharmacopeia (United States Pharmacopeia – USP) after 3 months of storage at a temperature of 40 ° C and a relative humidity of 75%.