Screening for congenital hypothyroidism with the Dutch T₄–TSH–TBG system

Kempers MJ et al. (2006) Neonatal screening for congenital hypothyroidism based on thyroxine, thyrotropin, and thyroxine-binding globulin measurement: potentials and pitfalls. J Clin Endocrinol Metab 91: 3370–3376

Children with untreated congenital hypothyroidism can experience impaired cognitive and motor development. In the Netherlands, neonates are screened by measurement of endogenous T₄ levels; additionally, TSH levels are measured if T₄ levels are marginally low, and both TSH and thyroxine-binding globulin (TBG) levels are measured if T₄ levels are definitely low. Patients with T₄–TSH–TBG results indicative of congenital hypothyroidism are referred to a pediatrician, and those with equivocal results are offered a repeat test before referral. Kempers et al. report that this screening program detects even mild or transient congenital hypothyroidism, of central or thyroidal origin; they suggest that the efficacy of T₄–TSH–TBG screening accounts for the very high incidence of congenital hypothyroidism in the Netherlands, compared with similarly developed, iodine-replete countries.

During 2002–2004, 99.7% of children born in the Netherlands underwent neonatal T₄–TSH–TBG screening. Of 772 children referred for abnormal or equivocal T₄–TSH–TBG results, 224 were diagnosed with congenital hypothyroidism. A further 13 cases were not detected by screening (3 were diagnosed before screening; of the 10 false-negative results, 4 were preterm babies screened only with TSH). The authors estimate that TSH-only screening would have missed 47 cases of congenital hypothyroidism.

Most referred children without congenital hypothyroidism were severely TBG-deficient, or were very ill patients in intensive care; Kempers et al. note that it remains unclear whether their altered thyroid state carried a risk of brain damage that could be alleviated by temporary T₄ supplementation.