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<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">ketendo</journal-id><journal-title-group><journal-title xml:lang="ru">Клиническая и экспериментальная тиреоидология</journal-title><trans-title-group xml:lang="en"><trans-title>Clinical and experimental thyroidology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1995-5472</issn><issn pub-type="epub">2310-3787</issn><publisher><publisher-name>Endocrinology Research Centre</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.14341/ket20128317-29</article-id><article-id custom-type="elpub" pub-id-type="custom">ketendo-4329</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>Статьи</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Проблемы заместительной терапии гипотиреоза: современность и перспективы</article-title><trans-title-group xml:lang="en"><trans-title>Challenges in replacement therapy of hypothyroidism: everyday practice and perspectives</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>Fadeyev</surname><given-names>V V</given-names></name></name-alternatives><bio xml:lang="ru"><p>доктор мед. наук, профессор кафедры эндокринологии Первого Московского государственного медицинского университета им. И.М. Сеченова, зам. директора ФГБУ Эндокринологический научный центр Минздравсоцразвития РФ</p></bio><email xlink:type="simple">walfad@mail.ru</email></contrib></contrib-group><pub-date pub-type="collection"><year>2012</year></pub-date><pub-date pub-type="epub"><day>15</day><month>09</month><year>2012</year></pub-date><volume>8</volume><issue>3</issue><issue-title>ТОМ 8, №3 (2012)</issue-title><fpage>17</fpage><lpage>29</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Fadeyev V.V., 2012</copyright-statement><copyright-year>2012</copyright-year><copyright-holder xml:lang="ru">Fadeyev V.V.</copyright-holder><copyright-holder xml:lang="en">Fadeyev V.V.</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.cet-endojournals.ru/jour/article/view/4329">https://www.cet-endojournals.ru/jour/article/view/4329</self-uri><abstract><p>Проблема заместительной терапии гипотиреоза, распространенность которого в общей популяции достигает 3,7% [<xref ref-type="bibr" rid="cit1">1</xref>], так или иначе касается любого заболевания щитовидной железы (ЩЖ), поскольку в клинической практике большинство из них гипотиреозом так или иначе заканчивается, как самопроизвольно, так и вследствие врачебных вмешательств. На первый взгляд, заместительная терапия гипотиреоза достаточно проста и в соответствии с многочисленными клиническими рекомендациями подразумевает ежедневный прием L-T4 под периодическим контролем уровня тиреотропного гормона (ТТГ). Тем не менее, даже если не считать такого важного момента, как приверженность пациента к правильному лечению, здесь есть много дискуссионных вопросов и сложностей, решение которых, по мнению автора этого обзора, и представляет перспективу в обсуждаемой области тиреоидологии.</p></abstract></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Aoki Y., Belin R.M., Clickner R. et al. Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999–2002). Thyroid 2007; 17: 1211–1223.</mixed-citation><mixed-citation xml:lang="en">Aoki Y., Belin R.M., Clickner R. et al. Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999–2002). Thyroid 2007; 17: 1211–1223.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Larsen P.R., Silva J.E., Kaplan M.M. Relationships between circulating and intracellular thyroid hormones: physiological and clinical implications. Endocr. Rev. 1981; 2; 87–102.</mixed-citation><mixed-citation xml:lang="en">Larsen P.R., Silva J.E., Kaplan M.M. Relationships between circulating and intracellular thyroid hormones: physiological and clinical implications. Endocr. Rev. 1981; 2; 87–102.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Fadeyev V.V., Morgunova T.B., Sytsh J.P., Melnichenko G.A. TSH and thyroid hormones concentrations in patients with hypothyroidism receiving replacement therapy with L-thyroxine alone or in combination with L-triiodthyronine. HORMONES 2005; 4 (2): 101–107.</mixed-citation><mixed-citation xml:lang="en">Fadeyev V.V., Morgunova T.B., Sytsh J.P., Melnichenko G.A. TSH and thyroid hormones concentrations in patients with hypothyroidism receiving replacement therapy with L-thyroxine alone or in combination with L-triiodthyronine. HORMONES 2005; 4 (2): 101–107.