Maturation of Human Hypothalamic-Pituitary-Thyroid Function and Control

Abstract

Measurements of serum thyrotropin (TSH) and free thyroxine (T4) concentrations were conducted in infants, children, and adults to assess maturation of the hypothalamic-pituitary-thyroid (HPT) feedback control axis. Serum free T4 and TSH concentration data were collated for cord blood of the midgestation fetus, for premature and term infants, and for peripheral blood from newborn infants, children, and adults. Mean values were plotted on a nomogram developed to characterize the reference ranges of the normal axis quantitatively based on data from 522 healthy subjects, 2 weeks to 54 years of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Samples for 75 patients with thyroid hormone resistance were also plotted. The characterized pattern of HPT maturation included a progressive decrease in the TSH/free T4 ratio with age, from 15 in the midterm fetus, to 4.7 in term infants, and 0.97 in adults. Maturation plotted on the nomogram was complex, suggesting increasing hypothalamic-pituitary T4 resistance during fetal development, probably secondary to increasing thyrotropin-releasing hormone (TRH) secretion, the marked, cold-stimulated TRH-TSH surge at birth with reequilibration by 2-20 weeks, and a final maturation phase characterized by a decreasing serum TSH with minimal change in free T4 concentration during childhood and adolescence. The postnatal maturative phase during childhood and adolescence correlates with the progressive decrease in thyroxine secretion rate (on a microg/kg per day basis) and metabolic rate and probably reflects decreasing TRH secretion.

Plasma Amino-Terminal Pro C-Type Natriuretic Peptide in the Neonate: Relation to Gestational Age and Postnatal Linear Growth

“…Notably, the dramatic increase occurs during a period of relative undernutrition (mean weight gain at 1 wk was Ϫ36 Ϯ 16 g), which in the healthy fetal and postnatal lamb impairs CNP synthesis. Although the mechanisms underpinning these changes, and factors regulating CNP synthesis in general, are not known, it is possible that perinatal changes in thyroid hormone concentrations or activity (22,23) play at least a permissive role. Thyroid hormones are crucial to growth and maturation of the growth plate (24), increase within a few days of birth, and could affect the cellular activity of growth plate-related tissues from which CNP is sourced (1).…”

Central Hypothyroidism in Infants Who Were Born to Mothers With Thyrotoxicosis Before 32 Weeks' Gestation: 3 Cases

“…3 The exposure of the fetal hypothalamic-pituitary-thyroid system to a higherthan-normal thyroid hormone concentration might impair its physiologic maturation, because there is a continuous significant decrease in the TSH/FT 4 ratio during development from the midgestational fetus to the young adult. 4 Since 1997, we have experienced 3 cases of central hypothyroidism, as described below, and on the basis of these cases, we conclude that the gestational period earlier than 32 weeks may be the critical time for development of central hypothyroidism in offspring. …”

“…1 In these cases, free thyroxine (T 4 ) levels at birth were higher than those at 5 days of age, suggesting that the fetal T 4 level was higher than that in the period immediately after birth, probably as a result of passive transfer from the mother during the last trimester. 2 The major negative feedback effect of thyroid hormones on thyrotropin (TSH) secretion is mediated by serum free T 4 , which is monodeiodinated to triiodothyronine (T 3 ) by type II deiodinase in the hypothalamus and pituitary thyrotroph cells. Undetectable TSH in the fetal cord serum in the presence of markedly elevated free T 4 (FT 4 ) suggests pituitary negative feedback at as early as 20 weeks' gestation.…”

Timing of Hormone Withdrawal in Children Undergoing ¹³¹I Whole-Body Scans for Thyroid Cancer

“…These findings complemented an older study by Haddad [6] where clearance half-times in a cohort of young children when compared to adults were about 1.5-1.8 times faster for L-T4 and almost 3 times faster for L-T3. Furthermore, it has been shown that children and adolescents have higher TSH/free T4 ratios than adults due to incomplete maturation of the hypothalamic-pituitary TSH secretion response to thyroid hormone levels [7] . Sanchez et al [8] studied 21 adult patients on L-T4 (group I) and 10 postoperative patients (group II).…”