Fetal hyperthyroidism associated with maternal thyroid autoantibodies: A case report

Abstract

A 33-year-old Caucasian woman was referred at 24 + 3 weeks of gestation due to fetal tachycardia and hydrops. She had an uncomplicated pregnancy 16 years previously and was on levothyroxine after total thyroidectomy for Graves' disease 6 years previously, when she developed moderate exophthalmos. Laboratory evaluation revealed appropriate thyroid function for this time of gestation: thyroid stimulating hormone (TSH) 1.7 μU/ml (1–3), fT4 18.53 pmol/l (12−22), with positive antibodies: anti-TPO 157 U/ml (<35), TSH receptor antibodies (TRAb) 171.95 U/l (<1.75). The diagnosis was fetal hyperthyroidism due to transplacental passage of stimulating maternal TRAb. Methimazole and digoxin were initiated. The patient remained euthyroid, with fT4 levels in the upper normal range. The fetus showed intrauterine growth retardation, oligohydramnios, aggravating hydrops, goiter with increased central vascularization and improved heart rate without signs of cardiac failure. At 30 + 3 weeks a hydropic hyperthyroid male newborn (birthweight 1560 g) was delivered by cesarean section and admitted to the neonatal intensive care unit. Cord serum showed neonatal hyperthyroidism. Methimazole and propranolol were administered to the newborn. On the 5th postnatal day the infant died because of severe infection inducing respiratory dysfunction, hemodynamic deterioration and cardiac asystole. Graves' disease occurs in about 0.2% of pregnancies. Hyperthyroidism occurs in 1–5% of neonates born to mothers with Graves' disease and the risk correlates with the maternal TRAb titer. Early diagnosis and treatment are crucial not only in pregnant women with active disease, but also in mothers with a history of Graves' disease, even after definitive treatment such as thyroidectomy or ablative therapy.

Hyperthyroid Fetal Goiter: A Case Report

“…The persistent presence of maternal thyroid-stimulating hormone receptor antibody (Trab) in patients with Graves' disease could cause fetal hyperthyroid goiter during pregnancy by stimulating the thyroid gland, leading to excessive thyroid hormone secretion. The risk correlates with the TRab titer [2]. We report here, a case of a hyperthyroid fetal goiter identified by ultrasound exam at 27 weeks 5 days of gestation in a women having Graves' disease and on antithyroid drugs therapy.…”

“…These immunoglobulins, IgG type, have two types of possible action: some stimulate the synthesis of Cyclic Adenosine Monophosphate by these cells, these are the thyroid stimulating immunoglobulins (TSI) while other antibodies will block the binding of TSH with its receptor, these are the thyroid binding inhibiting Immunoglobulins (TBII). Among pregnant women with Graves' disease, 0.2% develops clinical hyperthyroidism and, among them, 1 to 5% of their newborns will present a neonatal hyperthyroidism due to transplacental passage of TRAb [2,6]. Indeed, the fetal thyroid starts its synthesis of thyroid hormone from the 12th week of gestation.…”

“…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].…”

“…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]. Moreover the presence of autoantibodies can encourage the development of fetal goiter, responsible in rare cases to a compression of the trachea or fetal esophageal [6].…”

“…It can be caused by several different pathologies: including dysgenesis, dyshormonogenesis, maternal ingestion of antithyroid drugs, transplacental passage of maternal antibodies, thyroid stimulating hormone receptor mutation, or tumors [1]. Among fetal goiter, fetal hyperthyroidism goiter is more rare with an unknown incidence than the goitrous hypothyroidism which incidence is 1/30000-50000 live births [2]. Fetal hyperthyroid goiter can cause maternal, obstetric and fetal complications and has fetal mortality rate of 16% to 25% if untreated, requiring early diagnosis and appropriate treatment to restore euthyroidism [3][4].…”