Hypothyroidism, Congenital

Basics

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

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

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)

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