Related Experiment Video
Updated: Jan 16, 2026
Comparative Analysis of Human Growth Hormone in Serum Using SPRi, Nano-SPRi and ELISA Assays
Published on: January 7, 2016
Comparison of children with bioinactive growth hormone, small for gestational age, and idiopathic short stature
Esma Kaya Özdemir1, Esra Döğer1, M Orhun Çamurdan1
1Gazi University Faculty of Medicine, Department of Child Health and Diseases, Department of Pediatric Endocrinology, Ankara, Türkiye.
Insights
Children with bioinactive growth hormone (GH) show a distinct, highly responsive subgroup to recombinant human GH therapy. This condition, characterized by ineffective GH, leads to significant growth improvements and normal stature achievement.
Area of Science:
- Pediatric endocrinology
- Genetics and molecular biology
- Growth disorders
Background:
- Short stature affects numerous children, with rare growth hormone (GH) function disorders being a significant cause.
- Bioinactive GH, defined by immunoreactive but biologically ineffective GH, represents a specific phenotype within short stature.
- Understanding the treatment response in different short stature subgroups is crucial for effective management.
Purpose of the Study:
- To compare the growth response to recombinant human GH (rhGH) therapy in children with bioinactive GH versus those born small for gestational age (SGA) and idiopathic short stature (ISS).
Main Methods:
- Retrospective, single-center study analyzing medical records of short-statured patients (height ≤ -2 z-score) with normal peak GH response to stimulation tests.
- Exclusion of patients with chronic illnesses, malnutrition, syndromic/endocrine disorders, or prior pubertal suppression.
- Inclusion of eligible patients meeting definitions for bioinactive GH, SGA, or ISS.
Main Results:
- Bioinactive GH patients (n=8) had significantly lower baseline IGF-1 and IGFBP-3 levels compared to SGA (n=27) and ISS (n=74) groups (p < 0.001).
- Despite similar rhGH doses, bioinactive GH patients showed superior gains in growth velocity and height z-score.
- All bioinactive GH patients achieved normal final height, surpassing target height, unlike fewer SGA and ISS patients.
Conclusions:
- Children with bioinactive GH represent a distinct, highly treatment-responsive subgroup within non-GH deficient short stature.
- IGF-1 generation testing is highlighted as diagnostically valuable for identifying this subgroup.
- Further multicenter studies are needed to confirm findings and establish international diagnostic guidelines.
Introduction:
Short stature has many causes, including rare disorders of GH function. Bioinactive growth hormone (GH) refers to a phenotype characterized by immunoreactive but biologically ineffective GH. Importantly, it should not be regarded as a separate treatment but rather as a definable subgroup within the broader population of children receiving recombinant human growth hormone (rhGH) therapy. The aim of this study was to compare the growth response to rhGH among children with bioinactive GH, those born small for gestational age (SGA), and those with idiopathic short stature (ISS).
Methods:
In this retrospective, single-center study, we reviewed the medical records of short-statured patients with a height ≤ -2 z-score, a normal peak GH response (≥10 ng/mL) to clonidine or L-dopa stimulation tests, and a history of rhGH treatment. Patients with chronic illness, malnutrition, syndromic or endocrine disorders, diabetes, metabolic disease, anemia, or prior pubertal suppression were excluded. Eligible patients meeting the definitions of bioinactive GH, SGA, or ISS were included.
Statistical Analysis:
Data were analyzed with IBM SPSS Statistics 22.0 using parametric and non-parametric tests with Bonferroni correction; significance was set at p < 0.05.
Results:
Among 170 patients screened, 109 fulfilled the criteria for analysis (bioinactive GH, n=8; SGA, n=27; ISS, n=74). Baseline Insulin-like Growth Factor 1 (IGF-1) and Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) levels were markedly lower in the bioinactive GH group compared with SGA and ISS (p < 0.001). During rhGH therapy, patients with bioinactive GH exhibited the greatest gains in growth velocity and Δ height z-score, despite similar GH doses and a lower proportion of pubertal subjects. By final height, all patients with bioinactive GH achieved normal stature, with most surpassing target height, whereas fewer SGA and ISS patients reached their genetic potential.
Conclusion:
Children with bioinactive GH form a biologically distinct and highly treatment-responsive subgroup of non-GHD short stature. Our findings highlight the diagnostic value of IGF-1 generation testing in this context. Future multicenter studies with genetic and bioactivity confirmation are essential to refine diagnostic criteria and establish international guidelines.
Related Concept Videos
01:10Nature and Nurture
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism
01:18Polygenic Traits