Clinical guidelines “Congenital hypothyroidism”

Congenital hypothyroidism (CH) is an important issue of pediatric endocrinology. Early detection of this disease and timely initiation of treatment can prevent the development of severe mental retardation. Neonatal screening for CH in Russian Federation has been conducted since 1993. Updated in 2024 clinical guidelines are the main tool of a physicians. They briefly and structurally present main information about congenital hypothyroidism, its epidemiology and modern classification, methods of diagnosis and treatment, based on the principles of evidence-based medicine.

1. Peterkova V.A., Bezlepkina O.B., Shiryaeva T.U., et al. Clinical guideline of «congenital hypothyroidism». Problems of Endocrinology. 2022;68(2):90-103. (In Russ.) doi: https://doi.org/10.14341/probl12880.

2. Dedov II, Peterkova VA. Spravochnik detskogo endokrinologa. — 2020:109-125 (In Russ.)

3.

4. Sinnai G. Detskaya tireoidologiya // Per. s angl. pod red. Peterkovoj V.A. — M., 2016:304. (In Russ.)

5. Lain SJ, Bentley JP, Wiley V, et al. Association between borderline neonatal thyroid-stimulating hormone concentrations and educational and developmental outcomes: a population-based record-linkage study. Lancet Diabetes Endocrinol. 2016;4(9):756-765. doi: https://doi.org/10.1016/S2213-8587(16)30122-X

6. Zwaveling-Soonawala N, Van Trotsenburg ASP, Verkerk PH. The severity of congenital hypothyroidism of central origin should not be underestimated. J Clin Endocrinol Metab. 2015. doi: https://doi.org/10.1210/jc.2014-2871

7. Rovet JF. The Role of Thyroid Hormones for Brain Development and Cognitive Function. In: Endocrine Development. ; 2014:26-43. doi: https://doi.org/10.1159/000363153

8. Дедов И.И., Безлепкина О.Б., Вадина Т.А., Байбарина Е.Н., Чумакова О.В., и др. Скрининг на врожденный гипотиреоз в Российской Федерации // Проблемы эндокринологии. — 2018. — Т. 64. — №1. — С. 14-20. doi: https://doi.org/10.14341/probl8752

9. Barry Y, Bonaldi C, Goulet V, et al. Increased incidence of congenital hypothyroidism in France from 1982 to 2012: a nationwide multicenter analysis. Ann Epidemiol. 2016;26(2):100-105.e4. doi: https://doi.org/10.1016/j.annepidem.2015.11.005

10. Deladoëy J, Ruel J, Giguère Y, Van Vliet G. Is the incidence of congenital hypothyroidism really increasing? A 20-year retrospective population-based study in Québec. J Clin Endocrinol Metab. 2011. doi: https://doi.org/10.1210/jc.2011-1073

11. Neonatal’nyj skrining / Kutsev S.I.M. — M.: GEOTAR-Media, 2023. pp. 121-128. (In Russ.)

12. LaFranchi SH. Approach to the Diagnosis and Treatment of Neonatal Hypothyroidism. J Clin Endocrinol Metab. 2011;96(10):2959-2967. doi: https://doi.org/10.1210/jc.2011-1175

13. Grüters A, Krude H. Detection and treatment of congenital hypothyroidism. Nat Rev Endocrinol. 2012;8(2):104-113. doi: https://doi.org/10.1038/nrendo.2011.160

14. Shreder E.V., Vadina T.A., Konyukhova M.B., Nagaeva E.V., Shiryaeva T.Y., Zakharova S.M., Degtyarev M.V., Vyazmenov E.O., Bezlepkina O.B. Ectopic thyroid gland: clinical features and diagnostics in children. Problems of Endocrinology. 2022;68(3):76-85 doi: https://doi.org/10.14341/probl12876

15. Beck-Peccoz P, Rodari G, Giavoli C, Lania A. Central hypothyroidism - a neglected thyroid disorder. Nat Rev Endocrinol. 2017. doi: https://doi.org/10.1038/nrendo.2017.47

16. Makretskaya N.A. Molekulyarno-geneticheskie osnovy vrozhdennogo gipotireoza: analiz s primeneniem metodov vysokoeffktivnogo parallel’nogo sekvenirovaniya // avtoreferat kand. Dissertacii. 2018:28 (In Russ.)

