Long-term safety and effectiveness of growth hormone therapy in Korean children with growth disorders: 5-year results of LG Growth Study

PurposeThe aim of this registry study was to analyze the long-term safety and effectiveness of recombinant human growth hormone (rhGH) in South Korean pediatric patients (≥2 years of age) with growth hormone deficiency GHD) of idiopathic or organic etiology, idiopathic short stature, Turner syndrome, small for gestational age and chronic renal failure.MethodsThe study patients were followed-up till two years after the epiphyseal closure, with visits scheduled every six months. The outcome measures included the incidence of adverse events (AEs, in particular, neoplasia, glucose intolerance and hypothyroidism), as well as height standard deviation score (Ht SDS) and annual height velocity. The results of the interim analysis of a 5-year accumulated data for 2,024 patients (7,342 patient-years, PY) are presented.ResultsA total of 14 neoplasms were diagnosed (191/100,000 PY); 7 out of 9 malignancies were recurrent craniopharyngioma found in patients with organic GHD. Seven cases of glucose intolerance (95/100,000 PY) and 22 cases of hypothyroidism (300/100,000 PY) were detected; about half of the cases (4 and 10 cases each) were considered to be related with rhGH treatment. Most of the growth-retarded patients showed continuous improvement in Ht SDS, with the most prominent effect observed within a year of treatment initiation. The beneficial effect of rhGH on Ht SDS gain was maintained for 2–4 years.ConclusionsThe incidence of AEs of interest in rhGH-treated patients was low, and most of the neoplasms were benign and/or non-related to rhGH. Most patients benefited from the therapy in terms of height increment.

研究目的：本登记研究旨在分析重组人生长激素（recombinant human growth hormone, rhGH）用于韩国2岁及以上儿科患者的长期安全性与有效性，这些患者的病症包括特发性或器质性病因的生长激素缺乏症（growth hormone deficiency, GHD）、特发性矮小症、特纳综合征（Turner syndrome）、小于胎龄儿以及慢性肾衰竭。研究方法：本研究对入组患者进行随访，直至其骨骺闭合后两年，随访安排为每六个月一次。本研究的结局指标包括不良事件（adverse events, AEs）的发生率（重点关注肿瘤形成、糖耐量异常与甲状腺功能减退症），以及身高标准差评分（height standard deviation score, Ht SDS）与年身高增长速率。本文呈现了基于2024例患者的5年累积数据所开展的中期分析结果，累计随访时长共计7342患者年（patient-years, PY）。研究结果：共计确诊14例肿瘤，发病率为191/10万患者年；9例恶性肿瘤中7例为复发性颅咽管瘤，均发现于器质性GHD患者中。共检出7例糖耐量异常（95/10万患者年）与22例甲状腺功能减退症（300/10万患者年）；其中约半数病例（分别为4例和10例）被认为与rhGH治疗存在相关性。多数生长迟缓患者的Ht SDS呈持续改善态势，治疗启动后1年内效果最为显著，rhGH对Ht SDS提升的有益作用可维持2~4年。研究结论：接受rhGH治疗的患者所关注的不良事件发生率较低，且多数肿瘤为良性且/或与rhGH治疗无关。大多数患者可从该治疗中获得身高增长获益。