ketendoКлиническая и экспериментальная тиреоидологияClinical and experimental thyroidology1995-54722310-3787Endocrinology Research Centre10.14341/ket2015436-39ketendo-7699Research ArticleКлинический случайCase ReportСиндром резистентности к тиреотропному гормону: описание семейного случаяиндром резистентности к тиреотропному гормону: описание семейного случаяResistance to thyrotropin: familial case reportОсиповскаяМария АлександровнаOsipovskayaMariya Aleksandrovna

ординатор кафедры поликлинической педиатрии и педиатрии ФПК и ПП УГМУ

MD

docmarisha@yandex.ruКияевАлексей ВасильевичKiyaevAlexey Vasil'evich

доктор медицинских наук, доцент кафедры поликлинической педиатрии и педиатрии ФПК и ПП, главный детский эндокринолог МЗ Свердловской области

MD, PhD, Assistance professor

thyroend@mail.ruМакрецкаяНина АлексеевнаMakretskayaNina Alekseevna

аспирант ФГБУ «Эндокринологический научный центр» МЗ РФ, Москва, Россия

MD, PhD-student

genes@endocrincentr.ruВасильевЕвгений ВикторовичVasilievEvgeny Viktorovich

кандидат медицинских наук, старший научный сотрудник отделения наследственных эндокринопатий ФГБУ «Эндокринологический научный центр» МЗ РФ, Москва, Россия

MD, PhD

genes@endocrincentr.ruТюльпаковАнатолий НиколаевичTiulpakovAnatoly Nikolaevich

доктор медицинских наук, профессор, заведующий отделением наследственных эндокринопатий ФГБУ «Эндокринологический научный центр» МЗ РФ, Москва, Россия

MD, PhD, Professor

genes@endocrincentr.ruГБОУ ВПО “Уральский государственный медицинский университет”РоссияUral State Medical UniversityRussian FederationФГБУ “Эндокринологический научный центр”РоссияEndocrinology Research CentreRussian Federation2015090220161143639Copyright © Осиповская М.А., Кияев А.В., Макрецкая Н.А., Васильев Е.В., Тюльпаков А.Н., 20152015Осиповская М.А., Кияев А.В., Макрецкая Н.А., Васильев Е.В., Тюльпаков А.Н.Osipovskaya M.A., Kiyaev A.V., Makretskaya N.A., Vasiliev E.V., Tiulpakov A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.cet-endojournals.ru/jour/article/view/7699

В статье представлены результаты 5-летнего наблюдения двух сестер-близнецов с субклиническим первичным гипотиреозом, у которых по данным молекулярно-генетического обследования выявлена гомозиготная мутация в гене рецептора ТТГ (p.R450H). Обсуждаются показания к заместительной терапии левотироксином.

Two female dizygotic twins with subclinical primary hypothyroidism due to homozygous p.R450H mutation in TSHR gene are presented. A 5-year follow-up in both cases showed no progression of thyroid dysfunction. Indications for levothyroxine replacement in subclinical hypothyroidism are discussed.

