Idiopathic short stature (ISS) with advanced bone age and other related growth disorders: A comprehensive review of reported treatments for improving growth

Ashraf T Soliman; Ahmed Elawwa; Fawzia Alyafei; Shayma Ahmed Mohamed; Noora  AlHumaidi; Noor Hamed; Nada Alaaraj; Ahmed Khalil; Vincenzo De Sanctis

doi:10.23750/abm.2026.16637

Authors

Ashraf T Soliman Department of Pediatrics, Hamad General Hospital, Doha, Qatar https://orcid.org/0000-0002-7145-6561
Ahmed Elawwa Department of Pediatrics, Hamad General Hospital, Doha, Qatar
Fawzia Alyafei Department of Pediatrics, Hamad General Hospital, Doha, Qatar
Shayma Ahmed Mohamed Department of Pediatrics, Hamad General Hospital, Doha, Qatar
Noora AlHumaidi Department of Pediatrics, Hamad General Hospital, Doha, Qatar
Noor Hamed Department of Pediatrics, Hamad General Hospital, Doha, Qatar
Nada Alaaraj Department of Pediatrics, Hamad General Hospital, Doha, Qatar
Ahmed Khalil Department of Pharmacy, Hamad General Hospital, Doha, Qatar
Vincenzo De Sanctis Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara, Italy

Keywords:

idiopathic short stature, advanced bone age, growth hormone therapy, aromatase inhibitors, gonadotropin-releasing hormone agonists

Abstract

Background: Idiopathic short stature (ISS) with advanced bone age presents challenges in pediatric endocrinology due to accelerated skeletal maturation limiting height potential. Recombinant growth hormone (rGH) is a primary treatment in combining with aromatase inhibitors (AIs) or gonadotropin-releasing hormone agonists (GnRHa). Objectives: This review evaluates the effectiveness of rGH, AI, and GnRHa therapies, both individually and in combination, in managing subjects with ISS and advanced bone age. Additionally, it compares ISS treatment strategies with approaches for other growth disorders involving advanced bone age, including obesity, precocious puberty, congenital adrenal hyperplasia (CAH), and small for gestational age (SGA). Methods: A review of relevant studies was conducted, examining rGH, AI, and GnRHa treatment impacts on height, bone age progression, and quality of life (QoL) in ISS. Results: rGH therapy alone improves height in ISS; however, combination treatments, particularly rGH plus AI and rGH plus GnRHa, lead to greater height gains and QoL improvements, especially in adolescents. AI and GnRHa therapies effectively delayed skeletal maturation, enhancing final height outcomes. Genetic factors, like ACAN mutations, influenced treatment response, underscoring the importance of personalized therapy. Comparisons with other growth conditions reveal that ISS requires tailored protocols due to its unique hormonal drivers. Conclusions: rGH therapy combined with AI or GnRHa is recommended to optimize growth potential in ISS with advanced bone age. These combination therapies provide condition-specific solutions, optimizing growth and bone age control across various growth disorders. Future studies should investigate long-term safety and the influence of genetic factors to refine therapeutic protocols.

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