Maturation of human hypothalamic-pituitary-thyroid function and control

Measurements of serum thyrotropin (TSH) and free thyroxine (T-4) concentrat ions were conducted in infants, children, and adults to assess maturation o f the hypothalamic-pituitary-thyroid (HPT) feedback control axis. Serum fre e T-4 and TSH concentration data were collated for cord blood of the midges tation fetus, for premature and term infants, and for peripheral blood from newborn infants, children, and adults. Mean values were plotted on a nomog ram developed to characterize the reference ranges of the normal axis quant itatively based on data from 522 healthy subjects, 2 weeks to 54 years of a ge; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patie nts. Samples for 75 patients with thyroid hormone resistance were also plot ted. The characterized pattern of HPT maturation included a progressive dec rease in the TSH/free T-4 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-pitblitary T-4 resistance during fetal development, probably secondary to increasing thyrotropin-rele asing hormone (TRH) secretion, the marked, cold-stimulated TRH-TSH surge at birth with reequilibration by 2-20 weeks, and a final maturation phase cha racterized by a decreasing serum TSH with minimal change in free T-4 concen tration during childhood and adolescence. The postnatal maturative phase du ring childhood and adolescence correlates with the progressive decrease in thyroxine secretion rate (on a mu g/kg per day basis) and metabolic rate an d probably reflects decreasing TRH secretion.