Congenital hypothyroidism occurs in approximately 1 in2000 to 4000 live births and is caused by dysgenesis (agenesis, aplasia, ectopia) or, less often, dyshormonogenesis (e.g.,enzyme defects). Thyroid tissue usually is not palpable inthese sporadic nongoitrous conditions. Dyshormonogenesis, disorders of intrathyroid metabolism, or goitrous congenital hypothyroidism occurs in about 1 in 30,000 livebirths. A goiter reflects an inborn error of metabolism inthe pathway of iodide incorporation or thyroid hormonebiosynthesis or reflects the transplacental passage of antithyroid drugs given to the mother. The free T4 concentration is low, and the TSH level is elevated. Routine neonatal screening programs to measure cord blood or, more often,heel-stick TSH values occur in every state in the UnitedStates. An immediate confirmatory serum sample shouldbe obtained from any infant having a positive result on ascreening test. A low free T4 and high TSH confirm the finding.
Newborn No goiter Thyroid gland dysgenesis or ectopic location Exposure to iodides TSH deficiency TRH deficiency +/− Goiter Inborn defect in hormone synthesis* or effect Maternal goitrogen ingestion, including propylthiouracil, methimazole, iodides Severe iodide deficiency (endemic)
Goiter Hashimoto thyroiditis: chronic lymphocytic thyroiditis Inborn defect in hormone synthesis or effect Goitrogenic drugs infiltrative (sarcoid, lymphoma)
TRH, Thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone.
*Impaired iodide transport, defective thyroglobulin iodination, defective iodotyrosine dehalogenase, or defective thyroglobulin or its coupling to iodotyrosine.
Isolated secondary or tertiary hypothyroidism occurs in 1 in 100,000 live births; the free T4 is normal to low. When tertiary or secondary hypothyroidism is detected, assessment of other pituitary hormones and investigation of pituitary-hypothalamic anatomy via magnetic resonance imaging are indicated. Although not a hypothyroid condition, congenital thyroxine-binding globulin deficiency occurs in about 1 in 10,000 live births and is associated with low serum total T4 concentration, normal TSH, and normal serum free T4. This is a euthyroid condition and does not require treatment with thyroid hormone because it is merely a binding protein abnormality. It is commonly X-linked dominant.
Clinical manifestations of congenital hypothyroidism in the immediate newborn period usually are subtle but become more evident weeks or months after birth. By then it is too late to ensure that there is not a detriment to the infant’s cognitive development. Newborn screening is crucial to make an early diagnosis and initiate thyroid replacement therapy by younger than 1 month of age. Findings at various stages after birth include hypothermia, acrocyanosis, respiratory distress, large fontanels, abdominal distention, lethargy and poor feeding, prolonged jaundice, edema, umbilical hernia, mottled skin, constipation, large tongue, dry skin, and hoarse cry. Thyroid hormones are crucial for maturation and differentiation of tissues, such as bone and brain (most thyroid-dependent brain maturation occurs 2 to 3 years after birth) (Table 175-3).