Genetics, clinical management and natural history of congenital hypothyroidism

Congenital hypothyroidism has an incidence of 1:3000-4000 newborns. In the past, it was a common cause of mental retardation, although newborn screening has improved the prognosis. Several transcription factors are crucial to the early organogenesis of the thyroid, including TITF1, FOXE1, PAX8 and HHEX. Nevertheless, a small minority of humans with congenital hypothyroidism carry mutations in these genes. Long-term follow-up studies show that with appropriate therapy, the mental and physical development of congenital hypothyroidism patients is in the normal range, although somewhat delayed when compared with appropriate controls. Critical issues of treatment include early diagnosis and rapid correction of hypothyroidism by ensuring rapid initiation of treatment and rapid normalization of thyroid-stimulating hormone levels, especially in cases of severe congenital hypothyroidism. There has been recent question of the need to treat premature infants with hypothyroxinemia but no elevation of the thyroid-stimulating hormone concentration. Numerous controlled studies of the short- and long-term effects of thyroid hormone supplementation have not shown a consistent benefit in this group of patients. Future research will investigate further the genetic underpinnings of the condition. There is a worldwide need to prevent congenital hypothyroidism by ensuring adequate dietary iodine and to develop infrastructure to diagnose and treat congenital hypothyroidism in developing countries.