Congenital hypothyroidism (CH) affects approximately 1 in 3,500 newborns. There is a female preponderance. In areas of iodine insufficiency, the incidence is higher, since iodine is a key element in the synthesis of thyroid hormone. Approximately 85% of CH cases are sporadic, whereas 15% are hereditary. Thyroid hormone is essential for normal pre- and postnatal brain development. The importance of in utero thyroid hormone status is demonstrated by the fact that maternal hypothyroidism during pregnancy is known to result in cognitive and motor deficits in the offspring (Forrest 2004; Zoeller and Rovet 2004). Congenital hypothyroidism is already expressed in fetal life; maternal T4, transferred via the placenta, is not sufficient for normal brain development (Forrest 2004; Haddow et al. 1999; Opazo et al. 2008; Pop and Vulsma 2005). Prior to newborn screening, CH that went undiagnosed and untreated for more than 3 months was associated with permanent and significant mental retardation, as well as behavioral problems. Outcome is now significantly better. Children with CH have normal intelligence, although subtle and specific cognitive and behavioral problems occur. Congenital hypothyroidism can be caused by primary hypothyroidism, due to a defect of the thyroid gland, or by central hypothyroidism secondary to defective hypothalamic or pituitary regulation of thyroid hormone. Several types of primary thyroid abnormalities may occur. Thyroid dysgenesis is the result of a missing, ectopic, or hypoplastic gland. Proteins that are crucial for normal thyroid gland development include the thyroid transcription factors PAX8, TTF1, TTF2, FOXE1 and the thyroid stimulating hormone (TSH) receptor gene. Thyroid dyshormonogenesis is generally due to an autosomal recessive genetic defect in any of many stages of thyroid hormone synthesis, secretion and transport (Moreno and Visser 2007). One in 50,000 children has autosomal dominant thyroid hormone resistance (RTH) due to a mutation in the gene encoding for the TRb thyroid receptors (Hauser et al. 1993; Weiss et al. 1993). Iodine deficiency can also cause CH (endemic cretinism) (DeLange et al. 2000). Gaudino and colleagues (2005) determined the etiology of CH in 49 non-athyroid cases.
Increased plasma thyroid stimulating hormone in treated congenital hypothyroidism: relation to severity of hypothyroidism, plasma thyroid hormone status, and daily dose of thyroxine.