Near-final height outcomes in children with idiopathic short stature responsive to the IGF-1 generation test: a multicenter retrospective study of rhGH therapy.
In children with idiopathic short stature responsive to the IGF-1 generation test, rhGH therapy resulted in a statistically significant increase in height SDS, but the clinical relevance of this change is uncertain.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study assessed near-final height outcomes in children with idiopathic short stature (ISS) who were treated with recombinant human growth hormone (rhGH) therapy based on a positive IGF-1 generation test. The cohort included 63 patients, with a mean age of 10.8 years at treatment initiation. Height standard deviation score (SDS) increased significantly from -2.90 at baseline to -1.92 at near-final height (p<0.001).
Abstract
Background Children with idiopathic short stature (ISS) have reduced height potential without identifiable endocrine or systemic causes. Selecting appropriate candidates for recombinant human growth hormone (rhGH) therapy remains challenging. The aim of this study was to describe near-final height (NFH) outcomes and to identify clinical predictors of growth response in children with ISS who were selected for rhGH therapy based on a positive IGF-1 generation test (IGFGT). Methods In this multicenter retrospective study (2009-2018) across four centers in Türkiye, patients diagnosed with ISS, baseline IGF-1 < 0 SDS, and ≥ 20% IGF-1 increment after IGFGT were included. GH1 gene sequencing was performed to exclude biologically inactive GH, a condition marked by normal or elevated GH secretion but impaired biological activity. NFH was defined as bone age ≥ 14 years in girls and ≥ 16 years in boys. Height SDS gain from baseline to NFH was evaluated. Results Sixty-three patients (28 females, 19 pubertal) were enrolled, of whom 55 had NFH data and were included in the final analysis. Mean age at treatment initiation was 10.8 ± 3.0 years. No GH1 mutations were identified. Among 55 patients with NFH data, mean height SDS increased from - 2.90 ± 0.77 at baseline to -1.92 ± 0.90 at NFH (p < 0.001), with a mean height SDS gain of 0.93 ± 0.68. The median difference between NFH SDS and baseline predicted adult height (PAH) SDS was - 0.06 (- 0.32-0.07). Predictors of NFH gain included female gender, target height (TH) SDS, baseline height-TH difference, baseline height-PAH difference, and first-year growth velocity SDS. Conclusion rhGH therapy was associated with improvements in height SDS and NFH in this selected cohort of children with ISS. However, the absence of an untreated control group and the minimal difference between NFH and baseline PAH indicate that these findings should be interpreted with caution. Although no GH1 mutations were identified, the relatively high rate of parental consanguinity suggests that other genetic factors within the GH-IGF-1 axis or epiphyseal growth plate pathways may underlie the etiology of short stature. Clinical trial number Not applicable.
Background
This study addresses the challenge of selecting appropriate candidates for rhGH therapy in children with idiopathic short stature (ISS). Prior knowledge indicates that ISS has reduced height potential without identifiable causes, and the IGF-1 generation test is used to identify responsive patients. Understanding the near-final height outcomes in this specific cohort is essential for evaluating the effectiveness of rhGH therapy.
Methods
This multicenter retrospective study was conducted across four centers in Türkiye from 2009 to 2018. The study included patients diagnosed with ISS, with baseline IGF-1 < 0 SDS and at least a 20% IGF-1 increment after the IGFGT. GH1 gene sequencing was performed to exclude biologically inactive GH. The primary outcome measure was height SDS gain from baseline to near-final height (NFH).
Results
Among the 55 patients with NFH data, mean height SDS increased from -2.90 ± 0.77 at baseline to -1.92 ± 0.90 at NFH (p < 0.001). The mean height SDS gain was 0.93 ± 0.68. The median difference between NFH SDS and baseline predicted adult height (PAH) SDS was -0.06 (-0.32 to 0.07).
Interpretation
The findings indicate a statistically significant improvement in height SDS with rhGH therapy, but the clinical significance may be limited due to the small mean gain of 0.93. The absence of an untreated control group raises concerns about the robustness of the conclusions. Additionally, the minimal difference between NFH and baseline PAH suggests that while there is some improvement, it may not be clinically meaningful.
Key findings
- Mean height SDS increased from -2.90 ± 0.77 at baseline to -1.92 ± 0.90 at NFH (p < 0.001).
- Mean height SDS gain was 0.93 ± 0.68.
- Median difference between NFH SDS and baseline predicted adult height (PAH) SDS was -0.06 (-0.32 to 0.07).
- Sixty-three patients were enrolled, of whom 55 had NFH data.
- Mean age at treatment initiation was 10.8 ± 3.0 years.
Limitations
- Absence of an untreated control group.
- Minimal difference between NFH and baseline PAH.
- Retrospective study design.
- Small sample size (n=63).
- Potential confounding factors related to parental consanguinity.