субклинический гипотиреозрезистентность к ТТГген рецептора ТТГдетиsubclinical hypothyroidismresistance to thyrotropinTSHRchildrenReferencesStanbury JB, Rocmans P, Buhler UK, Ochi Y. Congenital Hypothyroidism with Impaired Thyroid Response to Thyrotropin. N Engl J Med. 1968;279(21):1132-1136. doi: 10.1056/nejm196811212792103.Stanbury JB, Rocmans P, Buhler UK, Ochi Y. Congenital Hypothyroidism with Impaired Thyroid Response to Thyrotropin. N Engl J Med. 1968;279(21):1132-1136. doi: 10.1056/nejm196811212792103.Calebiro D, Perzani L, Beck-Packos P. Clinical manifestations of mutations in RTSH: RTSH pathology. Thyroid international. 2005;3.Calebiro D, Perzani L, Beck-Packos P. Clinical manifestations of mutations in RTSH: RTSH pathology. Thyroid international. 2005;3.Nagayama Y, Kaufman KD, Seto P, Rapoport B. Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor. Biochem Biophys Res Commun. 1989;165(3):1184-1190. doi: 10.1016/0006-291x(89)92727-7.Nagayama Y, Kaufman KD, Seto P, Rapoport B. Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor. Biochem Biophys Res Commun. 1989;165(3):1184-1190. doi: 10.1016/0006-291x(89)92727-7.Vassart G, Parmentier M, Libert F, Dumont J. Molecular genetics of the thyrotropin receptor. Trends Endocrinol Metab. 1991;2(4):151-156. doi: 10.1016/1043-2760(91)90006-9.Vassart G, Parmentier M, Libert F, Dumont J. Molecular genetics of the thyrotropin receptor. Trends Endocrinol Metab. 1991;2(4):151-156. doi: 10.1016/1043-2760(91)90006-9.Libert F, Lefort A, Gerard C, et al. Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: Evidence for binding of autoantibodies. Biochem Biophys Res Commun. 1989;165(3):1250-1255. doi: 10.1016/0006-291x(89)92736-8.Libert F, Lefort A, Gerard C, et al. Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: Evidence for binding of autoantibodies. Biochem Biophys Res Commun. 1989;165(3):1250-1255. doi: 10.1016/0006-291x(89)92736-8.Stein SA, Oates EL, Hall CR, et al. Identification of a point mutation in the thyrotropin receptor of the hyt/hyt hypothyroid mouse. Mol Endocrinol. 1994;8(2):129-138. doi: 10.1210/me.8.2.129.Stein SA, Oates EL, Hall CR, et al. Identification of a point mutation in the thyrotropin receptor of the hyt/hyt hypothyroid mouse. Mol Endocrinol. 1994;8(2):129-138. doi: 10.1210/me.8.2.129.Sunthornthepvarakul T, Gottschalk ME, Hayashi Y, Refetoff S. Resistance to Thyrotropin Caused by Mutations in the Thyrotropin-Receptor Gene. N Engl J Med. 1995;332(3):155-160. doi: 10.1056/nejm199501193320305.Sunthornthepvarakul T, Gottschalk ME, Hayashi Y, Refetoff S. Resistance to Thyrotropin Caused by Mutations in the Thyrotropin-Receptor Gene. N Engl J Med. 1995;332(3):155-160. doi: 10.1056/nejm199501193320305.de Roux N, Misrahi M, Brauner R, et al. Four families with loss of function mutations of the thyrotropin receptor. J Clin Endocr Metab. 1996;81(12):4229-4235. doi: 10.1210/jcem.81.12.8954020.de Roux N, Misrahi M, Brauner R, et al. Four families with loss of function mutations of the thyrotropin receptor. J Clin Endocr Metab. 1996;81(12):4229-4235. doi: 10.1210/jcem.81.12.8954020.Tonacchera M, Agretti P, Pinchera A, et al. Congenital Hypothyroidism with Impaired Thyroid Response to Thyrotropin (TSH) and Absent Circulating Thyroglobulin: Evidence for a New Inactivating Mutation of the TSH Receptor Gene1. J Clin Endocr Metab. 2000;85(3):1001-1008. doi: 10.1210/jcem.85.3.6460.Tonacchera M, Agretti P, Pinchera A, et al. Congenital Hypothyroidism with Impaired Thyroid Response to Thyrotropin (TSH) and Absent Circulating Thyroglobulin: Evidence for a New Inactivating Mutation of the TSH Receptor Gene1. J Clin Endocr Metab. 2000;85(3):1001-1008. doi: 10.1210/jcem.85.3.6460.Hebrant A, van Staveren WCG, Maenhaut C, et al. Genetic hyperthyroidism: hyperthyroidism due to activating TSHR mutations. Eur J Endocrinol. 