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Saravanan P., Chau W.F., Roberts N. et al. Psychological well- being in patients on adequate doses of L-thyroxine: results of a large, controlled community-based questionnaire study. Clin. Endocrinol. (Oxf.) 2002; 57; 577–585.</mixed-citation><mixed-citation xml:lang="en">Saravanan P., Chau W.F., Roberts N. et al. Psychological well- being in patients on adequate doses of L-thyroxine: results of a large, controlled community-based questionnaire study. Clin. Endocrinol. (Oxf.) 2002; 57; 577–585.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Visser W.E., Friesema E.C., Visser T.J. Thyroid hormone transporters: the knowns and the unknowns. Mol. Endocrinol. 2011; 25: 1–14.</mixed-citation><mixed-citation xml:lang="en">Visser W.E., Friesema E.C., Visser T.J. Thyroid hormone transporters: the knowns and the unknowns. Mol. Endocrinol. 2011; 25: 1–14.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang J., Lazar M.A. The mechanism of action of thyroid hormones. Ann. Rev. Physiol. 2000; 62: 439–466.</mixed-citation><mixed-citation xml:lang="en">Zhang J., Lazar M.A. The mechanism of action of thyroid hormones. Ann. Rev. Physiol. 2000; 62: 439–466.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Ramadan W., Marsili A., Larsen P.R. et al. Type-2 iodothyronine 5-deiodinase in skeletal muscle of C57BL/6 mice. I. Identity, subcellular localization, and characterization. Endocrinology 2011; 152: 3082–3092.</mixed-citation><mixed-citation xml:lang="en">Ramadan W., Marsili A., Larsen P.R. et al. Type-2 iodothyronine 5-deiodinase in skeletal muscle of C57BL/6 mice. I. Identity, subcellular localization, and characterization. Endocrinology 2011; 152: 3082–3092.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Galton V.A. The roles of the iodothyronine deiodinases in mammalian development. Thyroid 2005; 15: 823–834.</mixed-citation><mixed-citation xml:lang="en">Galton V.A. The roles of the iodothyronine deiodinases in mammalian development. Thyroid 2005; 15: 823–834.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Medina M.C., Molina J., Gadea Y. et al. The thyroid hormone-in- activating type III deiodinase is expressed in mouse and human β-cells and its targeted inactivation impairs insulin secretion. Endocrinology 2011; 152: 3717–3727.</mixed-citation><mixed-citation xml:lang="en">Medina M.C., Molina J., Gadea Y. et al. The thyroid hormone-in- activating type III deiodinase is expressed in mouse and human β-cells and its targeted inactivation impairs insulin secretion. Endocrinology 2011; 152: 3717–3727.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Huang S.A., Bianco A.C. Reawakened interest in type III iodothyronine deiodinase in critical illness and injury. Nat. Clin. Pract. Endocrinol. Metab. 2008; 4: 148–155.</mixed-citation><mixed-citation xml:lang="en">Huang S.A., Bianco A.C. Reawakened interest in type III iodothyronine deiodinase in critical illness and injury. Nat. Clin. Pract. Endocrinol. Metab. 2008; 4: 148–155.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Gullo D., Latina A., Frasca F. et al. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One 2011; 6: e22552.</mixed-citation><mixed-citation xml:lang="en">Gullo D., Latina A., Frasca F. et al. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One 2011; 6: e22552.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Bianco A.C., Salvatore D., Gereben B. et al. Biochemistry, cellular and molecular biology and physiological roles of the iodothyronine selenodeiodinases. Endocr. Rev. 2002; 23: 38–89.</mixed-citation><mixed-citation xml:lang="en">Bianco A.C., Salvatore D., Gereben B. et al. Biochemistry, cellular and molecular biology and physiological roles of the iodothyronine selenodeiodinases. Endocr. Rev. 2002; 23: 38–89.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Schneider M.J., Fiering S.N., Pallud S.E. et al. Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. Mol. Endocrinol. 2001; 15: 2137–2148.</mixed-citation><mixed-citation xml:lang="en">Schneider M.J., Fiering S.N., Pallud S.E. et al. Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. Mol. Endocrinol. 2001; 15: 2137–2148.