cardiotomskСибирский журнал клинической и экспериментальной медициныSiberian Journal of Clinical and Experimental Medicine2713-29272713-265XTSU publishing10.29001/2073-8552-2022-37-3-90-97cardiotomsk-1507Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESФундаментальные и клинические аспекты заболеваний щитовидной железы и новые подходы для их лечения (обзор литературы)Thyroid diseases and new approaches for their treatmenthttps://orcid.org/0000-0003-2680-1909ФокинаЕ. А.FokinaE. A.

Фокина Екатерина Александровна, младший научный сотрудник, аспирант

194223, Санкт-Петербург, пр. Тореза, 44

Ekaterina A. Fokina, Junior Research Scientist, Post-Graduate Student

44, Toreza ave, Saint Petersburg, 194223

fokina-katrina@yandex.ruhttps://orcid.org/0000-0002-4293-3162ШпаковА. О.ShpakovA. O.

Шпаков Александр Олегович, д-р биол. наук, заведующий лабораторией молекулярной эндокринологии и нейрохимии

194223, Санкт-Петербург, пр. Тореза, 44

Alexander O. Shpakov, Dr. Sci. (Biol.), Head of the Laboratory of Molecular Endocrinology and Neurochemistry

44, Toreza ave, Saint Petersburg, 194223

alex_shpakov@list.ruИнститут эволюционной физиологии и биохимии имени И.М. Сеченова Российской академии наукРоссияSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesRussian Federation2022201020223739097Copyright © Фокина Е.А., Шпаков А.О., 20222022Фокина Е.А., Шпаков А.О.Fokina E.A., Shpakov A.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sibjcem.ru/jour/article/view/1507

Распространенность заболеваний щитовидной железы (ЩЖ), в том числе аутоиммунного гипертиреоза (болезни Грейвса), аутоиммунного тиреоидита, различных форм тиреоидного рака, с каждым годом возрастает, в то время как эффективность их лечения по-прежнему остается низкой и ограничивается в основном заместительной терапией тиреоидными гормонами и хирургическими и радиоизотопными методами. В настоящем обзоре представлено современное состояние проблемы фармакологической коррекции заболеваний ЩЖ, рассмотрены новые подходы, направленные на регуляцию функциональной активности компонентов системы синтеза тиреоидных гормонов в фолликулярных клетках ЩЖ, включая его начальный, сенсорный, компонент – рецептор тиреотропного гормона. Среди препаратов, которые разрабатываются в настоящее время, необходимо выделить аллостерические регуляторы рецептора тиреотропного гормона, специфичные к нему антитела, а также селективные агонисты β-изоформы рецепторов тиреоидных гормонов.

The prevalence of thyroid diseases including autoimmune hyperthyroidism (Graves’ disease), autoimmune thyroiditis, and different forms of thyroid cancer is increasing every year, while the effectiveness of their treatment remains low and is limited, mainly, to replacement therapy with thyroid hormones and surgical and radioisotope methods. This review presents the current state of the problem of pharmacological correction in thyroid diseases including new approaches to the regulation of the functional activity of the components of the thyroid hormone synthesis system in thyroid follicular cells, in particular, its initial, sensory component, the thyroid-stimulating hormone receptor. Among the drugs that are currently being developed, it is necessary to focus on allosteric regulators of the thyroid-stimulating hormone receptor, specific antibodies to it, as well as selective agonists of the β-isoform of thyroid hormone receptors.