2010;164(1):1-9. doi: 10.1530/eje-10-0775.Hebrant A, van Staveren WCG, Maenhaut C, et al. Genetic hyperthyroidism: hyperthyroidism due to activating TSHR mutations. Eur J Endocrinol. 2010;164(1):1-9. doi: 10.1530/eje-10-0775.Lüblinghoff J, Nebel IT, Huth S, et al. The Leipzig Thyrotropin Receptor Mutation Database: Update 2012. European Thyroid Journal. 2012;1(3):209-210. doi: 10.1159/000342918.Lüblinghoff J, Nebel IT, Huth S, et al. The Leipzig Thyrotropin Receptor Mutation Database: Update 2012. European Thyroid Journal. 2012;1(3):209-210. doi: 10.1159/000342918.Beck-Peccoz P, Persani L, Calebiro D, et al. Syndromes of hormone resistance in the hypothalamic–pituitary–thyroid axis. Best Practice & Research Clinical Endocrinology & Metabolism. 2006;20(4):529-546. doi: 10.1016/j.beem.2006.11.001.Beck-Peccoz P, Persani L, Calebiro D, et al. Syndromes of hormone resistance in the hypothalamic–pituitary–thyroid axis. Best Practice & Research Clinical Endocrinology & Metabolism. 2006;20(4):529-546. doi: 10.1016/j.beem.2006.11.001.Alberti L, Proverbio MC, Costagliola S, et al. Germline Mutations of TSH Receptor Gene as Cause of Nonautoimmune Subclinical Hypothyroidism. J Clin Endocr Metab. 2002;87(6):2549-2555. doi: 10.1210/jcem.87.6.8536.Alberti L, Proverbio MC, Costagliola S, et al. Germline Mutations of TSH Receptor Gene as Cause of Nonautoimmune Subclinical Hypothyroidism. J Clin Endocr Metab. 2002;87(6):2549-2555. doi: 10.1210/jcem.87.6.8536.Abramowicz MJ, Duprez L, Parma J, et al. Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. J Clin Invest. 1997;99(12):3018-3024. doi: 10.1172/jci119497.Abramowicz MJ, Duprez L, Parma J, et al. Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. J Clin Invest. 1997;99(12):3018-3024. doi: 10.1172/jci119497.Гарднер Д., Шобек Д. Базисная и клиническая эндокринология. / Пер. с англ. под ред. Мельниченко Г.А. и Фадеева В.В. – М.; 2011. – C. 356-357. [Gardner D, Shoback D. Greenspan's Basic and Clinical Endocrinology, Ninth Edition. McGraw-Hill Education; 2011.]Гарднер Д., Шобек Д. Базисная и клиническая эндокринология. / Пер. с англ. под ред. Мельниченко Г.А. и Фадеева В.В. – М.; 2011. – C. 356-357. [Gardner D, Shoback D. Greenspan's Basic and Clinical Endocrinology, Ninth Edition. McGraw-Hill Education; 2011.]Tenenbaum-Rakover Y, Grasberger H, Mamanasiri S, et al. Loss-of-Function Mutations in the Thyrotropin Receptor Gene as a Major Determinant of Hyperthyrotropinemia in a Consanguineous Community. J Clin Endocr Metab. 2009;94(5):1706-1712. doi: 10.1210/jc.2008-1938.Tenenbaum-Rakover Y, Grasberger H, Mamanasiri S, et al. Loss-of-Function Mutations in the Thyrotropin Receptor Gene as a Major Determinant of Hyperthyrotropinemia in a Consanguineous Community. J Clin Endocr Metab. 2009;94(5):1706-1712. doi: 10.1210/jc.2008-1938.Tsunekawa K, Yanagawa Y, Aoki T, et al. Frequency and Clinical Implication of the R450H Mutation in the Thyrotropin Receptor Gene in the Japanese Population Detected by Smart Amplification Process 2. BioMed Research International. 2014;2014:1-7. doi: 10.1155/2014/964635.Tsunekawa K, Yanagawa Y, Aoki T, et al. Frequency and Clinical Implication of the R450H Mutation in the Thyrotropin Receptor Gene in the Japanese Population Detected by Smart Amplification Process 2. BioMed Research International. 2014;2014:1-7. doi: 10.1155/2014/964635.Lazarus J, Brown RS, Daumerie C, et al. 2014 European Thyroid Association Guidelines for the Management of Subclinical Hypothyroidism in Pregnancy and in Children. European Thyroid Journal. 2014;3(2):76-94. doi: 10.1159/000362597.Lazarus J, Brown RS, Daumerie C, et al. 2014 European Thyroid Association Guidelines for the Management of Subclinical Hypothyroidism in Pregnancy and in Children. European Thyroid Journal. 2014;3(2):76-94. doi: 10.1159/000362597.

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