Background: Congenital hypothyroidism (CH) is the most frequent congenital endocrine disorder. The diagnosis in industrialized countries is usually made with population-based newborn screening that measures thyroid-stimulating hormone (TSH) or TSH and total thyroxine (T4) in dried blood spots in the first 3 days of life. In newborns with a screening result suspicious for hypothyroidism, the diagnosis of primary CH is confirmed when serum TSH levels are above and T4 (free T4) levels are below the age-related reference ranges. Hypothalamic-pituitary hypothyroidism is more difficult to diagnose. Most infants with this diagnosis are missed in screening programs unless T4 (free T4)/TSH or TSH/T4/thyroxine binding globulin is simultaneously measured. If hypothyroidism is confirmed by laboratory analysis, imaging studies should be performed immediately; however, it is not acceptable to delay hormone replacement therapy if imaging studies are not readily available. Conclusions: The goal of treatment of CH is to avoid disturbed mental development, and initial treatment can be adjusted to physiological conditions. To match the higher thyroid hormone concentrations in the first weeks of life, substitution with l-thyroxine should aim to achieve serum T4/free T4 levels in the upper half of the normal age-related reference range. Some newborns and infants will have persistently high TSH levels despite normalized T4/free T4 serum concentrations.
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