Hypothyroidism, Congenital



Primary thyroid failure present at birth


  • Increasing trend in the United States
    • Unclear etiology (definitional issues related to newborn screening vs. true increase from unidentified risk factors)
    • Had been 1 in 3,000–4,000 births, United States and worldwide
    • In 2007, U.S. incidence 1 in 2,370 births
  • Male-to-female ratio is 1:2–1:3.
  • 80% dysgenesis or agenesis; 20% dyshormonogenesis
  • Racial differences: prevalence in African American infants ∼1/3 that in whites
  • Higher prevalence of congenital hypothyroidism in low-birth-weight (>2,000 g) and macrosomic (≥4,500 g) babies

Risk Factors


  • Dysgenesis is usually sporadic.
    • Familial occurrence in 2%
    • Mutations have been found in the TSH-receptor gene and in the transcription factors PAX-8, TTF-1, and TTF-2 (FOXE1).
  • Dyshormonogenesis is inherited in an autosomal recessive pattern. Most commonly
    • Chromosome 2p: Mutations in the thyroid peroxidase gene result in partial or complete loss of iodide organification.
    • Chromosome 19p: Mutations in the sodium-iodide symporter gene result in an inability to maintain the normal thyroid-to-plasma iodine concentration difference.
  • Pendred syndrome (chromosome 7q): Mutations in PDS gene cause the most common syndromal form of deafness; a mild organification defect leads to goiter, usually in childhood.


  • Thyroid gland malformation
    • Agenesis: absent thyroid gland
    • Dysgenesis: ectopic (e.g., sublingual) or incorrectly formed (e.g., hemigland) thyroid
  • Dyshormonogenesis
    • 15 known defects of thyroxine (T4) synthesis, including those in iodide transport and iodide organification
  • Transient hypothyroidism
    • Maternal ingestion of antithyroid drugs
    • Transplacental transfer of maternal antithyroid antibodies (transient or permanent damage)
    • Exposure to high levels of iodine-povidone, (i.e., Pyodine, Betadine) in neonatal period

Commonly Associated Conditions

  • Down syndrome neonates have lower T4 (left-shifted normal distribution) and mildly elevated TSH, suggesting a mild hypothyroid state.
  • Newborns with congenital hypothyroidism have an increased risk for congenital heart defects, and vice versa (common embryologic developmental program).

There's more to see -- the rest of this topic is available only to subscribers.