щитовидная железарецептор тиреотропного гормонатиреоидные гормоныфармакотерапияантитиреоидные препаратыthyroid glandthyroid-stimulating hormone receptorthyroid hormonespharmacotherapyantithyroid drugsРабота поддержана Российским научным фондом (проект № 19-75-20122).ReferencesGBD 2017 Mortality Collaborators. Global, regional, and national age-sex-specifi c mortality and life expectancy, 1950–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1684–1735. DOI: 10.1016/S0140-6736(18)31891-9.GBD 2017 Mortality Collaborators. Global, regional, and national age-sex-specifi c mortality and life expectancy, 1950–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1684–1735. DOI: 10.1016/S0140-6736(18)31891-9.Vanderpump M.P.J. Epidemiology of thyroid disorders. In: Luster M., Duntas L., Wartofsky L. (eds.). The thyroid and its diseases. Springer International Publishing AG; 2019:75–85. DOI: 10.1007/978-3-319-72102-6_6.Vanderpump M.P.J. Epidemiology of thyroid disorders. In: Luster M., Duntas L., Wartofsky L. (eds.). The thyroid and its diseases. Springer International Publishing AG; 2019:75–85. DOI: 10.1007/978-3-319-72102-6_6.Vanderpump M.P. The epidemiology of thyroid disease. Br. Med. Bull. 2011;99:39–51. DOI: 10.1093/bmb/ldr030.Vanderpump M.P. The epidemiology of thyroid disease. Br. Med. Bull. 2011;99:39–51. DOI: 10.1093/bmb/ldr030.Chaker L., Razvi S., Bensenor I.M., Azizi F., Pearce E.N., Peeters R.P. Hypothyroidism Nat. Rev. Dis. Primers. 2022;8(1):30. DOI: 10.1038/s41572-022-00357-7.Chaker L., Razvi S., Bensenor I.M., Azizi F., Pearce E.N., Peeters R.P. Hypothyroidism Nat. Rev. Dis. Primers. 2022;8(1):30. DOI: 10.1038/s41572-022-00357-7.Burch H.B., Cooper D.S. Management of Graves Disease: A Review. JAMA. 2015;314(23):2544–2554. DOI: 10.1001/jama.2015.16535.Burch H.B., Cooper D.S. Management of Graves Disease: A Review. JAMA. 2015;314(23):2544–2554. DOI: 10.1001/jama.2015.16535.Wémeau J.L., Klein M., Sadoul J.L., Briet C., Vélayoudom-Céphise F.L. Graves’ disease: Introduction, epidemiology, endogenous and environmental pathogenic factors. Ann. Endocrinol. (Paris). 2018;79(6):599–607. DOI: 10.1016/j.ando.2018.09.002.Wémeau J.L., Klein M., Sadoul J.L., Briet C., Vélayoudom-Céphise F.L. Graves’ disease: Introduction, epidemiology, endogenous and environmental pathogenic factors. Ann. Endocrinol. (Paris). 2018;79(6):599–607. DOI: 10.1016/j.ando.2018.09.002.Brix T.H., Kyvik K.O., Christensen K., Hegedüs L. Evidence for a major role of heredity in Graves’ disease: a population-based study of two Danish twin cohorts. J. Clin. Endocrinol. Metab. 2001;86(2):930–934. DOI: 10.1210/jcem.86.2.7242.Brix T.H., Kyvik K.O., Christensen K., Hegedüs L. Evidence for a major role of heredity in Graves’ disease: a population-based study of two Danish twin cohorts. J. Clin. Endocrinol. Metab. 2001;86(2):930–934. DOI: 10.1210/jcem.86.2.7242.Antonelli A., Ferrari S.M., Ragusa F., Elia G., Paparo S.R., Ruffi lli I. et al. Graves’ disease: Epidemiology, genetic and environmental risk factors and viruses. Best Pract. Res. Clin. Endocrinol. Metab. 2020;34(1):101387. DOI: 10.1016/j.beem.2020.101387.Antonelli A., Ferrari S.M., Ragusa F., Elia G., Paparo S.R., Ruffi lli I. et al. Graves’ disease: Epidemiology, genetic and environmental risk factors and viruses. Best Pract. Res. Clin. Endocrinol. Metab. 