Prenatal diagnosis of fetal goiter revealing iodine utilization defect

We report on a case of fetal goitrous diagnosed on ultrasonogram done at 31 weeks of gestation. Thyroid maternal function was normal and no therapeutic was responsible. Hormonal test done on cord blood supported diagnosis of prenatal hypothyroidism. The infant was born prematurely at gestation age of 34 without antenatal treatment. He was eutrophic with clinical and biological signs of hypothyroidism and a large goiter. Therapy with thyroxine was instituted on the third day of life. At 9 months, growth and development are normal. Congenital hypothyroidism has an incidence of approximately 1 in every 4000-5000 live births. Rarely fetal goitrous hypothyroidism have been attributed to thyroid hormone dyshormonogenesis. When fetal goiter is diagnosed on ultrasonography, without maternal hypothyroidism or therapeutic and when hypothyroidism is confirmed on fetal blood, this diagnosis must be suspected.     

Intrauterine treatment of fetal goitrous hypothyroidism controlled by determination of thyroid-stimulating hormone in fetal serum. A case report and review of the literature

We report a rare case of fetal goitrous hypothyroidism complicated by polyhydramnios and preterm labor in a mother without thyroid gland pathology. The diagnosis was made in the 26th week by ultrasound and cordocentesis [TSH 170 microU/ml, free T(4) 0.2 ng/dl]. The therapeutic regime required repeated fetal blood sampling for determination of thyroid hormones. Five intra-amniotic administrations of 250 microg levothyroxine (LT4) weekly were initiated. Because of the persisting goiter and the elevated level of TSH (128 microU/ml in 32 weeks) in the fetal serum the dosage had to be adjusted to 500 microg LT4 in the next five injections. TSH in fetal serum declined to 49.2 microU/ml in 36 weeks. Normal fetal growth and an uncomplicated course of pregnancy between the 27th and 37th week of gestation were observed. Monitoring of intrauterine therapy by determination of TSH in fetal serum may provide more reliable data than measuring TSH in amniotic fluid. A review of 15 cases of fetal goitrous hypothyroidism in the English literature is presented.     

Fetal goitrous hypothyroidism followed by neonatal transient hyperthyroidism. A case report

We report a case of fetal goitrous hypothyroidism followed by neonatal transient hyperthyroidism. A fetal goiter (26 x 38 mm) was detected by ultrasound and magnetic resonance imaging at 29 weeks of gestation. Hypothyroidism was confirmed by cordocentesis, which revealed an elevated TSH (255 microIU/ml) and a low free T4 (0.4 ng/dl). The fetal goiter decreased in size after treatment with four 240-microgram intra-amniotic administrations of levothyroxine. A 2,829-gram male neonate was delivered vaginally at 37 weeks of gestation, showing an euthyroid status at birth. On day 3, free T3 was 6.9 pg/ml and free T4 was 6.4 ng/dl, indicating hyperthyroidism. This persisted for 4 months. His thyroid functions reverted to normal at 4 months of age and have been within normal range since. Undetermined factors might be involved in the development of thyroid dysfunction in the perinatal period.     

Early prenatal diagnosis and therapy of fetal hypothyroid goiter.

We report a case of early diagnosis of iodide-induced fetal hypothyroidism at 22 weeks of gestation, confirmed at 29 weeks by cordocentesis and successfully treated intra-amniotically. The ultrasonographic feature was the presence of two echogenic masses in the fetal neck; polyhydramnios was absent. Mild hypothyroidism was diagnosed based on fetal serum obtained by percutaneous umbilical blood sampling at 29 weeks of gestation. The persistence of fetal hypothyroidism in spite of maternal thyroid improvement was confirmed by a second cordocentesis at 35 weeks of gestation, and a single injection of intra-amniotic levothyroxine (250 micrograms) was performed. The serial ultrasonographic examinations showed disappearance of the fetal goiter. A healthy female baby (3,630 g) was delivered at term. At birth, the thyroid gland was not enlarged, and neonatal thyroid hormones were within the normal range. This case suggests that cordocentesis is a reliable method to assess the fetal thyroid status; moreover a single injection of intra-amniotic thyroxine was effective in treating fetal hypothyroid goiter.     

