Supplementary Material for: Prevention of Growth Failure in Turner Syndrome: Long-Term Results of Early Growth Hormone Treatment in the “Toddler Turner” Cohort

Introduction: In the randomized “Toddler Turner” study, girls who received growth hormone (GH) starting at ages 9 months to 4 years (early-treated [ET] group) had marked catch-up growth and were 1.6 ± 0.6 SD taller than untreated (early-untreated [EUT]) control girls after 2 years. However, whether the early catch-up growth would result in greater near-adult height (NAH) was unknown. Therefore, this extension study examined the long-term effects of toddler-age GH treatment on height, pubertal development, and safety parameters. Methods: Toddler Turner study participants were invited to enroll in a 10-year observational extension study for annual assessments of growth, pubertal status, and safety during long-term GH treatment to NAH for both ET and EUT groups. Results: The ET group was taller than the EUT group at all time points from preschool to maturity and was significantly taller at the onset of puberty (p = 0.016), however, the difference was not significant at NAH. For the full cohort (ET + EUT combined, n = 50) mean (± SD) NAH was 151.2 ± 7.1 cm at age 15.0 ± 1.3 years. NAH standard deviation score (SDS) was within the normal range (>−2.0) for 76% of ET and 60% of EUT subjects (68% overall) and correlated strongly with height SDS at GH start (r = 0.78; p < 0.01), which in turn had a modest inverse correlation with age at GH start (i.e., height SDS declined with increasing age in untreated girls [r = −0.30; p = 0.016]). No new safety concerns arose. Conclusion: Although the ET group was taller throughout, height SDS at NAH was not significantly different between groups due to catch-down growth of ET girls during lapses in GH treatment after the Toddler study and similar long-term GH exposure overall. Early initiation of GH by age 6 years, followed by uninterrupted treatment during childhood, can prevent ongoing growth failure and enable attainment of height within the normal range during childhood, adolescence, and adulthood.

引言：在随机对照的‘幼儿转导’研究中，从9个月至4岁开始接受生长激素（GH）治疗的女孩（早期治疗组[ET]）表现出显著的生长追赶，并在2年后比未接受治疗（早期未治疗[ETU]）的控制组女孩高出1.6 ± 0.6 个标准差。然而，早期生长追赶是否会导致成年早期身高（NAH）增加尚不清楚。因此，本扩展研究旨在探讨幼儿期GH治疗对身高、青春期发育及安全性参数的长期影响。方法：幼儿转导研究的参与者被邀请参加一项为期10年的观察性扩展研究，对ET和ETU两组在达到NAH期间的长期GH治疗进行年度的生长、青春期状态和安全性评估。结果：ET组在从学龄前到成年的所有时间点都比ETU组更高，且在青春期开始时显著更高（p = 0.016），然而在NAH时差异并不显著。对于整个队列（ET + ETU合并，n = 50），在15.0 ± 1.3岁时，平均（±标准差）NAH为151.2 ± 7.1厘米。NAH标准差分数（SDS）在ET组的76%和ETU组的60%（总体为68%）的受试者中处于正常范围内（>−2.0），并且与GH开始时的身高SDS高度相关（r = 0.78；p < 0.01），这反过来又与GH开始时的年龄呈适度负相关（即，未经治疗的女孩的身高SDS随年龄增加而下降[r = −0.30；p = 0.016]）。未出现新的安全担忧。结论：尽管ET组在整个过程中身高更高，但由于ET女孩在幼儿研究后GH治疗中断期间的追赶生长以及总体上类似的长期GH暴露，NAH的身高SDS在两组之间并无显著差异。在6岁前早期开始GH治疗，并在儿童期不间断治疗，可以防止持续的生长障碍，并使儿童、青春期和成年期间达到正常的身高水平。