Dr. Alexandra Markova graduated from the Medical University – Sofia in 2012. She obtained a specialty in “Endocrinology and Metabolic Diseases” in 2021 after specialization at UMBAL “Alexandrovska”. In the same year, he obtained a scientific and educational degree “doctor” after defending a dissertation work in the field of diabetology. He is the author of publications in Bulgarian and international journals with an impact factor. There are participations in national and international congresses. – Dr. Markova, what disease is Hashimoto’s and why in the last 15 years do we often hear it mentioned as a diagnosis? Hashimoto’s thyroiditis is an autoimmune disease of the thyroid gland. It is an endocrine organ located in the front of the neck and secretes the hormones thyroxine and triiodothyronine (T4 and T3). In autoimmune thyroiditis or the so-called Hashimoto’s, we have an autoimmune inflammation of the gland, which leads to disruption of its structure and function. It is a defect in the immune system in which the thyroid gland is perceived as a foreign organ and is attacked by white blood cells. Before the implementation of iodine prophylaxis in Bulgaria in 1993, the most common cause of an increase in the thyroid gland – goitre, and hypothyroidism was iodine deficiency. After controlling the iodine status of the population, autoimmune thyroiditis emerged as the leading cause of reduced thyroid function. That is why it is increasingly sought and found among patients with established changes in thyroid hormones or in the structure of the gland during ultrasound examination, as well as in women and men with infertility. – What is the reason for this increase in Hashimoto’s cases in women? And are we to think that men are not affected? Women have always been the more affected gender when it comes to autoimmune diseases and Hashimoto’s thyroiditis in particular. The reason is believed to lie in the extra X chromosome. Some studies have shown that a defect in the X chromosome is the cause of autoimmunity, and having two copies in women reinforces this effect. Another theory suggests that female sex hormones – estrogens – strengthen the immune system and its response to inflammatory processes. A typical example of this is pregnancy, which is associated with great dynamics in sex hormones. During pregnancy, the immune system is more tolerant to antigenic stimuli, including the growing baby, with which autoimmune diseases usually improve. After childbirth, however, the immune system seems to “wake up” anew, and there is often an exacerbation or the appearance of a new autoimmune disease in predisposed women. Although autoimmune thyroiditis occurs up to 8 times more often in women, men are not spared either. However, men are proud carriers of one X-chromosome from which they can inherit the defect in the immune system. Hashimoto’s thyroiditis is a hereditary disease that occurs with increased frequency in members of the same family. The myth that men are not affected by autoimmune thyroiditis,leads to reduced diagnosis in this gender and poses a risk that the disease will remain unrecognized for a long time. – Is there a way to prevent Hashimoto’s and how do we know that we are prone to it? As I already mentioned, autoimmune thyroiditis is hereditary and there are often other family members with this disease. It often goes hand-in-hand with other autoimmune diseases, so if you have type 1 diabetes, vitiligo, rheumatoid arthritis, lupus, multiple sclerosis, etc., it’s a good idea to check for thyroid disease as well. The reasons for the occurrence of the autoimmune response are not fully understood, which makes prevention very difficult. Iodine status is thought to matter – both iodine deficiency and excess can alter gland function – stress, certain infectious diseases, smoking and other harmful environmental toxins. Therefore, the best prevention strategy is to stop smoking, reduce alcohol intake and take iodized salt, combined with a balanced diet, physical activity and sufficient time for sleep and rest to reduce stress on the body . These measures may not be able to stop the autoimmune process, but at least they can keep the hormone levels normal for a longer time. – Once Hashimoto’s has appeared, is there a cure? And mastering? There is a difference between being positive for Hashimoto’s antibodies and having the disease. Positive antibodies are not always related to a hormonal problem. They serve as an alarming signal of a possible disorder in the function of the thyroid gland in the future. Unfortunately, there is currently no effective treatment for autoimmune thyroiditis. Only its consequences are treated. Therefore, the presence of antibodies, without evidence of thyroid dysfunction, requires control of thyroid-stimulating hormone (TSH) at least once a year. When it goes out of the norm, the appropriate treatment is undertaken. – What is the therapy? And how useful and harmful can iodine, selenium and other vitamins and trace elements be? What does medicine tell us? Autoimmune thyroiditis is usually associated with reduced thyroid function. The gold standard in hypothyroidism therapy is hormone replacement therapy with levothyroxine (LT4). The medication is dosed according to TSH levels. It is important to know that thyroid hormones are inversely related to TSH, i.e. in