Congenital Hypothyroidism

Abstract

Because thyroid hormone is essential for normal brain development, children born with congenital hypothyroidism who lack thyroid hormone during a circumscribed period of early development are at risk of brain damage and mental retardation. Since the advent of newborn screening programs in the 1980s, the diagnosis and treatment of this condition are now provided in the first 2-3 weeks of birth in most regions. While this is usually sufficient to prevent mental retardation, the children so identified attain mildly reduced IQs from expectation, and may still experience subtle and specific neurocognitive deficits. Their particular deficits are related to the brief period of thyroid hormone insufficiency they undergo, especially factors reflecting the severity of hypothyroidism at the time of diagnosis, the duration of hypothyroidism in infancy, and thyroid hormones at time of testing. In this article, we review the specific kinds of deficits demonstrated by children with congenital hypothyroidism who were diagnosed by screening and treated early, as well as the factors associated with their disease and its management that contribute to these deficits. The disease-related factors that will be reviewed will include the etiology of hypothyroidism and severity of disease at the time of diagnosis, while the treatment-related factors will include age at onset of therapy, starting and subsequent dose levels, compliance, and treatment-adequacy issues. Also examined will be the effects of hormone levels at the time of testing. In addition, the role of moderating variables such as social, genetic, and environmental influences, as well as the child's gender, will be discussed. Furthermore, several new issues including the quality of subsequent management, ultimate outcome, and pregnancy will be additionally reviewed. In conclusion, while outcome in congenital hypothyroidism is substantially improved by screening, affected children do still experience mild neuropsychologic deficits. To reduce the impact of persisting deficits, further research is needed to determine the optimal starting dose for the different etiologies, guidelines for subsequent management, and alternative therapies. Moreover, now that the original samples are reaching adulthood and, in females, childbearing age, further research is also needed regarding treatment during pregnancy in women with congenital hypothyroidism, as is research to determine how this population ultimately fares in adulthood.

Reversing Neurodevelopmental Disorders in Adults

“…A recent study with an animal model of schizophrenia (Li et al, 2007) showed that a brief induction of a DISC1 mutant allele during postnatal development, but not in adults, is sufficient to trigger many of the phenotypes associated with this neurodevelopmental disorder (Weinberger, 1987). Clinical experience with endocrine and metabolic disorders also stresses the importance of insults during vulnerable periods of development: hypothyroidism and phenylketonuria, for example, can lead to profound and irreversible cognitive disability when left uncorrected during developmental periods, while they appear to have milder effects in adults (Davis and Tremont, 2007; Dugbartey, 1998; Hanley, 2004; Rovet and Daneman, 2003; Zoeller and Rovet, 2004). Nevertheless, there are many other examples of pathologies where the opposite is true: for example, trauma, infection, and ischemia may have much of the same or even more dire effects in adults than in developing organisms (Kolb et al, 2000; Vannucci and Hagberg, 2004).…”

Adult reversal of cognitive phenotypes in neurodevelopmental disorders

“…For example, mutations leading to phenylketonuria have serious effects during development, but stopping treatment results only in mild phenotypes in adults [2]. Similarly, untreated congenital hypothyroidism can lead to profound and irreversible cognitive deficits, while hypothyroidism in adults has milder effects on cognitive function [3–6]. Although development may be an especially fragile period, there are also examples of manipulations that result in far more serious effects in adults than in development.…”

Neonatal effects of thyroid diseases in pregnancy and approach to the infant with increased TSH: Turkish Neonatal and Pediatric Endocrinology and Diabetes Societies consensus report

“…Numerous studies have shown that CH screening enables normal progression of cognitive development with early diagnosis and treatment in children with severe CH and the time to normalization of thyroid hormones affects developmental outcomes (20-22). On the other hand, it was observed that a notable developmental negativity did not ocur in mild or subclinical (diagnosed only with moderately elevated TSH) hypothyroidism when studies evaluating developmental outcomes of screening were reviewed.…”