Congenital goiter is usually sporadic and can result from a fetal thyroxine (T₄) synthetic defect or from administration of antithyroid drugs or iodides during pregnancy for the treatment of maternal thyrotoxicosis. Goitrogenic drugs and iodides cross the placenta and at high doses can interfere with synthesis of thyroid hormone, resulting in goiter and hypothyroidism in the fetus. The concomitant administration of thyroid hormone with the goitrogen does not prevent this effect, because insufficient amounts of T₄ cross the placenta. Iodides are included in many proprietary cough preparations used to treat asthma; these preparations should be avoided during pregnancy because they have often been reported to cause congenital goiter. Amiodarone, an antiarrhythmic drug with 37% iodine content, has also caused congenital goiter with hypothyroidism. Even when the infant is clinically euthyroid, there may be retardation of osseous maturation, low levels of T₄, and elevated levels of TSH. In women with Graves disease receiving antithyroid drugs, these effects can occur when the mother takes propylthiouracil at only 100-200 mg/24 hr; all such infants should undergo thyroid studies at birth. Administration of thyroid hormone to affected infants may be indicated to treat clinical hypothyroidism, to hasten the disappearance of the goiter, and to prevent brain damage. Because the condition is rarely permanent, thyroid hormone may be safely discontinued after the antithyroid drug has been excreted by the neonate, usually after 1-2 wk.

Enlargement of the thyroid at birth may occasionally be sufficient to cause respiratory distress that interferes with nursing and can even cause death. The head may be maintained in extreme hyperextension. When respiratory obstruction is severe, partial thyroidectomy rather than tracheostomy is indicated (Fig. 561-1).

Figure 561-1 Congenital goiter in infancy. A, Large congenital goiter in an infant born to a mother with thyrotoxicosis who had been treated with iodides and methimazole during pregnancy. B, A different infant, 6 wk old, with increasing respiratory distress and cervical mass since birth. The operation revealed a large goiter that almost completely encircled the trachea. Notice the anterior deviation and posterior compression of the trachea. Partial thyroidectomy completely relieved the symptoms. It is apparent why a tracheostomy is not adequate treatment for these infants. The cause for the goiter was not found.

Goiter is almost always present in the infant with neonatal Graves’ disease. These goiters usually are not large; the infant manifests clinical symptoms of hyperthyroidism. The mother often has a history of Graves disease, although discovery of neonatal hyperthyroidism can lead to the diagnosis of maternal Graves’ disease. Thyroid enlargement results from transplacental passage of maternal thyroid-stimulating immunoglobulin (Chapter 562.1). TSH receptor-activating mutations are also a recognized cause of congenital goiter and hyperthyroidism.

When no causative factor is identifiable, a defect in synthesis of thyroid hormone should be suspected. Neonatal screening programs find congenital hypothyroidism caused by such a defect in 1/30,000-50,000 live births. It is advisable to treat immediately with thyroid hormone and to postpone more-detailed studies for later in life. If a specific defect is suspected, genetic tests to identify a mutation may be undertaken (Chapter 559). Because these defects are transmitted by recessive genes, a precise diagnosis is helpful for genetic counseling. Monitoring subsequent pregnancies with ultrasonography can be useful in detecting fetal goiters (Chapter 90).

Pendred’s syndrome, characterized by familial goiter and neurosensory deafness, is caused by a mutation in the pendrin gene, which codes for a chloride-iodide transport protein present in the thyroid gland and cochlea. This defect results in abnormal iodide organification in the thyroid and can cause a goiter at birth. The more common presentation is a euthyroid goiter and deafness later in life.

Iodine deficiency as a cause of congenital goiter is rare in developed countries but persists in isolated endemic areas (see later). More important is the recognition that severe iodine deficiency early in pregnancy can cause neurologic damage during fetal development, even in the absence of goiter. The iodine deficiency can result in maternal and fetal hypothyroidism, preventing the partially protective transfer of maternal thyroid hormones.

When the “goiter” is lobulated, asymmetric, firm, or large to an unusual degree, a teratoma within or in the vicinity of the thyroid must be considered in the differential diagnosis (Chapter 563).