hypothyroidism we have low levels of T4 and T3 and elevated TSH. Its target levels take into account age, co-morbidities and the presence of pregnancy. As an exception, the active form of thyroid hormones, namely T3, can be taken in combination with LT4. In general, this scheme is not recommended, except in strictly defined cases. The problem with T3 is that it has a very short half-life and must be taken twice daily. In addition, its levels are very variable and overdose with symptoms of hyperfunction is often reached. Currently, the T4/T3 combination is only recommended in caseswhen on the background of monotherapy with LT4 and reached normal TSH levels, there are still symptoms of hypothyroidism. Some trace elements, such as iodine, selenium and iron, are extremely important for the formation of thyroid hormones. But both their deficiency and their excess can lead to health problems. Iodine deficiency is associated with an enlarged thyroid gland and hypothyroidism. The recommended daily intake of iodine is about 150 mcg, which can be obtained from iodized salt. In general, the use of dietary supplements – for example kelp, containing high concentrations of iodine – is not recommended. Amounts above 500 mcg are considered toxic and can disrupt thyroid function. Only pregnant women who have higher needs – about 250 mcg daily – can take an additional 100-150 mcg of iodine in the form of a supplement. In addition to hormone production, selenium also acts as an antioxidant, has an anti-inflammatory effect and modulates the immune response. The benefits of its additional intake in the form of a supplement in autoimmune thyroiditis have not been conclusively proven. The results of the studies are conflicting, with some showing a reduction in antibodies and improvement in complaints, while others do not. Taking high doses of selenium can also have a negative impact on health. A connection has been established between its long-term intake and the development of type 2 diabetes. That is why it is necessary to develop specific recommendations for standardizing the dose and duration of treatment. At this stage, it is better to take foods rich in selenium, such as Brazil nuts, whole wheat, rye, sunflower seeds, mushrooms, tuna, oysters and meat. Currently, the generally accepted guidelines of reputable organizations, such as the American and European Thyroid Associations, do not recommend the use of nutritional supplements for the treatment of autoimmune thyroiditis and hypothyroidism. Perhaps only consideration should be given to correcting vitamin D deficiency, as there is evidence for the benefit of vitamin D in modulating the immune response. In addition, its replacement is cheap and has minimal side effects, and its overall benefits for the body are many. – They say that with Hashimoto’s the consumption of certain foods is unfavorable – for example, that vegetables from the cruciferous family are not suitable. How much should we listen to such claims? There is no conclusive scientific evidence to show that dietary changes can significantly affect thyroid function. Cruciferous vegetables, such as cabbage, cauliflower, broccoli, kale, contain natural goitrogens. These are substances that reduce the absorption of iodine by the gland and lead to its increase. However, for this to happen, these vegetables need to be taken raw and in large quantities. Their heat treatment destroys goitrogens. However, there are no clinical studies that say exactly what amount is harmful.Therefore, it is not necessary to exclude them from the diet, but to accept them within the framework of a standard balanced diet. Another popular belief is that gluten intake should be limited. At the moment, there is a lack of definitive data in the scientific literature on the benefit of a gluten-free diet on thyroid health. Although there are some small studies that show a drop in antibodies from gluten restriction, lifelong adherence to a gluten-free diet is difficult and expensive. At the moment, this way of eating is only recommended for proven gluten intolerance. – What happens if we give up Hashimoto’s therapy? Will we harm each other and how much? Untreated hypothyroidism can have serious health consequences. Thyroid hormones are important for metabolism, heart, gastrointestinal tract, nerve and muscle function. In its milder forms, hypothyroidism has non-specific symptoms, such as easy fatigue, sleepiness, weight gain, swelling, hair loss, dry skin, constipation, depression, emotional lability, menstrual disorders, infertility, etc. The thought process and concentration are disturbed. In the long term, the risk of cardiovascular events and heart failure increases. Untreated hypothyroidism during pregnancy is especially dangerous, since thyroid hormones are extremely important for the proper development of the fetus. Severe thyroid hypofunction can lead to the life-threatening condition myxedema, in which there are disturbances in consciousness, effusions in body cavities – pleura, pericardium, low body temperature and arterial pressure, slow pulse. The mortality rate for this condition is very high. Fortunately, in modern medicine it is less and less common. – Are there and what are the unwanted effects of long-term therapy with levothyroxine? Wouldn’t that teach the thyroid to be lazy? Taking LT4 is