Hypothyroidism, Congenital



Primary thyroid failure present at birth


  • Increasing incidence worldwide
    • Due to stricter newborn screening thresholds, changing demographics
    • Overall incidence: about 1 in 2,000 births
    • Severe congenital hypothyroidism: 1 in 3,000 to 4,000 births
  • Male-to-female ratio is 1:2 to 1:3 among severe cases but 1:1 among mild cases.
  • 70% dysgenesis; 30% dyshormonogenesis

Risk Factors


  • Dysgenesis is usually sporadic.
    • Familial occurrence in 2–5%
    • Mutations have been found in the TSH receptor (TSHR) and in thyroid transcription factors PAX8, NKX2.1, and FOXE1.
  • Dyshormonogenesis is often inherited in autosomal recessive fashion, but many cases do not have a defined genetic cause.
    • Most commonly mutated genes are thyroglobulin (TG), thyroperoxidase (TPO), DUOX2, and TSHR (relative distribution depends on ethnicity).
    • Pendred syndrome: Mutations in SLC26A4 cause a common syndromic form of deafness, as well as a mild iodine organification defect that can cause hypothyroidism, usually later in childhood.


  • Dysgenesis: failure of normal thyroid gland formation. Includes:
    • Agenesis—absent thyroid gland
    • Ectopy—failure to descend to normal position
    • Abnormally formed (e.g., hypoplastic) thyroid
  • Dyshormonogenesis
    • Defects in thyroxine (T4) synthesis, including in iodide transport and organification
  • Transient hypothyroidism
    • Maternal treatment with antithyroid drugs (methimazole, propythiouracil)
    • Transplacental transfer of maternal TSH receptor-blocking antibodies
    • Iodine deficiency or exposure to high levels of iodine (e.g., topical antiseptics, radiographic contrast)
    • Mild forms of dyshormonogenesis

Commonly Associated Conditions

  • Infants with trisomy 21 have a significantly increased incidence of congenital hypothyroidism.
  • Newborns with congenital hypothyroidism have a slightly increased risk for congenital heart and kidney malformations.
  • Higher incidence of congenital hypothyroidism in infants with low birth weight (<2,500 g), preterm birth (<37 weeks)

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