European Journal of Pediatrics

, Volume 175, Issue 2, pp 253–259 | Cite as

Changes in the incidence and etiology of congenital hypothyroidism detected during 30 years of a screening program in central Serbia

  • Katarina MitrovicEmail author
  • Rade Vukovic
  • Tatjana Milenkovic
  • Sladjana Todorovic
  • Jovana Radivojcevic
  • Dragan Zdravkovic
Original Article


Congenital hypothyroidism (CH) is the most frequent congenital endocrine disorder. The purpose of the present study was to determine the incidence of CH in Central Serbia from 1983 to 2013. Newborn screening for CH was based on measuring neonatal thyroid-stimulating hormone (TSH) using a 30 mU/l cutoff (CO) until 12/1987 (P1), 15 mU/l until 12/1997 (P2), 10 mU/l until 12/2006 (P3), and 9 mU/l thereafter (P4). During the study period, there were 1,547,122 live births screened for CH. Primary CH was detected in 434 newborns, with incidence of 1:3728. With gradual lowering of the CO, the incidences of CH increased from 1:5943 in P1 to 1:1872 in P4 (p < 0.001). Incidence of CH with ectopic and enlarged gland doubled (p < 0.001), while prevalence of athyreosis remained relatively constant. The most prominent finding was the increase in the transient CH from none in P1 to 35 % of all CH patients in P4.

Conclusion: The overall incidence of CH in Central Serbia during study period nearly tripled, with a significant increase in almost all etiological categories, and was associated with lowering TSH cutoffs as well as other yet unidentified factors. Further studies are needed to identify other factors associated with increasing incidence of CH.

What is Known:

Congenital hypothyroidism (CH) is the main cause of preventable mental retardation.

Recent reports have indicated a progressive increase in the incidence of primary CH throughout the world, partially explained by lowering of the TSH cutoff values.

What is New:

During the study period associated with lowering of the TSH cutoffs, the overall incidence of CH in Serbia tripled, including transient CH, ectopy, and dyshormonogenesis, while prevalence of athyreosis remained stable during 30 years.

Significant increase in the incidence of both permanent and transient CH was observed, associated with lowering of TSH cutoffs as well as other yet unidentified factors.


Congenital hypothyroidism Neonatal screening Thyroid-stimulating hormone Cutoff Incidence 





Congenital hypothyroidism


Immunofluorometric assay






Thyroid-stimulating hormone



The authors acknowledge the neonatology and pediatric centers in Central Serbia that conveyed the clinical information to the Central Laboratory for Neonatal Screening, situated at the Institute for Mother and Child Health Care of Serbia in Belgrade. The authors thank B. Opancina, O. Spasojevic, and M. Trajkovic (Central Laboratory for Neonatal Screening) for their skillful technical contribution.