well tolerated and rarely produces side effects. These can occur with an overdose of the medication. In this case, the complaints resemble hyperfunction of the thyroid gland – rapid pulse and skipping of the heart, weight loss, increased sweating, nervousness, headache, insomnia. LT4 is indicated for replacement therapy in reduced thyroid function. Usually, in autoimmune thyroiditis, hypothyroidism is permanent and requires lifelong treatment. Dosing is carried out according to the current levels of thyroid hormones, as often the gland has a residual own secretion, which, however, is not sufficient to maintain normal hormone levels. In these cases, the intake of LT4 has only a complementary role to achieve hormonal balance. When it is discontinued, the hormones return to their original position. – How long does the levothyroxine dose continue to increase and is there any way we can control this? As I already mentioned, non-LT4 intake has a supporting function. Its dose escalation depends on TSH levels, which are monitored 6 to 8 weeks after each adjustment.The dose stops changing when the TSC reaches the normal range. It is important to know that autoimmune thyroiditis is a chronic disease and thyroid function progressively declines over time, increasing the need for LT4. In cases where it has completely lost its function, the body relies solely on the intake of LT4, which is in a full replacement dose. Usually it ranges between 1.6 and 1.8 mcg per kilogram of weight. If we take much higher than the indicated doses, but the TSH levels are still outside the optimal limits, we should think about the way of taking the medication. A number of factors can impair the absorption of LT4 tablets. They must be taken on an empty stomach, the most convenient being in the morning after waking up. Intake of food, coffee, tea and drinks other than water can interfere with the absorption of the medication. The same applies to other medications, especially proton pump inhibitors, which change the acidity of gastric juices. That is why the recommendation is to take LT4 in the morning on an empty stomach, at least 30 minutes before food and other medications, and for caffeine-containing drinks, it is best to wait at least an hour or two. Certain diseases of the stomach, such as atrophic gastritis, can also be associated with impaired absorption of LT4. In these cases, the liquid form of the preparation (in the form of a syrup) is preferred, which does not need the acidic pH of the stomach to be absorbed. – When and by what signs should we recognize that we need to update the therapy? Until recently, it was claimed that TSH levels change during the transition from warm to cold semesters and vice versa. Signs of suboptimal intake of LT4 can be both hypothyroidism at an insufficient dose and thyrotoxicosis at a high dose. If complaints recur before starting therapy or signs of overdose appear, it is a good idea to examine the TSC to verify that the current dose is adequate. Usually, when a stable replacement dose is reached, TSH levels should be checked every 6 to 12 months. Generally, there are variations in thyroid hormone levels during different seasons of the year. In the cold months, TSH rises because higher levels of T4 and T3 are then needed to maintain body temperature, while in the summer, needs are lower and TSH falls. This is especially important in people with autoimmune thyroiditis who are not yet on therapy. Often, the establishment of a slightly elevated TSH in the winter can be taken for hypothyroidism and therapy can be started, but in reality there is no need for such. It is therefore recommended that hormone levels be re-monitored after 2-3 months and treatment considered if high values ??persist. In patients on replacement therapy, however, a substantial dose adjustment is rarely required. – At what blood indicators can we count,that we control the state? What TSC should we aim for according to age and circumstances � for example when planning a pregnancy? Control of hypothyroidism is primarily based on TSH, with T4 and T3 having a secondary role. We usually strive to bring TSH within the normal range with the intake of LT4. In some cases, however, individualized norms are applied according to age and accompanying diseases. In elderly patients who often have concomitant cardiac problems, control may be more liberal and TSH levels up to 2-2.5 times the upper limit are allowed. In younger patients with heart rhythm disorders and ischemia, it is also recommended that TSH moves in the upper limit of the norm. On the other hand, in women with autoimmune thyroiditis planning pregnancy, the control should be much stricter. TSH levels are recommended to be in the lower limit of normal (<2.5 mIU/ml) before pregnancy. In this way, we can be sure that the baby will receive a sufficient amount of thyroid hormones for its proper development. During pregnancy itself, thyroid hormone needs increase, necessitating frequent follow-up, especially in the first trimester. Women who were on replacement therapy before pregnancy should increase the dose of LT4 by about 20-25% immediately after a positive pregnancy test, after which they are subject to periodic control. Trimester-specific norms for TSH are applied, and if it moves outside them, a dose adjustment or initiation of therapy is