대한유전성대사질환학회지 (Journal of The Korean Society of Inherited Metabolic disease)

대한유전성대사질환학회 (The Korea Society of Inherited Metabolic Disease)
권호 표지

한국인 선천성 갑상선기능저하증에 대한 신생아선별검사의 14년간의 후향적 연구; 발생빈도와 유효성

Evaluation of the Congenital Hypothyroidism for Newborn Screening Program in Korea: A 14-year Retrospective Cohort Study

  • 윤혜란 (덕성여자대학교 약학대학 생의약분석실) ;
  • 안선현 (서울의과학연구소 특수분석팀) ;
  • 이향자 (서울의과학연구소 특수분석팀)
  • Yoon, Hye-Ran (Pharmaceutical & Biomedical analysis Lab, Duksung Women's University) ;
  • Ahn, Sunhyun (Department of Special Chemistry, Seoul Clinical Laboratories (SCL)) ;
  • Lee, Hyangja (Department of Special Chemistry, Seoul Clinical Laboratories (SCL))
  • 발행 : 2019.04.30
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⟨ 이전 논문 다음 논문 ⟩

초록

목적: 선천성 갑상선기능저하증(Congenital hypothyroidism, CH)은 전세계적으로 출생아 3,000-4,000명 당 1명의 빈도로 발생하는 신생아기에 가장 흔한 내분비질환이다. 본 연구는 1991년부터 2004년까지 남한의 선천성 갑상선기능저하증 발생률의 빈도 및 현재까지 적용되어온 광범위한 신생아 선별검사의 검사방법과 결과를 재평가하기 위해 수행되었다. 방법: 서울 지역에 위치하지만 전국적인 지사를 운영하고 있는 검사기관 서울의과학 연구소(SCL)에서는 서울 외 6개 광역시(부산, 인천, 대구, 대전, 광주, 울산)와 9개도(경기, 강원, 충북, 충남, 전북, 전남, 경북, 경남, 제주)로 한국을 15개 지역으로 분류하였다. 15개 지역으로부터 신생아의 채혈지를 수집하여 서울본원에서 수집하여, TSH 및 유리 T4를 ELISA 검사법으로 신생아선별검사를 수행하였다. SCL 데이터 및 복지부에 보고된 전국적인 양성자수를 검토하였다. 선천성갑상선기능저하증에 대한 신생아선별 검사법의 cut-off 치는 신생아 갑상선자극호르몬(TSH) 측정을 위해서는 20 mIU/L를 유리 T4의 검사를 위해서는 0.8 ng/dL 이하를 사용하였다. TSH 및 유리 T4 ELISA 분석에 기초한 선천성 갑상선기능저하증에 대해 1차 선별검사에서 선천성 갑상선기능저하증 양성은 신생아 671,805명 중 신생아 159명에서 발견되었으며, 이의 발병빈도는 4,225명 중 1명으로 추정되었다 결과: TSH 분석에서 cut-off 20 mIU/ L를 사용했을 때 민감도, 특이도 및 양성 측도(PPV)는 각각 100.0%, 99.7% 및 10.8%였다. 유리 T4 분석을 위해 0.8 ng/dL cut-off를 사용했을 때 민감도, 특이도 및 양성 예측도는 각각 100.0%, 98.5% 및 3.9%였다. 결론: NBS를 통해 얻은 CH의 발병빈도는 2004년 이전에 해외의 여러 국가에서 보고 된 발병빈도와 비교할 만큼 유사하였다.

