Endocrine Phenotype and GH1 Sequence Variation in Children with Short Stature: Five-Year Growth Outcomes of Growth Hormone Therapy

Background: Growth hormone (GH) stimulation tests have limited diagnostic precision in childhood short stature (SS), and the relationships among endocrine phenotype, GH1 variation, and long-term treatment response remain unclear. We examined the clinical, endocrine, genetic, and five-year growth outcomes of children receiving recombinant GH. Methods: In this retrospective cohort study, 74 children with SS were classified as idiopathic SS (ISS; n = 28) or growth hormone deficiency (GHD; n = 46) using available GH stimulation-test results together with the integrated clinical, auxological, biochemical, radiological, and treatment-eligibility assessments documented in the medical records. Results: Median annual height velocity was 9.0 cm/year, median height gain was 1.80 standard deviation scores (SDS), and median IGF-1 increased from 125.5 to 306 µg/L. GH dose, endocrine parameters, annual height velocity, height gain SDS, and mean post-treatment height and weight gain did not differ significantly between groups. Height and weight increased over follow-up (both p < 0.001), with no significant group or time-by-group interaction. GH1 sequencing predominantly identified common promoter/upstream and intronic polymorphisms; no pathogenic or likely pathogenic variants were detected. Exploratory genetic clustering showed no clinically meaningful association with endocrine phenotype or treatment response. Conclusions: Adjusted models detected no statistically significant between-group differences in height or weight trajectories. This finding does not establish equivalent treatment efficacy.