Skip to main content
SpringerLink
Log in

Incidence of primary congenital hypothyroidism and relationship between diagnostic categories and associated malformations

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

The incidence of primary congenital hypothyroidism (CH) has grown progressively and literature data indicate an association between CH and congenital malformations. The purpose of this study is to establish the current incidence of CH in the Italian Region of Piedmont and verify the relationship between CH diagnostic categories and associated malformations.

Methods

The biochemical and clinical data of 105 newborns with CH diagnosed in the period January 2014 to December 2019 were analyzed.

Results

The incidence of CH in the Italian Piedmont region in the 2014–2019 period increased to 1:1090. Thyroid dysgenesis was responsible for 47.6% (50/105) of all cases, with agenesis in 14.3% (15/105), while ectopia and hypoplasia in 23.8% (25/105) and 9.5% (10/105) of the cases, respectively; dyshormonogenesis defects were found in 52.4% (55/105) of cases. Congenital extra-thyroid anomalies were identified in 33/105 (31.4%) of newborns with CH and mainly involve the cardiac system (17/85, 16.1%), urogenital tract (7/85, 6.7%), gastrointestinal tract (5/105, 4.8%), and the musculoskeletal system (5/105, 4.8%). The highest rate of malformations was observed in patients with thyroid agenesis and dyshormonogenesis, respectively, in 53.5% and 36.4% of cases, while in the presence of thyroid ectopia and hypoplasia, the rate was 12% and 20%, respectively, (p = 0.03).

Conclusion

In the Italian region of Piedmont, the incidence of primary CH has been increased over time, with a variation in the percentage of the different forms of CH. Congenital malformations, especially affecting the cardiovascular, urogenital, gastrointestinal, and musculoskeletal systems, seem to be mainly associated with thyroid agenesis or defects in hormonogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. C. Peters, A.S.P. van Trotsenburg, N. Schoenmakers, Congenital hypothyroidism: update and perspectives. Eur. J. Endocrinol. 179, R297–R317 (2018)

    Article  CAS  Google Scholar 

  2. L. Persani, G. Rurale, T. de Filippis, E. Galazzi, M. Muzza, L. Fugazzola, Genetics and management of congenital hypothyroidism. Best Pract. Res. Clin. Endocrinol. Metab. 32, 387–396 (2018)

    Article  CAS  Google Scholar 

  3. A.J. Wassner, Congenital hypothyroidism. Clin. Perinatol. 45, 1–18 (2018)

    Article  Google Scholar 

  4. A.K. Topaloglu, Athyreosis, dysgenesis, and dyshormonogenesis in congenital hypothyroidism. Pediatr. Endocrinol. Rev. Suppl 3, 498–502 (2006)

    Google Scholar 

  5. J. Kratzsch, F. Pulzer, Thyroid gland development and defects. Best Pract. Res. Clin. Endocrinol. Metab. 22, 57–75 (2008)

    Article  CAS  Google Scholar 

  6. M.C. Vigone, S. Caiulo, M. Di Frenna, S. Ghirardello, C. Corbetta, F. Mosca, G. Weber, Evolution of thyroid function in preterm infants detected by screening for congenital hypothyroidism. J. Pediatr. 164, 1296–1302 (2014)

    Article  CAS  Google Scholar 

  7. M. Hashemipour, S. Hovsepian, A. Ansari, M. Keikha, P. Khalighinejad, N. Niknam, Screening of congenital hypothyroidism in preterm, low birth weight and very low birth weight neonates: a systematic review. Pediatr. Neonatol. 59, 3–14 (2018)

    Article  Google Scholar 

  8. S. Lain, C. Trumpff, S.D. Grosse, A. Olivieri, G. Van Vliet, Are lower TSH cutoffs in neonatal screening for congenital hypothyroidism warranted? Eur. J. Endocrinol. 177, D1–D12 (2017)

    Article  CAS  Google Scholar 

  9. G. Ford, S.H. LaFranchi, Screening for congenital hypothyroidism: a worldwide view of strategies. Best Pract. Res. Clin. Endocrinol. Metab. 28, 175–187 (2014)

    Article  CAS  Google Scholar 

  10. A. Cassio, C. Corbetta, I. Antonozzi, F. Calaciura, U. Caruso, G. Cesaretti, R. Gastaldi, E. Medda, F. Mosca, E. Pasquini et al. Italian Society for Pediatric Endocrinology and Diabetology; Italian Society for the Study of Metabolic Diseases and Neonatal Screening; Italian National Institute of Health; Italian National Coordinating Group for Congenital Hypothyroidism; Italian Thyroid Association; Italian Society of Pediatrics; Italian Society of Neonatology; Italian Society of Endocrinology; Associazione Medici Endocrinologi. The Italian screening program for primary congenital hypothyroidism: actions to improve screening, diagnosis, follow-up, and surveillance. J. Endocrinol. Investig. 36, 195–203 (2013)

