Measurements of serum concentrations of free T 4 , T 3 , TSH, and thyroglobulin (Tg) were conducted in 42 infants (2-9 months of age) detected and treated through the Northwest Newborn Regional Screening Program and 63 children and adolescents (1-18 yr of age) with congenital hypothyroidism (CH) detected and managed in the Northern California Kaiser Permanente Medical Care Program. Normal feedback control axis data were developed by Quest Diagnostics, Inc. -Nichols Institute Diagnostics and

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... Linda University, from free T 4 and TSH measurements in 589 healthy subjects, 2 months to 54 yr of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Twenty-four of the 42 CH infants and 57 of the 63 CH children manifested serum TSH concentrations appropriate for the measured free T 4 level. In the remaining 18 infants and 6 children, serum free T 4 values were increased 0.2-1.4 ng/dL (2.6 -18.0 pmol/L) for the prevailing TSH level, suggesting a state of mild to moderate pituitary-thyroid hormone resistance. In the treated children, the mean T 3 concentration was lower (by 32%, 102 vs. 150 ng/dL; 1.57 vs. 2.31 nmol/L) than in normal children, in agreement with earlier data in hypothyroid adults treated with exogenous T 4 . Serum Tg concentrations were normal or elevated in 90% of the 19 children with ectopic glands and 93% of 27 children with eutopic glands in whom measurements were available. There was a positive correlation between serum TSH and Tg concentrations (P Ͻ 0.001), suggesting significant endogenous thyroid hormone production in these children. Our results suggest that the majority of infants and children with CH have a normal hypothalamic-pituitary-thyroid negative feedback control axis during treatment and that the measurement of serum TSH is a useful marker complementing the free T 4 measurement in the management of children with CH. A minority have variable pituitarythyroid hormone resistance, with relatively elevated serum TSH levels for their prevailing serum free T 4 concentration. The prevalence of resistance is greater (43%) in young infants (Ͻ1 yr of age) than in older children (10%), indicating that, in most children, the resistance improves with age. (J Clin Endocrinol Metab 85: