Growth Pattern of Untreated Boys with Simple Virilizing Congenital Adrenal Hyperplasia Indicates Relative Androgen Insensitivity during the First Six Months of Life

Context: Mild forms of simple virilizing congenital adrenal
hyperplasia (CAH) may be missed in newborn screening. In the
pre-newborn-screening era, missed diagnosis of simple virilizing
CAH was not infrequent in boys. Elevated adrenal androgens lead to
accelerated growth and bone maturation. Traditional treatment of CA
H consists of the suppression of ACTH through glucocorticoid
replacement, in an attempt to reduce excessive androgen production.
Objective: To retrospectively analyze early growth pattern and bone
maturation in untreated boys with simple virilizing CAH. Patients:
In the pre-newborn screening era, 13 boys had a late diagnosis of
simple virilizing classical CAH. Diagnosis of 21-hydroxylase
deficiency was confirmed by mutation analysis of the CYP21A2 gene
in all patients. Growth data were retrospectively collected from
standarized preventive medical checkups at the regular pediatrician
until the time of diagnosis of CAH. Results: Length was 0.1 +/- 0.8
SDS (mean +/- SD) at birth, 0.2 +/- 1 SDS at 3 months, 0.2 +/- 0.9
SDS at 6 months, 0.7 +/- 1 SDS at 1 year, +1.1 +/- 0.9 SDS at 2
years and +1.8 +/- 1.2 SDS at 4 years. At diagnosis, mean
chronological age was 4.4 +/- 1.6 years and height SDS was 2 +/-
1.7. Bone age was accelerated (9.4 +/- 4 years) at diagnosis. Signs
that had led to diagnosis were pubic hair (n = 11), accelerated
growth rate (n = 6) and birth of an affected sister (n = 3).
Despite late start of hydrocortisone treatment, mean final height
was 1 +/- 0.9 SDS. Seven of 18 patients had a final height within 1
SD of target height. Conclusion: Height velocity is not markedly
increased in untreated boys with simple virilizing CAH in the first
6 months of life, indicating that infants are relatively androgen
insensitive during that period. After the first 6 months of life,
growth velocity increases significantly and elevated androgens lead
to advanced skeletal maturation. This observation has implications
for lower hydrocortisone doses to be used in CAH children during
the first 6 months of life. In addition, staying alert for clinical
symptoms and signs of simple virilizing CAH is still warranted,
since mild forms may be missed in newborn screening. Copyright (C)
20105. Karger AG, Basel