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.

The Key Role of Newborn Thyroid Scintigraphy With Isotopic Iodide (123I) in Defining and Managing Congenital Hypothyroidism

“…We have long claimed that maximal diagnostic data, including results of scintigraphy, offer parents and clinicians an optimal opportunity for the most effective counseling and lifetime management of CH, beginning at birth. 5,6 We report results of thyroid scintigraphy using 123 I or technetium Tc 99m pertechnetate in 210 infants with CH diagnosed during the 24-year period from 1978 through 2002; these cases include 63 previously reported cases 7 ), which we believe support the clinical value of this imaging procedure, particularly when 123 I is used. Additionally, recent discovery of gene abnormalities in CH and in thyroid embryogenesis 2,[8][9][10][11][12][13][14][15][16] suggests that combining results of 123 I thyroid scintigraphy and results of genetic studies may facilitate characterization of the genetic mechanisms of CH.…”

The different requirement of l-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic–pituitary level

“…The inappropriately elevated serum TSH levels are more evident during the early months of treatment and, in some instances, the serum TSH levels have remained relatively elevated in treated CH infants, 5 years of age and older, and the elevated levels do not seem accountable to serum FT 4 (22). This relative hyperthyrotropinemia in many treated CH children has been attributed to suboptimal therapy or abnormal setting of the T 4 negative feedback control of pituitary TSH secretion (22).…”

Excesso de tiroxina materna associado ao hipertireoidismo pós-natal reduz o crescimento ósseo e o perfil proliferativo e angiogênico das cartilagens de crescimento de ratos

“…Adicionalmente, as avaliações morfológicas e morfométricas da tireoide da prole também endossaram as alterações plasmáticas. O aumento do diâmetro folicular associado à redução do epitélio da tireoide do grupo hipertireoideo constituem achados similares aos observados em pesquisas que induziram hipertireoidismo em ratos e camundongos adultos (Serakides et al, 2000;Ferreira et al, 2007) e são decorrentes do feedback negativo exercido pelo excesso de hormônios sobre a glândula (Fisher et al, 2000;Higuchi et al, 2005).…”