Comparison of Bioinactive Growth Hormone Cases with Small for Gestational Age and Idiopathic Short Stature Cases

Background Short stature can result from various causes, including rare forms of growth hormone (GH) dysfunction like bioinactive GH, where GH is immunoreactive but biologically inactive due to GH1 gene mutations. Although GH levels are normal, affected children have low IGF-1 levels and show an increase in IGF-1 in response to rhGH therapy. This study compares the rhGH response in children with bioinactive GH to those with small for gestational age (SGA) and idiopathic short stature (ISS). Methods This retrospective study included 109 children with normal GH stimulation test results (≥10 ng/mL) and height ≤ -2 SDS. Individuals with chronic illnesses, malnutrition, syndromic conditions (including Turner, Noonan, or Russell-Silver syndromes), or those who had experienced pubertal suppression were excluded from the study. IGF-1 generation tests identified bioinactive GH cases. Patients were categorized as bioinactive GH (n=8), SGA (n=27), or ISS (n=74). Auxological and hormonal data, growth responses at years 1–3, and final height outcomes were analyzed. Results In this study, children with bioinactive GH exhibited a marked growth response to rhGH therapy. Height SDS gain in the bioinactive group was greater than in the SGA and ISS groups at the end of the first year, over the total of the first three years, and at final height. Additionally, both growth velocity and height SDS improvement remained superior regardless of the GH dose administered. Conclusion These results suggest that children with suspected bioinactive GH represent a distinct subgroup of non-GHD short stature with superior responsiveness to rhGH.