Disease summary: Congenital hypothyroidism is a common preventable cause of mental retardation. The overall incidence is approximately 1:4,000. Females are affected about twice as often as males. Approximately 85% of cases are sporadic, while 15% are hereditary. The most common sporadic aetiology is thyroid dysgenesis, with ectopic glands being more common than aplasia or hypoplasia. In untreated patients, symptoms and signs include the decreased activity, large anterior fontanelle, poor feeding, short stature or failure to thrive, jaundice, decreased stooling or constipation, hypotonia, and hoarse cry. The physical findings of hypothyroidism may or may not be present at birth. Signs include the coarse facial features, macroglossia, large fontanelles, umbilical hernia, mottled, cool, and dry skin, developmental delay, pallor, myxoedema, goitre. In patients properly treated, there are no clinical signs.
While the pathogenesis of dysgenesis is largely unknown, some cases are now discovered to be the result of mutations in the transcription factors PAX-8, FOXE1 (TTF-2), NKX2-1 (TTF-1), NKX2-5, GLIS3, and others. Loss of function mutations in the thyrotropin (TSH) receptor have been demonstrated to cause some familial forms of athyreosis. The most common hereditary aetiology is the inborn errors of thyroxine (T4) synthesis. Recent mutations have been described in the genes coding for the sodium/iodide symporter, thyroid peroxidase (TPO), and thyroglobulin. The transplacental passage of a maternal thyrotropin receptor blocking antibody (TRB-Ab) causes a transient form of familial congenital hypothyroidism. The vast majority of infants are now diagnosed after detection in newborn screening programs using a primary T4-backup TSH or primary TSH test. Screening test results must be confirmed by serum thyroid function tests. Thyroid scintigraphy, using 99mTc or 123I, is the most accurate diagnostic test to detect thyroid dysgenesis or one of the inborn errors of T4 synthesis. Thyroid sonography is nearly as accurate, but it may miss some cases of ectopic glands. If maternal antibody-mediated hypothyroidism is suspected, measurement of maternal and/or neonatal TRB-Ab will confirm the diagnosis. The goals of treatment are to raise the serum T4 as rapidly as possible into the normal range, adjust the levothyroxine dose with growth to keep the serum T4 (or free T4) in the upper half of the normal range and the TSH normal, and maintain normal growth and development while avoiding overtreatment. An initial starting dose of 10-15μg/kg per day is recommended; this dose will decrease on a weight basis over time. Serum T4 (or free T4) and TSH should be monitored every 1-2 months in the first year of life and every 2-3 months in the second and third years, and less frequently thereafter. Rarely, congenital hypothyroidism is due to pituitary deficiency. In this case, other pituitary hormones, overall GH and ACTH, may be undetectable causing hypoglycaemia and adrenal insufficiency.