From Replacement to Tailoring: Evolving Concepts in the Therapy for Short Stature

Growth Hormone (GH) therapy is a cornerstone in managing pediatric growth disorders, yet individual responses vary significantly despite standardized protocols. This variability underscores the need for a comprehensive predictive framework to guide clinical decisions and optimize outcomes. Key determinants of growth response include the underlying diagnosis and degree of GH sensitivity, with conditions like severe GH deficiency typically responding better than disorders such as idiopathic short stature (ISS), small for gestational age (SGA), or Turner syndrome. Patient-specific factors—including age at treatment initiation, bone age delay, mid-parental height and auxological parameters—further shape therapeutic outcomes. Definitions of poor response remain debated, typically relying on first-year height gain or height velocity metrics. A suboptimal response should prompt reassessment of the diagnosis and therapeutic strategy. Emerging therapies offer promising alternatives and adjuncts aimed at improving adherence, targeting specific etiologies, and enhancing outcomes. Despite early success, these interventions require further validation regarding long-term efficacy, safety, and cost-effectiveness. Together, these innovations reflect a broader shift toward mechanism-driven, personalized therapy in pediatric endocrinology.