Skip to main content
NCBI home page
Archives of Disease in Childhood. Fetal and Neonatal Edition logoLink to Archives of Disease in Childhood. Fetal and Neonatal Edition
. 2005 Jan;90(1):F69–F72. doi: 10.1136/adc.2003.039065

Contribution of genetic factors to neonatal transient hypothyroidism

D Niu, C Lin, B Hwang, T Jap, C Liao, J Wu
PMCID: PMC1721821  PMID: 15613581

Abstract

Background: The causes of neonatal transient hypothyroidism (NTH) remain incompletely understood. Whether it is influenced by genetic background is rarely discussed and remains unproven. A defect in thyroid peroxidase is a common cause of dyshormonogenesis of the thyroid gland in Taiwanese, with a novel mutation (2268insT) present in nearly 90% of alleles studied.

Objective: To determine if the presence of this common mutation is associated with NTH in Taiwan.

Methods: A mismatched primer was designed and used for this specific 2268insT mutation to screen 1000 normal babies and 260 babies with confirmed NTH.

Results: The carrier rate for 2268insT in normal babies (1/200) was significantly lower than in babies with NTH (1/13; p<0.0001).

Conclusions: The results strongly suggest that the presence of this thyroid peroxidase mutation contributes to the development of NTH. Likely pathogenetic explanations include the effect of the stress of extrauterine adaptation during labour on an immature pituitary-thyroid axis in genetically predisposed individuals, combined with environmental triggers such as iodine deficiency, perinatal iodine exposure, and/or goitrogen contamination.