Effective method for prediction of transient hypothyroidism in neonates born to mothers with chronic thyroiditis

An effective method of prediction of neonatal transient hypothyroidism was examined in 105 neonates (including a pair of twins) born to mothers with chronic thyroiditis (92 mothers with goitrous Hashimoto's disease and 12 with primary atrophic hypothyroidism). Antithyroid microsomal antibody was measured by a hemagglutination technique (MCHA), and antithyroid-stimulating hormone (TSH) receptor antibody by both radioreceptor assay (TBII) and biologic thyroid-stimulation blocking assay (TSBAb). For generalization of predictive criteria, the expression of TBII activity was standardized using standard serum made taking units of MRC-LATS-standard B as a reference, and that of TSBAb activity was standardized as the degree of dilution with normal pooled serum to attain 50% inhibition of TSH (100 microU/ml)-induced cyclic adenosine monophosphate increase (TSBAb50). The MCHA titer in maternal serum at delivery correlated well with that of the corresponding cord serum, but not with the free thyroxine (T4) index or the TSH level in cord serum. TBII activity was positive in only 4 of 12 mothers with primary atrophic hypothyroidism, TSBAb activity was also positive only in these four mothers, and neonatal thyroid dysfunction was observed in three of their neonates. Two of these neonates developed transient hypothyroidism requiring T4 treatment, and the t third developed mild transient hyperthyrotropinemia with normal T4 and triidothyronine levels. The mothers whose neonates showed transient hypothyroidism had TBII activities of more than 300 U/ml and TSBAb50 activities of more than 300. Ninety-two mothers with goitrous Hashimoto's disease had neither TBII nor TSBAb activity, irrespective of their thyroid function, and delivered euthyroid babies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Successful in utero treatment of fetal goitrous hypothyroidism: case report and review of the literature

In this report, we present a case of fetal goiter with overdistended fetal neck and mild polyhydramnios. Amniocentesis and cordocentesis were conducted at 32 weeks' gestation and fetal goitrous hypothyroidism was diagnosed. Intra-amniotic injection of l-thyroxine (T4) was performed with a weekly dose of 150 microg four times between 33 and 36 weeks' gestation. In response to this in utero treatment, the goiter was reduced and polyhydramnios was improved. The mother gave birth to a healthy live male infant with normal thyroid function. From our case report and review of previous literature, we recommend that the amount of l-thyroxine start as low as 150 microg, and that repeat cordocentesis be avoided as long as other clinical and laboratory parameters indicate improvement of the fetal conditions.     

Prenatal diagnosis and early in utero management of fetal dyshormonogenetic goiter

We present a case of a fetal dyshormonogenetic goiter diagnosed by ultrasound examination at 24 weeks of gestation, in a woman with no past history of thyroid disease or goitrogen treatment and with normal thyroid tests, including absence of auto-antibodies. In this situation, fetal goiter may only be associated with fetal hypothyroidism, therefore cord blood sampling was not performed but early treatment was initiated. Amniotic fluid instillation of thyroid hormone led to a rapid decrease in amniotic fluid volume and a clear reduction in thyroid goiter. However, fetal thyroid volume did not totally normalise, and cord blood analysis at birth showed elevated fetal TSH level. As prenatal treatment of fetal hypothyroidism remains controversial in euthyroid mothers, the main objective is to prevent obstetrical complications of large goiters. Therefore, in some selected cases with no maternal history of thyroid disease and normal thyroid function tests, cordocentesis is not necessary to confirm fetal thyroid status or to adjust fetal treatment.     

Antenatal diagnosis and treatment of hypothyroid fetal goiter in an euthyroid mother: a case report and review of literature

Fetal goiter is an extremely rare complication of pregnancy. Its incidence is 1 in 40?000 deliveries. Antithyroid maternal therapy is responsible for 10–15% of fetal congenital hypothyroidism and can be considered as the most frequent underlying cause for this condition. The frequency of fetal goiter that is associated with fetal hypothyroidism and normal maternal thyroid function, as in our case, is even less frequent. Fetal goiter is associated with increased rate of perinatal complications and long-term morbidity, due to peripartum complications including labor dystocia due to its mass effect, as well as neonatal airway obstruction that may lead to hypoxic-ischemic brain injury and death. We present, in this study, a case report of late antenatal fetal goiter in an euthyroid woman and a literature review of the diagnosis and treatment of these cases.     

