Genetic defects in thyroid hormone production result in increased levels of thyroid-stimulating hormone (TSH), which in turn can cause congenital goiter. Goiter is present in about 15% of cases of congenital hypothyroidism. There are a number of gene abnormalities that cause dyshormonogenesis; they commonly have an autosomal recessive form of inheritance, and many are single-gene defects.

Dyshormonogenesis can result from a defect in any of the steps in thyroid hormone biosynthesis, including

Children with Pendred syndrome have mild hypothyroidism or euthyroidism, goiter, and sensorineural hearing loss due to a genetic abnormality of a protein (pendrin) involved in iodine transport and cochlear function. Although Pendred syndrome is caused by a genetic defect, it rarely manifests in the newborn period.

Women with an autoimmune thyroid disorder produce antibodies that may cross the placenta during the 3rd trimester. Depending on the disorder, the antibodies either block TSH receptors, causing hypothyroidism, or stimulate them, causing hyperthyroidism. Typically, in affected infants, the changes in hormone secretion and the associated goiter resolve spontaneously within 3 to 6 mo.

Goitrogens such as amiodarone or antithyroid drugs (eg, propylthiouracil, methimazole) can cross the placenta, sometimes causing hypothyroidism and rarely causing goiter.