Published online January 3, 2005
PEDIATRICS Vol. 115 No. 1 January 2005, pp. e52-e57 (doi:10.1542/peds.2004-1492)
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ELECTRONIC ARTICLE

Children With Congenital Hypothyroidism and Their Siblings: Do They Really Differ?

Joanne F. Rovet, PhD

From the Departments of Pediatrics and Psychology, Brain and Behavior Program, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

Objective. Although favorable outcome is typically described in follow-up studies of children with congenital hypothyroidism (CH) identified by newborn screening, IQ reductions and persistent cognitive deficits are still reported. These findings are accounted for by disease and treatment variables as well as methodologic factors including choice of comparison group. Although siblings are ideal because they control for genetic and environmental influences, by definition they have different ages when tested, which can also introduce bias. Because we followed children with CH and their siblings over an extended period of time, there were a number of occasions when both groups were tested at the same age. The purpose of this study was to compare the results of children with CH and their unaffected siblings at the same age and with the same test.

Methods. The sample consisted of 42 children with CH detected between 1975 and 1985 and their 42 siblings, all of whom were tested with the McCarthy or Wechsler Intelligence Scale for Children—Revised (WISC-R) intelligence tests. Nineteen pairs of children were evaluated at 6 years with the McCarthy, and 30 pairs of children were evaluated at 7 or 9 years with the WISC-R. Recorded for children with CH were disease etiology, bone age and thyroxine levels at diagnosis, age at onset of treatment, and starting dosage of levothyroxine.

Results. Paired t tests revealed that the CH group scored lower than siblings by 8.1 IQ points on the McCarthy and 6.2 points on the WISC-R. Factors contributing to the size of the CH-sibling IQ difference were (1) the etiology of hypothyroidism, reflecting the larger differences by those with athyreosis or an ectopic gland than dyshormonogenesis, and (2) the starting dosage of levothyroxine, with those initially treated with ≥8.2 µg/kg per day having smaller CH-sibling differences than those given lower starting doses. There were no effects of bone age, thyroxine levels at diagnosis, or age at treatment onset.

Conclusion. Children with CH treated early in life due to newborn screening may have reduced IQ relative to siblings.

Key Words: congenital hypothyroidism • intelligence • outcome • L-thyroxine • management

Abbreviations: CH, congenital hypothyroidism • T4, thyroxine • L-T4, levothyroxine • HSC, Hospital for Sick Children • WISC-R, Wechsler Intelligence Scale for Children–Revised

Accepted Aug 20, 2004.




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