Disorders of thyroid function in neonates often present a diagnostic dilemma. The initial clinical signs and symptoms are often subtle or misleading. A good understanding of the unique thyroid physiology, assessment of thyroid function, and a sense of urgency are necessary to recognize, diagnose, and treat thyroid disorders early. As an example, congenital hypothyroidism can cause neurologic intellectual development issues unless thyroid therapy is initiated within 2 weeks of birth.
I. FETAL AND NEONATAL THYROID FUNCTION
Embryogenesis. Thyroid gland forms from invagination of foregut endoderm at the floor of the pharynx beginning in the third week of gestation, with thyroglobulin synthesis detected by 4 to 6 weeks, thyrotropin-releasing hormone (TRH) synthesis by 6 to 8 weeks, and iodine trapping by 8 to 10 weeks through 12 weeks of gestation. At that time, thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) secretion can be detected. Thyroid activity remains low until midgestation and then increases slowly until term.
Thyroid hormones undergo rapid and dramatic changes in the immediate postnatal period.
An acute release of thyroid-stimulating hormone occurs within minutes after birth. Peak values of 60 to 80 mU/L are seen at 30 to 90 minutes attributed to exposure of the infant to a colder postnatal environment, clamping of the cord, and the stress of delivery. Levels decrease to <10 mU/L by the end of the first postnatal week.
Stimulated by the thyroid-stimulating hormone surge, thyroxine, free thyroxine, and triiodothyronine rapidly increase, reaching peak levels by 24 to 36 hours. TSH level decreases slowly over the first 2 weeks of life to values slightly higher than what are found typically in adults.
Thyroid function in the premature infant. Similar changes in TSH, T4, and T3 are seen in premature infants; however, absolute values are lower in proportion to the gestational age and birthweight. TSH levels return to normal by 5 to 10 days of life.
II. PHYSIOLOGIC ACTION OF THYROID HORMONES
Thyroid hormones have profound effects on growth and neurologic development. They also influence oxygen consumption, thermogenesis, and the metabolic rate of many organs. Maternal T4 is critical for normal central nervous system maturation in the fetus.
III. BIOCHEMICAL STEPS INVOLVED IN THYROID HORMONE SYNTHESIS
Thyroid hormone production involves the steps of iodide transport/trapping, thyroglobulin synthesis, organification of iodide, monoiodotyrosine and diiodotyrosine coupling, thyroglobulin endocytosis, proteolysis, and release. In addition, T4 is converted to T3 in peripheral tissue.
IV. MATERNAL THYROID DISEASE AND PREGNANCY OUTCOME
Maternal thyroid diseases (hypo- and hyperthyroidism) are associated with increased risk for pregnancy complications including miscarriage, preeclampsia, placental abruption, preterm birth, and cesarean section. Maternal symptoms of autoimmune thyroid diseases tend to improve during pregnancy. Maintaining euthyroidism and achieving a serum total T4 in the upper limit of normal throughout pregnancy is key to reducing the ...