Clinical Effectiveness and Cost-Effectiveness of the Use of the Thyroxine/ Thyroxine-Binding Globulin Ratio to Detect Congenital Hypothyroidism of Thyroidal and Central Origin in a Neonatal Screening Program

Context. Since the introduction of screening for congenital hypothyroidism (CH) in 1974, the optimal laboratory strategy has been the subject of debate. Objective. To assess the clinical effectiveness and cost-effectiveness of various types of thyroxine (T-4)-based strategies to screen for CH. Design, Setting, and Participants. In the Netherlands, since January 1, 1995, a primary T-4 determination with supplemental thyroid-stimulating hormone (TSH) and T-4-binding globulin (TBG) measurements has been used. Results were calculated from cumulative findings for 1 181 079 children screened between January 1, 1995, and December 31, 2000. Main Outcome Measures. Rates of detection of patients with CH of thyroidal origin (CH-T) or CH of central origin (CH-C), false-positive rates, laboratory costs, and costs of initial diagnostic evaluations. Results. All known infants (n = 393) with CH-T and 92% (n = 66) of infants with CH- C were detected on the basis of low T-4 levels, TSH elevation, and/or low T-4/TBG ratios. If the decision to refer had been based solely on TSH elevation, then 94% of patients with CH- T and none of the patients with CH-C would have been detected. If low T-4 levels (<= -3.0 SD) and TSH elevation had been used as the criteria for referral, then the rates of detection would have been 96% for CH-T and 31% for CH-C. The false-positive rates for the 3 approaches were 0.5, 3.3, and 4.7 cases per case detected, respectively. The introduction of the T-4/TBG ratio into a program using a primary T-4 with supplemental TSH approach generates an extra cost of $ 11 206 per additional case detected. The average costs to detect 1 patient are comparable for the 3 approaches. In addition, our data revealed a substantially greater prevalence of CH-C than reported previously (1 case per 16 404 children, compared with earlier estimates of 1 case per 26 000 infants to 1 case per 29 000 infants). Conclusions. The T-4 plus TSH plus TBG approach is a recommendable strategy for neonatal CH screening. It offers outstanding detection of patients with CH-C, in addition to those with CH-T, with acceptable costs.