Author contributions

KM and DZ helped in the conception, study design, and article drafting. RV and TM contributed to the study design, acquisition, analysis, and interpretation of data. ST and JR contributed to the study design, data acquisition, and article revision. KM revising the article critically for important intellectual content. All authors reviewed and approved the final version of the manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The study was approved by the Hospital Ethics Committee and performed in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Albert BB, Cutfield WS, Webster D, Carll J, Derraik JGB, Jefferies C, Gunn AJ, Hofman PL (2012) Etiology of increasing incidence of congenital hypothyroidism in New Zealand from 1993–2010. J Clin Endocrinol Metab 97:3155–3160CrossRefPubMedGoogle Scholar
  2. 2.
    Banicevic M, Subotic Z, Kurt N (1987) Clinical and laboratory characteristics of congenital hypothyroidism in neonates detected in a screening program. Srp Arh Celok Lek 115:677–697PubMedGoogle Scholar
  3. 3.
    Botler J, Camacho LA, Cruz MM (2012) Phenylketonuria, congenital hypothyroidism and haemoglobinopathies: public health issues for Brazilian newborn screening program. Cad Saude Publica 28:1623–1631CrossRefPubMedGoogle Scholar
  4. 4.
    Chiesa A, Prieto L, Mendez V, Papendieck P, De Lujan CM, Gruneiro-Papendieck L (2013) Prevalence and etiology of congenital hypothyroidism detected through an Argentine neonatal screening program (1997–2010). Horm Res Paediatr 80:185–192CrossRefPubMedGoogle Scholar
  5. 5.
    Corbetta C, Weber G, Cortinovis F, Calebrio D, Passoni A, Vigone MC, Beck-Peccoz P, Chiumello G, Persani L (2009) A 7-year experience with low blood TSH cutoff levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH). Clin Endocrinol 71:739–745CrossRefGoogle Scholar
  6. 6.
    Deladoey J, Ruel J, Giguere Y, Van Vliet G (2011) Is the incidence of congenital hypothyroidism on the increasing really increasing? A 20-years retrospective population-based study in Quebec. J Clin Endocrinol Metab 96:2422–2429CrossRefPubMedGoogle Scholar
  7. 7.
    Ford G, LaFranchi SH (2014) Screening for congenital hypothyroidism: a worldwide view of strategies. Best Pract Res Clin Endocrinol Metab 28:175–187CrossRefPubMedGoogle Scholar
  8. 8.
    Harris KB, Pass KA (2007) Increase in congenital hypothyroidism in New York State and in the United States. Mol Genet Metab 91:268–277CrossRefPubMedGoogle Scholar
  9. 9.
    Hinton CF, Harris KB, Borgfeld L, Drummond-Borg M, Eaton R, Lorey F, Therrell BL, Wallace J, Pass KA (2010) Trends in incidence rates of congenital hypothyroidism related to select demographic factors: data from the United States, California, Massachusetts, New York and Texas. Pediatrics 125:S37–S47CrossRefPubMedGoogle Scholar
  10. 10.
    Jovic D, Knezevic T, Van der Haar F, Jovic A (2010) Both iodized salt and iodine supplements are important sources of iodine for pregnant women in Serbia. International Council for Control of Iodine Deficiency Newsletter
  11. 11.
    Kurinczuk JJ, Bower C, Lewis B, Byrne G (2002) Congenital hypothyroidism in Western Australia 1981–1998. J Paediatr Child Health 38:187–191CrossRefPubMedGoogle Scholar
  12. 12.
    LaFranchi SH (2011) Increasing incidence of congenital hypothyroidism: some answers, more questions. J Clin Endocrinol Metab 96:2395–2397CrossRefPubMedGoogle Scholar
  13. 13.
    Leger J, Olivieri A, Donaldson M, Torresani T, Krude H, Van Vliet G, Polak M, Butler G (2014) European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis and management of congenital hypothyroidism. J Clin Endocrinol Metab 99:363–384PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Loeber JG (2007) Neonatal screening in Europe; the situation in 2004. J Inherit Metab Dis 30:430–438CrossRefPubMedGoogle Scholar
  15. 15.
    Mengreli C, Kanaka-Gantenbein C, Girginoudis P, Magiakou MA, Christakopoulou I, Giannoulia-Karantana A, Chrousos GP, Dacou-Voutetakis C (2010) Screening for congenital hypothyroidism: the significance of threshold limit in false-negative results. J Clin Endocrinol Metab 95:4283–4290CrossRefPubMedGoogle Scholar
  16. 16.
    Pearce MS, Korada M, Day J, Turner S, Allison D, Kibirige M, Cheetham TD (2010) Increasing incidence, but lack of seasonality, of elevated TSH levels, on newborn screening, in the North of England. J Thyroid Res 101948Google Scholar
  17. 17.
    Rose SR, Brown RS, Wilkins L (2006) Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics 117:2290–2303CrossRefPubMedGoogle Scholar
  18. 18.
    Zung A, Tenenbaum-Rakovert Y, Barkan S, Hanukoglu A, Hershkovitz E, Pinhas-Hamiel O, Bistritzer T, Zadik Z (2010) Neonatal hyperthyreotropinaemia: population characteristics, diagnosis, management and outcome after cessation of therapy. Clin Endocrinol 72:264–271CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of EndocrinologyInstitute for Mother and Child Healthcare of Serbia “Dr Vukan Čupić”BelgradeSerbia
  2. 2.Medical FacultyUniversity of BelgradeBelgradeSerbia

Personalised recommendations