Brief clinical and laboratory observation

Neonatal thyrotoxicosis: Intellectual impairment and craniosynostosis in later years

Thyroid hormone signaling is required for both fetal and pediatric development. Hypothyroidism and hyperthyroidism may present in the neonatal period. Hypothyroidism is more common, and the goal of thyroid hormone replacement in neonates is to optimize normal growth and development. In neonates with hyperthyroidism, there is a risk of acute morbidity and mortality and some evidence to suggest the potential for long-term adverse neurocognitive outcomes. This chapter reviews the etiology for both thyroid states (including genetic and clinical risk factors, thyroid hormone metabolism, transport, and receptor function) and the evaluation and treatment of neonatal thyroid disorders. Further clinical research is needed to understand the consequences of fetal and neonatal hypothyroxinemia as well as thyrotoxicosis, especially for preterm and/or critically ill infants, to better understand the potential benefits and risks of treatment.

Thyroid hormones (THs) are instrumental in promoting the molecular mechanisms which underlie the complex nature of neural development and function within the central nervous system (CNS) in vertebrates. The key neurodevelopmental process of myelination is conserved between humans and rodents, of which both experience peak fetal TH concentrations concomitant with onset of myelination. The importance of supplying adequate levels of THs to the myelin producing cells, the oligodendrocytes, for promoting their maturation is crucial for proper neural function. In this review we examine the key TH distributor and transport proteins, including transthyretin (TTR) and monocarboxylate transporter 8 (MCT8), essential for supporting proper oligodendrocyte and myelin health; and discuss disorders with impaired TH signalling in relation to abnormal CNS myelination in humans and rodents. Furthermore, we explore the importance of using novel TH analogues in the treatment of myelination disorders associated with abnormal TH signalling.

Thyroid hormone (TH) is indispensable for normal embryonic and fetal development. Throughout gestation TH is provided by the mother via the placenta, later in pregnancy the fetal thyroid gland makes an increasing contribution. Maternal thyroid dysfunction, resulting in lower or higher than normal (maternal) TH levels and transfer to the embryo/fetus, can disturb normal early development. (Maternal) thyroid dysfunction is mostly caused by autoimmune hypo- or hyperthyroidism, i.e. Hashimoto and Graves disease. Autoimmune hyperthyroidism is caused by stimulating TSH receptor antibodies (TSHR Ab), patients with autoimmune hypothyroidism may have blocking TSHR Ab. Maternal TSHR Ab cross the placenta from mid gestation and may cause fetal and transient neonatal hyper- or hypothyroidism. Anti-thyroid drugs taken for autoimmune hyperthyroidism cross the placenta throughout gestation, and may cause fetal and transient neonatal hypothyroidism. This review focusses on the consequences of maternal hypo- and hyperthyroidism for fetus and neonate, and provides a practical approach to clinical management of neonates born to mothers with thyroid dysfunction.

Thyroid disease can present with overt symptoms, insidiously, or with isolated thyromegaly. Thyroid disease in children can encompass isolated biochemical abnormalities that have little or no physiologic consequence or with overt clinical symptoms. Clinically, hypothyroidism occurs more commonly than hyperthyroidism. Thyroid nodules and masses occur much less commonly than functional disorders but can portend the presence of thyroid cancer. This chapter focuses on the most common conditions that affect the thyroid gland of children and adolescents.

Maternal Graves’ disease is the most common cause of fetal goiter. Fetal goiter can cause complications attributable either to the physical effects of the goiter itself or to thyroid dysfunction, which can be life-threatening and cause neurological impairment. Determining whether a goiter is caused by fetal hyperthyroidism or hypothyroidism is the main clinical problem, and in utero evaluations and management are essential. Ultrasonography combined with color Doppler and magnetic resonance imaging are helpful for the initial diagnosis and monitoring, but these imaging techniques have a limited ability to discriminate between fetal hyperthyroidism and hypothyroidism. To determine the fetal thyroid status, fetal blood sampling using cordocentesis is reliable but hazardous, and the indications must be considered carefully. Amniocentesis is an easier and safer alternative, but the correlations between the amniotic fluid and fetal serum thyroid hormone levels remain unclear. If a fetal goiter is accompanied by hypothyroidism, administering thyroid hormone intra-amniotically may be effective and relatively safe. However, the wide variety of approaches to treatment exemplifies the lack of guidelines, and no systematic studies have been conducted to date. Therefore, intrauterine treatment should be reserved for selected patients at a high risk of complications. Moreover, when intrauterine treatment fails and a fetal goiter can cause airway obstruction, intrapartum management, such as ex utero intrapartum treatment, may be required; however, reports describing the use of this procedure for fetal goiter are limited. This review summarizes the current knowledge about fetal goiter associated with maternal Graves’ disease and evaluates the most significant new findings regarding its in utero and peripartum management.