Near-final height outcomes in children with idiopathic short stature responsive to the IGF-1 generation test: a multicenter retrospective study of rhGH therapy.

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.