ESPE Abstracts

Background: An increased prevalence of extra-thyroidal congenital malformations in infants with congenital hypothyroidism (CH) is well established. However, accurate estimation of prevalence figures requires careful distinction between permanent and transient CH. Moreover, the mechanisms resulting in congenital malformations are not well understood.

Study aim: To estimate the prevalence of cardiac, extra-cardiac and/or syndromic malformation in permanent and transient CH; and to compare patterns and prevalence of malformations in proven thyroid dysgenesis (thyroid ectopia, athyreosis, and thyroid hypoplasia in situ) with thyroid dyshormonogenesis.

Methods: Thyroid status of all newborn screening referrals in Scotland from August 1979 to December 2015 were reviewed. Information on patients in whom status remained uncertain was updated via clinical electronic medical records, and by contacting the appropriate paediatricians.

Results: Of 903 infants referred during the study period permanent CH was confirmed in 661 (73.2%) and transient CH in 218, while status remains uncertain in 22, of whom 14 died before a definitive diagnosis could be made. Malformations were present in 68 (10.3%) permanent, 61 (27.9%) transient and 15 (68.2%) Status Uncertain patients. These prevalence figures fell to 8%, 21.1% and 54.5 % after excluding 15, 15, and 3 patients with Down syndrome. Malformations and/or syndromes in the 55 transient CH patients comprised cardiac (n=11), extra-cardiac (18) and both (11), with Down syndrome in 15. These patients with transient CH were usually categorised as ‘sick’ at the time of screening. Of 241 patients with proven dysgenesis on thyroid imaging, 17 (7.05%) had malformation and/or syndromes: cardiac (n=3 [17.6%]), extracardiac (e.g. skeletal) (n=8 [47%]), syndromic (n=6 - Down syndrome n=2, Sotos syndrome n=1, unclassified syndrome n=1). Of 75 patients with dyshormonogenesis 11 (14.6 %) had malformations, comprising cardiac (n=3), extracardiac (n=3) including sisters with metaphyseal dysplasia, and Pendred syndrome (n=2).

Conclusions: Prevalence figures for permanent and transient CH will vary from study to study since they are influenced by syndromic disorders, notably Down syndrome; and the duration of follow-up, since definitive categorisation may take years to establish; while status will remain uncertain in some patients. Mechanisms for transient CH include the effect of factors associated with ‘sickness’ on thyroid function. In thyroid dysgenesis, congenital malformations could result from the teratogenic effect of gene defects and syndromic disorders on both thyroid and extra-thyroidal tissues. By contrast, extra-thyroidal malformations in dyshormonogenesis may reflect the effect of separate recessive genes which have also been inherited from the parents.