Fetal Thyroid Masses and Fetal Goiter

Definition

Fetal goiter is an enlargement of the thyroid gland ( Figs. 72.1 and 72.2 ). It is defined on ultrasound (US) as a thyroid circumference or diameter greater than the 95th centile for gestational age. It is frequently associated with maternal thyroid dysfunction, generally hypothyroidism.

Prevalence and Epidemiology

The prevalence of goitrous hypothyroidism is 0.2 : 10,000 to 0.3 : 10,000 live births in Europe and North America; the prevalence of the less frequent goitrous hyperthyroidism is unknown. In areas with endemic iodine deficiency, there is a higher prevalence of congenital cretinism, which may be accompanied by a fetal goiter. Iodine deficiency is still considered a major health problem worldwide.

Etiology and Pathophysiology

Congenital goiters are most commonly diagnosed in mothers with known thyroid disease, usually Graves disease. Graves disease is a common cause of hyperthyroidism that is present in 0.2% of pregnant women. This condition is treated with antithyroid drugs, including both propylthiouracil and methimazole because it passes less easily through the placenta. Reports of aplasia cutis in the fetus after first-trimester exposure to methimazole and long-term complications in the mother from propylthiouracil, particularly hepatotoxicity, have led to recommendations of first-trimester treatment with propylthiouracil then second-trimester and third-trimester management with methimazole. Fetuses of mothers with thyroid disease are especially susceptible to develop congenital hyperthyroid goiter owing to the passage of antibodies against the thyroid-stimulating hormone (TSH) receptor, also called thyroid-stimulating immunoglobulin, found in 1% of children born from mothers with Graves disease. Fetuses can also develop congenital goitrous hypothyroidism because of the transplacental passage of propylthiouracil or occasionally inhibitory immunoglobulins. Different authors have reported how maternal exposure to iodine as nutritional supplements or as a contrast used for hysterosalpingography periconceptionally could be linked to the detection of fetal goiter.

When considering all cases of congenital goitrous hypothyroidism, almost 80% are caused by thyroid dysgenesis and may be related to somatic mutations in the TSH receptor. Nearly 15% of cases are caused by dyshormonogenesis or transplacental passage of TSH receptor blocking antibodies. Dyshormonogenesis is the most frequent cause in the absence of maternal thyroid disease or iodine deficiency; it is frequently caused by recessively inherited biochemical defects in one or more steps in the pathway leading to the normal synthesis of thyroid hormones. Less than 5% of the cases are caused by hypothalamic pituitary disorders and central hypothyroidism. Endemic iodine deficiency, the use of goitrogens (expectorants with potassium iodine or povidone-iodine), and excess maternal iodine ingestion are considered less frequent causes of fetal goiters. Congenital goitrous hyperthyroidism is most frequently caused by maternal antibodies or dyshormonogenesis.