title: The hypothalamic-pituitary-thyroid negative feedback control axis in children with treated congenital hypothyroidism.
abstract: 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.
authors.affiliation: Quest Diagnostics, Inc - Nichols Institute, San Juan Capistrano, California 92690-6130, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Fisher
authors.forename: E J
authors.initials: EJ
authors.lastname: Schoen
authors.forename: S
authors.initials: S
authors.lastname: La Franchi
authors.forename: S H
authors.initials: SH
authors.lastname: Mandel
authors.forename: J C
authors.initials: JC
authors.lastname: Nelson
authors.forename: E I
authors.initials: EI
authors.lastname: Carlton
authors.forename: J H
authors.initials: JH
authors.lastname: Goshi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism; D005246:Feedback; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007037:Hypothyroidism / Q000188:drug therapy* / Q000503:physiopathology*; D007223:Infant; D008297:Male; D013954:Thyroglobulin / Q000032:analysis; D013961:Thyroid Gland / Q000002:abnormalities / Q000503:physiopathology*; D013963:Thyroid Hormones / Q000627:therapeutic use; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*
chemical_list: D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin; D013954:Thyroglobulin; D013974:Thyroxine