Fetal goiter and bilateral ovarian cysts

A unique case of fetal goiter accompanied by bilateral ovarian cysts in a mother treated with methimazole for Graves'disease is reported. The abnormal findings were detected by ultrasound at 31 weeks of gestation. Umbilical fetal blood sampling revealed elevated serum TSH, normal concentrations of free T 4 , normal FSH and LH and high concentrations of E 2 . A series of weekly amniocenteses and intra-amniotic injections of levothyroxine was initiated, along with a reduction of the mother's methimazole dosage. The level of TSH in amniotic fluid was initially high, but was considerably reduced by each injection and followed by a gradual reduction of fetal goiter as well as the left ovarian cyst. The right cyst ruptured spontaneously. At 36 weeks + 4 days, the patient underwent elective caesarean section and gave birth to a female, weighing 2,880 g with 1- and 5-min Apgar scores of 10. The thyroid gland appeared normal in size, and cord blood TSH and free T 4 were both within normal limits. At ultrasound control 6 days later, the right ovarian cyst was not visible, while the left cyst was still present. Thus, our report supports previous findings that fetal goiter can be treated successfully with intra-amniotic injection of levothyroxine.More importantly, it shows that fetal hypothyroidism with elevated levels of TSH can be accompanied by ovarian cysts,suggesting interference between thyreotropic and gonadotropic hormones.     

The influence of iodine deficiency during pregnancy of fetal and neonatal development

The iodine is fundamental substrate for thyroid hormones synthesis. Thyroxine and triiodothyronine play a crucial role in human brain development and maturation. It is well known, that not only fetal, but also maternal thyroid hormones are essential for normal prenatal central nervous system development. During pregnancy complex changes of maternal thyroid function occur and they are influenced by the maternal iodine supply. With decreasing iodine intake, maternal goiter and hypothyroxinemia as well as fetal and neonatal hypothyroidism become more prevalent. The severity of iodine deficiency and hypothyroidism in the mother during early and midgestation is related to the severity of the neural damage in the fetus. In severe iodine deficiency, central nervous system damage is already irreversible at birth and can only be prevented by correction of the maternal iodine deficiency early in pregnancy. Therefore iodine supplementation during pregnancy is now strongly recommended.     

Onset of Graves’ disease during pregnancy in a woman with established hypothyroidism

Background: Pregnancy strongly influences the thyroid gland and its function. Thyroid guidelines recommend a 30 to 50% increase of the preconceptional levothyroxine dose in women with hypothyroidism, when pregnancy is diagnosed.

Case: A 33 year-old, 8-week pregnant woman with hypothyroidism, presents with a 2-week history of palpitations, sweating, nervousness and fatigue. Physical examination shows tachycardia (108 bpm), distal tremors and diffuse goiter. After biochemical confirmation of hyperthyroidism, her levothyroxine dose is reduced and finally interrupted. Propylthiouracil is started and maintained until after the delivery of a healthy baby at week 40. Two weeks postpartum, hyperthyroidism worsens and propylthiouracil is replaced by methimazole. Eighteen months after delivery 7.5?mCi 131Iodine was given. Two months later, hypothyroidism developed and levothyroxine was initiated.

Conclusion: Although conversion of Hashimoto's hypothyroidism into Graves' disease is exceptional in pregnancy, pregnant women with autoimmune hypothyroidism should ideally have their TSH concentrations measured before empirically increasing their levothyroxine dose.     

Efficacy of oral iodide therapy on neonatal hyperthyroidism caused by maternal Graves' disease

OBJECTIVE: To verify the efficacy of oral iodide therapy in treating a case of early neonatal hyperthyroidism due to maternal Graves' disease. METHODS: We report a case of neonatal hyperthyroidism which occurred in a 2,650-gram, female baby, born at 39 weeks' gestational age (GA) to a 30-year-old mother affected by Graves' disease and treated with thionamides (propylthiouracil) from the 20th week of gestation. A fetal goiter, due to maternal therapy, had been observed by ultrasound scan at 31 and 35 weeks of gestation, with contemporary low cord thyroid hormone levels. Two intra-amniotic injections of levothyroxine were then performed at 34 and 36 weeks of gestation, which led to a significant reduction of fetal goiter and to normalization of cord thyroid hormone levels. The neonatal clinical course was characterized by symptoms of hyperthyroidism from the 2nd to 3rd days of life (irritability, tachycardia, tachypnea, hyperphagia), mostly during feeding. Oral treatment with potassium iodide (KI, 8 mg x 3 times a day) was started at 23 days of life. RESULTS: Treatment with KI led to a significant reduction of neonatal clinical symptoms and to a normalization of hormone levels within 4 days of therapy. The treatment was discontinued in 13th week of life because of neonatal well-being and normal hormone levels. CONCLUSIONS: We believe that KI therapy is effective in treating neonatal hyperthyroidism and does not cause suppression of neonatal thyroid activity, which is possible using antithyroid drugs like thionamides.     