17. Grasberger H, Refetoff S. Genetic causes of congenital hypothyroidism due to dyshormonogenesis. Curr Opin Pediatr. 2011;23(4):421-428. doi: https://doi.org/10.1097/MOP.0b013e32834726a4

18. Fernández LP, López-Márquez A, Santisteban P. Thyroid transcription factors in development, differentiation and disease. Nat Rev Endocrinol. 2015. doi: https://doi.org/10.1038/nrendo.2014.186

19. Peters C, van Trotsenburg ASP, Schoenmakers N. Congenital hypothyroidism: update and perspectives. European Journal of Endocrinology. 2018;179:297–317. doi: https://doi.org/10.1530/EJE-18-0383

20. Szinnai G. Clinical genetics of congenital hypothyroidism. Endocrine Development. 2014;26: 60–78. doi: https://doi.org/10.1159/000363156

21. van Trotsenburg P, Stoupa A, Léger J, et al. Congenital Hypothyroidism: A 2020–2021 Consensus Guidelines Update— An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. Thyroid. 2021;31(3):387-419. doi: https://doi.org/10.1089/thy.2020.0333

22. Shreder EV, Shiryaeva TY, Nagaeva EV, Bezlepkina OB. Consensus guidelines of congenital hypothyroidism by the European Society for pediatric endocrinology and the European Society for Endocrinology: key points and comments. Clinical and experimental thyroidology. 2021;17(2):4-12. (In Russ.)] doi: https://doi.org/10.14341/ket12703

23. Park IS, Yoon JS, So CH, Lee HS, Hwang JS. Predictors of transient congenital hypothyroidism in children with eutopic thyroid gland. Ann Pediatr Endocrinol Metab. 2017;22(2):115. doi: https://doi.org/10.6065/apem.2017.22.2.115

24. Nicholas AK, Jaleel S, Lyons G, et al. Molecular spectrum of TSHβ subunit gene defects in central hypothyroidism in the UK and Ireland. Clin Endocrinol (Oxf ). 2017;86(3):410-418. doi: https://doi.org/10.1111/cen.13149

25. Hermanns P, Couch R, Leonard N, Klotz C, Pohlenz J. A novel deletion in the thyrotropin beta-subunit gene identified by array comparative genomic hybridization analysis causes central congenital hypothyroidism in a boy originating from Turkey. Horm Res Paediatr. 2014. doi: https://doi.org/10.1159/000362413

26. Tenenbaum-Rakover Y, Almashanu S, Hess O, et al. Long-term outcome of loss-of-function mutations in thyrotropin receptor gene. Thyroid. 2015. doi: https://doi.org/10.1089/thy.2014.0311

27. García M, González de Buitrago J, Jiménez-Rosés M, Pardo L, Hinkle PM, Moreno JC. Central Hypothyroidism Due to a TRHR Mutation Causing Impaired Ligand Affinity and Transactivation of Gq. J Clin Endocrinol Metab. 2017;102(7):2433-2442. doi: https://doi.org/10.1210/jc.2016-3977

28. Zwaveling-Soonawala N, van Trotsenburg ASP, Verkerk PH. TSH and FT4 concentrations in congenital central hypothyroidism and mild congenital thyroidal hypothyroidism. J Clin Endoсrinol Metab. January 2018. doi: https://doi.org/10.1210/jc.2017-01577

29. Ahmad N, Irfan A, Al Saedi S. Congenital hypothyroidism: Screening, diagnosis, management, and outcome. J Clin Neonatol. 2017;6(2):64. doi: https://doi.org/10.4103/jcn.JCN_5_17

30. Corbetta C, Weber G, Cortinovis F, et al. A 7-year experience with low blood TSH cutoff levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH). Clin Endocrinol (Oxf ). 2009. doi: https://doi.org/10.1111/j.1365-2265.2009.03568.x

31. Langham S, Hindmarsh P, Krywawych S, Peters C. Screening for Congenital Hypothyroidism: Comparison of Borderline Screening Cut-Off Points and the Effect on the Number of Children Treated with Levothyroxine. Eur Thyroid J. 2013. doi: https://doi.org/10.1159/000350039

32. Peters C, Brooke I, Heales S, et al. Defining the newborn blood spot screening reference interval for TSH: Impact of ethnicity. J Clin Endocrinol Metab. 2016. doi: https://doi.org/10.1210/jc.2016-1822

33. Ford G, LaFranchi SH. Screening for congenital hypothyroidism: A worldwide view of strategies. Best Pract Res Clin Endocrinol Metab. 2014;28(2):175-187. doi: https://doi.org/10.1016/j.beem.2013.05.008 33. Kilberg MJ, Rasooly IR, LaFranchi SH, Bauer AJ, Hawkes CP. Newborn Screening in the US May Miss Mild Persistent Hypothyroidism. J Pediatr. 2018;192:204-208. doi: https://doi.org/10.1016/j.jpeds.2017.09.003

34. Adachi M, Soneda A, Asakura Y, et al. Mass screening of newborns for congenital hypothyroidism of central origin by free thyroxine measurement of blood samples on filter paper. European Journal of Endocrinology. 2012;166:829–838. doi: https://doi.org/10.1530/EJE-11-0653

