Zenaty Delphine, Garel Catherine, Limoni Costanzo, Czernichow Paul, Léger Juliane
Paediatric Endocrinology Unit, Radiology Department, Paris, France.
Clin Endocrinol (Oxf). 2003 May;58(5):647-52.
The factors influencing the highly variable growth response to GH treatment in GH-deficient children are not fully understood. Despite a real benefit with GH treatment in term of growth response, most of these patients attain a mean adult height below their target height and the strategy to optimise final height has to be improved. The aim of this study was to investigate whether the presence of congenital abnormalities of the hypothalamic-pituitary axis on magnetic resonance imaging (MRI) could be a determinant of the growth response in nonacquired prepubertal GH-deficient children, and to identify which pretreatment variables most significantly affect the first 3 years growth response to human GH (hGH) therapy.
The growth response to hGH treatment (0.55 +/- 0.1 IU/kg/week) was evaluated in 69 prepubertal children with nonacquired GH deficiency, according to the absence (group A: chronological age = 4.8 +/- 2.4 years, n= 37) or the presence (group B: chronological age = 3.4 +/- 2.7 years, n= 32) of developmental abnormalities on cerebral magnetic imaging and, after controlling for GH dose, age, height, height velocity (SDS) and body mass index at start of treatment, maximum stimulated GH peak concentration, GH deficiency type (isolated vs. multiple deficiency), parental height, size at birth and sex.
After 3 years of treatment, the mean height gain was significantly higher in patients of group B vs. group A (2.2 +/- 1.3 vs. 1.6 +/- 1 SDS; P < 0.05). In a multiple regression analysis, age (r2 = 0.19, negatively correlated), pretreatment height velocity (r2 = 0.11, negatively correlated), GH dose (r2 = 0.05, positively correlated) and presence of magnetic resonance imaging developmental abnormalities (r2 = 0.05, positively correlated) were found to significantly explain 40% of the variability in growth response.
The detection of congenital abnormalities in the hypothalamic-pituitary area on MRI is more important than the level of maximum stimulated GH to predict the growth response to hGH treatment in prepubertal nonacquired GH-deficient children. Although the persistence of GH deficiency remains to be confirmed during follow-up by reassessment of GH secretion in isolated GH-deficient patients with normal MRI findings, further studies are needed to evaluate whether an increased hGH dose in these patients could improve long-term growth response.
生长激素（GH）缺乏儿童对GH治疗的生长反应高度可变，其影响因素尚未完全明确。尽管GH治疗在生长反应方面确实有益，但大多数此类患者的成年平均身高低于其目标身高，优化最终身高的策略仍有待改进。本研究的目的是调查磁共振成像（MRI）显示下丘脑 - 垂体轴先天性异常是否可能是非后天性青春期前GH缺乏儿童生长反应的决定因素，并确定哪些治疗前变量对人GH（hGH）治疗的前3年生长反应影响最为显著。
对69例青春期前非后天性GH缺乏儿童进行hGH治疗（0.55±0.1 IU/kg/周）的生长反应评估，根据脑磁共振成像有无发育异常分为两组（A组：实足年龄 = 4.8±2.4岁，n = 37）和（B组：实足年龄 = 3.4±2.7岁，n = 32），并在控制GH剂量、年龄、身高、治疗开始时的身高生长速度（标准差分值）、体重指数、最大刺激GH峰值浓度、GH缺乏类型（孤立性与多发性缺乏）、父母身高、出生时大小和性别后进行分析。
治疗3年后，B组患者的平均身高增长显著高于A组（2.2±1.3 vs. 1.6±1标准差分值；P < 0.05）。在多元回归分析中，发现年龄（r2 = 0.19，负相关）、治疗前身高生长速度（r2 = 0.11，负相关）、GH剂量（r2 = 0.05，正相关）和磁共振成像发育异常的存在（r2 = 0.05，正相关）可显著解释生长反应变异性的40%。
对于预测青春期前非后天性GH缺乏儿童对hGH治疗的生长反应，MRI检测下丘脑 - 垂体区域的先天性异常比最大刺激GH水平更重要。尽管在随访期间仍需通过重新评估MRI结果正常的孤立性GH缺乏患者的GH分泌来确认GH缺乏的持续性，但仍需要进一步研究来评估增加这些患者的hGH剂量是否能改善长期生长反应。
