Endocrine Abstracts

JOINT951

Background: Idiopathic short stature (ISS) with advanced bone age presents unique challenges in pediatric endocrinology, as accelerated skeletal maturation reduces growth potential and limits final height. Growth hormone (GH) therapy has been widely used, but adjunctive therapies such as aromatase inhibitors (AIs) and gonadotropin-releasing hormone agonists (GnRHa) show promise in optimizing height outcomes by delaying bone maturation. This review evaluates these therapies individually and in combination for managing ISS with advanced bone age.

Objectives: This review aims to assess the efficacy of GH, AIs, and GnRHa, alone or in combination, in improving height outcomes and controlling bone age progression in children with ISS. It also explores the impact of these therapies on height standard deviation scores (HtSDS), growth velocity, and predicted adult height (PAH) to identify the most effective treatment approaches.

Methods: A systematic analysis of 19 studies published between 1994 and 2024 was conducted. The studies included children diagnosed with ISS and advanced bone age, treated with GH, AIs, GnRHa, or combinations of these therapies. Outcomes such as PAH improvement, HtSDS gain, bone age control, and treatment safety profiles were examined to draw Conclusions on therapeutic efficacy.

Results: Across 19 studies, GH monotherapy improved HtSDS modestly, with gains ranging from +0. 62 to +1. 21 over treatment durations of one to three years. Predicted adult height increased by 8. 5 ± 3. 7 cm in some cases, with short-term benefits evident in prepubertal children. However, GH monotherapy often advanced bone age proportionally to height gain, limiting final height outcomes. Combination therapies of GH with GnRHa or AIs consistently outperformed GH alone. These combinations delayed skeletal maturation, prolonged growth periods, and yielded greater PAH gains, often exceeding 10 cm. GH + GnRHa therapy was particularly effective in early puberty, while GH + AI therapy showed substantial height improvements in boys with advanced skeletal maturity. Triple therapy (GH + GnRHa + AI) demonstrated the most robust outcomes, achieving significant PAH gains and effective bone age control, although mild side effects such as acne and mood changes were noted in some cases.

Discussion: Combination therapies provide superior height outcomes by synergistically addressing skeletal maturation and growth stimulation. GnRHa delays puberty and reduces bone age advancement, while AIs inhibit estrogen-mediated-growth plate closure.

Conclusion: Combination therapies involving GH, GnRHa, and/or AIs are highly effective for ISS with advanced bone age, offering substantial height gains and controlled bone maturation. Long-term studies are needed to assess safety and treatment protocols.