35. Trumpff C, Grosse SD, Olivieri A, et al. Are lower TSH cutoffs in neonatal screening for congenital hypothyroidism warranted? European Journal of Endocrinology/European Federation of Endocrine Societies. 2017;177:D1–D12. doi: https://doi.org/10.1530/EJE-17-0107

36. Приказ Минздрава России от 27.12.2022 №808н «Об утверждении перечней федеральных государственных медицинских организаций и государственных медицинских организаций, относящихся к ведению субъектов Российской Федерации, осуществляющих расширенный неонатальный скрининг, а также осуществляющих проведение подтверждающей биохимической, и (или) молекулярногенетической, и (или) молекулярно-цитогенетической диагностики, и прикрепленных к ним субъектов Российской Федерации« (Зарегистрировано в Минюсте России 30.12.2022 №71922)

37. Chang YW, Lee DH, Hong YH, Hong HS, Choi DL, Seo DY. Congenital hypothyroidism: Analysis of discordant US and scintigraphic findings. Radiology. 2011. doi: https://doi.org/10.1148/radiol.10100290

38. Schoen EJ, Clapp W, To TT, Fireman BH. The Key Role of Newborn Thyroid Scintigraphy With Isotopic Iodide (123I) in Defining and Managing Congenital Hypothyroidism. Pediatrics. 2004;114(6):e683-e688. doi: https://doi.org/10.1542/peds.2004-0803

39. van Engelen K, Mommersteeg MTM, Baars MJH, et al. The Ambiguous Role of NKX2-5 Mutations in Thyroid Dysgenesis. Ludgate M, ed. PLoS One. 2012;7(12):e52685. doi: https://doi.org/10.1371/journal.pone.0052685

40. de Filippis T, Gelmini G, Paraboschi E, et al. A frequent oligogenic involvement in congenital hypothyroidism. Hum Mol Genet. 2017;26(13):2507-2514. doi: https://doi.org/10.1093/hmg/ddx145

41. Carré A, Stoupa A, Kariyawasam D, et al. Mutations in BOREALIN cause thyroid dysgenesis. Hum Mol Genet. December 2016:ddw419. doi: https://doi.org/10.1093/hmg/ddw419

42. Targovnik HM, Citterio CE, Rivolta CM. Iodide handling disorders (NIS, TPO, TG, IYD). Best Pract Res Clin Endocrinol Metab. 2017;31(2):195-212. doi: https://doi.org/10.1016/j.beem.2017.03.006

43. Park K-J, Park H-K, Kim Y-J, et al. DUOX2 Mutations Are Frequently Associated With Congenital Hypothyroidism in the Korean Population. Ann Lab Med. 2016;36(2):145-153. doi: https://doi.org/10.3343/alm.2016.36.2.145

44. Шрёдер Е.В., Вадина Т.А., Солодовникова Е.Н., Захарова В.В., Дегтярев М.В., и др. Патогенные варианты гена TSHR у детей с дисгенезией щитовидной железы // Проблемы эндокринологии. — 2023. — Т. 69. — №1. — С. 76-85. doi: https://doi.org/10.14341/probl13210

45. Muzza M, Fugazzola L. Disorders of H2O2 generation. Best Pract Res Clin Endocrinol Metab. 2017;31(2):225-240. doi: https://doi.org/10.1016/j.beem.2017.04.006

46. Srichomkwun P, Takamatsu J, Nickerson DA, Bamshad MJ, Chong JX, Refetoff S. DUOX2 Gene Mutation Manifesting as Resistance to Thyrotropin Phenotype. Thyroid. 2017;27(1):129-131. doi: https://doi.org/10.1089/thy.2016.0469

47. Abu-Khudir R, Paquette J, Lefort A, et al. Transcriptome, Methylome and Genomic Variations Analysis of Ectopic Thyroid Glands. Toland AE, ed. PLoS One. 2010;5(10):e13420. doi: https://doi.org/10.1371/journal.pone.0013420

48. Kang HS, Kumar D, Liao G, et al. GLIS3 is indispensable for TSH/TSHR-dependent thyroid hormone biosynthesis and follicular cell proliferation. J Clin Invest. 2017;127(12):4326-4337. doi: https://doi.org/10.1172/JCI94417

49. Cherella CE, Wassner AJ. Congenital hypothyroidism: insights into pathogenesis and treatment. Int J Pediatr Endocrinol. 2017;2017(1):11. doi: https://doi.org/10.1186/s13633-017-0051-0

50. Francis GL, Waguespack SG, Bauer AJ, et al. Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2015;25(7):716-759. doi: https://doi.org/10.1089/thy.2014.0460

51. Vadina T.A. Vrozhdennyj gipotireoz: epidemiologiya, struktura i social’naya adaptaciya // avtoreferat kand. Dissertacii. 2011:26 (In Russ.)