Thyroid hormone is a potent regulator of metabolic rate and is essential to the function of most organ systems. In addition, the maintenance of normal thyroid status through childhood is necessary for normal growth and neurodevelopment. Best outcome in pediatric thyroid disease requires early detection as well as appropriate therapy with careful monitoring. These tasks are generally accomplished through successful collaboration between primary care providers and endocrine specialists. With an appropriate index of suspicion, pediatric thyroid disease can be detected in early stages and outcome is usually excellent. This chapter begins with a review of thyroid physiology and clinical testing. We then present diagnostic approaches to common pediatric thyroid disorders, grouped into the categories of hypothyroidism, thyrotoxicosis, and nodular thyroid disease.
The fetal thyroid begins as a thickening of the pharyngeal floor which forms a diverticulum that descends caudally into the resting position of the mature thyroid gland. During this migration, a track called the thyroglossal duct is formed that connects the pharyngeal floor to the thyroid bed. This thyroglossal duct normally involutes and, by embryonic day 50, the thyroid primordium has fused with the ventral aspect of the fourth pharyngeal pouch to form a bilobed structure. The cells of this primordium differentiate into thyroid follicular cells that synthesize thyroid hormone. Thyroid C cells, which produce calcitonin, have a distinct embryologic origin and are derived from the ultimobranchial glands.
By 11 to 12 weeks of gestation, the fetal thyroid is capable of concentrating iodine and synthesizing thyroxine (T4). Prior to this point, the human fetus is dependent on maternal thyroid hormone. Even in later pregnancy, transplacental passage remains an important source of fetal thyroid hormone, as evidenced by the fact that T4 is detectable in the serum of infants born with complete thyroid agenesis.
Analyses of serum obtained through cordocentesis indicate that the fetal relationship of thyrotropin (also called thyroid-stimulating hormone [TSH]) to T4 matures throughout gestation. Compared to maternal serum, fetal serum has low concentrations of both thyroxine (T4) and triiodothyronine (T3). Birth is associated with a robust but transient peak in both serum TSH and T4 (referred to as the neonatal surge), followed by rapid changes in the metabolism of thyroid hormone in peripheral tissues. This normal neonatal thyroid surge typically lasts 1 to2 days, which is the rationale for delaying newborn screening until 2 days after birth.
From a clinical standpoint, deviation from the normal anatomic development of the thyroid (termed thyroid dysgenesis) is the most common cause of congenital hypothyroidism. As described in the following text, the study of patients with thyroid dysgenesis has provided valuable insight into the molecular biology of normal thyroid development.
Thyroid Hormone Synthesis
The sole physiologic function ...