    CAS  Google Scholar 

  11. R. Abu-Khudir, S. Larrivée-Vanier, J.D. Wasserman, J. Deladoëy, Disorders of thyroid morphogenesis. Best Pract. Res. Clin. Endocrinol. Metab. 31, 143–159 (2017)

    Article  CAS  Google Scholar 

  12. M. Castanet, M. Polak, J. Léger, Familial forms of thyroid dysgenesis. Endocr. Dev. 10, 15–28 (2007)

    Article  Google Scholar 

  13. A. Grüters, H. Krude, H. Biebermann, Molecular genetic defects in congenital hypothyroidism. Eur. J. Endocrinol. 151(Suppl 3), U39–U44 (2004)

    Article  Google Scholar 

  14. M. Polak, S. Sura-Trueba, A. Chauty, G. Szinnai, A. Carré, M. Castanet, Molecular mechanisms of thyroid dysgenesis. Horm. Res. 62(Suppl 3), 14–21 (2004)

    CAS  PubMed  Google Scholar 

  15. N. Zwaveling-Soonawala, P. van Trotsenburg, Genetics of primary congenital hypothyroidism. Pediatr. Endocrinol. Rev. 15, 200–215 (2018)

    PubMed  Google Scholar 

  16. A. Stoupa, D. Kariyawasam, A. Carré, M. Polak, Update of thyroid developmental genes. Endocrinol. Metab. Clin. North Am. 45, 243–254 (2016)

    Article  Google Scholar 

  17. G. Szinnai, Clinical genetics of congenital hypothyroidism. Endocr. Dev. 26, 60–78 (2014)

    Article  Google Scholar 

  18. M.J. Kempers, H.M. Ozgen, T. Vulsma, J.H. Merks, K.H. Zwinderman, J.J. de Vijlder, M.C. Hennekam, Morphological abnormalities in children with thyroidal congenital hypothyroidism. Am. J. Med. Genet. A 149A, 943–951 (2009)

    Article  Google Scholar 

  19. H. Jacob, C.S. Peters, diagnosis and management of congenital hypothyroidism: European Society for Paediatric Endocrinology Consensus Guideline. Arch Dis. Child. Educ. Pract. Ed. 100, 260–263 (2015)

    Article  Google Scholar 

  20. P.B. Kaplowitz, Neonatal thyroid disease: testing and management. Pediatr. Clin. North Am. 66, 343–352 (2019)

    Article  Google Scholar 

  21. S.H. LaFranchi, Approach to the diagnosis and treatment of neonatal hypothyroidism. J. Clin. Endocrinol. Metab. 96, 2959–2967 (2011)

    Article  CAS  Google Scholar 

  22. H. Krude, P. Kühnen, H. Biebermann, Treatment of congenital thyroid dysfunction: achievements and challenges. Best Pract. Res. Clin. Endocrinol. Metab. 29, 399–413 (2015)

    Article  CAS  Google Scholar 

  23. K. Rahmani, S. Yarahmadi, K. Etemad, A. Koosha, Y. Mehrabi, N. Aghang, H. Soori, Congenital hypothyroidism: optimal initial dosage and time of initiation of treatment: a systematic review. Int. J. Endocrinol. Metab. 14, e36080 (2016)

    Article  Google Scholar 

  24. J. Léger, Long term outcome of children with congenital hypothyroidism. Arch. Pediatr. 15, 763–765 (2008)

    Article  Google Scholar 

  25. J.S. Bamforth, I. Hughes, J. Lazarus, R. John, Congenital anomalies associated with hypothyroidism. Arch. Dis. Child. 61, 608–609 (1986)

    Article  CAS  Google Scholar 

  26. J.H. Lazarus, I.A. Hughes, Congenital abnormalities and congenital hypothyroidism. Lancet. 2, 52 (1988)

    Article  CAS  Google Scholar 

  27. New England Congenital Hypothyroidism Collaborative., Congenital concomitants of infantile hypothyroidism. J. Pediatr. 112, 244–247 (1988)

    Article  Google Scholar 

  28. N.A. Al-Jurayyan, A.S. Al-Herbish, M.I. El-Desouki, A.A. Al-Nuaim, A.M. Abo-Bakr, M.A. Al-Husain, Congenital anomalies in infants with congenital hypothyroidism: is it a coincidental or an associated finding? Hum. Hered. 47, 33–37 (1997)

    Article  CAS  Google Scholar 

  29. T. Chao, J.R. Wang, B. Hwang, Congenital hypothyroidism and concomitant anomalies. J. Pediatr. Endocrinol. Metab. 10, 217–221 (1997)

    Article  CAS  Google Scholar 

  30. H.E. Roberts, C.A. Moore, P.M. Fernhoff, A.L. Brown, M.J. Khoury, Population study of congenital hypothyroidism and associated birth defects, Atlanta, 1979-1992. Am. J. Med. Genet. 71, 29–32 (1997)

