Congenital hypothyroidism: etiology and pathogenesis

Congenital hypothyroidism is a frequently occurring condition with possibly severe and irreversible consequences. Most of the cases are due to thyroid ectopia, aplasia or hypoplasia and are sporadic in occurrence. Inherited defects of thyroid hormone biosynthesis, secretion and utilization represent a minor, although not insignificant, fraction of the cases of congenital hypothyroidism. In a number of cases, transient congenital hypothyroidism can be due to such causes as maternal exposure to antithyroid drugs or excess iodine, transplacental transfer of blocking antibodies or endemic iodine deficiency. The latter is still a matter of concern in selected geographical areas. Both sporadic and familial cases of hypothalamic-pituitary hypothyroidism are quite rare. Early diagnosis of congenital hypothyroidism by mass screening programs is of the foremost importance for the prevention of long-term sequelae. The molecular defect has been elucidated in a number of inherited defects of thyroid hormone biosynthesis, secretion and utilization. These include impaired thyroidal response to thyroid-stimulating hormone (TSH) due to an altered TSH receptor, defective synthesis of thyroglobulin, defective synthesis of thyroid peroxidase, generalized resistance to thyroid hormone, and familial isolated TSH deficiency. It is anticipated that, as more mutations become available for detailed molecular analysis, further advances in our knowledge of the molecular aspects of thyroid function will ensue in the near future.