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Новый взгляд на старую дилемму: лечение гипотиреоза при помощи комбинированной терапии L-тироксина и L-трийодтиронина

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В данном обзоре приведена информация о последних исследованиях в области комбинированного лечения гипотиреоза L-тироксином и L-трийодтированином. Не смотря на то, что были опубликованы достоверные данные об эффективности комбинированной терапии Т3 и Т4 у крыс после тиреоидэктомии, последние исследования и мета-анализы не указывают на значимое преимущество комбинированной терапии по сравнению с монотерапией Т4. Более того, у пациентов, получающих комбинированную терапию, чаще развиваются побочные эффекты, такие как тахикардия, нервозность и общая слабость. Тем не менее, по сравнению с комбинированной терапией L-T4+L-T3, при монотерапии Т4 обычно наблюдается сниженный уровень свободного Т3 и повышенный уровень свободного Т4 сыворотки крови, при этом отношение свТ3/свТ4 ближе к показателям, характерным для здорового человека. Согласно рекомендациям ЕТА и АТА, на сегодняшний день монотерапия Т4 считается первоочередной в лечении гипотиреоза. Тем не менее, во многих случаях рекомендации не соблюдаются, и пациенты принимают высушенные экстракты щитовидной железы или разнообразные «препараты» Т3 доступные в интернете. Недавно было выявлено, что однонуклеотидный полиморфизм (ОНП) генов дейодиназы 1-го (Д1) и 2-го (Д2) типов, а также гена фосфодиэстеразы 8В ассоциированы со снижением уровня свободного Т3 и дисфункцией щитовидной железы. Данные наблюдения подчеркивают необходимость в дальнейших исследованиях эффективности применения готовых комбинированных препаратов, а также в разработке долгожданных формул L-T3 c отсроченным действием или низко-дозированных (капсулы или таблетки по 5 мкг) препаратов L-T3, с целью облегчения подбора правильной дозы при комбинированной терапии с препаратами L-Т4 в контексте персонализированного подхода к лечению. Последние данные о возможном влиянии ОНП генов дейодиназ или белков-переносчиков тиреоидных гормонов на концентрацию свободного Т3 в тканях открывают путь к генотипированию пациентов с тиреоидэктомией в анамнезе, предъявляющих характерные жалобы и имеющих низкое отношение свТ3/свТ4.

Ключевые слова:
L-тироксин, L-трийодтиронин, гипотиреоз, однонуклеотидный полиморфизмы, Thr92Ala, отношение свТ3/свТ4, L-thyroxine, L-triiodothyronine, hypothyroidism, single nucleotide polymorphisms (SNPs), Thr92Ala, FT3:FT4 ratio

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New aspects of an old dilemma: treatment of hypothyroidism with L-thyroxine combined with L-triiodothyronine

The current review summarizes the most recent developments in the field of combined treatment with LT4+LT3 in hypothyroidism. Though it was well established for the past 20 years that T3 combined with T4 was best able to achieve euthyroidism in hypothyroidectomized rats, several recent studies and meta-analyses did not demonstrate any increased benefit of combined treatment as compared with T4 monotherapy. Moreover, patients under combination treatment are more prone to experience adverse effects, such as tachycardia, nervousness and fatigue. Conversely, T4 monotherapy usually leads to lower FT3 and higher serum FT4 levels as compared to the LT4+LT3 regimen thus resulting in a FT3:FT4 ratio closer to that of healthy subjects. Today, T4 monotherapy constitutes first-line treatment of hypothyroidism according to both the ETA and ATA Guidelines. However, in many cases the guidelines are not followed, with patients often taking compounded desiccated thyroid hormones or various T3 preparations available on the web. Recently, single nucleotide polymorphisms (SNPs) in the deiodinase type 1 (DIO1) and type 2 (DIO2) genes and in the phosphodiesterase 8B gene have been associated with T3 decrease and thyroid dysfunction. The above observations point to the necessity for more research into the application of customized treatment as well as to the need for the long-awaited LT3-retard formulations or low-dose (about 5?g/tablet/capsule) LT3 preparations to be appropriately dosed with LT4 in the context of a personalized treatment strategy. The recent finding that SNPs in DIOs or in thyroid hormone transporter genes may affect serum T3 in tissues opens up the way to the genotyping of those thyroidectomized patients who complain of symptoms and have a lower FT3:FT4 ratio.

Keywords:
L-тироксин, L-трийодтиронин, гипотиреоз, однонуклеотидный полиморфизмы, Thr92Ala, отношение свТ3/свТ4, L-thyroxine, L-triiodothyronine, hypothyroidism, single nucleotide polymorphisms (SNPs), Thr92Ala, FT3:FT4 ratio