Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance

Abstract

Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAbs) are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs), blocking (TBAbs), or neutral (N-TRAbs) depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy) occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery) before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism) are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and fetal function.

The Effect of Radioiodine Treatment on TRAb, Anti-TPO, and Anti-TG in Graves’ Disease

“…However, some patients will still have detectable TRAb in the late third trimester [20]. In addition, patients treated with radioiodine several years before pregnancy may also have detectable TRAb during the whole pregnancy period.…”

Alternating hyperthyroidism and hypothyroidism in Graves’ disease

“…Unfortunately, we do not have the availability of TBAb measurement at our institution and only recently have been able to quantify TSAb. Monitoring of TRAb is important in pregnant women with GD, as TSAb and TBAb can cause neonatal thyrotoxicosis and hypothyroidism, respectively, and affect neonatal development . Thyroid peroxidase antibodies (TPO Ab), which are associated with Hashimoto's thyroiditis, can exist in patients with GD.…”

“…Monitoring of TRAb is important in pregnant women with GD, as TSAb and TBAb can cause neonatal thyrotoxicosis and hypothyroidism, respectively, and affect neonatal development. 8 Thyroid peroxidase antibodies (TPO Ab), which are associated with Hashimoto's thyroiditis, can exist in patients with GD. Although TPO Ab were not frequently requested in our case, the titer of TPO Ab increased during the hypothyroid phase.…”

Hyperthyroid Fetal Goiter: A Case Report

“…Therefore, these autoantibodies can focus on the fetus TSH-receptors and induce an excessive biosynthesis of hormones responsible for fetal hyperthyroidism. This explains why fetal hyperthyroidism doesn't appear until the second half of pregnancy, and also in patients with a rate of higher autoantibodies (TRAb) [2,5,[7][8]. The fetal risk concerns both the fetuses of mothers with the past or current Graves' disease and includes: intrauterine growth retardation, prematurity, intrauterine fetal death (15-25% if untreated), fetal Graves' disease [2][3]6].…”