2020;34(1):101387. DOI: 10.1016/j.beem.2020.101387.Kisiel B., Bednarczuk T., Kostrzewa G., Kosińska J., Miśkiewicz P., Płazińska M.T. et al. Polymorphism of the oestrogen receptor beta gene (ESR2) is associated with susceptibility to Graves’ disease. Clin. Endocrinol. (Oxf.). 2008;68(3):429–434. DOI: 10.1111/j.1365-2265.2007.03060.x.Kisiel B., Bednarczuk T., Kostrzewa G., Kosińska J., Miśkiewicz P., Płazińska M.T. et al. Polymorphism of the oestrogen receptor beta gene (ESR2) is associated with susceptibility to Graves’ disease. Clin. Endocrinol. (Oxf.). 2008;68(3):429–434. DOI: 10.1111/j.1365-2265.2007.03060.x.Cury S.S., Oliveira M., Síbio M.T., Clara S., Luvizotto Rd. A., Conde S. et al. Gene expression of estrogen receptor-alpha in orbital fi broblasts in Graves’ ophthalmopathy. Arch. Endocrinol. Metab. 2015;59(3):273–276. DOI: 10.1590/2359-3997000000050.Cury S.S., Oliveira M., Síbio M.T., Clara S., Luvizotto Rd. A., Conde S. et al. Gene expression of estrogen receptor-alpha in orbital fi broblasts in Graves’ ophthalmopathy. Arch. Endocrinol. Metab. 2015;59(3):273–276. DOI: 10.1590/2359-3997000000050.Brix T.H., Knudsen G.P., Kristiansen M., Kyvik K.O., Orstavik K.H., Hegedüs L. High frequency of skewed X-chromosome inactivation in females with autoimmune thyroid disease: A possible explanation for the female predisposition to thyroid autoimmunity. J. Clin. Endocrinol. Metab. 2005;90(11):5949–5953. DOI: 10.1210/jc.2005-1366.Brix T.H., Knudsen G.P., Kristiansen M., Kyvik K.O., Orstavik K.H., Hegedüs L. High frequency of skewed X-chromosome inactivation in females with autoimmune thyroid disease: A possible explanation for the female predisposition to thyroid autoimmunity. J. Clin. Endocrinol. Metab. 2005;90(11):5949–5953. DOI: 10.1210/jc.2005-1366.Simmonds M.J., Kavvoura F.K., Brand O.J., Newby P.R., Jackson L.E., Hargreaves C.E. et al. Skewed X chromosome inactivation and female preponderance in autoimmune thyroid disease: An association study and meta-analysis. J. Clin. Endocrinol. Metab. 2014;99(1):E127–E131. DOI: 10.1210/jc.2013-2667.Simmonds M.J., Kavvoura F.K., Brand O.J., Newby P.R., Jackson L.E., Hargreaves C.E. et al. Skewed X chromosome inactivation and female preponderance in autoimmune thyroid disease: An association study and meta-analysis. J. Clin. Endocrinol. Metab. 2014;99(1):E127–E131. DOI: 10.1210/jc.2013-2667.Ferrari S.M., Fallahi P., Antonelli A., Benvenga S. Environmental issues in thyroid diseases. Front. Endocrinol. (Lausanne). 2017;8:50. DOI: 10.3389/fendo.2017.00050.Ferrari S.M., Fallahi P., Antonelli A., Benvenga S. Environmental issues in thyroid diseases. Front. Endocrinol. (Lausanne). 2017;8:50. DOI: 10.3389/fendo.2017.00050.Bürgi H. Iodine excess. Best Pract. Res. Clin. Endocrinol. Metab. 2010;24(1):107–115. DOI: 10.1016/j.beem.2009.08.010.Bürgi H. Iodine excess. Best Pract. Res. Clin. Endocrinol. Metab. 2010;24(1):107–115. DOI: 10.1016/j.beem.2009.08.010.Kahaly G.J., Bartalena L., Hegedüs L. The American Thyroid Association/American Association of Clinical Endocrinologists guidelines for hyperthyroidism and other causes of thyrotoxicosis: A European perspective. Thyroid. 2011;21(6):585–591. DOI: 10.1089/thy.2011.2106.ed3.Kahaly G.J., Bartalena L., Hegedüs L. The American Thyroid Association/American Association of Clinical Endocrinologists guidelines for hyperthyroidism and other causes of thyrotoxicosis: A European perspective. Thyroid. 