<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">avk</journal-id><journal-title-group><journal-title xml:lang="ru">Архивъ внутренней медицины</journal-title><trans-title-group xml:lang="en"><trans-title>The Russian Archives of Internal Medicine</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2226-6704</issn><issn pub-type="epub">2411-6564</issn><publisher><publisher-name>“SINAPS” LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.20514/2226-6704-2020-10-4-262-271</article-id><article-id custom-type="elpub" pub-id-type="custom">avk-1071</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОРНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEW ARTICLES</subject></subj-group></article-categories><title-group><article-title>Прямые и опосредованные эффекты трийодтиронина</article-title><trans-title-group xml:lang="en"><trans-title>Metabolic Systemic Effects Triiodothyronine</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Трошина</surname><given-names>Е. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Troshina</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мо сква</p></bio><bio xml:lang="en"><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7960-8315</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сенюшкина</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Senyushkina</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мо сква</p></bio><bio xml:lang="en"><p>Moscow</p></bio><email xlink:type="simple">EvgeniyaSenyushkina@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Endocrinology Research Centre</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>29</day><month>07</month><year>2020</year></pub-date><volume>10</volume><issue>4</issue><fpage>262</fpage><lpage>271</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Трошина Е.А., Сенюшкина Е.С., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Трошина Е.А., Сенюшкина Е.С.</copyright-holder><copyright-holder xml:lang="en">Troshina E.A., Senyushkina E.S.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.medarhive.ru/jour/article/view/1071">https://www.medarhive.ru/jour/article/view/1071</self-uri><abstract><p>Трийодтиронин (Т3, 3,5,3’-L-трийодтиронин) — гормон щитовидной железы, секреция которого осуществляется непосредственно как самой железой (в меньшей степени), так и вне ее (основное количество; в результате периферического дейодирования тироксина (Т4)). Проникая в ядра клеток, Т3 взаимодействует со специфическими ядерными рецепторами тканей-мишеней, что определяет его биологическую активность. Данное взаимодействие приводит к активации транскрипции ряда генов.</p><p>В гипофизе и периферических тканях действие тиреоидных гормонов модулируется локальными дейодиназами, превращающими Т4 в более активный Т3, молекулярные эффекты которого в отдельных тканях зависят от подтипов рецепторов Т3 и их взаимодействия с другими лигандами, коактиваторами и корепрессорами, а также от активации или репрессии специфических генов.</p><p>Причиной недостаточной продукции Т3 является, прежде всего, дефицит йода в питании, реже — дефект генов, кодирующих белки, которые участвуют в биосинтезе Т3. В результате низкого поступления йодида в организм срабатывает так называемый адаптационный механизм, заключающийся в увеличении доли синтезируемого Т3, что повышает метаболическую эффективность тиреоидных гомонов. При недостаточности в диете такого микроэлемента как селен, снижается превращение Т4 в Т3.</p><p>Гормоны щитовидной железы играют жизненно важную роль в регуляции гомеостаза и скорости метаболизма клеток и тканей человека и млекопитающих. Они необходимы для физического и умственного развития. Недостаточная их выработка на этапе формирования внутренних органов плода и в детском возрасте может привести к различным патологиям, прежде всего к патологии центральной нервной системы, и, как следствие, к задержке роста и умственной отсталости. Во взрослом возрасте гипотиреоз приводит к снижению метаболизма, ухудшению памяти, депрессивным расстройствам, нарушению фертильности. Множество дискуссий и неоднозначных заключений получено в отношении комбинированных препаратов (левотироксин натрия + лиотиронин) для лечения гипотиреоза. В данной статье будут рассмотрены метаболические эффекты Т3, гормона щитовидной железы, обладающего наибольшей активностью.