Purpose: Congenital hypothyroidism (CH) is the most common congenital endocrine disorder. The purpose of the present study was to determine the incidence of CH in South Korea during the period from January 1991 to March 2004. Methods: Central data from each city branch of SCL (Seoul Clinical Reference Laboratories) in Yongin, South Korea, was gathered and collectively analyzed. Newborn screening (NBS) for CH was based on measuring the levels of neonatal thyroid stimulating hormone (TSH) and free T4 (a cut-off of 20 mIU/L and less than 0.8 ng/dL, respectively). Results: During the study period, 671,805 live births were screened for CH based on TSH and free T4 ELISA assays. A total of 159 newborns were deemed positive for CH out of 671,805, with a corresponding incidence of 1 in 4,225. When a cut-off of 20 mIU/L was used in TSH assays, the associated sensitivity, specificity, and positive predictive values (PPV) were 100.0%, 99.7%, and 10.8%, respectively. When a cut-off of 0.8 ng/dL in free T4 assays was used, the associated sensitivity, specificity, and PPV were 100.0%, 98.5%, and 3.9%, respectively. Conclusion: CH incidence in South Korea as evidenced by the results of NBS was compared with its incidence and comparable to the other countries prior to 2004.

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참고문헌

  1. Olivieri A, Fazzini C, Medda E. Multiple factors influencing the incidence of congenital hypothyroidism detected by neonatal screening. Horm Res Paediatr 2015; 83(2):86-93. https://doi.org/10.1159/000369394
  2. Johnny Deladoey. Thyroid Diseases in Childhood. Switzerland: Springer international publishing. 2015.
  3. Nasheeda CM, Philip P, Shenoy RD, Shetty S. Diagnostic Utility of Cord Blood Thyroid Stimulating Hormone in Congenital Hypothyroidism in the Era of Expanded Newborn Screening. Indian J Clin Biochem 2018;33(4):461-6. https://doi.org/10.1007/s12291-017-0697-7
  4. LaFranchi S. Treatment and prognosis of congenital hypothyroidism. Mol Genet Metab 2008;94(1):140-2. https://doi.org/10.1016/j.ymgme.2007.03.013
  5. Delange F. Neonatal screening for congenital hypothyroidism: results and perspectives. Horm Res 1997;48(2):51-61. https://doi.org/10.1159/000185485
  6. Braslavsky D, Mendez MV, Prieto L, Keselman A, Enacan R, Gruneiro-Papendieck L et al. Pilot Neonatal Screening Program for Central Congenital Hypothyroidism: Evidence of Significant Detection. Horm Res Paediatr 2017;88(3):274-80. https://doi.org/10.1159/000480293
  7. Katharine BH, Kenneth AP. Corrigendum to "Increase in congenital hypothyroidism in New York State and in the United States". Mol Genet Metab 2007;91:268-77. https://doi.org/10.1016/j.ymgme.2007.03.012
  8. Aronson R, Robert M. Ehrlich, John D. Bailey, Joanne F. Rovef. Growth in children with congenital hypothyroidism detected by neonatal screening. Horm Res Paediatr 1990;116(1):33-7.
  9. Bhattacharya K, Wotton T, Wiley V. The evolution of blood-spot newborn screening. Transl Pediatr 2014;3(2):63-70.
  10. Uchiyama A, Sugihara S, Kusuda S. National survey on concepts for congenital hypothyroidism screening in neonatal intensive care units in Japan. Pediatr Int 2016;58(12):1311-5. https://doi.org/10.1111/ped.13037
  11. Soneda A, Adachi M, Muroya K, Asakura Y, Yamagami Y, Hirahara F. Overall usefulness of newborn screening for congenital hypothyroidism by using free thyroxine measurement. Endocr J 2014;61(10):1025-30. https://doi.org/10.1507/endocrj.EJ14-0143
  12. Fu C, Lu S, Li Y, Li Q, Hu X, Li M, et al. The incidence of congenital hypothyroidism (CH) in Guangxi, China and the predictors of permanent and transient CH. Endocrine Connections 2017;6:926-34. https://doi.org/10.1530/EC-17-0289