2011;21(6):585–591. DOI: 10.1089/thy.2011.2106.ed3.Kahaly G.J., Bartalena L., Hegedüs L., Leenhardt L., Poppe K., Pearce S.H. 2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism. Eur. Thyroid J. 2018;7(4):167–186. DOI: 10.1159/000490384.Kahaly G.J., Bartalena L., Hegedüs L., Leenhardt L., Poppe K., Pearce S.H. 2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism. Eur. Thyroid J. 2018;7(4):167–186. DOI: 10.1159/000490384.Burch H.B., Cooper D.S. Antithyroid drug therapy: 70 years later. Eur. J. Endocrinol. 2018;179(5):R261–R274. DOI: 10.1530/EJE-18-0678.Burch H.B., Cooper D.S. Antithyroid drug therapy: 70 years later. Eur. J. Endocrinol. 2018;179(5):R261–R274. DOI: 10.1530/EJE-18-0678.Bartalena L., Piantanida E., Gallo D., Ippolito S., Tanda M.L. Management of Graves’ hyperthyroidism: Present and future. Expert Rev. Endocrinol. Metab. 2022;17(2):153–166. DOI: 10.1080/17446651.2022.2052044.Bartalena L., Piantanida E., Gallo D., Ippolito S., Tanda M.L. Management of Graves’ hyperthyroidism: Present and future. Expert Rev. Endocrinol. Metab. 2022;17(2):153–166. DOI: 10.1080/17446651.2022.2052044.Vos X.G., Endert E., Zwinderman A.H., Tijssen J.G., Wiersinga W.M. Predicting the risk of recurrence before the start of antithyroid drug therapy in patients with graves’ hyperthyroidism. J. Clin. Endocrinol. Metab. 2016;101(4):1381–1389. DOI: 10.1210/jc.2015-3644.Vos X.G., Endert E., Zwinderman A.H., Tijssen J.G., Wiersinga W.M. Predicting the risk of recurrence before the start of antithyroid drug therapy in patients with graves’ hyperthyroidism. J. Clin. Endocrinol. Metab. 2016;101(4):1381–1389. DOI: 10.1210/jc.2015-3644.Azizi F., Ataie L., Hedayati M., Mehrabi Y., Sheikholeslami F. Eff ect of long-term continuous methimazole treatment of hyperthyroidism: comparison with radioiodine. Eur. J. Endocrinol. 2005;152(5):695–701. DOI: 10.1530/eje.1.01904.Azizi F., Ataie L., Hedayati M., Mehrabi Y., Sheikholeslami F. Eff ect of long-term continuous methimazole treatment of hyperthyroidism: comparison with radioiodine. Eur. J. Endocrinol. 2005;152(5):695–701. DOI: 10.1530/eje.1.01904.Aung E.T., Zammitt N.N., Dover A.R., Strachan M.W.J., Seckl J.R., Gibb F.W. Predicting outcomes and complications following radioiodine therapy in Graves’ thyrotoxicosis. Clin. Endocrinol. (Oxf.). 2019;90(1):192– 199. DOI: 10.1111/cen.13873.Aung E.T., Zammitt N.N., Dover A.R., Strachan M.W.J., Seckl J.R., Gibb F.W. Predicting outcomes and complications following radioiodine therapy in Graves’ thyrotoxicosis. Clin. Endocrinol. (Oxf.). 2019;90(1):192– 199. DOI: 10.1111/cen.13873.Bonnema S.J., Hegedüs L. Radioiodine therapy in benign thyroid diseases: Eff ects, side eff ects, and factors aff ecting therapeutic outcome. Endocr. Rev. 2012;33(6):920–980. DOI: 10.1210/er.2012-1030.Bonnema S.J., Hegedüs L. Radioiodine therapy in benign thyroid diseases: Eff ects, side eff ects, and factors aff ecting therapeutic outcome. Endocr. Rev. 2012;33(6):920–980. DOI: 10.1210/er.2012-1030.Walter M.A., Briel M., Christ-Crain M., Bonnema S.J., Connell J., Cooper D.S. et al. Eff ects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials. BMJ. 2007;334(7592):514. DOI: 10.1136/bmj.39114.670150.BE.Walter M.A., Briel M., Christ-Crain M., Bonnema S.J., Connell J., Cooper D.S. et al. Eff ects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials. BMJ. 2007;334(7592):514. DOI: 10.1136/bmj.39114.670150.BE.Metso S., Jaatinen P., Huhtala H., Auvinen A., Oksala H., Salmi J. Increased cardiovascular and cancer mortality after radioiodine treatment for. J. Clin. Endocrinol. Metab. 