</p></abstract><trans-abstract xml:lang="en"><p>Triiodothyronine (T3, 3,5,3’-L-triiodothyronine) is a thyroid hormone (thyroid), the secretion of which is carried out directly both by the gland (to a lesser extent) and outside it (the main amount; as a result of peripheral deiodination of thyroxine (T4)). Getting into the nuclei of cells, T3 interacts with specific nuclear receptors of target tissues, which determines its biological activity. This interaction leads to the activation of transcription of a number of genes.</p><p>In the pituitary gland and peripheral tissues, the action of thyroid hormones is modulated by local deiodinases, which convert T4 to more active T3, the molecular effects of which in individual tissues depend on subtypes of T3 receptors and their interaction with other ligands, coactivators and corepressors, as well as on the activation or repression of specific genes.</p><p>The reason for the lack of T3 production is primarily a deficiency of iodine in the diet, less often, a defect in the genes encoding the proteins that are involved in T3 biosynthesis. As a result of the low intake of iodide in the body, the so-called adaptive mechanism is activated, which consists in increasing the proportion of synthesized T3, which increases the metabolic efficiency of thyroid homones. With a deficiency in the diet of such a trace element as selenium, the conversion of T4 to T3 is reduced.</p><p>Thyroid hormones play a vital role in the regulation of homeostasis and the metabolic rate of cells and tissues of humans and mammals. They are necessary for physical and mental development. Their insufficient production at the stage of formation of the internal organs of the fetus and in childhood can lead to various pathologies, primarily to pathology of the central nervous system, and as a result, growth retardation and mental retardation. In adulthood, hypothyroidism leads to a decrease in metabolism, memory impairment, depressive disorders, impaired fertility. Many discussions and ambiguous conclusions have been obtained regarding combination drugs (sodium levothyroxine + lyothironon) for the treatment of hypothyroidism. This article will examine the metabolic effects of T3, the thyroid hormone with the highest activity. </p></trans-abstract><kwd-group xml:lang="ru"><kwd>щитовидная железа</kwd><kwd>трийодтиронин</kwd><kwd>изоформы трийодтиронина</kwd></kwd-group><kwd-group xml:lang="en"><kwd>thyroid gland</kwd><kwd>triiodothyronine</kwd><kwd>triiodothyronine isoforms</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Поисково-аналитическая работа по подготовке рукописи проведена в рамках государственного задания «Эпидемиологические и молекулярно-клеточные характеристики опухолевых, аутоиммунных и йододефицитных тиреопатий, как основа профилактики осложнений и персонализации лечения». Рег. № АААА-А20-120011790180-4.</funding-statement><funding-statement xml:lang="en">Search and analytical work on the preparation of the manuscript was carried out as part of the state task «Epidemiological and molecular-cellular characteristics of tumor, autoimmune and iodine deficiency thyroidopathies as the basis for the prevention of complications and personalization of treatment». Reg. № AAAA-A20-120011790180-4.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Gomes-Lima C., Burman K.D. Reverse T3 or perverse T3? Still puzzling after 40 years. Cleveland Clinic Journal of Medicine. 2018;85(6):450-5. doi: 10.3949/ccjm.85a.17079.