Endocrine Abstracts

JOINT509

Background: Children with advanced bone age (ABA) and short stature present a therapeutic challenge. Idiopathic short stature (ISS) with ABA often involves delayed height gain despite treatment, contrasting with other conditions like congenital adrenal hyperplasia (CAH), obesity-related short stature, precocious puberty, and small for gestational age (SGA), which may show better therapeutic outcomes. The purpose of this review is to compare the efficacy of growth hormone (GH), GnRH analogs (GnRHa), and aromatase inhibitors (AIs) in ISS vs other ABA conditions.

Objectives: To compare therapeutic outcomes in ISS with ABA vs other conditions with ABA, identifying key differences in response to treatment combinations involving GH, GnRHa, and AIs.

Methods: This structured review analyzed 25 studies published between 1994 and 2024, focusing on treatments for ISS and other ABA conditions. Data were extracted regarding patient characteristics, treatment modalities, and main outcomes, and stratified into ISS and specific conditions like CAH, obesity-related short stature, precocious puberty, and SGA. Outcome measures included height standard deviation scores (SDS), predicted adult height (PAH), and bone age progression.

Results: In ISS, combination therapies of GH and GnRHa, or GH and AIs, yielded modest improvements in PAH (5–10 cm), with greater benefits observed in early interventions. However, ABA progression often resumes after treatment discontinuation. Conditions like CAH and precocious puberty responded more robustly to GH, GnRHa, and AI combinations, achieving PAH improvements exceeding 15 cm in certain cases, particularly in prepubertal patients. GH monotherapy showed limited height SDS improvement in obesity-related short stature while adding GnRHa or AIs significantly delayed ABA progression and enhanced final height. SGA cases demonstrated consistent improvements in height SDS with GH and GH+AIs, especially when initiated early, with less adverse impact on ABA. Across conditions, therapy in ISS was less effective at sustaining height gains and controlling ABA compared to CAH, precocious puberty, and obesity-related short stature.

Discussion: The comparative analysis reveals that ISS with ABA has a limited response to GH-based therapies relative to other ABA conditions, underscoring the need for early intervention and tailored approaches. The significant height gains in CAH and precocious puberty highlight the potential of combined therapies in ABA management.

Conclusion: ISS with ABA responds less robustly to therapy compared to other ABA conditions. Combined GH, GnRHa, and AI therapies are more effective in controlling ABA progression and improving height outcomes in CAH, precocious puberty, and SGA, suggesting condition-specific treatment strategies are critical for optimal growth outcomes.