medwireNews: Women diagnosed with non-classical congenital adrenal hyperplasia (NCCAH) during childhood or adolescence do not typically reach their target height, but this is not related to glucocorticoid treatment duration and dose, research shows.
Instead, the results suggest “that the androgen excess in itself may be responsible for the compromised height outcome” found in this patient population, say Rachel Bello and colleagues, from the Schneider Children’s Medical Center of Israel in Petach Tikva.
They explain in Hormone Research in Paediatrics that data regarding the need to treat NCCAH is controversial and “clinicians generally weigh the benefits of treatment against its risks.”
Previous work by the team has shown that NCCAH diagnosed in childhood, whether treated or untreated, is not associated with an increased risk of overweight, obesity or metabolic disorders in adolescence and early adulthood, but long-term data on adult height outcomes are lacking.
To address this, the investigators reviewed data for 109 girls diagnosed with NCCAH before 18 years of age (mean age at diagnosis, 9.7 years) and who had reached their adult height. Of these, 41.3% were pre-pubertal (Tanner 1) at diagnosis, 26.6% were in active puberty (Tanner 2–4) and 32.1% were fully pubertal (Tanner 5).
The majority (84.4%) of participants were treated with hydrocortisone, at a mean dose of 11.0 mg/m2. Treatment was initiated at 9.7 years of age, on average, and was given for a mean of 7.6 years.
The researchers report that the adult height-standard deviation score (SDS) for the cohort was significantly lower than the height-SDS at diagnosis (−0.8 vs +0.2). In addition, adult height was a significant 2.7 cm (–0.3 SDS) shorter than the sex-adjusted mid-parental target height, with average measurements of 157.9 and 160.6 cm, respectively.
When the team looked at outcomes by treatment group, they found no significant differences in height-, weight- or body mass index-SDS at last clinic visits between patients who did and did not receive glucocorticoids.
There was no significant difference in mean adult height for girls with a homozygous V281L mutation (n=62) and those who were compound heterozygous for V281L and another more severe mutation (12splice, Q318X or I172N, n=18), at 158.5 and 158.4 cm, respectively.
There were also no significant adult height differences among patients who were pre-pubertal, pubertal, or fully pubertal, at diagnosis (158.1, 157.5, and 158.0 cm, respectively).
Bello et al note that the difference between bone age (BA) and chronological age was greater in the 43 girls who presented with central precocious puberty or early puberty (CPP/EP), at 1.9 and 1.7 years for those treated and not treated with a gonadotropin-releasing hormone (GnRH) analogue, respectively, than in those with timely puberty, at 0.9 years.
But adult height was comparable among the three groups, regardless of puberty timing and GnRH analogue treatment.
The investigators also point out that two-thirds of the girls who were pre-pubertal or in active puberty at presentation had BA advancement of more than 1 year, and their predicted adult height before glucocorticoid treatment was already shorter than their height-SDS at diagnosis.
“This could imply that [adult height] loss is caused by the endocrine disorder rather than by [glucocorticoid] therapy,” they write.
The authors add that this hypothesis is supported by the fact that they found no significant correlation between adult height-SDS and glucocorticoid treatment duration or dose.
There was also no correlation with age at diagnosis or the extent of BA advancement, but adult height-SDS correlated significantly with target height and height-SDS at diagnosis.
Finally, when assessing only the girls who were diagnosed before attaining their adult height and did not have fully matured growth plates, the mean adult height was 156.1 cm. This was significantly shorter than predicted at diagnosis using accelerated BA (158.2 cm) but significantly taller than that predicted at diagnosis using average BA (153.7 cm).
They therefore remark: “As [glucocorticoid] therapy has little effect on [adult height], and [adult height] cannot be accurately predicted according to BA at diagnosis, predicted [adult height] apparently merits less attention than it has been given, in considering [glucocorticoid] therapy in females with NCCAH.”
However, they stress that this conclusion “should be taken with caution” due to the retrospective nature of the study.
By Laura Cowen
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