</mixed-citation><mixed-citation xml:lang="en">Gomes-Lima C., Burman K.D. Reverse T3 or perverse T3? Still puzzling after 40 years. Cleveland Clinic Journal of Medicine. 2018;85(6):450-5. doi: 10.3949/ccjm.85a.17079.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Трошина Е.А. Зоб. М.: Медицинское информационное агентство. 2012; 334 с.</mixed-citation><mixed-citation xml:lang="en">Troshina E.A. Goiter. Moscow: Meditsinskoe informatsionnoe agenstvo. 2012; 334 р. [In Russian].</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Трошина Е.А., Сенюшкина Е.С., Терехова М.А. Роль селена в патогенезе заболеваний щитовидной железы. Клиническая и экспериментальная тиреоидология. 2018;14(4):192-205. doi: 10.14341/ket10157.</mixed-citation><mixed-citation xml:lang="en">Troshina E.A., Senyushkina E.S., Terekhova M.A. The role of selenium in the pathogenesis of thyroid diseases. Clinical and experimental thyroidology. 2018;14(4):192-205. doi: 10.14341 / ket10157. [In Russian].</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Fraczek-Jucha M., Zbierska-Rubinkiewicz K., Kabat M. et al. Low triiodothyronine syndrome and selenium deficiency — undervalued players in advanced heart failure? A single center pilot study. BMC Cardiovasc Disord. 2019;19(1):133. doi:10.1186/s12872-019-1118-z.</mixed-citation><mixed-citation xml:lang="en">Fraczek-Jucha M., Zbierska-Rubinkiewicz K., Kabat M. et al. Low triiodothyronine syndrome and selenium deficiency — undervalued players in advanced heart failure? A single center pilot study. BMC Cardiovasc Disord. 2019;19(1):133. doi:10.1186/s12872-019-1118-z.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Batista G., Hensch T.K. Critical Period Regulation by Thyroid Hormones: Potential Mechanisms and Sex-Specific Aspects. Frontiers in Molecular Neuroscience. April 2019; 12: 77. doi: 10.3389/fnmol.2019.00077.</mixed-citation><mixed-citation xml:lang="en">Batista G., Hensch T.K. Critical Period Regulation by Thyroid Hormones: Potential Mechanisms and Sex-Specific Aspects. Frontiers in Molecular Neuroscience. April 2019; 12: 77. doi: 10.3389/fnmol.2019.00077.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Fan P., Luo C.Z., Tang N., et al. Advanced Maternal Age, Mode of Delivery, and Thyroid Hormone Levels in Chinese Newborns. Frontiers in Endocrinology. 2020; 10: 913. doi: 10.3389/ fendo.2019.00913.</mixed-citation><mixed-citation xml:lang="en">Fan P., Luo C.Z., Tang N., et al. Advanced Maternal Age, Mode of Delivery, and Thyroid Hormone Levels in Chinese Newborns. Frontiers in Endocrinology. 2020; 10: 913. doi: 10.3389/ fendo.2019.00913.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Гарднер Д., Шобек Д. Базисная и клиническая эндокринология. Книга 2. М.: БИНОМ. 2018; 696 с.</mixed-citation><mixed-citation xml:lang="en">Gardner D., Shoback D. Basic &amp; Clinical Endocrinology. Book 2. Moscow: BINOM. 2018; 696 р. [In Russian].</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Гончаров Н.П., Кация Г.В., Колесникова Г.С. Ключевые гормоны в эндокринологии и методы их определения. М.: Издательство «АдамантЪ». 2014; 230 с.</mixed-citation><mixed-citation xml:lang="en">Goncharov N.P., Katsiya G.V., Kolesnikova G.S. Key hormones in endocrinology and methods for their determination. M.: Publishing house «Adamant». 2014; 230 р. [In Russian].</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Rastogi L., Godbole M.M., Sinha R.A. et al. Reverse triiodothyronine (rT3) attenuates ischemia-reperfusion injury. Biochemical and Biophysical Research Communications. 2018;506(3):597-603. doi:10.1016/j.bbrc.2018.10.031.</mixed-citation><mixed-citation xml:lang="en">Rastogi L., Godbole M.M., Sinha R.A. et al. Reverse triiodothyronine (rT3) attenuates ischemia-reperfusion injury. Biochemical and Biophysical Research Communications. 2018;506(3):597-603. doi:10.1016/j.bbrc.2018.10.031.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Salazar P., Cisternas P., Martinez M. et al. Hypothyroidism and Cognitive Disorders during Development and Adulthood: Implications in the Central Nervous System. Molecular Neurobiology. 