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Escobar-Morreale H.F., Obregón M.J., Escobar del Rey F., Morreale de Escobar G. Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats. J. Clin. Invest. 1995; 96: 2828–2838.</mixed-citation><mixed-citation xml:lang="en">Escobar-Morreale H.F., Obregón M.J., Escobar del Rey F., Morreale de Escobar G. Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats. J. Clin. Invest. 1995; 96: 2828–2838.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Andersen S., Bruun N.H., Pedersen K.M., Laurberg P. Biologic variation is important for interpretation of thyroid function tests. Thyroid 2003; 13: 1069–1078.</mixed-citation><mixed-citation xml:lang="en">Andersen S., Bruun N.H., Pedersen K.M., Laurberg P. Biologic variation is important for interpretation of thyroid function tests. Thyroid 2003; 13: 1069–1078.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Bianco A.C., Silva J.E. Cold exposure rapidly induces virtual saturation of brown adipose tissue nuclear T3 receptors. Am. J. Physiol. 1988; 255: 496–503.</mixed-citation><mixed-citation xml:lang="en">Bianco A.C., Silva J.E. Cold exposure rapidly induces virtual saturation of brown adipose tissue nuclear T3 receptors. Am. J. Physiol. 1988; 255: 496–503.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Dumitrescu A.M., Liao X.H., Abdullah M.S. et al. Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nat. Gen. 2005; 37: 1247–1252.</mixed-citation><mixed-citation xml:lang="en">Dumitrescu A.M., Liao X.H., Abdullah M.S. et al. Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nat. Gen. 2005; 37: 1247–1252.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Schneider M.J., Fiering S.N., Thai B. et al. Targeted disruption of the type 1 selenodeiodinase gene (Dio1) results in marked changes in thyroid hormone economy in mice. Endocrinology 2006; 147: 580–589.</mixed-citation><mixed-citation xml:lang="en">Schneider M.J., Fiering S.N., Thai B. et al. Targeted disruption of the type 1 selenodeiodinase gene (Dio1) results in marked changes in thyroid hormone economy in mice. Endocrinology 2006; 147: 580–589.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Dayan C.M., Panicker V. Novel insights into thyroid hormones from the study of common genetic variation. Nat. Rev. Endocrinol. 2009; 5: 211–218.</mixed-citation><mixed-citation xml:lang="en">Dayan C.M., Panicker V. Novel insights into thyroid hormones from the study of common genetic variation. Nat. Rev. Endocrinol. 2009; 5: 211–218.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">De Jong F.J., Peeters R.P., den Heijer T. et al. The association of polymorphisms in the type 1 and 2 deiodinase genes with circulating thyroid hormone parameters and atrophy of the medial temporal lobe. J. Clin. Endocrinol. Metab. 2007; 92: 636–640.</mixed-citation><mixed-citation xml:lang="en">De Jong F.J., Peeters R.P., den Heijer T. et al. The association of polymorphisms in the type 1 and 2 deiodinase genes with circulating thyroid hormone parameters and atrophy of the medial temporal lobe. J. Clin. Endocrinol. Metab. 2007; 92: 636–640.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Crantz F.R., Silva J.E., Larsen P.R. Analysis of the sources and quantity of 3,5,3-triiodothyronine specifically bound to nuclear receptors in rat cerebral cortex and cerebellum. Endocrinology 1982; 110: 367–375.</mixed-citation><mixed-citation xml:lang="en">Crantz F.R., Silva J.E., Larsen P.R. Analysis of the sources and quantity of 3,5,3-triiodothyronine specifically bound to nuclear receptors in rat cerebral cortex and cerebellum. Endocrinology 1982; 110: 367–375.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Canani L.H., Capp C., Dora J.M. et al. The type 2 deiodinase A/G (Thr92Ala) polymorphism is associated with decreased enzyme velocity and increased insulin resistance in patients with type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 2005; 90: 3472–3478.</mixed-citation><mixed-citation xml:lang="en">Canani L.H., Capp C., Dora J.M. et al. The type 2 deiodinase A/G (Thr92Ala) polymorphism is associated with decreased enzyme velocity and increased insulin resistance in patients with type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 2005; 90: 3472–3478.