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Combination therapy optimizes pubertal growth in children with idiopathic short stature
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Children with idiopathic short stature and normal but early pubertal timing may see an increase in adult height when prescribed combination growth hormone and gonadotropin-releasing hormone analogue therapy, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
“The addition of [gonadotropin-releasing hormone analogue] to GH therapy in these challenging groups enabled not only an attainment of an [adult height] within the normal population range and comparable to that of the [idiopathic short statue] patients treated with GH alone, but also an [adult height] exceeding their [target height] range,” Liora Lazar, MD, an associate professor at the Institute of Endocrinology and Diabetes at Schneider Children's Medical Center in Petah Tikva, Israel, and colleagues wrote. “This beneficial effect was more pronounced in children who were prepubertal at initiation of GH therapy and in girls.”
In a single-center, observational study, Lazar and colleagues analyzed data from 192 children born between 1985 and 2000 with a diagnosis of idiopathic short stature who had pubertal onset within the normal range (110 boys) and initiated GH therapy between 2003 to 2013 until reaching adult height. Researchers evaluated the effect of GH alone vs. combined GH/gonadotropin-releasing hormone analogue (GnRHa) treatment on adult height via four measures: absolute height (measured in centimeters and adult height standard deviation score [SDS]), gain in height SDS, adult height vs. predicted adult height and adult height vs. target height.
At the initiation of GH therapy, 65.6% of children were prepubertal and 34.4% were pubertal. Within the cohort, 70% of children were treated with GH alone (71% prepubertal) and 30% were treated with combined GH/GnRHa therapy (53% prepubertal). Researchers found that children who were already pubertal at the initiation therapy were more likely to be prescribed combined therapy vs. those who were prepubertal (40.9% vs. 24.6%; P = .02). Girls were also more likely to be prescribed combination therapy vs. boys (prepubertal, 36.5% vs. 16.2%; pubertal, 63.3% vs. 22.2%; P < .001 for both), according to researchers.
Most boys and girls attained an adult height within their mid-parental height range regardless of treatment, according to researchers. Mean attained adult height SDS was –0.73 for boys and –0.85 for girls. In an analysis of the joint effect of sex, pubertal status at GH initiation and treatment modality, researchers found that prepubertal status at the initiation of GH therapy was associated with taller adult height SDS (P = .049), whereas sex and treatment modality did not affect attained adult height. Prepubertal status at GH initiation was also associated with greater gain-in-height SDS (P < .001), increased adult height vs. predicted adult height (P < .001) and adult height vs. target height (P = .042).
In the same analyses, researchers also found that combined GH/GnRHa therapy was associated with increased adult height vs. predicted adult height (P < .001) and adult height vs. target height (P = .035).
The researchers noted that the study cannot provide a clear answer as to whether combined GH/GnRHa therapy might be superior to GH therapy alone in children with idiopathic short stature.
“Furthermore, as the decision to add GnRHa therapy to GH-treated children was taken in accordance with the clinical judgment of the treating endocrinologist, it is plausible that some children met the described criteria for combined therapy but did not receive it,” the researchers wrote. “Our study does, however, indicate the possible benefit of combined therapy, as seen in the positive effect of the combined therapy in two challenging groups of [idiopathic short stature] patients with poor height prognosis, due either to relatively early puberty or late referral to endocrine consultation.” – by Regina Schaffer
Disclosures: One of the study authors reports he has served as a member of scientific advisory boards for Novo Nordisk and Pfizer, has received lecture fees from Sandoz and serves as a principal investigator to Novo Nordisk for a daily GH treatment.
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