2019;56(4):2952–63. doi:10.1007/s12035-018-1270-y.</mixed-citation><mixed-citation xml:lang="en">Salazar P., Cisternas P., Martinez M. et al. Hypothyroidism and Cognitive Disorders during Development and Adulthood: Implications in the Central Nervous System. Molecular Neurobiology. 2019;56(4):2952–63. doi:10.1007/s12035-018-1270-y.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Sevinc Odabasi Gunes, Ayca Torel Ergur, Fatma Nisanci Kilinc The Effect of Subclinical Hypothyroidism on Body Composition Parameters in Children. Int J Clin Pract 2020 May 27;e13554. doi: 10.1111/ijcp.13554.</mixed-citation><mixed-citation xml:lang="en">Sevinc Odabasi Gunes, Ayca Torel Ergur, Fatma Nisanci Kilinc The Effect of Subclinical Hypothyroidism on Body Composition Parameters in Children. Int J Clin Pract 2020 May 27;e13554. doi: 10.1111/ijcp.13554.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Gebreegziabher T., Woltamo T., Thomas D.G. et al. Iodine supplementation of lactating women and assessment of infant visual information processing and maternal and infant thyroid function: A randomized trial. PLoS One. 2019;14(10):e0223348. doi: 10.1371/journal.pone.0223348.</mixed-citation><mixed-citation xml:lang="en">Gebreegziabher T., Woltamo T., Thomas D.G. et al. Iodine supplementation of lactating women and assessment of infant visual information processing and maternal and infant thyroid function: A randomized trial. PLoS One. 2019;14(10):e0223348. doi: 10.1371/journal.pone.0223348.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Armstrong M., Aziz N., Fingeret A. Physiology, Thyroid Function. StatPearls Publishing LLC. 2020; 10 p.</mixed-citation><mixed-citation xml:lang="en">Armstrong M., Aziz N., Fingeret A. Physiology, Thyroid Function. StatPearls Publishing LLC. 2020; 10 p.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Clyde P.W., Harari A.E., Getka E.J. et al. Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. Journal of the American Medical Association. 2003;290(22):2952–8. doi: 10.1001/jama.290.22.2952.</mixed-citation><mixed-citation xml:lang="en">Clyde P.W., Harari A.E., Getka E.J. et al. Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. Journal of the American Medical Association. 2003;290(22):2952–8. doi: 10.1001/jama.290.22.2952.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Fadeyev V.V., Morgunova T.B., Melnichenko G.A. et al. Combined therapy with L-thyroxine and L-triiodothyronine compared to L-thyroxine alone in the treatment of primary hypothyroidism. Hormones. 2010;9(3):245–52. doi: 10.14310/horm.2002.1274.</mixed-citation><mixed-citation xml:lang="en">Fadeyev V.V., Morgunova T.B., Melnichenko G.A. et al. Combined therapy with L-thyroxine and L-triiodothyronine compared to L-thyroxine alone in the treatment of primary hypothyroidism. Hormones. 2010;9(3):245–52. doi: 10.14310/horm.2002.1274.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Fraczek-Jucha M., Zbierska-Rubinkiewicz K., Kabat M., et al. Low triiodothyronine syndrome and selenium deficiency — undervalued players in advanced heart failure? A single center pilot study.BMC Cardiovasc Disord. 2019;19(1):105. doi:10.1186/s12872-019-1076-5.</mixed-citation><mixed-citation xml:lang="en">Fraczek-Jucha M., Zbierska-Rubinkiewicz K., Kabat M., et al. Low triiodothyronine syndrome and selenium deficiency — undervalued players in advanced heart failure? A single center pilot study.BMC Cardiovasc Disord. 2019;19(1):105. doi:10.1186/s12872-019-1076-5.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Danzi S., Klein I. Thyroid Abnormalities in Heart Failure. Heart Failure Clinics. 2020;16(1):1–9. doi:10.1016/j.hfc.2019.08.002.</mixed-citation><mixed-citation xml:lang="en">Danzi S., Klein I. Thyroid Abnormalities in Heart Failure. Heart Failure Clinics. 2020;16(1):1–9. doi:10.1016/j.hfc.2019.08.002.