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Published on: November 14, 2013
Maturation of human hypothalamic-pituitary-thyroid function and control
D A Fisher1, J C Nelson, E I Carlton
1Quest Diagnostics Nichols Institute, San Juan Capistrano, California 92629, USA.
Insights
The hypothalamic-pituitary-thyroid (HPT) axis matures with age, showing a decreasing thyrotropin (TSH) to free thyroxine (T4) ratio from fetus to adulthood. This maturation involves complex changes in TSH and T4 levels, reflecting thyroid hormone feedback regulation.
Area of Science:
- Endocrinology
- Developmental Biology
- Pediatric Medicine
Background:
- The hypothalamic-pituitary-thyroid (HPT) axis regulates metabolism and development through thyroid hormones.
- Understanding the maturation of the HPT axis is crucial for diagnosing and managing thyroid disorders in children and adults.
Purpose of the Study:
- To assess the maturation of the HPT feedback control axis in infants, children, and adults.
- To quantitatively characterize reference ranges for the normal HPT axis using a nomogram.
- To analyze HPT axis function in individuals with thyroid hormone resistance.
Main Methods:
- Serum thyrotropin (TSH) and free thyroxine (T4) concentrations were measured across various age groups, from fetal life to adulthood.
- Data from 522 healthy subjects, 83 hypothyroid patients, 116 hyperthyroid patients, and 75 patients with thyroid hormone resistance were collated.
- Mean values were plotted on a nomogram to characterize HPT axis maturation and reference ranges.
Main Results:
- A progressive decrease in the TSH/free T4 ratio was observed with age, from 15 in the midterm fetus to 0.97 in adults.
- HPT axis maturation involved increasing hypothalamic-pituitary T4 resistance during fetal development and a significant TSH surge at birth.
- Postnatal maturation included decreasing TSH with stable free T4 in childhood and adolescence, correlating with reduced thyroxine secretion and metabolic rate.
Conclusions:
- The HPT axis undergoes complex maturation from fetal development through childhood and adolescence.
- Thyroid hormone feedback regulation and sensitivity change significantly during development.
- The study provides a quantitative framework for assessing HPT axis maturation and identifying thyroid dysfunction.
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.
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