Jul 21, 2016 - A novel study by Samantha Lain and colleagues in. The Lancet Diabetes & Endocrinology5 is the first large epidemiological study to suggest a ...
Comment
Well recognised thyroid disease entities such as Hashimoto’s thyroiditis, cretinism, and congenital hypothyroidism have taught us many things about thyroid hormone action during early life. Although thyroid disease is generally considered a dichotomous outcome, subclinical thyroid dysfunction, and variation within the normal range of thyroid function, likely also leads to clinical disease, albeit in milder form. This continuous spectrum is illustrated by studies showing that pregnant women with a suboptimum thyroid function, with or without subclinical disease, have offspring with a lower intelligence quotient (IQ) and a higher risk of neurobehavioral disease.1–3 The importance of such findings is emphasised by the fact that the incidence of subclinical thyroid disease is at least ten times higher than overt thyroid disease. The association of thyroid dysfunction with neurobehavioral disease has always been of special interest because the brain is a target organ for thyroid hormone, and even small differences in neurobehavioural outcomes can have major public health consequences.4 However, investigating the consequences of subclinical forms of thyroid disease is difficult because mild phenotypes are not always obvious. Consequently, the potential adverse effects need to be actively investigated and large numbers of individuals are needed to show relatively small effects. A novel study by Samantha Lain and colleagues in The Lancet Diabetes & Endocrinology5 is the first large epidemiological study to suggest a link between a biochemically defined, subclinical form of congenital hypothyroidism in neonates and suboptimum brain development, based on the results of educational and developmental tests administered later in life. The outcome of neurobehavioural tests are affected by many factors which makes them notoriously prone to measurement error. For educational outcomes, measurement error is likely to be even higher because educational outcomes are more reflective of long-term factors (motivation, environment) and learning skills, which do not necessarily reflect cognitive capacity and are also less likely to be properly assessed at a single timepoint, and therefore studies investigating
such outcomes require large study populations. Small studies6,7 have not shown a consistent association between fetal or neonatal thyroid hormone availability and educational outcomes similar to those measured by Lain and colleagues. But Lain and colleagues were able to study over 500 000 children, by linking individual records from multiple data sources in Australia. The authors investigated the association of neonatal thyroid-stimulating hormone concentrations, obtained during routine heel-prick screening, with educational results for numeracy or reading at age 7–15 years (n=354 137), and with vulnerability in developmental domains or special needs at age 4–6 years (n=149 569). The data showed a positive dosedependent association between neonatal thyroidstimulating hormone and the risk of scoring below national minimum standard for numeracy and reading. A higher risk was shown at concentrations deemed negative for congenital hypothyroidism during routine screening (90th percentile onwards), finally reaching a 75% and 42% higher risk for values ranging between the 95th–98th and the 99·5th–99·9th centiles, respectively when compared to the