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Dora J.M., Machado W.E., Rheinheimer J. et al. Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case-control study and meta-analysis. Eur. J. Endocrinol. 2010; 163: 427–434.</mixed-citation><mixed-citation xml:lang="en">Dora J.M., Machado W.E., Rheinheimer J. et al. Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case-control study and meta-analysis. Eur. J. Endocrinol. 2010; 163: 427–434.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Guo T.W., Zhang F.C., Yang M.S. et al. Positive association of the DIO2 (deiodinase type 2) gene with mental retardation in the iodine-deficient areas of China. J. Med. Genet. 2004; 41: 585–590.</mixed-citation><mixed-citation xml:lang="en">Guo T.W., Zhang F.C., Yang M.S. et al. Positive association of the DIO2 (deiodinase type 2) gene with mental retardation in the iodine-deficient areas of China. J. Med. Genet. 2004; 41: 585–590.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Gumieniak O., Perlstein T.S., Williams J.S. et al. Ala92 type 2 deio- dinase allele increases risk for the development of hypertension. Hypertension 2007; 49: 461–466.</mixed-citation><mixed-citation xml:lang="en">Gumieniak O., Perlstein T.S., Williams J.S. et al. Ala92 type 2 deio- dinase allele increases risk for the development of hypertension. Hypertension 2007; 49: 461–466.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Meulenbelt I., Min J.L., Bos S. et al. Identification of DIO2 as new susceptibility locus for symptomatic osteoarthritis. Hum. Mol. Genet. 2008; 17: 1867–1875.</mixed-citation><mixed-citation xml:lang="en">Meulenbelt I., Min J.L., Bos S. et al. Identification of DIO2 as new susceptibility locus for symptomatic osteoarthritis. Hum. Mol. Genet. 2008; 17: 1867–1875.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">He B., Li J., Wang G. et al. Association of genetic polymorphisms in the type II deiodinase gene with bipolar disorder in a subset of Chinese population. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2009; 33: 986–990.</mixed-citation><mixed-citation xml:lang="en">He B., Li J., Wang G. et al. Association of genetic polymorphisms in the type II deiodinase gene with bipolar disorder in a subset of Chinese population. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2009; 33: 986–990.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Torlontano M., Durante C., Torrente I. et al. Type 2 deiodinase polymorphism (Thr92Ala) predicts L-thyroxine dose to achieve target TSH levels in thyroidectomized patients. J. Clin. Endocrinol. Metab. 2008; 93: 910–913.</mixed-citation><mixed-citation xml:lang="en">Torlontano M., Durante C., Torrente I. et al. Type 2 deiodinase polymorphism (Thr92Ala) predicts L-thyroxine dose to achieve target TSH levels in thyroidectomized patients. J. Clin. Endocrinol. Metab. 2008; 93: 910–913.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Butler P.W., Smith S.M., Linderman J.D. et al. The Thr92Ala 5-type 2 de-iodinase gene polymorphism is associated with a delayed triiodothyronine secretion in response to the thyrotropin-releasing hormone-stimulation test: a pharmacogenomic study. Thyroid. 2011; 20: 1407–1412.</mixed-citation><mixed-citation xml:lang="en">Butler P.W., Smith S.M., Linderman J.D. et al. The Thr92Ala 5-type 2 de-iodinase gene polymorphism is associated with a delayed triiodothyronine secretion in response to the thyrotropin-releasing hormone-stimulation test: a pharmacogenomic study. Thyroid. 2011; 20: 1407–1412.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Ng L., Lyubarsky A., Nikonov S.S. et al. Type 3 deiodinase, a thy- roidhormone-inactivating enzyme, controls survival and matura- tion of cone photoreceptors. // J. Neurosci. 2010; 30: 3347–3357.</mixed-citation><mixed-citation xml:lang="en">Ng L., Lyubarsky A., Nikonov S.S. et al. Type 3 deiodinase, a thy- roidhormone-inactivating enzyme, controls survival and matura- tion of cone photoreceptors. // J. Neurosci. 2010; 30: 3347–3357.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Mohacsik P., Zeold A., Bianco A.C., Gereben B. Thyroid hormone and the neuroglia: both source and target. J. Thyroid. Res. 2011; 2011: 215718.</mixed-citation><mixed-citation xml:lang="en">Mohacsik P., Zeold A., Bianco A.C., Gereben B. Thyroid hormone and the neuroglia: both source and target. J. Thyroid. Res. 2011; 2011: 215718.