2007;92(6):2190–2196. DOI: 10.1210/jc.2006-2321.Metso S., Jaatinen P., Huhtala H., Auvinen A., Oksala H., Salmi J. Increased cardiovascular and cancer mortality after radioiodine treatment for. J. Clin. Endocrinol. Metab. 2007;92(6):2190–2196. DOI: 10.1210/jc.2006-2321.Bartalena L., Piantanida E., Tanda M.L. Can a patient-tailored treatment approach for Graves’ disease reduce mortality? Lancet Diabetes Endocrinol. 2019;7(4):245–246. DOI: 10.1016/S2213-8587(19)30057-9.Bartalena L., Piantanida E., Tanda M.L. Can a patient-tailored treatment approach for Graves’ disease reduce mortality? Lancet Diabetes Endocrinol. 2019;7(4):245–246. DOI: 10.1016/S2213-8587(19)30057-9.Pearce S.H.S., Dayan C., Wraith D.C., Barrell K., Olive N., Jansson L. et al. Antigen-pecifi c Immunotherapy with Thyrotropin Receptor Peptides in Graves’ Hyperthyroidism: A Phase I Study. Thyroid. 2019;29(7):1003–1011. DOI: 10.1089/thy.2019.0036.Pearce S.H.S., Dayan C., Wraith D.C., Barrell K., Olive N., Jansson L. et al. Antigen-pecifi c Immunotherapy with Thyrotropin Receptor Peptides in Graves’ Hyperthyroidism: A Phase I Study. Thyroid. 2019;29(7):1003–1011. DOI: 10.1089/thy.2019.0036.Furmaniak J., Sanders J., Sanders P., Li Y., Rees Smith B. TSH receptor specifi c monoclonal autoantibody K1-70TM targeting of the TSH receptor in subjects with Graves› disease and Graves› orbitopathy – Results from a phase I clinical trial. Clin. Endocrinol. (Oxf.). 2022;96(6):878–887. DOI: 10.1111/cen.14681.Furmaniak J., Sanders J., Sanders P., Li Y., Rees Smith B. TSH receptor specifi c monoclonal autoantibody K1-70TM targeting of the TSH receptor in subjects with Graves› disease and Graves› orbitopathy – Results from a phase I clinical trial. Clin. Endocrinol. (Oxf.). 2022;96(6):878–887. DOI: 10.1111/cen.14681.Krause G., Eckstein A., Schülein R. Modulating TSH receptor signaling for therapeutic benefi t. Eur. Thyroid. J. 2020;9(1):66–77. DOI: 10.1159/000511871.Krause G., Eckstein A., Schülein R. Modulating TSH receptor signaling for therapeutic benefi t. Eur. Thyroid. J. 2020;9(1):66–77. DOI: 10.1159/000511871.Kang S.Y., Seo J., Kang H.R. Desensitization for the prevention of drug hypersensitivity reactions. Korean J. Intern. Med. 2022;37(2):261–270. DOI: 10.3904/kjim.2021.438.Kang S.Y., Seo J., Kang H.R. Desensitization for the prevention of drug hypersensitivity reactions. Korean J. Intern. Med. 2022;37(2):261–270. DOI: 10.3904/kjim.2021.438.Cox L. Grand challenges in allergen immunotherapy. Front. Allergy. 2021;2:710345. DOI: 10.3389/falgy.2021.710345.Cox L. Grand challenges in allergen immunotherapy. Front. Allergy. 2021;2:710345. DOI: 10.3389/falgy.2021.710345.Pavanello F., Zucca E., Ghielmini M. Rituximab: 13 open questions after 20-years of clinical use. Cancer Treat. Rev. 2017;53:38–46. DOI: 10.1016/j.ctrv.2016.11.015.Pavanello F., Zucca E., Ghielmini M. Rituximab: 13 open questions after 20-years of clinical use. Cancer Treat. Rev. 2017;53:38–46. DOI: 10.1016/j.ctrv.2016.11.015.Lane L.C., Cheetham T.D., Perros P., Pearce S.H.S. New therapeutic horizons for Graves’ hyperthyroidism. Endocr. Rev. 2020;41(6):873–884. DOI: 10.1210/endrev/bnaa022.Lane L.C., Cheetham T.D., Perros P., Pearce S.H.S. New therapeutic horizons for Graves’ hyperthyroidism. Endocr. Rev. 2020;41(6):873–884. DOI: 10.1210/endrev/bnaa022.El Fassi D., Nielsen C.H., Junker P., Hasselbalch H.C., Hegedüs L. Systemic adverse events following rituximab therapy in patients with Graves’ disease. J. Endocrinol. Invest. 