Diagnosis and Management of Hypothyroidism in Pregnancy

Hypothyroidism is not a common occurrence in pregnancy, but it is important that nurse practitioners recognize it early. Complications of hypothyroidism in pregnancy are pregnancy-induced hypertension, preeclampsia, abruptio placentae, low birth weight and stillbirth, and fetal distress in labor. Careful monitoring of pregnant women for hypothyroidism and correction with levothyroxine therapy can prevent these complications. During pregnancy, the thyroxine needs of women with hypothyroidism are increased, and their dosage of levothyroxine should be individualized. Nurse practitioners can provide holistic care to the woman with hypothyroidism to ensure optimal maternal and fetal health     

Non-invasive management of fetal goiter during maternal treatment of hyperthyroidism in Grave's disease

There is an increased risk of fetal goiter in patients who have a history of Grave's disease and undergo propylthiouracil (PTU) treatment during pregnancy. In this report, we describe a case of a fetal goiter detected by antenatal ultrasound at the 26th week of gestation in a mother treated with PTU for Grave's disease. A 32 x 38 x 20 mm fetal goiter was detected, each lobe measured 30 x 18 x 18 mm and estimated volume was 10 cm3. Subsequently, fetal thyroid function was assessed by umbilical fetal blood sampling. Cord blood showed elevated serum TSH (40.2 mU/l) and normal concentrations of free T4 (9.5 pmol/l) and free T3 (2.6 pmol/l). There were no other ultrasonographic signs of fetal hypothyroidism. Based on the above findings, the mother's PTU dosage was reduced to 50 mg daily from a total of 150 mg and weekly ultrasonographic examinations were performed. Six weeks after the initial ultrasound, a complete regression of the fetal goiter was noted. At the 34th week of gestation, the patient was delivered due to intrauterine growth restriction and oligohydramnios and gave birth to a male, weighing 1,920 g. The newborn thyroid was not palpable and thyroid ultrasonography was normal. Cord blood TSH was normal (8.4 mU/l) and free T4 was within lower normal limit (9.03 pmol/l). Ten days later, newborn thyroid function was normal and the baby did well afterwards. In conclusion, after the evaluation of fetal thyroid status, selected cases with fetal goiter can be initially managed without intrauterine treatment.     

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.     

Prospective evaluation of pregnant women with hypothyroidism: Implications for treatment

Pregnancy is characterized by a series of maternal hormonal and metabolic changes which can affect thyroid function and the course of thyroid dysfunction in different ways. Moreover, hypothyroidism is also associated with obstetric complications and morbidity to the fetus. The aim of the present study was to evaluate the influence of hypothyroidism during the course of pregnancy and the necessity of adjusting the dose of levothyroxine. We prospectively followed 16 patients with previous diagnosis of hypothyroidism. In ten patients (62.5%) it was necessary to raise the dose of levothyroxine, with a median increase of 20.7%. One pregnancy was complicated by premature amniorrhexis and two by pre-eclampsia. The screening for congenital hypothyroidism was negative in all newborns. We conclude that it is very important to offer screening to high-risk patients who wish to become pregnant. Dose adjustment based on serum levels of thyroid-stimulating hormone (TSH) is essential. In patients in whom TSH is not measured during the first weeks of pregnancy, a good approach could be to increase the dose of replacement therapy by 20–25% to avoid hypothyroidism.     

Prospective evaluation of pregnant women with hypothyroidism: implications for treatment.