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Dumitrescu A.M., Liao X.H., Best T.B. et al. A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am. J. Hum. Genet. 2004; 74: 168–175.</mixed-citation><mixed-citation xml:lang="en">Dumitrescu A.M., Liao X.H., Best T.B. et al. A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am. J. Hum. Genet. 2004; 74: 168–175.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Sugiyama D., Kusuhara H., Taniguchi H. et al. Functional charac- terization of rat brain-specific organic anion transporter (Oatp14) at the blood-brain barrier: high affinity transporter for thyroxine. J. Biol. Chem. 2003; 278: 43489–43495.</mixed-citation><mixed-citation xml:lang="en">Sugiyama D., Kusuhara H., Taniguchi H. et al. Functional charac- terization of rat brain-specific organic anion transporter (Oatp14) at the blood-brain barrier: high affinity transporter for thyroxine. J. Biol. Chem. 2003; 278: 43489–43495.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Van der Deure W., Appelhof B.C., Peeters R.P. et al. Polymorphism in the brain-specific thyroid hormone transporter OATP-C1 are associated with fatigue and depression in hypothyroid patients. Clin. Endocrinol. 2008; 69: 804–811.</mixed-citation><mixed-citation xml:lang="en">Van der Deure W., Appelhof B.C., Peeters R.P. et al. Polymorphism in the brain-specific thyroid hormone transporter OATP-C1 are associated with fatigue and depression in hypothyroid patients. Clin. Endocrinol. 2008; 69: 804–811.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Canaris G.J., Manowitz N.R., Mayor G., Ridgway E.C. The Colorado thyroid disease prevalence study. Arch. Intern. Med. 2000; 28: 526–534.</mixed-citation><mixed-citation xml:lang="en">Canaris G.J., Manowitz N.R., Mayor G., Ridgway E.C. The Colorado thyroid disease prevalence study. Arch. Intern. Med. 2000; 28: 526–534.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Katon W., Schulberg H. Epidemiology of depression in primary care. Gen Hosp. Psychiatry 1992; 14: 237–247.</mixed-citation><mixed-citation xml:lang="en">Katon W., Schulberg H. Epidemiology of depression in primary care. Gen Hosp. Psychiatry 1992; 14: 237–247.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Paunkovic N., Paunkovic J., Pavlovic O., Paunovic Z. The significant increase in incidence of Graves' disease in eastern Serbia during the civil war in the former Yugoslavia (1992 to 1995). Thyroid. 1998; 8: 37–41.</mixed-citation><mixed-citation xml:lang="en">Paunkovic N., Paunkovic J., Pavlovic O., Paunovic Z. The significant increase in incidence of Graves' disease in eastern Serbia during the civil war in the former Yugoslavia (1992 to 1995). Thyroid. 1998; 8: 37–41.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Louwerens M., Appelhof B.C., Verloop H. et al. Fatigue and fatigue- related symptoms in patients treated for different causes of hypothyroidism. Eur. J. Endocrinol. 2012; Sep (in press).</mixed-citation><mixed-citation xml:lang="en">Louwerens M., Appelhof B.C., Verloop H. et al. Fatigue and fatigue- related symptoms in patients treated for different causes of hypothyroidism. Eur. J. Endocrinol. 2012; Sep (in press).</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Walsh J. P., Ward L. C., Burke V. et al. Small changes in thyroxine dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life: results of a double-blind, randomized clinical trial. J. Clin. Endocrinol. Metab. 2006; 91: 2624–2630.</mixed-citation><mixed-citation xml:lang="en">Walsh J. P., Ward L. C., Burke V. et al. Small changes in thyroxine dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life: results of a double-blind, randomized clinical trial. J. Clin. Endocrinol. Metab. 2006; 91: 2624–2630.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Подзолков А.В., Фадеев В.В. Оценка динамики показателей липидного спектра и ранних предикторов эндотелиальной дисфункции при первичным гипотиреозе в зависимости от уровня ТТГ в пределах референсного диапазона. Клин. и экспер. тиреоидол. 2010; 3: 54–59.</mixed-citation><mixed-citation xml:lang="en">Подзолков А.В., Фадеев В.В. Оценка динамики показателей липидного спектра и ранних предикторов эндотелиальной дисфункции при первичным гипотиреозе в зависимости от уровня ТТГ в пределах референсного диапазона. Клин. и экспер. тиреоидол. 