Ahmad Tariq, Geffner Mitchell, Parks John, Brown Milton, Fisher Lynda, Costin Gertrude
Center for Endocrinology, Diabetes, and Metabolism, Childrens Hospital Los Angeles, Los Angeles, CA, USA.
Growth Horm IGF Res. 2011 Feb;21(1):37-43. doi: 10.1016/j.ghir.2010.12.003. Epub 2011 Jan 12.
Growth hormone 1 (GH1) gene deletions occur in approximately 10-15% of patients with severe isolated, GH deficiency (GHD). The standard treatment for GHD is GH replacement. Individuals with GH gene defects, however, may form GH antibodies that interfere with the efficacy of exogenous recombinant GH (rhGH) therapy.
We describe the growth measures and metabolic studies of two Hispanic sisters with the same 7.6-kb GH1 gene deletion who presented with short stature and increased body fat, and who developed neutralizing GH antibodies secondary to rhGH exposure.
The younger sister has now been treated with recombinant human insulin-like growth factor-I (rhIGF-I) for 4 years, and is continuing treatment. The older sister was not given rhIGF-I based on her normal height velocity and age. After the first 4 years of rhIGF-I treatment of the younger sister, we summarized the longitudinal anthropometric measures and serial laboratory studies, including GH surrogates, fasting lipid studies, oral glucose tolerance tests, and HbA1c, of both sisters. Body composition was quantified using DEXA analysis.
The older sister achieved an adult stature at the low end of her mid-parental target height range, having been treated only with rhGH for ~2.5 years (between 11 months and 3.5 years of age). Treatment of the younger sister with rhIGF-I for 4 years has led to persistent improvement in height velocity, but was associated with adverse short-term effects on all lipids. Her BMI increased modestly (+4.1 kg/m(2)) during rhIGF-I treatment, though her change in percent body fat was negligible by DEXA (Δ -0.7%).
In individuals with a GH gene deletion, rhIGF-I promotes increased height velocity, but may be associated with adverse effects on lipids and BMI. It is clear that the long-term effects of rhIGF-I on lipid metabolism and body composition require further monitoring and assessment with continued treatment.
生长激素1（GH1）基因缺失约发生在10%-15%的严重孤立性生长激素缺乏（GHD）患者中。GHD的标准治疗方法是生长激素替代治疗。然而，患有生长激素基因缺陷的个体可能会形成生长激素抗体，从而干扰外源性重组生长激素（rhGH）治疗的疗效。
我们描述了两名西班牙裔姐妹的生长指标和代谢研究情况，她们具有相同的7.6 kb GH1基因缺失，表现为身材矮小和体脂增加，并在接受rhGH治疗后产生了中和性生长激素抗体。
妹妹现已接受重组人胰岛素样生长因子-I（rhIGF-I）治疗4年，且仍在继续治疗。姐姐因其正常的身高增长速度和年龄未接受rhIGF-I治疗。在妹妹接受rhIGF-I治疗的前4年之后，我们总结了姐妹俩的纵向人体测量指标和系列实验室研究结果，包括生长激素替代指标、空腹血脂研究、口服葡萄糖耐量试验和糖化血红蛋白（HbA1c）。使用双能X线吸收法（DEXA）分析对身体成分进行量化。
姐姐仅接受了约2.5年（11个月至3.5岁之间）的rhGH治疗，最终成年身高处于其父母身高目标范围的低端。妹妹接受rhIGF-I治疗4年导致身高增长速度持续改善，但对所有血脂均有不良短期影响。在rhIGF-I治疗期间，她的体重指数（BMI）适度增加（+4.1 kg/m²），不过通过DEXA测量，其体脂百分比变化可忽略不计（Δ -0.7%）。
对于生长激素基因缺失的个体，rhIGF-I可促进身高增长速度加快，但可能对血脂和BMI产生不良影响。显然，rhIGF-I对脂质代谢和身体成分的长期影响需要在持续治疗过程中进一步监测和评估。