    CAS  Google Scholar 

  31. J. Kumar, R. Gordillo, F.J. Kaskel, C.M. Druschel, R.P. Woroniecki, Increased prevalence of renal and urinary tract anomalies in children with congenital hypothyroidism. J. Pediatr. 154, 263–266 (2009)

    Article  CAS  Google Scholar 

  32. A. Grüters, H. Krude, Detection and treatment of congenital hypothyroidism. Nat. Rev. Endocrinol. 8, 104–113 (2011)

    Article  Google Scholar 

  33. Z. Razavi, A. Yavarikia, S. Torabian, Congenital anomalies in infant with congenital hypothyroidism. Oman Med. J. 27, 364–367 (2012)

    Article  CAS  Google Scholar 

  34. Y.H. Gu, S. Harada, T. Kato, H. Inomata, K. Aoki, F. Hirahara, Increased incidence of extrathyroidal congenital malformations in Japanese patients with congenital hypothyroidism and their relationship with Down syndrome and other factors. Thyroid. 19, 869–879 (2009)

    Article  Google Scholar 

  35. P.A. Reddy, G. Rajagopal, C.V. Harinarayan, V. Vanaja, D. Rajasekhar, V. Suresh, A. Sachan, High prevalence of associated birth defects in congenital hypothyroidism. Int. J. Pediatr. Endocrinol. 2010, 940980 (2010). https://doi.org/10.1155/2010/940980

  36. C. Stoll, B. Dott, Y. Alemsik, C. Koehl, Congenital anomalies associated with congenital hypothyroidism. Ann. Genet. 42, 17–20 (1999)

    CAS  PubMed  Google Scholar 

  37. E. Kreisner, E.C. Neto, J.L. Gross, High prevalence of extrathyroid malformations in a cohort of Brazilian patients with permanent primary congenital hypothyroidism. Thyroid. 15, 165–169 (2005)

    Article  CAS  Google Scholar 

  38. A. Olivieri, M.A. Stazi, P. Mastroiacovo, C. Fazzini, E. Medda, A. Spagnolo, S. De Angelis, M.E. Grandolfo, D. Taruscio, V. Cordeddu et al. Study Group for Congenital Hypothyroidism. A population-based study on the frequency of additional congenital malformations in infants with congenital hypothyroidism: data from the Italian Registry for Congenital Hypothyroidism (1991-1998). J. Clin. Endocrinol. Metab. 87, 557–562 (2002)

    CAS  PubMed  Google Scholar 

  39. V.N. Baş, S. Ozgelen, S. Cetinkaya, Z. Aycan, Diseases accompanying congenital hypothyroidism. J. Pediatr. Endocrinol. Metab. 27, 485–489 (2014)

    PubMed  Google Scholar 

  40. M. El Kholy, M.E. Fahmi, A.E. Nassar, S. Selim, H.H. Elsedfy, Prevalence of minor musculoskeletal anomalies in children with congenital hypothyroidism. Horm. Res. 68, 272–275 (2007)

    CAS  PubMed  Google Scholar 

  41. Health Regional Department. To be Born in Piedmont: Regional Birth Route (Health Regional Department, Turin, 2018). https://www.epi.piemonte.it/pubblicazioni/atlanti/nascere_in_piemonte_2006_2016.pdf

  42. A. Olivieri, C. Di Cosmo, S. De Angelis, R. Da Cas, P. Stacchini, A. Pastorelli, P. Vitti, The way forward in Italy for iodine. Regional observatories for goiter prevention. Minerva Med. 108, 159–168 (2017)

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Endocrinology, Regina Margherita Children’s Hospital, City of Health and Science University Hospital of Turin, Turin, Italy

    Gerdi Tuli, Jessica Munarin, Daniele Tessaris, Patrizia Matarazzo, Silvia Einaudi & Luisa de Sanctis

  2. Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy

    Gerdi Tuli, Jessica Munarin, Daniele Tessaris, Patrizia Matarazzo, Silvia Einaudi & Luisa de Sanctis

Authors
  1. Gerdi Tuli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jessica Munarin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniele Tessaris
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patrizia Matarazzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Silvia Einaudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luisa de Sanctis
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors whose names appear on the submission have contributed sufficiently to the scientific work and therefore share collective responsibility and accountability for the results. G.T. has contributed to the study design, statistical analysis, and manuscript writing. J.M. has contributed to data collection and checking references. D.T. has contributed to the study design and to the writing of the manuscript. S.E. and P.M. have contributed to the study design and to the conceptual part of the manuscript. L.d.S. has contributed to the study design and final revision of the manuscript.

Corresponding author

Correspondence to Gerdi Tuli.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

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

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tuli, G., Munarin, J., Tessaris, D. et al. Incidence of primary congenital hypothyroidism and relationship between diagnostic categories and associated malformations. Endocrine 71, 122–129 (2021). https://doi.org/10.1007/s12020-020-02370-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-020-02370-w

Keywords

Search

Navigation