2011;34(7):e163–e167. DOI: 10.3275/7411.El Fassi D., Nielsen C.H., Junker P., Hasselbalch H.C., Hegedüs L. Systemic adverse events following rituximab therapy in patients with Graves’ disease. J. Endocrinol. Invest. 2011;34(7):e163–e167. DOI: 10.3275/7411.Shpakov A.O. Endogenous and synthetic regulators of the peripheral components of the hypothalamo-hypophyseal-gonadal and – thyroid axes. Neurosci. Behav. Physi. 2021;51:332–345. DOI: 10.1007/s11055-021-01076-4.Shpakov A.O. Endogenous and synthetic regulators of the peripheral components of the hypothalamo-hypophyseal-gonadal and – thyroid axes. Neurosci. Behav. Physi. 2021;51:332–345. DOI: 10.1007/s11055-021-01076-4.Latif R., Realubit R.B., Karan C., Mezei M., Davies T.F. TSH receptor signaling abrogation by a novel small molecule. Front. Endocrinol. (Lausanne). 2016;7:130. DOI: 10.3389/fendo.2016.00130.Latif R., Realubit R.B., Karan C., Mezei M., Davies T.F. TSH receptor signaling abrogation by a novel small molecule. Front. Endocrinol. (Lausanne). 2016;7:130. DOI: 10.3389/fendo.2016.00130.Marcinkowski P., Kreuchwig A., Mendieta S., Hoyer I., Witte F., Furkert J. et al. Thyrotropin receptor: Allosteric modulators illuminate intramolecular signaling mechanisms at the interface of ecto- and transmembrane domain. Mol. Pharmacol. 2019;96(4):452–462. DOI: 10.1124/mol.119.116947.Marcinkowski P., Kreuchwig A., Mendieta S., Hoyer I., Witte F., Furkert J. et al. Thyrotropin receptor: Allosteric modulators illuminate intramolecular signaling mechanisms at the interface of ecto- and transmembrane domain. Mol. Pharmacol. 2019;96(4):452–462. DOI: 10.1124/mol.119.116947.Derkach K.V., Bakhtyukov A.A., Sorokoumov V.N., Shpakov A.O. New Thieno-[2,3-d]pyrimidine-based functional antagonist for the receptor of thyroid stimulating hormone. Dokl. Biochem. Biophys. 2020;491(1):77–80. DOI: 10.1134/S1607672920020064.Derkach K.V., Bakhtyukov A.A., Sorokoumov V.N., Shpakov A.O. New Thieno-[2,3-d]pyrimidine-based functional antagonist for the receptor of thyroid stimulating hormone. Dokl. Biochem. Biophys. 2020;491(1):77–80. DOI: 10.1134/S1607672920020064.Bakhtyukov A., Derkach K., Sorokoumov V., Fokina E., Shpakov A.O. The development of new low-molecular-weight allosteric antagonists of thyroid-stimulating hormone receptor and their eff ect on the basal and thyroliberin-stimulated production of thyroid hormones. FEBS Open Bio. 2021;11(1):87–88. DOI: 10.1002/2211-5463.13205.Bakhtyukov A., Derkach K., Sorokoumov V., Fokina E., Shpakov A.O. The development of new low-molecular-weight allosteric antagonists of thyroid-stimulating hormone receptor and their eff ect on the basal and thyroliberin-stimulated production of thyroid hormones. FEBS Open Bio. 2021;11(1):87–88. DOI: 10.1002/2211-5463.13205.Hollowell J.G., Staehling N.W., Flanders W.D., Hannon W.H., Gunter E.W., Spencer C.A. 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(2):489–499. DOI: 10.1210/jcem.87.2.8182.Hollowell J.G., Staehling N.W., Flanders W.D., Hannon W.H., Gunter E.W., Spencer C.A. 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(2):489–499. DOI: 10.1210/jcem.87.2.8182.Stoppa-Vaucher S., Van Vliet G., Deladoëy J. Variation by ethnicity in the prevalence of congenital hypothyroidism due to thyroid dysgenesis. Thyroid. 2011;21(1):13–18. DOI: 10.1089/thy.2010.0205.Stoppa-Vaucher S., Van Vliet G., Deladoëy J. Variation by ethnicity in the prevalence of congenital hypothyroidism due to thyroid dysgenesis. Thyroid. 