Fetal and Neonatal Hyperthyroidism

Abstract

Fetal and neonatal hyperthyroidism are usually produced by transplacental passage of thyroid-stimulating immunoglobulins. Most commonly, the thyroid-stimulating immunoglobulins are a component of active maternal Graves' disease. However, such antibodies may continue to be produced after ablation of the thyroid by surgery, radioiodine, or by the immune mechanisms of Hashimoto's thyroiditis. Other mechanisms that have produced fetal and neonatal hyperthyroidism include activating mutations of the stimulatory G protein in McCune-Albright syndrome and activating mutations of the thyrotropin (TSH) receptor. Fetal hyperthyroidism may be associated with intrauterine growth retardation, nonimmune fetal hydrops, craniosynostosis, and intrauterine death. Features of this condition in the neonate include hyperkinesis, diarrhea, poor weight gain, vomiting, ophthalmopathy, cardiac failure and arrhythmias, systemic and pulmonary hypertension, hepatosplenomegaly, jaundice, hyperviscosity syndrome, thrombocytopenia, and craniosynostosis. The time course of thyrotoxicosis depends on etiology. Remission by 20 weeks is most common in neonatal Graves' disease; remission by 48 weeks is nearly always seen. A subset of these patients may have persistent disease when there is a strong family history of Graves' diseases. Disease persistence is characteristic of patients with activating mutations of the TSH receptor. Treatment of fetal hyperthyroidism comprises administration of antithyroid drugs to the mother. Fetal heart rate and fetal growth should be monitored. Ultrasonography may reveal changes in thyroid size. At times, cordocentesis may be useful for monitoring fetal thyroid function. Hyperthyroid neonates may be treated with antithyroid drugs, beta-adrenergic receptor blocking agents, iodine, or iodinated contrast agents, and at times, with glucocorticoids and digoxin. Nonremitting causes of neonatal hyperthyroidism require ablative treatments such as thyroidectomy.

Resistance to diet-induced obesity in mice globally overexpressing OGH/GPB5

“…However, other that the shortening of a few facial bones, the skeletons of OGH-TG mice are normal. Although premature craniosynostosis is one of the bone maladies that is associated with congenital hyperthyroidism in humans (38)(39)(40), it is not clear at this point how that corresponds to the facial abnormality that we observed. One confounding issue is that, in contrast to our findings, thyroid hormone has been reported to induce an increase in facial length in young rats (41).…”

Management of Graves' hyperthyroidism in pregnancy: focus on both maternal and foetal thyroid function, and caution against surgical thyroidectomy in pregnancy

“…Lack of thyroid hormones for more than a few weeks during vulnerable periods of development involves a risk of permanent cerebral impairment (25). On the other hand, excess amounts of thyroid hormones may lead to growth retardation and accelerated bone maturation, and it is associated with an increase in the risk of foetal death (26). In the brain, local concentrations of thyroid hormone are among other factors dependent on the activity of thyroid hormone activating and inactivating deiodinases.…”

“…After birth the antithyroid drugs from the mother will disappear from the foetal circulation and thyroid within the first days, and after some delay, neonatal hyperthyroidism may develop until the maternal antibodies are cleared (26). High-serum levels of maternal TSHreceptor antibodies in late pregnancy indicate a risk of neonatal hyperthyroidism (3).…”

Predictive value of maternal second-generation thyroid-binding inhibitory immunoglobulin assay for neonatal autoimmune hyperthyroidism

“…Among them, 1% will give birth to a hyperthyroid neonate (3,4,5). During normal fetal development, the thyroid gland begins to synthesize thyroid hormones from 10 to 12 weeks of gestation, and the thyroid-stimulating hormone receptor (TSHR) responsiveness to TSH develops at about 20 weeks of pregnancy (6,7,8,9).…”