2010; 3: 54–59.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Подзолков А.В., Фадеев В.В. Высоко- и низконормальный уровень ТТГ: клиническая картина, психоэмоциональная сфера и качество жизни пациентов с гипотиреозом. Клин. и экспер. тиреоидол. 2010; 4: 58–68.</mixed-citation><mixed-citation xml:lang="en">Подзолков А.В., Фадеев В.В. Высоко- и низконормальный уровень ТТГ: клиническая картина, психоэмоциональная сфера и качество жизни пациентов с гипотиреозом. Клин. и экспер. тиреоидол. 2010; 4: 58–68.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Bunevicius R., Kazanavicius G., Zalinkevicius R., Prange A.J. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. Engl. J. Med. 1999; 340: 424–429.</mixed-citation><mixed-citation xml:lang="en">Bunevicius R., Kazanavicius G., Zalinkevicius R., Prange A.J. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. Engl. J. Med. 1999; 340: 424–429.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Bunevicius R., Jakubonien N., Jurkevicius R. et al. Thyroxine vs. thyroxine plus triiodothyronine in treatment of hypothyroidism after thyroidectomy for Graves’ disease. Endocrine 2002; 18: 129–133.</mixed-citation><mixed-citation xml:lang="en">Bunevicius R., Jakubonien N., Jurkevicius R. et al. Thyroxine vs. thyroxine plus triiodothyronine in treatment of hypothyroidism after thyroidectomy for Graves’ disease. Endocrine 2002; 18: 129–133.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</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. Eur. J. Endocrinol. 2009; 161: 895–902.</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. Eur. J. Endocrinol. 2009; 161: 895–902.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Grozinsky-Glasberg S., Fraser A., Nahshoni E. et al. Thyroxine-tri- iodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials. J. Clin. Endocrinol. Metab. 2006; 91: 2592–2599.</mixed-citation><mixed-citation xml:lang="en">Grozinsky-Glasberg S., Fraser A., Nahshoni E. et al. Thyroxine-tri- iodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials. J. Clin. Endocrinol. Metab. 2006; 91: 2592–2599.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Garber J.R., Cobin R.H., Gharib H. et al. Clinical Practice Guidelines for Hypothyroidism in Adults: Co-sponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr. Pract. 2012; 11: 1–207.</mixed-citation><mixed-citation xml:lang="en">Garber J.R., Cobin R.H., Gharib H. et al. Clinical Practice Guidelines for Hypothyroidism in Adults: Co-sponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr. Pract. 2012; 11: 1–207.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Wiersinga W., Duntas L., Fadeyev V. et al. The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism. Eur. Thyroid. J. 2012; 1: 55–71.</mixed-citation><mixed-citation xml:lang="en">Wiersinga W., Duntas L., Fadeyev V. et al. The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism. Eur. Thyroid. J. 2012; 1: 55–71.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Фадеев В.В. По материалам клинических рекомендаций Европейской тиреоидной ассоциации по использованию комбинированной терапии L-T4 + L-T3 в лечении гипотиреоза. Клин. и экспер. тиреоидол. 2012; 2: 14–18.</mixed-citation><mixed-citation xml:lang="en">Фадеев В.В. По материалам клинических рекомендаций Европейской тиреоидной ассоциации по использованию комбинированной терапии L-T4 + L-T3 в лечении гипотиреоза. Клин. и экспер. тиреоидол. 2012; 2: 14–18.</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Fadeyev V.V., Morgunova T.B., Melnichenko G.A., Dedov I.I. Combined therapy with L-Thyroxine and L-Triiodothyronine compared to L-Thyroxine alone in the treatment of primary hypothyroidism. Hormones (Athens) 2010; 9: 245–252.</mixed-citation><mixed-citation xml:lang="en">Fadeyev V.V., Morgunova T.B., Melnichenko G.A., Dedov I.I. Combined therapy with L-Thyroxine and L-Triiodothyronine compared to L-Thyroxine alone in the treatment of primary hypothyroidism. Hormones (Athens) 2010; 9: 245–252.</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Panicker V., Saravanan P., Vaidya B. et al. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. J. Clin. Endocrinol. Metab. 2009; 94: 1623–1629.