2011;21(1):13–18. DOI: 10.1089/thy.2010.0205.Teumer A., Chaker L., Groeneweg S., Li Y., Di Munno C., Barbieri C. et al. Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. Nat. Commun. 2018;9(1):4455. DOI: 10.1038/s41467-018-06356-1.Teumer A., Chaker L., Groeneweg S., Li Y., Di Munno C., Barbieri C. et al. Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. Nat. Commun. 2018;9(1):4455. DOI: 10.1038/s41467-018-06356-1.Garber J.R., Cobin R.H., Gharib H., Hennessey J.V., Klein I., Mechanick J.I. et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr. Pract. 2012;18(6):988–1028. DOI: 10.4158/EP12280.GL.Garber J.R., Cobin R.H., Gharib H., Hennessey J.V., Klein I., Mechanick J.I. et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr. Pract. 2012;18(6):988–1028. DOI: 10.4158/EP12280.GL.Huang S.A., Fish S.A., Dorfman D.M., Salvatore D., Kozakewich H.P., Mandel S.J. et al. A 21-year-old woman with consumptive hypothyroidism due to a vascular tumor expressing type 3 iodothyronine deiodinase. J. Clin. Endocrinol. Metab. 2002;87(10):4457–4461. DOI: 10.1210/jc.2002-020627.Huang S.A., Fish S.A., Dorfman D.M., Salvatore D., Kozakewich H.P., Mandel S.J. et al. A 21-year-old woman with consumptive hypothyroidism due to a vascular tumor expressing type 3 iodothyronine deiodinase. J. Clin. Endocrinol. Metab. 2002;87(10):4457–4461. DOI: 10.1210/jc.2002-020627.Mouat F., Evans H.M., Cutfield W.S., Hofman P.L., Jefferies C. Massive hepatic hemangioendothelioma and consumptive hypothyroidism. J. Pediatr. Endocrinol. Metab. 2008;21(7):701–703. DOI: 10.1515/jpem.2008.21.7.701.Mouat F., Evans H.M., Cutfield W.S., Hofman P.L., Jefferies C. Massive hepatic hemangioendothelioma and consumptive hypothyroidism. J. Pediatr. Endocrinol. Metab. 2008;21(7):701–703. DOI: 10.1515/jpem.2008.21.7.701.Jonklaas J., Bianco A.C., Bauer A.J., Burman K.D., Cappola A.R., Celi F.S. et al. Guidelines for the treatment of hypothyroidism: Prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670–1751. DOI: 10.1089/thy.2014.0028.Jonklaas J., Bianco A.C., Bauer A.J., Burman K.D., Cappola A.R., Celi F.S. et al. Guidelines for the treatment of hypothyroidism: Prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670–1751. DOI: 10.1089/thy.2014.0028.Ettleson M.D., Bianco A.C. Individualized therapy for Hypothyroidism: Is T4 enough for everyone? J. Clin. Endocrinol. Metab. 2020;105(9):e3090–e3104. DOI: 10.1210/clinem/dgaa430.Ettleson M.D., Bianco A.C. Individualized therapy for Hypothyroidism: Is T4 enough for everyone? J. Clin. Endocrinol. Metab. 2020;105(9):e3090–e3104. DOI: 10.1210/clinem/dgaa430.McAninch E.A., Bianco A.C. The history and future of treatment of hypothyroidism. Ann. Intern. Med. 2016;164(1):50–56. DOI: 10.7326/M15-1799.McAninch E.A., Bianco A.C. The history and future of treatment of hypothyroidism. Ann. Intern. Med. 2016;164(1):50–56. DOI: 10.7326/M15-1799.Grover G.J., Mellström K., Malm J. Therapeutic potential for thyroid hormone receptor-beta selective agonists for treating obesity, hyperlipidemia and diabetes. Curr. Vasc. Pharmacol. 2007;5(2):141–154. DOI: 10.2174/157016107780368271.Grover G.J., Mellström K., Malm J. Therapeutic potential for thyroid hormone receptor-beta selective agonists for treating obesity, hyperlipidemia and diabetes. Curr. Vasc. Pharmacol. 2007;5(2):141–154. DOI: 10.2174/157016107780368271.Brent G.A. Mechanisms of thyroid hormone action. J. Clin. Invest. 