Graves' disease complicated by fetal goitrous hypothyroidism treated with intra-amniotic administration of levothyroxine.

Fetal goitrous hypothyroidism is a rare entity and is caused mainly by maternal treatment of Graves' disease (GD). We report a case of a 22-year-old woman referred at 12 weeks of gestation due to hyperthyroidism subsequent to recently diagnosed GD. She started treatment with propylthiouracil and, at 21 weeks of gestation, fetal goitre was detected. A cordocentesis confirmed the diagnosis of fetal goitrous hypothyroidism, and intra-amniotic administration of levothyroxine (LT4) was performed and repeated through the pregnancy due to maintenance of fetal goitre. The pregnancy proceeded without further complications and a healthy female infant was born at 37 weeks of gestation, with visible goitre and thyroid function within the normal range at birth. Although there is no consensus on the optimal dose, the number of injections and the interval between them, intra-amniotic LT4 administration is recommended once fetal goitrous hypothyroidism is suspected, in order to prevent long-term complications of fetal hypothyroidism.

Fetal thyroid disorders: Pathophysiology, diagnosis and therapeutic approaches.

Fetal thyroid disorders while uncommon in general, have significant morbidity and profound effects in the neonate. Pregnancy provides the opportunity not only for the diagnosis of these conditions but also for therapeutic interventions. In careful balance, these disorders range from hypothyroidism to hyperthyroidism, both may manifest with fetal thyroid goiters as well. The intrauterine therapeutic approach of these must also weight the balance in this range as well as the maternal well being which may also express thyroid dysfunction. In this review we explore the different fetal manifestations of thyroid disease, describe the pathophysiology and therapeutic approaches both in practice and in development.

Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroid-stimulating hormone receptor antibody after ablative therapy.

High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure.

Conservatively managed fetal goiter: an alternative to in utero therapy.

Fetal goiter may arise from a variety of etiologies including iodine deficiency, overtreatment of maternal Graves' disease, inappropriate maternal thyroid replacement and, rarely, congenital hypothyroidism. Fetal goiter is often associated with a retroflexed neck and polyhydramnios, raising concerns regarding airway obstruction in such cases. Prior reports have advocated for cordocentesis and intra-amniotic thyroid hormone therapy in order to confirm the diagnosis of fetal thyroid dysfunction, reduce the size of the fetal goiter, reduce polyhydramnios, aid with the assistance of maternal thyroid hormone therapy and reduce fetal malpresentation. We report two cases of conservatively managed fetal goiter, one resulting in a vaginal delivery, and no evidence of postnatal respiratory distress despite the presence of polyhydramnios and a retroflexed neck on prenatal ultrasound.

[Assessment of thyroid hormones and androgens in amniotic fluid: clinical interest]. / Dosage des hormones thyroïdiennes et surrénaliennes dans le liquide amniotique: aide au diagnostic.

Ultrasound scanning is able to detect foetal goiter due either to an hypothyroidy either to an hyperthyroidy, or clitoris hypertrophia resulting from adrenal hyperplasia in female, during the second half of pregnancy. The diagnosis of these rare diseases is of interest because the treatment can be started during pregnancy. An amniotic fluid punction can be discussed and its biochemical analysis may be of interest even though very few commercial assays have been tested on amniotic fluid. Our aim was two investigate the practicability and the value of free thyroxin (FT4), thyrotropin (TSH), 17alpha hydroxyprogesterone (17-OHP) and delta 4 androstenedione (Delta4A) measurement on amniotic fluid using commercially available assays for serum. FT4 and TSH are detectable at low levels in amniotic fluid. FT4 significantly increases from 2.1 pmol/L to 4.2 pmol/L while TSH significantly decreases from 0.27 mU/L to 0.12 mU/L during the second half of pregnancy. An increase in amniotic fluid TSH concentration contributes to the diagnosis of foetal hypothyroidy while the measurement of amniotic fluid FT4 is not informative in case of foetal goiter. 17-OHP and Delta4A are present in amniotic fluid at the same level as in serum. 17-OHP significantly decreases from 1.9 ng/mL to 1 ng/mL during the second half of pregnancy while Delta4A significantly increases from 0.5 ng/mL to 0.8 ng/mL. Absence of increase in their concentrations excludes any severe adrenal hyperplasia.

Tumores fetales: I parte / Fetal tumors: Part I

Se presenta una revisión sistemática y resumida de los diferentes tumores fetales, haciendo énfasis en su diagnóstico prenatal y posibles tratamientos intrauterinos. En esta primera parte se introduce el tema y se analizan tumores del sistema nervioso central, cara y cuello.

Serial in utero ultrasonographic measurements of the fetal thyroid: a new complementary tool in the management of maternal hyperthyroidism in pregnancy.

