The Beneficial Effect of Combined GH/GnRHa Therapy in Increasing Adult Height Outcome in Children With ISS

• Published in: The journal of clinical endocrinology and metabolism 2019-08, Vol.104 (8), p.3287-3295
• Main Authors: Lazar, Liora, Levy, Sigal, Oron, Tal, Meyerovitch, Joseph, de Vries, Liat, Shalitin, Shlomit, Tenenbaum, Ariel, Phillip, Moshe, Lebenthal, Yael
• Format: Article
• Language: English
• Subjects: Adolescent; Adolescents; Adult; Body height; Body Height - drug effects; Children; Children & youth; Clinical trials; Drug Therapy, Combination; Female; Girls; Gonadotropin-Releasing Hormone - administration & dosage; Growth Disorders - complications; Growth Disorders - drug therapy; Growth Disorders - physiopathology; Growth Hormone - administration & dosage; Human Growth Hormone - administration & dosage; Humans; Male; Puberty; Puberty - drug effects; Puberty, Precocious - complications; Puberty, Precocious - drug therapy; Puberty, Precocious - physiopathology; Retrospective Studies; Sex; Time Factors; Treatment Outcome
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2019-00233

Abstract Context Management of GH-treated children with idiopathic short stature (ISS) with early puberty and adolescents in midpuberty at initiation of treatment is challenging. Objective To assess the effect of combined GH/GnRHa therapy during puberty on achieved adult height (AHt) in these children with ISS and to determine whether outcome depended on sex and pubertal status at initiation of GH therapy. Design Retrospective, single-center observational study from 2003-2018. Setting Tertiary endocrine center. Patients One hundred ninety-two GH-treated children with ISS; 58 of 192 were treated by GH/GnRHa during puberty; 31 of 58 were prepubertal (19 girls) and 27 of 58 pubertal (19 girls) at initiation of GH. Main Outcome Measures AHt, gain-in-height standard deviation score (SDS), AHt vs predicted adult height (PAHt), AHt vs target height (THt). Results Most boys and girls attained AHt SDS within the normal range (−0.73 ± 0.60 and −0.85 ± 0.65, respectively). Treatment modality, pubertal status, and sex were tested for their joint effect on growth outcome measures. Combined GH/GnRHa therapy increased AHt vs PAHt (P < 0.001) and AHt vs THt (P = 0.035). Prepubertal status at onset of GH treatment increased AHt (P = 0.049), gain-in-height SDS (P < 0.001), AHt vs PAHt (P < 0.001), and AHt vs THt (P = 0.042). Female sex increased AHt vs PAHt (P < 0.001). Conclusions Our study demonstrated a beneficial effect of combined GH/GnRHa therapy in increasing AHt outcome in children with ISS with early/normal puberty and in adolescents naïve to GH treatment who are in midpuberty at initiation of therapy. This effect was more pronounced in the prepubertal group and in girls. Prospective randomized controlled trials are needed to assess whether GnRHa can increase AHt in GH-treated children with ISS. Combined GH/GnRHa therapy is beneficial in increasing AHt outcome in children with ISS with early/normal puberty and in adolescents naïve to GH treatment who are in midpuberty at start of therapy.