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Noli L., Khorsandi S.E., Pyle A. et al. Effects of Thyroid Hormone on Mitochondria and Metabolism of Human Preimplantation Embryos. Stem Cells. 2020;38(3):369-81. doi: 10.1002/stem.3129.</mixed-citation><mixed-citation xml:lang="en">Noli L., Khorsandi S.E., Pyle A. et al. Effects of Thyroid Hormone on Mitochondria and Metabolism of Human Preimplantation Embryos. Stem Cells. 2020;38(3):369-81. doi: 10.1002/stem.3129.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Nygaard B., Jensen E.W., Kvetny J. et al. Effect of combination therapy with thyroxine (T4) and 3,5,3’-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study. European Journal of Endocrinology. 2009;161(6):895–902. doi: 10.1530/EJE-09-0542.</mixed-citation><mixed-citation xml:lang="en">Nygaard B., Jensen E.W., Kvetny J. et al. Effect of combination therapy with thyroxine (T4) and 3,5,3’-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study. European Journal of Endocrinology. 2009;161(6):895–902. doi: 10.1530/EJE-09-0542.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Bunevicius R., Kazanavicius G., Zalinkevicius R. et al. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. New England Journal of Medicine. 1999; 340: 424–9. doi: 10.1056/NEJM199902113400603.</mixed-citation><mixed-citation xml:lang="en">Bunevicius R., Kazanavicius G., Zalinkevicius R. et al. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. New England Journal of Medicine. 1999; 340: 424–9. doi: 10.1056/NEJM199902113400603.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Appelhof B.C., Fliers E., Wekking E.M. et al. Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial. Journal of Clinical Endocrinology and Metabolism. 2005;90(5):2666–74. doi: 10.1210/jc.2004-2111.</mixed-citation><mixed-citation xml:lang="en">Appelhof B.C., Fliers E., Wekking E.M. et al. Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial. Journal of Clinical Endocrinology and Metabolism. 2005;90(5):2666–74. doi: 10.1210/jc.2004-2111.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Clyde P.W., Harari A.E., Getka E.J. et al. Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. Journal of the American Medical Association. 2003;290(22):2952–8. doi: 10.1001/jama.290.22.2952.</mixed-citation><mixed-citation xml:lang="en">Clyde P.W., Harari A.E., Getka E.J. et al. Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. Journal of the American Medical Association. 2003;290(22):2952–8. doi: 10.1001/jama.290.22.2952.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Kaminski J., Miasaki F.Y., Paz-Filho G. et al. Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study. Arch Endocrinol Metab. 2016; 60(6):562–72. doi: 10.1590/2359-3997000000192.</mixed-citation><mixed-citation xml:lang="en">Kaminski J., Miasaki F.Y., Paz-Filho G. et al. Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study. Arch Endocrinol Metab. 2016; 60(6):562–72. doi: 10.1590/2359-3997000000192.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Rodriguez T., Lavis V.R., Meininger J.C. et al. Substitution of liothyronine at a 1:5 ratio for a portion of levothyroxine: effect on fatigue, symptoms of depression, and working memory versus treatment with levothyroxine alone. Endocrine Practice. 2005;11(4):223–33. doi: 10.4158/EP.11.4.223.</mixed-citation><mixed-citation xml:lang="en">Rodriguez T., Lavis V.R., Meininger J.C. et al. Substitution of liothyronine at a 1:5 ratio for a portion of levothyroxine: effect on fatigue, symptoms of depression, and working memory versus treatment with levothyroxine alone. Endocrine Practice. 2005;11(4):223–33. doi: 10.4158/EP.11.4.223.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Sawka A.M., Gerstein H.C., Marriott M.J. et al. Does a combination regimen of thyroxine (T4) and 3,5,3’-triiodothyronine improve depressive symptoms better than T4 alone in patients with hypothyroidism? Results of a double-blind, randomized, controlled trial. Journal of Clinical Endocrinology and Metabolism. 