OBJECTIVE: Treatment of maternal hyperthyroidism during pregnancy is complicated by the lack of readily available measures of the thyroid status of the fetus. The aim of this study is to describe the use of serial in utero ultrasound measurements of fetal thyroid in patients being treated for Graves' disease in pregnancy. METHODS: Over a 24-month period, all pregnant women with Graves' disease attending our special Fetal Thyroid Unit were followed. Maternal thyroid status was assessed by thyroid function tests. Fetal thyroid size was measured serially by transvaginal ultrasonography between 14 and 17 weeks of gestation and by abdominal ultrasonography between 18 and 37 weeks of gestation in 20 women with Grave's disease. RESULTS: In 15 fetuses, thyroid width and circumference were within the 95% confidence interval of the normal population. In five fetuses, thyroid size was above the 95th percentile for gestational age. In three of them, thyroid size decreased concurrently with a decrease in maternal thionamide dosage, reaching normal range. These three fetuses were born euthyroid. In two fetuses, thyroid size was unaffected by a decrement in maternal drug dosage. Both had neonatal thyrotoxicosis at birth. CONCLUSIONS: Serial in utero ultrasonography measuring fetal thyroid size in mothers with Graves' disease can serve as an effective noninvasive tool for the early detection of enlarged fetal thyroid. These findings can be used to monitor the maternal antithyroid drug dosage, thereby preventing intrauterine hypothyroidism in some cases. When a dosage reduction does not cause a decrease in fetal thyroid size, transplacental passage of thyroid-stimulating antibodies causing fetal thyrotoxicosis should be suspected.

Biochemical investigation of foetal and neonatal thyroid function using the ACS-180SE analyser: clinical application.

Despite sonographic detection of foetal goitre, uncertainty persists in the initial diagnosis of thyrotoxicosis and hypothyroidism. The aim of this study was to establish foetal and neonatal iodothyronine and thyrotrophin reference values for the ACS-180SE analyser. From 22 to 36 weeks of gestation, median foetal serum free thyroxine (FT4) levels increased from 6.0 pmol/L to 143 pmol/L, while free tri-iodothyronine (FT3) levels increased from 0.7 pmol/L to 1.9 pmol/L and mean thyrotrophin (TSH) levels remained stable (10.2 +/- 3.8mU/L; n = 33). At birth, concentrations were independent of gender and gestational age. Among the 10 cases of sonographically detected foetal goitre, serum TSH and FT4 were measured in five, showing hypothyroidism (3/5) or hyperthyroidism (2/5). Cord blood TSH levels reflected the efficacy of prenatal therapy. Measurement of foetal FT4 and TSH can be used to confirm foetal thyroid dysfunction, whereas treatment efficacy can be assessed sonographically and confirmed by measurement of TSH assay at birth.

Management of fetal thyroid goitres: a report of 11 cases in a single perinatal unit.

Fetal thyroid goitres may reveal hormonal imbalance. This can jeopardize neurological development and fetal outcome even when early postnatal treatment is provided. We report a series of 11 goitres diagnosed antenatally in women with past or present thyroid disorders or discovered fortuitously on ultrasound scan. Fetuses presented with hyperthyroidism in three cases and hypothyroidism in eight. Hypothyroidism was iatrogenic in five cases, due to maternal anti-thyroid drugs. Hyperthyroidism was induced by transplacental transfer of thyroid stimulating antibodies (TSHrab). Accurate diagnosis of fetal thyroid status was obtained by fetal blood sampling but this invasive method was deemed necessary only in four cases as maternal clinical and biological data and ultrasound signs provided sufficient information to infer the type of thyroid disorder in the remaining patients. Fetal therapy relied on reduction of maternal antithyroid medication and, in selected cases, intra-amniotic injection of levothyroxin in hypothyroidism, and on administration of antithyroid drugs in hyperthyroidism. All newborns were healthy and none displayed consequences of severe thyroid imbalance. No caesarean section was performed for dystocia. Fetal thyroid goitres can be managed successfully with selected use of invasive diagnostic and therapeutic techniques.

[Prenatal diagnosis and treatment of fetal hypothyroid goiter]. / Diagnostic et traitement anténataux d'un goitre foetal hypothyroïdien.

We report on a case of fetal goitrous hypothyroidism confirmed by the study of fetal thyroid function. Two injections of intra amniotic levo-thyroxine were performed at 35 and 36 WA. The serial ultra sonographic examination showed the disappearance of the fetal goiter. A healthy baby were delivered by cesarean section at 37 WA. At birth, the thyroid gland was slightly enlarged and the neonatal thyroid hormones were within the normal range. This case suggests that cordocentesis is a reliable method of assessing the status of the fetal thyroid, and that even as early as 35 WA a prenatal treatment of fetal goitrous hypothyroidism is possible by amniocentesis.

Intrauterine treatment of thyroid goiters.

A fetal thyroid goiter detected by ultrasonography at 20 weeks of amenorrhea (WA) was diagnosed at 23 WA by a second ultrasound examination and a TSH assay in amniotic fluid. Since a sample of fetal blood at 27 WA showed that hypothyroidism was compensated and that goiter size and amniotic fluid volume were stable, intra-amniotic injection of 300 micrograms of L-thyroxine was delayed until 36 WA. This injection was performed before delivery to avoid potential perinatal complications (dystocia and neonatal respiratory distress) caused by large goiters.