Measurement of environmental modulators of thyroid hormone biosynthesis, and investigation of their aetiological role in congenital hypothyroidism.

Dr Nadia Schoenmakers, Wellcome Intermediate Clinical Fellow and Honorary Consultant Endocrinologist, Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge

Congenital hypothyroidism (CH) (thyroid underactivity from birth) results in low concentrations of thyroxine, a hormone which is essential for development of the nervous system and brain. Without treatment, children with CH develop severe learning difficulties. The introduction of the UK newborn screening programme in 1981 enables early diagnosis and treatment of CH and has almost abolished severe associated developmental sequelae. However, increasing numbers of babies are being diagnosed with mild or transient CH for which the underlying cause is unclear. This places an economic burden on the health service and a psychological burden on families of babies with CH.

Minerals such as iodine, iron and selenium play important roles in thyroid hormone biosynthesis. Iodine is an integral component of thyroid hormones and iodine deficiency leads to hypothyroidism which may be exacerbated if levels of iron and selenium are also suboptimal. Emerging data suggests that even mild-moderately reduced iodine concentrations in pregnant women can also lead to impaired brain function and school performance in their children which is concerning, since studies in the UK suggest that iodine deficiency is relatively common in this country. Environmental pollutants such as perchlorate, thiocyanate and nitrate may also interfere with the ability of the thyroid gland to take up iodine for thyroid hormone synthesis and since exposure to these chemicals in the UK is universal, these pollutants are also candidates for disrupting thyroid function in newborn babies. The combined role of genetic factors, mineral deficiencies and pollutant exposure in causing CH has not previously been evaluated. Since iodine is usually measured on a urine sample, this may be difficult to assess in a newborn baby, and there are no readily available UK assays for perchlorate, thiocyanate or nitrate.

We wish to investigate the potential link between deficiencies of minerals (iodine, selenium and iron) and/or excesses of environmental pollutants (perchlorate, thiocyanate and nitrate) and CH using the established CH service at Great Ormond Street Hospital. We hypothesise that the iodine status of the UK population in particular, in addition to aberrant concentrations of these other factors, may be leading to increases in both the diagnosis of mild CH and the number of children prescribed levothyroxine treatment. In the first instance, we will establish more practical biochemical techniques for measuring these minerals and chemicals which will subsequently be of use to other researchers and clinicians in the NHS. We will then compare levels of these substances in children with CH and children with normal thyroid function to see if we can detect any differences. In particular, if we are able to implicate iodine or selenium deficiency in the development of CH, this may lead to future recommendations for the use of supplements to prevent or treat thyroid dysfunction in deficient cases.

Interim report - Dec 2022

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