Thyroxine-binding globulin in neonates and children.

Abstract

To the editor, Congenital thyroxine-binding globulin (TBG) deficiency is an X-chromosome-linked chromosomal condition with an estimated incidence of 1 per 2,500 live births.1 It needs to be distinguished from congenital hypothyroidism. Measurement of TBG is important when caring for neonates screened for congenital hypothyroidism who have low levels of total thyroxine (T4) but normal levels of thyrotropin in dried blood spots (collected on Guthrie cards). Boys with TBG deficiency have mild, moderate, or severe alterations in thyroid hormone values. Severe deficiency is rare in girls.2 The normal reference values of TBG are generally high at birth, decreasing towards infancy and childhood, and reaching adult values in late adolescence.3,4​4 Table 1 Values of TBG in neonates and children For many years in the United States, the most common method used to screen for congenital hypothyroidism was the measurement of T45 levels. Today, this strategy is gradually changing—for example, in California, T4 measurement in neonates has been replaced by measurement of thyrotropin levels. With this strategy, however, babies who have normal thyrotropin levels but transitory or permanent hypothyroxinemia will be missed. It is, therefore, useful to measure serum levels of TBG in babies in whom thyroid disease is suspected. Advances in immunoassay technology over the last few decades have allowed new insights into thyroid function in health and disease, but pediatric reference ranges for the different methods used are hard to find in the literature. Furthermore, most manufacturers do not test their measuring techniques in neonates and children. Distinguishing between congenital hypothyroidism and congenital TBG deficiency requires measurement of TBG, thyrotropin, and free and total T4 levels. These values must, however, be compared with standardized reference ranges specifically evaluated in neonates and children. Reference ranges for neonates and children have not been validated for the chemiluminescent Immulite TBG kit (Euro/DPC Ltd, UK), according to the manufacturer's package insert. We measured the levels of TBG in serum specimens from 500 subjects without hepatic or thyroid illness. All analyses were performed using serum specimens from apparently healthy neonates, children, and adolescents who had blood taken for other blood tests. Lipemic, icteric, or hemolysed specimens were excluded. Subjects were divided into 6 age groups, as suggested by Tietz4: 3 to 30 days, 1 to 12 months, 1 to 5 years, 5 to 10 years, and 10 to 15 years. There were 50 boys and 50 girls in each age group; the results are shown in the table. The chemiluminescent TBG kit detected low levels of TBG, suggesting that it is suitable for use in neonates and children to identify congenital TBG deficiency and to discriminate transitory hypothyroxinemia from TBG deficiency.