required in untreated women. - What should women with Hashimoto's on hormone replacement therapy know when they need some kind of stimulation for the purpose of pregnancy? Is the hormone situation under control? According to the recommendations of the European Thyroid Association, women with autoimmune thyroiditis on LT4 hormone replacement therapy should achieve TSH levels <2.5 mIU/ml before starting planned ovarian stimulation. The dose should be adjusted until the desired TSC is reached. In women who do not take LT4 but have a TSH > 4 mIU/ml, initiation of replacement therapy is also recommended. In cases where the TSH is between 2.5 and 4 mIU/ml before stimulation, the inclusion of low-dose LT4 (25-50 mcg daily) may be considered, especially in women over 35 years of age, with recurrent abortions or with ovarian causes for subfertility. When pregnancy occurs, the same rules for follow-up and treatment apply as for other women.On the other hand, in women with autoimmune thyroiditis planning pregnancy, the control should be much stricter. TSH levels are recommended to be in the lower limit of normal (<2.5 mIU/ml) before pregnancy. In this way, we can be sure that the baby will receive a sufficient amount of thyroid hormones for its proper development. During pregnancy itself, thyroid hormone needs increase, necessitating frequent follow-up, especially in the first trimester. Women who were on replacement therapy before pregnancy should increase the dose of LT4 by about 20-25% immediately after a positive pregnancy test, after which they are subject to periodic control. Trimester-specific norms for TSH are applied, and if it moves outside them, a dose adjustment or initiation of therapy is required in untreated women. - What should women with Hashimoto's on hormone replacement therapy know when they need some kind of stimulation for pregnancy? Is the hormone situation under control? According to the recommendations of the European Thyroid Association, women with autoimmune thyroiditis on LT4 hormone replacement therapy should achieve TSH levels <2.5 mIU/ml before starting planned ovarian stimulation. The dose should be adjusted until the desired TSC is reached. In women who do not take LT4 but have a TSH > 4 mIU/ml, initiation of replacement therapy is also recommended. In cases where the TSH is between 2.5 and 4 mIU/ml before stimulation, the inclusion of low-dose LT4 (25-50 mcg daily) may be considered, especially in women over 35 years of age, with recurrent abortions or with ovarian causes for subfertility. When pregnancy occurs, the same rules for follow-up and treatment apply as for other women.On the other hand, in women with autoimmune thyroiditis planning pregnancy, the control should be much stricter. TSH levels are recommended to be in the lower limit of normal (<2.5 mIU/ml) before pregnancy. In this way, we can be sure that the baby will receive a sufficient amount of thyroid hormones for its proper development. During pregnancy itself, thyroid hormone needs increase, necessitating frequent follow-up, especially in the first trimester. Women who were on replacement therapy before pregnancy should increase the dose of LT4 by about 20-25% immediately after a positive pregnancy test, after which they are subject to periodic control. Trimester-specific norms for TSH are applied, and if it moves outside them, a dose adjustment or initiation of therapy is required in untreated women. - What should women with Hashimoto's on hormone replacement therapy know when they need some kind of stimulation for pregnancy? Is the hormone situation under control? According to the recommendations of the European Thyroid Association, women with autoimmune thyroiditis on LT4 hormone replacement therapy should achieve TSH levels <2.5 mIU/ml before starting planned ovarian stimulation. The dose should be adjusted until the desired TSC is reached. In women who do not take LT4 but have a TSH > 4 mIU/ml, initiation of replacement therapy is also recommended. In cases where the TSH is between 2.5 and 4 mIU/ml before stimulation, the inclusion of low-dose LT4 (25-50 mcg daily) may be considered, especially in women over 35 years of age, with recurrent abortions or with ovarian causes for subfertility. When pregnancy occurs, the same rules for follow-up and treatment apply as for other women.The dose should be adjusted until the desired TSC is reached. In women who do not take LT4 but have a TSH > 4 mIU/ml, initiation of replacement therapy is also recommended. In cases where the TSH is between 2.5 and 4 mIU/ml before stimulation, the inclusion of low-dose LT4 (25-50 mcg daily) may be considered, especially in women over 35 years of age, with recurrent abortions or with ovarian causes for subfertility. When pregnancy occurs, the same rules for follow-up and treatment apply as for other women.The dose should be adjusted until the desired TSC is reached. In women who do not take LT4 but have a TSH > 4 mIU/ml, initiation of replacement therapy is also recommended. In cases where the TSH is between 2.5 and 4 mIU/ml before stimulation, the inclusion of low-dose LT4 (25-50 mcg daily) may be considered, especially in women over 35 years of age, with recurrent abortions or with ovarian causes for subfertility. When pregnancy occurs, the same rules for follow-up and treatment apply as for other women.