Pregnancy is characterized by a series of maternal hormonal and metabolic changes which can affect thyroid function and the course of thyroid dysfunction in different ways. Moreover, hypothyroidism is also associated with obstetric complications and morbidity to the fetus. The aim of the present study was to evaluate the influence of hypothyroidism during the course of pregnancy and the necessity of adjusting the dose of levothyroxine. We prospectively followed 16 patients with previous diagnosis of hypothyroidism. In ten patients (62.5%) it was necessary to raise the dose of levothyroxine, with a median increase of 20.7%. One pregnancy was complicated by premature amniorrhexis and two by pre-eclampsia. The screening for congenital hypothyroidism was negative in all newborns. We conclude that it is very important to offer screening to high-risk patients who wish to become pregnant. Dose adjustment based on serum levels of thyroid-stimulating hormone (TSH) is essential. In patients in whom TSH is not measured during the first weeks of pregnancy, a good approach could be to increase the dose of replacement therapy by 20-25% to avoid hypothyroidism.     

Hypothyroidism and pregnancy: still a controversial issue

Abstract

Subclinical hypothyroidism (SCH) in pregnancy is common, according to literature, affecting up to 15% of pregnancies. It still represents a controversy weather levothyroxine has beneficial effects on pregnancy outcomes. In this retrospective and prospective cohort study, we assessed fetal and maternal outcomes in women with known thyroid status pre-pregnancy, and hypothyroidism during pregnancy. We included 393 pregnant women, 90 (22.9%) diagnosed with overt and 303 with SCH (77.1%). A total of 94 (56%) had positive anti-TPO antibodies. Levothyroxine substitution across all observational periods was suboptimal, mostly during first trimester in both groups of patients (85.4%). There was a difference in the number of live births in favor of group with SCH (p?=?.004). Women with overt hypothyroidism were more likely to develop complications during pregnancy (RR = 1.153, 95%CI = 0.775???1.714) and had positive TPO-antibodies more often (p?=?.022). The only significant association was found between fetal outcomes in women with SCH and positive TPO-antibodies (p?=?.018), while positive Tg-antibodies did not affect the pregnancy outcomes of women with SCH. Moreover, no correlation was observed between outcomes and adequacy of levothyroxine substitution. These results indicate that TPO-antibody positivity could be the most important factor of pregnancy outcomes independent of the TSH levels or adequacy of levothyroxine therapy.     

Graves' disease in pregnancy: prospective evaluation of a selective invasive treatment protocol

OBJECTIVE: Graves' disease in pregnancy carries a risk of fetal thyrotoxicosis from the transplacental transfer of thyroid-stimulating antibodies or fetal hypothyroidism from transplacental transfer of antithyroid drugs and thyroid-blocking antibodies. STUDY DESIGN: From 1991 through 2002, all pregnant women with Graves' disease underwent follow-up evaluations that included serial thyroid-stimulating antibody level, thyroid function, and ultrasound examinations. Umbilical blood sampling was recommended if the thyroid-stimulating antibody level was abnormally high or if fetal tachycardia, goiter, intrauterine growth retardation, or hydrops were present. For fetal hyperthyroidism, the mother received antithyroid drugs; for fetal hypothyroidism, maternal antithyroid treatment was reduced, and thyroxine was injected into the amniotic sac. RESULTS: Of 40000 deliveries, 24 pregnancies (26 fetuses) occurred in 18 women with Graves' disease. Nine of 14 mothers with positive findings elected umbilical blood sampling. In 4 of the mothers, the results were normal. Hyperthyroidism and hypothyroidism were diagnosed in 2 and 3 fetuses, respectively. All the fetuses were treated successfully by the protocol with up to four repeated umbilical blood samplings. No complications were recorded in any of the 20 umbilical blood sampling. In the 5 patients who had only elevated thyroid-stimulating antibody levels and who did not elect umbilical blood sampling, sonographic findings remained normal up to term, and the newborn infants were normal. One of 12 children (in whose case we did not recommend umbilical blood sampling) was born with transient hypothyroidism caused by maternal propylthiouracil treatment. All children, whose cases were followed for up to 9 years, are normal. CONCLUSION: In women with Graves' disease, umbilical blood sampling in selected cases may improve the control of fetal thyroid function.     

Large fetal goiter due to placental passage of maternal antithyroperoxidase antibodies

We report a case of fetal goiter in a pregnant woman with Graves-Basedow disease. It was diagnosed in the third trimester by a routine ultrasound, and the cordocentesis verified increased levels of thyroxine (T4) and increased autoantibodies (antithyroperoxidase antibodies) that were also increased in maternal blood. Fetal goiter got smaller on the follow-up scans, and the newborn presented hypothyroidism. Current notions on the diagnosis and management of fetal goiter are briefly discussed.