2003;88(10):4551–5. doi: 10.1210/jc.2003-030139.</mixed-citation><mixed-citation xml:lang="en">Sawka A.M., Gerstein H.C., Marriott M.J. et al. Does a combination regimen of thyroxine (T4) and 3,5,3’-triiodothyronine improve depressive symptoms better than T4 alone in patients with hypothyroidism? Results of a double-blind, randomized, controlled trial. Journal of Clinical Endocrinology and Metabolism. 2003;88(10):4551–5. doi: 10.1210/jc.2003-030139.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Wiersinga W.M., Duntas L., Fadeyev V. et al. 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism European Thyroid Journal. 2012;1(2):55-71. doi: 10.1159/000339444.</mixed-citation><mixed-citation xml:lang="en">Wiersinga W.M., Duntas L., Fadeyev V. et al. 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism European Thyroid Journal. 2012;1(2):55-71. doi: 10.1159/000339444.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Siegmund W., Spieker K., Weike A.I. et al. Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14:1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism. Clinical Endocrinology. 2004;60(6):750–7. doi: 10.1111/j.1365-2265.2004.02050.x.</mixed-citation><mixed-citation xml:lang="en">Siegmund W., Spieker K., Weike A.I. et al. Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14:1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism. Clinical Endocrinology. 2004;60(6):750–7. doi: 10.1111/j.1365-2265.2004.02050.x.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Peterson S.J., Cappola A.R., Castro M.R. et al. An Online Survey of Hypothyroid Patients Demonstrates Prominent Dissatisfaction. Thyroid. 2018;28(6):707-21. doi: 10.1089/thy.2017.0681.</mixed-citation><mixed-citation xml:lang="en">Peterson S.J., Cappola A.R., Castro M.R. et al. An Online Survey of Hypothyroid Patients Demonstrates Prominent Dissatisfaction. Thyroid. 2018;28(6):707-21. doi: 10.1089/thy.2017.0681.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Jonklaas J., Tefera E., Shara N. Physician Choice of Hypothyroidism Therapy: Influence of Patient Characteristics. Thyroid. 2018;28(11):1416-24. doi: 10.1089/thy.2018.0325.</mixed-citation><mixed-citation xml:lang="en">Jonklaas J., Tefera E., Shara N. Physician Choice of Hypothyroidism Therapy: Influence of Patient Characteristics. Thyroid. 2018;28(11):1416-24. doi: 10.1089/thy.2018.0325.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Jonklaas J., Tefera E., Shara N. Prescribing Therapy for Hypothyroidism: Influence of Physician Characteristics. Thyroid. 2019;29(1):44-52. doi: 10.3389/fendo.2019.00031</mixed-citation><mixed-citation xml:lang="en">Jonklaas J., Tefera E., Shara N. Prescribing Therapy for Hypothyroidism: Influence of Physician Characteristics. Thyroid. 2019;29(1):44-52. doi: 10.3389/fendo.2019.00031</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Goldman J.M., Line B.R., Aamodt R.L., et al. Influence of triiodothyronine withdrawal time on 131I uptake postthyroidectomy for thyroid cancer. Journal of Clinical Endocrinology and Metabolism.1980;50(4):734-9.</mixed-citation><mixed-citation xml:lang="en">Goldman J.M., Line B.R., Aamodt R.L., et al. Influence of triiodothyronine withdrawal time on 131I uptake postthyroidectomy for thyroid cancer. Journal of Clinical Endocrinology and Metabolism.1980;50(4):734-9.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Hoermann R., Midgley JEM., Larisch R. et al., Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options. Drugs in Context. 2019 Aug; 13; 8: 212597. doi: 10.7573/dic.212597.</mixed-citation><mixed-citation xml:lang="en">Hoermann R., Midgley JEM., Larisch R. et al., Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options. Drugs in Context. 2019 Aug; 13; 8: 212597. doi: 10.7573/dic.212597.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
