The changing epidemiology of congenital hypothyroidism: fact or artifact?

Abstract

Screening increases prevalence estimates for most diseases and congenital hypothyroidism (CH) is no exception, affecting one in 6700 children by clinical ascertainment and one in 3500 in the first surveys of systematic biochemical screening of newborns. Importantly, screening has resulted in the disappearance of intellectual disability due to CH. A further doubling in prevalence estimates has recently been reported, mostly accounted for by changes in screening algorithms; accordingly, the prevalence of overt CH has remained stable. Population-based registries that distinguish confirmed diagnoses from positive screening results have proved invaluable. These registries should include: etiology of CH based on imaging, ideally technetium scintigraphy; ethnicity; socio-educational data; input from the screening laboratories and pediatric endocrinologists. Efforts should now be directed at increasing the proportion of the world’s newborns screened for overt CH (currently 30%) and at determining if neonates with mild hyperthyrotropinemia also benefit from early treatment.

Keywords::

• athyreosis
• birth defects
• congenital hypothyroidism
• cutoffs
• dyshormonogenesis
• neonatal screening
• overdiagnosis
• overtreatment
• thyroid ectopy
• thyrotropin

Acknowledgements

We thank Y Giguère and the staff of the Québec Neonatal Screening Laboratory for continuous cooperation, KJ Barrington (Chief, Neonatology Service, Sainte-Justine Hospital) for helpful discussions and S Turpin and L Garel (Medical Imaging Department, Sainte-Justine Hospital) for their help in producing Figures 1 and 2.

Financial & competing interests disclosure

The authors were supported by a grant from the Canadian Institutes of Health Research (MOP-130390 to JD) and by private donations to the Girafonds/ Fondation du CHU Sainte-Justine (to JD and GVV). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Systematic biochemical screening of newborns for congenital hypothyroidism (CH), most commonly by measuring TSH, has led to the disappearance of intellectual disability due to this condition and to a 10- to 20-points upward shift in the mean IQ of patients with CH.

• Prevalence estimates for CH have increased from one in 6700 children before screening to one in 3500 in the first two decades after screening was implemented.

• A further increase in prevalence over the last 20 years is almost entirely due to changing screening algorithms and cutoffs; the additional cases identified have mild functional disorders, the causes and consequences of which are largely unknown.

• It is essential to distinguish between screening and diagnosis and to establish population-based databases including ethnicity and socioeducational level, to record whether CH is permanent and to document outcome, with a focus on cognitive abilities.

• In 50% of cases of CH, hypothyroidism results from a defect in thyroid migration during embryogenesis, leading to an ectopic lingual thyroid, which is best revealed by sodium pertechnetate scintigraphy; this establishes the permanent and sporadic nature of CH and is, therefore, an essential decision aid for clinicians and for parents.

• The molecular mechanisms underpinning mild isolated hyperthyrotropinemia with normal thyroid anatomy need to be studied and whether affected children picked up at neonatal screening benefit from early treatment should be established.

• Emerging countries that have attained iodine sufficiency should consider screening for CH, focusing on severe CH and adapting the process to local public health needs and circumstances.

Notes