Congenital hypothyroidism (ORPHA:442)
Congenital hypothyroidism (CH) is defined as a thyroid hormone deficiency present from birth.
Epidemiology
It occurs in approximately 1/2,000 to 1/4,000 newborns and is more common in Asian, Native American, and Hispanic infants.
Clinical description
The clinical manifestations are often subtle or not present at birth, probably as a result of trans-placental passage of some maternal thyroid hormone and the fact that many infants have some thyroid production of their own. More specific symptoms often do not develop until several months of age. Common clinical features include decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, a distended abdomen with umbilical hernia, and hypotonia. Slow linear growth and developmental delay are usually apparent by 4-6 months of age. Without treatment CH results in severe intellectual deficit and short stature.
Etiology
CH can be divided into permanent (with primary, secondary, or peripheral causes) or transient forms (see these terms). Causes of primary CH include thyroid dysgenesis (85% of cases) and inborn errors of thyroid hormone biosynthesis (dyshormonogenesis, 10-15% of cases) (see these terms). The cause of thyroid dysgenesis remains unknown in the vast majority of cases. Secondary or central CH results from thyroid-stimulating hormone (TSH) deficiency and is usually associated with congenital hypopituitarism. Peripheral CH results from defects in thyroid hormone transport, metabolism, or action as in Allan-Herndon-Dudley syndrome or as a result of peripheral resistance to thyroid hormones (see these terms). CH may also occur as part of a syndrome, for example in the Pendred and Bamforth-Lazarus syndromes (see these terms). Transient CH most commonly occurs in preterm infants born in areas of endemic iodine deficiency. In Western countries, transient hypothyroidism is more likely to be associated with exposure to excess iodine, or with maternal thyroid blocking antibodies.
Diagnostic methods
In countries with newborn screening programs (with either a primary thyroxine (T4)-follow-up TSH or primary TSH test), infants are diagnosed after detection by screening tests finding an elevated serum TSH level and low T4 or free T4 level. Other diagnostic tests (thyroid radionuclide uptake and scan, thyroid sonography, or serum thyroglobulin determination) may help pinpoint the underlying etiology and separate transient from permanent cases.
Genetic counseling
If a familial form of CH is discovered, this will guide genetic counseling. Thyroid dysgenesis is usually a sporadic disorder; thyroid dyshormonogenesis is autosomal recessive, with a recurrence risk of 25%.
Management and treatment
Etiological diagnosis is not necessary when initiating thyroid hormone treatment. Levothyroxine is the treatment of choice; the recommended starting dose is 10-15 mcg/kg/day. The immediate goals of treatment are to raise the serum T4 above 130 nmol/L (10 ug/dL) as rapidly as possible; with these starting doses, serum TSH usually normalizes in 2-4 weeks. Frequent laboratory monitoring in infancy is essential to ensure optimal neurocognitive outcome. Serum TSH and T4 or free T4 should be measured every 1-2 months in the first 6 months of life, every 3 months between 6 months and 3 years of age, and 4 weeks after any dose change.
Prognosis
The prognosis of infants started on treatment early is excellent, with IQs similar to sibling or classmate controls. Lower neurocognitive outcomes may occur in those infants started after more than 30 days of age, on lower l-thyroxine doses than currently recommended, and in those infants with more severe hypothyroidism.

                            Last update: 
                            August 2010


                            - Expert reviewer(s): 
                            Dr Stephen LAFRANCHI  - Dr Maynika RASTOGI