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

J Clin Endocrinol Metab. 2000 Aug;85(8):2722-7. doi: 10.1210/jcem.85.8.6718.


Measurements of serum concentrations of free T4, T3, 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 Loma Linda University, from free T4 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 T4 level. In the remaining 18 infants and 6 children, serum free T4 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 T3 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 T4. 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 < 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 T4 measurement in the management of children with CH. A minority have variable pituitary-thyroid hormone resistance, with relatively elevated serum TSH levels for their prevailing serum free T4 concentration. The prevalence of resistance is greater (43%) in young infants (< 1 yr of age) than in older children (10%), indicating that, in most children, the resistance improves with age.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Congenital Hypothyroidism
  • Feedback
  • Female
  • Hormone Replacement Therapy
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Hypothyroidism / drug therapy*
  • Hypothyroidism / physiopathology*
  • Infant
  • Male
  • Thyroglobulin / analysis
  • Thyroid Gland / abnormalities
  • Thyroid Gland / physiopathology*
  • Thyroid Hormones / therapeutic use
  • Thyrotropin / blood*
  • Thyroxine / blood*
  • Triiodothyronine / blood*


  • Thyroid Hormones
  • Triiodothyronine
  • Thyrotropin
  • Thyroglobulin
  • Thyroxine