Neonatal Screening for Congenital Hypothyroidism: What Can We Learn From Discordant Twins?

J Clin Endocrinol Metab. 2019 Dec 1;104(12):5765-5779. doi: 10.1210/jc.2019-00900.


Context: Newborn screening program for congenital hypothyroidism (CH) adopting rescreening in at-risk neonates.

Objectives: To estimate the concordance rate for CH in twin pairs discordant at the first screening; to verify whether long-term follow-up of healthy cotwins belonging to CH discordant pairs may be useful to diagnose thyroid hypofunction during development; to evaluate the importance of genetic and environmental influences on liability to permanent and transient CH.

Design and patients: Forty-seven screening discordant twin pairs were investigated. Proband was defined as the twin in the pair with a positive test at the first screening and a confirmed diagnosis of CH.

Results: Seven screening discordant twin pairs became concordant for CH within the first month of life (pairwise concordance of 14.9%) because seven screening negative cotwins showed high TSH values when retested. During long-term follow-up (range, 3 to 21 years), hypothyroidism was diagnosed in two monozygotic screening negative cotwins at the age of 9 months and 12 years, respectively. Furthermore, the twin analysis showed that 95% of liability to transient CH was explained by genetic factors and 5% by environmental (unshared) factors, whereas 64% of phenotypic variance of permanent CH was explained by common environmental factors (shared during the fetal life) and 36% by unshared environmental factors.

Conclusions: This study showed that the introduction of rescreening permits the diagnosis of CH in a greater number of twins. It also showed the importance of long-term follow-up in both twins in the pair, and the role of nongenetic factors in the etiology of permanent CH.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Congenital Hypothyroidism / diagnosis*
  • Congenital Hypothyroidism / genetics
  • Diseases in Twins / diagnosis*
  • Diseases in Twins / genetics
  • Female
  • Humans
  • Infant, Newborn
  • Male
  • Neonatal Screening / methods*
  • Twins, Dizygotic / genetics*
  • Twins, Monozygotic / genetics*