van Pareren Yvonne K, de Muinck Keizer-Schrama Sabine M P F, Stijnen Theo, Sas Theo C J, Jansen Maarten, Otten Barto J, Hoorweg-Nijman J J Gera, Vulsma Thomas, Stokvis-Brantsma Wilhelmina H, Rouwé Catrienus W, Reeser H Maarten, Gerver Willem-Jan, Gosen Jos J, Rongen-Westerlaken Ciska, Drop Stenvert L S
Department of Pediatrics, Division of Endocrinology, Erasmus University MC/Sophia Children's Hospital, 3015 GJ Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2003 Mar;88(3):1119-25. doi: 10.1210/jc.2002-021171.
Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age. Girls were randomly assigned to group A (4 IU/m(2).d; approximately 0.045 mg/kg/d), group B (first year, 4 IU/m(2).d; thereafter 6 IU/m(2).d), or group C (first year, 4 IU/m(2).d; second year, 6 IU/m(2).d; thereafter, 8 IU/m(2).d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 +/- 0.7 yr, low dose micronized 17beta-estradiol was given orally. After a mean duration of GH treatment of 8.6 +/- 1.9 yr, FH was reached at a mean age of 15.8 +/- 0.9 yr. FH, expressed in centimeters or SD score, was 157.6 +/- 6.5 or -1.6 +/- 1.0 in group A, 162.9 +/- 6.1 or -0.7 +/- 1.0 in group B, and 163.6 +/- 6.0 or -0.6 +/- 1.0 in group C. The difference in FH in centimeters, corrected for height SD score and age at start of treatment, was significant between groups A and B [regression coefficient, 4.1; 95% confidence interval (CI), 1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3, 7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI, -1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH SD score, more than -2). After starting estrogen treatment, the decrease in height velocity (HV) changed significantly to a stable HV, without affecting bone maturation (change in bone age/change in chronological age). The following variables contributed significantly to predicting FH SD score: GH dose, height SD score (ref. normal girls), chronological age at start of treatment, and HV in the first year of GH treatment. GH treatment was well tolerated. In conclusion, GH treatment leads to a normalization of FH in most girls, even when puberty is induced at a normal pubertal age. The optimal GH dosage depends on height and age at the start of treatment and first year HV.
尽管生长激素（GH）治疗特纳综合征的身材矮小在许多国家已被认可，但使用何种GH剂量以及何时开始诱导青春期仍是存在争议的问题。本研究显示了60例特纳综合征女孩在一项随机剂量反应试验中的最终身高（FH），该试验在相对年轻的年龄将GH治疗与低剂量雌激素联合应用。女孩们被随机分配到A组（4 IU/m²·d；约0.045 mg/kg/d）、B组（第一年，4 IU/m²·d；此后6 IU/m²·d）或C组（第一年，4 IU/m²·d；第二年，6 IU/m²·d；此后，8 IU/m²·d）。在至少4年的GH治疗后，平均年龄为12.7±0.7岁时，口服低剂量微粉化17β-雌二醇。在平均GH治疗持续时间为8.6±1.9年后，平均年龄为15.8±0.9岁时达到FH。以厘米或标准差（SD）评分表示的FH，A组为157.6±6.5或-1.6±1.0，B组为162.9±6.1或-0.7±1.0，C组为163.6±6.0或-0.6±1.0。校正身高SD评分和治疗开始时的年龄后，A组与B组之间FH以厘米计的差异具有统计学意义[回归系数，4.1；95%置信区间（CI），1.4，6.9；P<0.01]，A组与C组之间也具有统计学意义（系数，5.0；95%CI，2.3，7.7；P<0.001），但B组与C组之间无统计学意义（系数，0.9；95%CI，-1.8，3.6）。60例女孩中有50例（83%）达到了正常的FH（FH SD评分，大于-2）。开始雌激素治疗后，身高增长速度（HV）显著下降至稳定的HV，而不影响骨成熟（骨龄变化/实际年龄变化）。以下变量对预测FH SD评分有显著贡献：GH剂量、身高SD评分（参照正常女孩）、治疗开始时的实际年龄以及GH治疗第一年的HV。GH治疗耐受性良好。总之，即使在正常青春期年龄诱导青春期，GH治疗也能使大多数女孩的FH正常化。最佳GH剂量取决于治疗开始时的身高和年龄以及第一年的HV。