Full Text

The Full Text of this article is available as a PDF (78.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bakker B., Bikker H., Vulsma T., de Randamie J. S., Wiedijk B. M., De Vijlder J. J. Two decades of screening for congenital hypothyroidism in The Netherlands: TPO gene mutations in total iodide organification defects (an update). J Clin Endocrinol Metab. 2000 Oct;85(10):3708–3712. doi: 10.1210/jcem.85.10.6878. [DOI] [PubMed] [Google Scholar]
  2. Bremer H. J., Neumann W. Tolerance of phenylalanine after ntravenous administration in phenylketonurics, heterozygous carriers, and normal adults. Nature. 1966 Mar 12;209(5028):1148–1149. doi: 10.1038/2091148a0. [DOI] [PubMed] [Google Scholar]
  3. Brown R. S., Bellisario R. L., Botero D., Fournier L., Abrams C. A., Cowger M. L., David R., Fort P., Richman R. A. Incidence of transient congenital hypothyroidism due to maternal thyrotropin receptor-blocking antibodies in over one million babies. J Clin Endocrinol Metab. 1996 Mar;81(3):1147–1151. doi: 10.1210/jcem.81.3.8772590. [DOI] [PubMed] [Google Scholar]
  4. Calaciura Francesca, Motta Rosa Maria, Miscio Giuseppe, Fichera Graziella, Leonardi Daniela, Carta Anna, Trischitta Vincenzo, Tassi Vittorio, Sava Lidia, Vigneri Riccardo. Subclinical hypothyroidism in early childhood: a frequent outcome of transient neonatal hyperthyrotropinemia. J Clin Endocrinol Metab. 2002 Jul;87(7):3209–3214. doi: 10.1210/jcem.87.7.8662. [DOI] [PubMed] [Google Scholar]
  5. Cheron R. G., Kaplan M. M., Larsen P. R., Selenkow H. A., Crigler J. F., Jr Neonatal thyroid function after propylthiouracil therapy for maternal Graves' disease. N Engl J Med. 1981 Feb 26;304(9):525–528. doi: 10.1056/NEJM198102263040907. [DOI] [PubMed] [Google Scholar]
  6. Corral J., Martín C., Pérez R., Sánchez I., Mories M. T., San Millan J. L., Miralles J. M., González-Sarmiento R. Thyroglobulin gene point mutation associated with non-endemic simple goitre. Lancet. 1993 Feb 20;341(8843):462–464. doi: 10.1016/0140-6736(93)90209-y. [DOI] [PubMed] [Google Scholar]
  7. Daliva A. L., Linder B., DiMartino-Nardi J., Saenger P. Three-year follow-up of borderline congenital hypothyroidism. J Pediatr. 2000 Jan;136(1):53–56. doi: 10.1016/s0022-3476(00)90049-0. [DOI] [PubMed] [Google Scholar]
  8. Delange F. Neonatal screening for congenital hypothyroidism in Europe. Report of the Newborn Committee of the European Thyroid Association. Acta Endocrinol Suppl (Copenh) 1979;223:3–29. [PubMed] [Google Scholar]
  9. Delange F. Screening for congenital hypothyroidism used as an indicator of the degree of iodine deficiency and of its control. Thyroid. 1998 Dec;8(12):1185–1192. doi: 10.1089/thy.1998.8.1185. [DOI] [PubMed] [Google Scholar]
  10. Gruters A. Congenital hypothyroidism. Pediatr Ann. 1992 Jan;21(1):15, 18-21, 24-8. doi: 10.3928/0090-4481-19920101-06. [DOI] [PubMed] [Google Scholar]
  11. Lin C. P., Chen W., Wu K. W. Povidone-iodine in umbilical cord care interferes with neonatal screening for hypothyroidism. Eur J Pediatr. 1994 Oct;153(10):756–758. doi: 10.1007/BF01954494. [DOI] [PubMed] [Google Scholar]
  12. Lin H. D., Lo J. G., Ching K. N. Amount of urinary iodine excretion in residents of Taipei City--a hospital-based study. Zhonghua Yi Xue Za Zhi (Taipei) 1991 Jul;48(1):20–24. [PubMed] [Google Scholar]
  13. Niu Dau-Ming, Hwang Betau, Chu Yum-Kung, Liao Chun-Ju, Wang Pei-Ling, Lin Ching-Yuang. High prevalence of a novel mutation (2268 insT) of the thyroid peroxidase gene in Taiwanese patients with total iodide organification defect, and evidence for a founder effect. J Clin Endocrinol Metab. 2002 Sep;87(9):4208–4212. doi: 10.1210/jc.2002-020153. [DOI] [PubMed] [Google Scholar]
  14. Nose O., Harada T., Miyai K., Hata N., Ogawa M., Maki I., Kanaya S., Kimura S., Shimizu K., Yabuuchi H. Transient neonatal hypothyroidism probably related to immaturity of thyroidal iodine organification. J Pediatr. 1986 Apr;108(4):573–576. doi: 10.1016/s0022-3476(86)80838-1. [DOI] [PubMed] [Google Scholar]
  15. Ringold Daniel A., Nicoloff John T., Kesler Matthew, Davis Heather, Hamilton Ann, Mack Thomas. Further evidence for a strong genetic influence on the development of autoimmune thyroid disease: the California twin study. Thyroid. 2002 Aug;12(8):647–653. doi: 10.1089/105072502760258613. [DOI] [PubMed] [Google Scholar]
  16. Schönberger W., Grimm W., Gempp W., Dinkel E. Transient hypothyroidism associated with prematurity, sepsis, and respiratory distress. Eur J Pediatr. 1979 Oct;132(2):85–92. doi: 10.1007/BF00447374. [DOI] [PubMed] [Google Scholar]
  17. Tsai W. Y., Lee J. S., Chao M. C., Chen L. Y., Lin S. J., Wu K. H., Wang T. R., Chen J. S., Chuang S. M. Prevalence of permanent primary congenital hypothyroidism in Taiwan. J Formos Med Assoc. 1995 May;94(5):271–273. [PubMed] [Google Scholar]
  18. Weber G., Vigone M. C., Rapa A., Bona G., Chiumello G. Neonatal transient hypothyroidism: aetiological study. Italian Collaborative Study on Transient Hypothyroidism. Arch Dis Child Fetal Neonatal Ed. 1998 Jul;79(1):F70–F72. doi: 10.1136/fn.79.1.f70. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood. Fetal and Neonatal Edition are provided here courtesy of BMJ Publishing Group

RESOURCES