Trisomy 21 causes persistent congenital hypothyroidism presumably of thyroidal origin.
OBJECTIVE
Lowered neonatal plasma thyroxine (T(4)) and mildly elevated thyrotropin concentrations together with developmental benefits from neonatally started T(4) treatment in a randomized clinical trial demonstrated Down syndrome (DS) neonates to be mildly hypothyroid, at least during their first weeks of life. To prove that this hypothyroid state persists beyond this period in all, and to elucidate its etiology, we evaluated the course of the thyroid function determinants in all DS infants participating in this 24-month trial.


RESULTS
Mean plasma thyrotropin concentrations and thyrotropin frequency distributions of 97 placebo-treated infants were persistently shifted to substantially higher concentrations, while free T(4) frequency distributions were in the lower two thirds of the reference interval. Mean thyroglobulin concentrations were normal. To normalize plasma thyrotropin, T(4)-treated DS infants (N = 99) needed rather high free T(4) concentrations, like T(4)- treated non-DS children with thyroidal congenital hypothyroidism. At ages 12 and 24 months, thyroid peroxidase antibodies were detected in 1.1% and 5.4% of all DS infants.


CONCLUSIONS
These findings suggest that as a group DS infants have a novel type of persistent mild congenital hypothyroidism, presumably of thyroidal origin. The group character suggests a direct relation with the trisomic state of chromosome 21, hypothetically through genomic dosage imbalance of dosage-sensitive genes interfering with thyroid hormone production.
van Trotsenburg
A S Paul
AS
Departments of Pediatric Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. a.s.vantrotsenburg@amc.uva.nl
Kempers
Marlies J E
MJ
Endert
Erik
E
Tijssen
Jan G P
JG
de Vijlder
Jan J M
JJ
Vulsma
Thomas
T
D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D004311:Double-Blind Method; D004314:Down Syndrome / Q000150:complications / Q000235:genetics*; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D007453:Iodide Peroxidase / Q000378:metabolism; D010919:Placebos; D013954:Thyroglobulin / Q000378:metabolism; D013961:Thyroid Gland / Q000473:pathology*; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D014314:Trisomy
D010919:Placebos; D013954:Thyroglobulin; D007453:Iodide Peroxidase; D013974:Thyroxine