van Teunenbroek A, de Muinck Keizer-Schrama S, Stijnen T, Waelkens J, Wit J M, Vulsma T, Gerver W J, Reeser H, Delemarre-van de Waal H, Jansen M, Drop S
Department of Pediatrics, Sophia Children's Hospital, Rotterdam, The Netherlands.
Clin Endocrinol (Oxf). 1997 Apr;46(4):451-9. doi: 10.1046/j.1365-2265.1997.1610972.x.
GH is known to improve height velocity in girls with Turner syndrome (TS) but the optimal dosage regimen has yet to be defined.
We attempted to improve the growth response by trying to mimic normal pulsatile GH secretion more closely.
In a 2-year study the effect of fractionated twice daily (BID) was compared with once daily (OD) s.c. injections of a total GH dose of 6 IU/m2/day. BID injections were administered as two-thirds at bedtime and one-third in the morning. The subjects concurrently received low dose ethinyl oestradiol (0.05 mg/kg/day, orally).
Nineteen girls with TS aged 11 years or over, who were previously involved in a 10-week GH cross-over study.
Height and bone age were evaluated in relation to untreated Turner reference data. Final height (FH) was predicted using the Bayley and Pinneau (BP) method, the modified index of Potential Height (mIPHRUS), and a recently developed Turner-specific method (PTSRUS) based on regression coefficients for height (H), chronological age (CA) and bone age (BA). Plasma levels of GH, GHBP, IGF-1, and IGFBP-3 were determined by RIA.
After 2 years treatment the growth response expressed as HV, HVSDS, the change in HSDSCA, the gain in height over estimated untreated values and in FH prediction all showed significant improvements. Although mean values tended to be higher with OD injections, significant differences between groups were not found. Bone maturation was similar between groups and compared with untreated estimated values. Independent of treatment group, the change in HSDSCA after 2 years of GH treatment was related negatively to the baseline CA and HSDSCA, and positively to BA delay at baseline. After 18 months of GH treatment the significant decrease in GHBP plasma levels observed after 6 months was no longer significant. In contrast, IGF-1 and IGFBP-3 plasma levels and the IGF-1 to IGFBP-3 ratio increased significantly during 18 months GH therapy. None of these growth related factors showed a difference between groups in their 18 months change. Relevant side-effects were not observed during the first 2 years of GH treatment.
The present growth data are in conformity with the data of the earlier 24-hour GH profiles. The growth response and plasma levels of growth related factors after 2 years GH on a total dose of 6 IU/m2/day in combination with low-dose oestrogens were not significantly different between the once daily and the twice daily GH injection regimen.
已知生长激素(GH)可提高特纳综合征(TS)女孩的身高增长速度,但最佳剂量方案尚未确定。
我们试图通过更紧密地模拟正常的脉冲式GH分泌来改善生长反应。
在一项为期2年的研究中,比较了每日两次(BID)分剂量皮下注射与每日一次(OD)皮下注射总剂量为6IU/m²/天的GH的效果。BID注射在睡前注射三分之二,早上注射三分之一。受试者同时口服低剂量乙炔雌二醇(0.05mg/kg/天)。
19名11岁及以上的TS女孩,她们之前参与了一项为期10周的GH交叉研究。
根据未治疗的特纳参考数据评估身高和骨龄。使用贝利和皮诺(BP)方法、改良的潜在身高指数(mIPHRUS)以及最近开发的基于身高(H)、实足年龄(CA)和骨龄(BA)回归系数的特纳特异性方法(PTSRUS)预测最终身高(FH)。通过放射免疫分析法测定血浆中GH、GHBP、IGF-1和IGFBP-3的水平。
经过2年治疗,以身高增长速度(HV)、身高标准差得分变化(HVSDS)、身高标准差与实足年龄变化(HSDSCA)、身高超过未治疗估计值的增加量以及FH预测值等表示的生长反应均显示出显著改善。虽然OD注射的平均值往往较高,但两组之间未发现显著差异。两组之间的骨成熟情况相似,且与未治疗的估计值相比。独立于治疗组,GH治疗2年后HSDSCA的变化与基线CA和HSDSCA呈负相关,与基线时的骨龄延迟呈正相关。GH治疗18个月后,6个月时观察到的GHBP血浆水平的显著下降不再显著。相反,在18个月的GH治疗期间,IGF-1和IGFBP-3血浆水平以及IGF-1与IGFBP-3的比值显著增加。这些与生长相关的因素在18个月的变化中两组之间均未显示出差异。在GH治疗的前2年未观察到相关的副作用。
目前的生长数据与早期24小时GH谱的数据一致。在总剂量为6IU/m²/天并联合低剂量雌激素的情况下,每日一次和每日两次GH注射方案在2年GH治疗后的生长反应和生长相关因子的血浆水平无显著差异。