The hypothalamic-pituitary-thyroid negative feedback control axis in children with treated congenital hypothyroidism

Measurements of serum concentrations of free T-4, T-3, TSH, and thyroglobul in (Tg) were conducted in 42 infants (2-9 months of age) detected and treat ed through the Northwest Newborn Regional Screening Program and 63 children and adolescents (1-18 yr of age) with congenital hypothyroidism (CH) detec ted and managed in the Northern California Kaiser Permanente Medical Care P rogram. Normal feedback control axis data were developed by Quest Diagnosti cs, Inc. - Nichols Institute Diagnostics and Loma Linda University, from fr ee T-4 and TSH measurements in 589 healthy subjects, 2 months to 54 yr of a ge; 83 untreated hypothyroid patients; and 116 untreated hype-thyroid patie nts. Twenty-four of the 42 CH infants and 57 of the 63 CH children manifest ed 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 increa sed 0.2-1.4 ng/dL (2.6-18.0 pmol/L) for the prevailing TSH level, suggestin g 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 ea rlier data in hypothyroid adults treated with exogenous T-4. Serum Tg conce ntrations were normal or elevated in 90% of the 19 children with ectopic gl ands and 93% of 27 children with eutopic glands in whom measurements were a vailable. There was a positive correlation between serum TSH and Tg concent rations (P < 0.001), suggesting significant endogenous thyroid hormone prod uction 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 TS H is a useful marker complementing the free T-4 measurement in the manageme nt of children with CH. A minority have variable pituitary-thyroid 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 (<1 yr of age) than in older children (10%), indicating t hat, in most children, the resistance improves with age.