  13. Tan M, Huang Y, Jiang X, Li P, Tang C, Jia X, et al. The Prevalence, Clinical, and Molecular Characteristics of Congenital Hypothyroidism Caused by DUOX2 Mutations: A Population-Based Cohort Study in Guangzhou. Horm Metab Res 2016;48(9):581-8. https://doi.org/10.1055/s-0042-112224
  14. Desai MP, Sharma R, Riaz I, Sudhanshu S, Parikh R, Bhatia V. Newborn Screening Guidelines for Congenital Hypothyroidism in India: Recommendations of the Indian Society for Pediatric and Adolescent Endocrinology (ISPAE) - Part I: Screening and Confirmation of Diagnosis. Indian J Pediatrics 2018;85(6):440-7. https://doi.org/10.1007/s12098-017-2575-y
  15. Mehran L, Khalili D, Yarahmadi S, Delshad H, Mehrabi Y, Amouzegar A, et al. Evaluation of the congenital hypothyroidism screening programme in Iran: a 3-year retrospective cohort study. Archives of Disease in Childhood - Fetal & Neonatal Edition, March 2018.
  16. Connelly KJ, Pierce MJ, Hanna C, LaFranchi SH. Detecting Congenital Central Hypothyroidism by Newborn Screening: Difficulty in Distinguishing from Congenital Thyroxine-Binding Globulin Deficiency. Horm Res Paediatr 2017;88:331-8. https://doi.org/10.1159/000479367
  17. Mitchell ML, Hsu HW. Unresolved Issues in the Wake of Newborn Screening for Congenital Hypothyroidism. J Pediatr 2016;173:228-31. https://doi.org/10.1016/j.jpeds.2016.03.024
  18. Mitrovic K, Vukovic R, Milenkovic T, Todorovic S, Radivojcevic J, Zdravkovic D. Changes in the incidence and etiology of congenital hypothyroidism detected during 30 years of a screening program in central Serbia. Eur J of Pediatr 2016;175(2)253-9. https://doi.org/10.1007/s00431-015-2630-5
  19. Lee JM, Choi TY, Lee DW, Lee DH. Recheck Rate, Recall rate and reference range of the neonatal screening test for congenital hypothyroidism. J Clin Pathol Qual Control 2001;23(1):215-20.
  20. Jones JH, Smith S, Dorrian C, Mason A, Shaikh MG. Permanent congenital hypothyroidism with blood spot thyroid stimulating hormone <10 mU/L. Arch Dis Child 2018;103:65-7. https://doi.org/10.1136/archdischild-2015-309564
  21. Knowles RL, Oerton J, Cheetham T, Butler G, Cavanagh C, Tetlow L, et al. Newborn Screening for Primary Congenital Hypothyroidism: Estimating Test Performance at Different TSH Thresholds. J Clin Endocrinol Metab 2018;103(10):3720-8. https://doi.org/10.1210/jc.2018-00658
  22. Vieites A, Enacan R, Gotta G, Junco M, Ropelato G, Chiesa A. Etiology and severity of congenital hypothyroid children detected through neonatal screening: a cut-off based analysis. ESPE Abstracts 2016;86P-P1-919 CEDIE.
  23. Kaluarachchi DC, Colaizy TT, Pesce LM, Tansey M, Klein JM. Congenital hypothyroidism with delayed thyroid-stimulating hormone elevation in premature infants born at less than 30 weeks gestation. J Perinatol 2017;37(3):277-82. https://doi.org/10.1038/jp.2016.213
  24. Barry Y, Bonaldi C, Goulet V, Coutant R, Leger J, Paty AC, et al. Increased incidence of congenital hypothyroidism in France from 1982 to 2012: a nationwide multicenter analysis. Ann Epidemiol 2016;26(2):100-5. https://doi.org/10.1016/j.annepidem.2015.11.005
  25. Corbetta C, Weber G, Cortinovis F, Calebiro D, Passoni A, Vigone MC, et al. A 7-year experience with low blood TSH cut off levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH). Clin Endocrinol 2009;71(5):739-45. https://doi.org/10.1111/j.1365-2265.2009.03568.x
  26. Mengreli C, Kanaka-Gantenbein C, Girginoudis P, Magiakou MA, Christakopoulou I, Giannoulia-Karantana A, et al. Screening for congenital hypothyroidism: the significance of threshold limit in false-negative results. J Clin Endocrinol Metab 2010:95:4283-90. https://doi.org/10.1210/jc.2010-0057