2012;122(9):3035–3043. DOI: 10.1172/JCI60047.Brent G.A. Mechanisms of thyroid hormone action. J. Clin. Invest. 2012;122(9):3035–3043. DOI: 10.1172/JCI60047.Mendoza A., Hollenberg A.N. New insights into thyroid hormone action. Pharmacol. Ther. 2017;173:135–145. DOI: 10.1016/j.pharmthera.2017.02.012.Mendoza A., Hollenberg A.N. New insights into thyroid hormone action. Pharmacol. Ther. 2017;173:135–145. DOI: 10.1016/j.pharmthera.2017.02.012.Saponaro F., Sestito S., Runfola M., Rapposelli S., Chiellini G. Selective thyroid hormone receptor-beta (TRβ) agonists: New perspectives for the treatment of metabolic and neurodegenerative disorders. Front. Med. (Lausanne). 2020;7:331. DOI: 10.3389/fmed.2020.00331.Saponaro F., Sestito S., Runfola M., Rapposelli S., Chiellini G. Selective thyroid hormone receptor-beta (TRβ) agonists: New perspectives for the treatment of metabolic and neurodegenerative disorders. Front. Med. (Lausanne). 2020;7:331. DOI: 10.3389/fmed.2020.00331.Meruvu S., Ayers S.D., Winnier G., Webb P. Thyroid hormone analogues: where do we stand in 2013? Thyroid. 2013;23(11):1333–1344. DOI: 10.1089/thy.2012.0458.Meruvu S., Ayers S.D., Winnier G., Webb P. Thyroid hormone analogues: where do we stand in 2013? Thyroid. 2013;23(11):1333–1344. DOI: 10.1089/thy.2012.0458.Jeong S.W. Nonalcoholic fatty liver disease: A drug revolution is coming. Diabetes Metab. J. 2020;44(5):640–657. DOI: 10.4093/dmj.2020.0115.Jeong S.W. Nonalcoholic fatty liver disease: A drug revolution is coming. Diabetes Metab. J. 2020;44(5):640–657. DOI: 10.4093/dmj.2020.0115.Bakhtyukov A.A., Derkach K.V., Fokina E.A., Sorokoumov V.N., Zakharova I.O., Bayunova L.V. et al. Development of low-molecular-weight allosteric agonist of thyroid-stimulating hormone receptor with thyroidogenic activity. Dokl. Biochem. Biophys. 2022;503(1):67–70. DOI: 10.1134/S1607672922020016.Bakhtyukov A.A., Derkach K.V., Fokina E.A., Sorokoumov V.N., Zakharova I.O., Bayunova L.V. et al. Development of low-molecular-weight allosteric agonist of thyroid-stimulating hormone receptor with thyroidogenic activity. Dokl. Biochem. Biophys. 2022;503(1):67–70. DOI: 10.1134/S1607672922020016.Shpakov A.O., Shpakova E.A., Derkach K.V. The sensitivity of the adenylyl cyclase system in rat thyroidal and extrathyroidal tissues to peptides corresponding to the third intracellular loop of thyroid-stimulating hormone receptor. Current Topics in Peptide & Protein Research. 2012;13:61–73.Shpakov A.O., Shpakova E.A., Derkach K.V. The sensitivity of the adenylyl cyclase system in rat thyroidal and extrathyroidal tissues to peptides corresponding to the third intracellular loop of thyroid-stimulating hormone receptor. Current Topics in Peptide & Protein Research. 2012;13:61–73.Derkach K.V., Shpakova E.A., Titov A.K. et al. Intranasal and intramuscular administration of lysine-palmitoylated peptide 612–627 of thyroid-stimulating hormone receptor increases the level of thyroid hormones in rats. Int. J. Pept. Res. Ther. 2015;21:249–260. DOI: 10.1007/s10989-014-9452-6.Derkach K.V., Shpakova E.A., Titov A.K. et al. Intranasal and intramuscular administration of lysine-palmitoylated peptide 612–627 of thyroid-stimulating hormone receptor increases the level of thyroid hormones in rats. Int. J. Pept. Res. Ther. 2015;21:249–260. DOI: 10.1007/s10989-014-9452-6.

The authors declare that there are no conflicts of interest present.