</mixed-citation><mixed-citation xml:lang="en">Panicker V., Saravanan P., Vaidya B. et al. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. J. Clin. Endocrinol. Metab. 2009; 94: 1623–1629.</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Hollowell J.G., Staehling N.W., Flanders W.D. et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J. Clin. Endocrinol. Metab. 2002; 87: 489–499.</mixed-citation><mixed-citation xml:lang="en">Hollowell J.G., Staehling N.W., Flanders W.D. et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J. Clin. Endocrinol. Metab. 2002; 87: 489–499.</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Völzke H., Schmidt C.O., John U. et al. Reference levels for serum thyroid function tests of diagnostic and prognostic significance. Horm. Metab. Res. 2010; 42: 809–814.</mixed-citation><mixed-citation xml:lang="en">Völzke H., Schmidt C.O., John U. et al. Reference levels for serum thyroid function tests of diagnostic and prognostic significance. Horm. Metab. Res. 2010; 42: 809–814.</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Фадеев В.В., Берковская М.А., Мельниченко Г.А. Результаты опроса эндокринологов по проблемам нарушения функции щитовидной железы. Клин. и экспер. тиреоидол. 2008; 2: 41–47.</mixed-citation><mixed-citation xml:lang="en">Фадеев В.В., Берковская М.А., Мельниченко Г.А. Результаты опроса эндокринологов по проблемам нарушения функции щитовидной железы. Клин. и экспер. тиреоидол. 2008; 2: 41–47.</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Свиридонова М.А., Фадеев В.В., Ильин А.В. Циркадианная и индивидуальная вариабельность уровня ТТГ и тиреоидных гормонов у лиц с субклиническим гипотиреозом. Клин. и экспер. тиреоидол. 2010; 3: 35–41.</mixed-citation><mixed-citation xml:lang="en">Свиридонова М.А., Фадеев В.В., Ильин А.В. Циркадианная и индивидуальная вариабельность уровня ТТГ и тиреоидных гормонов у лиц с субклиническим гипотиреозом. Клин. и экспер. тиреоидол. 2010; 3: 35–41.</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Свиридонова М.А., Ильин А.В., Фадеев В.В. Циркадианная и индивидуальная вариабельность уровня ТТГ у лиц, получающих заместительную терапию гипотиреоза. Клин. и экспер. тиреоидол. 2010; 4: 52–57.</mixed-citation><mixed-citation xml:lang="en">Свиридонова М.А., Ильин А.В., Фадеев В.В. Циркадианная и индивидуальная вариабельность уровня ТТГ у лиц, получающих заместительную терапию гипотиреоза. Клин. и экспер. тиреоидол. 2010; 4: 52–57.</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Свиридонова М.А., Ильин А.В., Фадеев В.В. Циркадианная вариабельность уровня ТТГ на фоне супрессивной терапии левотироксином. Клин. и экспер. тиреоидол. 2011; 1: 55–57.</mixed-citation><mixed-citation xml:lang="en">Свиридонова М.А., Ильин А.В., Фадеев В.В. Циркадианная вариабельность уровня ТТГ на фоне супрессивной терапии левотироксином. Клин. и экспер. тиреоидол. 2011; 1: 55–57.</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Stagnaro-Green A., Abalovich M., Alexander E. et al. Guidelines of the American thyroid association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011; 21 (21): 1081–1125.</mixed-citation><mixed-citation xml:lang="en">Stagnaro-Green A., Abalovich M., Alexander E. et al. Guidelines of the American thyroid association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011; 21 (21): 1081–1125.</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Фадеев В.В. По материалам клинических рекомендаций по диагностике и лечению заболеваний щитовидной железы во время беременности и в послеродовом периоде Американской тиреоидной ассоциации. Клин. и экспер. тиреоидол. 2012; 1: 7–18.</mixed-citation><mixed-citation xml:lang="en">Фадеев В.В. По материалам клинических рекомендаций по диагностике и лечению заболеваний щитовидной железы во время беременности и в послеродовом периоде Американской тиреоидной ассоциации. Клин. и экспер. тиреоидол. 2012; 1: 7–18.</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">De Groot L., Abalovich M., Alexander E.K. et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 2012, 97: 2543–2565.</mixed-citation><mixed-citation xml:lang="en">De Groot L., Abalovich M., Alexander E.K. et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 2012, 97: 2543–2565.</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>
