Department of Clinical Science, Pediatrics, Umeå University, Umeå, Sweden.
Department of Pediatrics, Institute of Clinical Sciences, Göteborg Pediatric Growth Research Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Front Endocrinol (Lausanne). 2023 Jul 17;14:1197897. doi: 10.3389/fendo.2023.1197897. eCollection 2023.
To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH). However, age at diagnosis will limit treatment possibilities.
National multicenter investigator-initiated studies (TNR 87-052-01 and TNR 88-072) in girls with TS, age 3-16 years at GH start during year 1987-1998, with AH in 2003-2011. Of the 144 prepubertal girls with TS, 132 girls were followed to AH (intention to treat), while 43 girls reduced dose or stopped treatment prematurely, making n=89 for Per Protocol population. Age at GH start was 3-9 years (young; n=79) or 9-16 years (old; n=53). Treatment given were recombinant human (rh)GH (Genotropin Kabi Peptide Hormones, Sweden) 33 or 67 µg/kg/day, oral ethinyl-estradiol (2/3) or transdermal 17β-estradiol (1/3), and, after age 11 years, mostly oxandrolone. Gain in height, AH, and age at PO and at AH were evaluated.
At GH start, height was -2.8 (versus non-TS girls) for all subgroups and mean age for young was 5.7 years and that of old was 11.6 years. There was a clear dose-response in both young and old TS girls; the mean difference was (95%CI) 0.66 (-0.91 to -0.26) and 0.57 (-1.0 to -0.13), respectively. The prepubertal gain (1.3-2.1) was partly lost during puberty (-0.4 to -2.1). Age/height at PO ranged from 13 years/-0.42 for GH to 15.2 years/-1.47 for GH. At AH, GH group became tallest (17.2 years; 159.9 cm; -1.27 SDS; total gain, 1.55) compared to GH group being least delayed (16.1 years; 157.1 cm; -1.73 SDS; total, 1.08). The shortest was the GH group (17.3 years; 153.7 cm: -2.28 SDS; total gain, 0.53), and the most delayed was the GH group, (18.5 years; 156.5 cm; -1.82 SDS; total gain, 0.98).
For both young and old TS girls, there was a GH-dose growth response, and for the young, there was less delayed age at PO and at AH. All four groups reached an AH within normal range, despite partly losing the prepubertal gain during puberty. Depending on age at diagnosis, low age at start with higher GH dose resulted in greater prepubertal height gain, permitting estrogen to start earlier at normal age and attaining normal AH at normal age, favoring physiological treatment and possibly also bone health, hearing, uterine growth and fertility, psychosocial wellbeing during adolescence, and the transition to adulthood.
研究生长激素（GH）剂量和开始使用 GH 的年龄对特纳综合征（TS）女孩的影响，目标是达到正常身高和青春期开始年龄（PO）以及成年身高（AH）。然而，诊断时的年龄将限制治疗的可能性。
在 1987 年至 1998 年期间，对年龄在 3-16 岁的 TS 女孩进行了国家多中心的研究者发起的研究（TNR 87-052-01 和 TNR 88-072），并在 2003 年至 2011 年期间测量了 AH。在 144 名青春期前的 TS 女孩中，132 名女孩一直随访到 AH（意向治疗），而 43 名女孩提前减少剂量或停止治疗，因此，符合方案人群为 89 名。GH 开始的年龄为 3-9 岁（年轻组；n=79）或 9-16 岁（年长组；n=53）。给予的治疗为重组人生长激素（rh）GH（Genotropin Kabi Peptide Hormones，瑞典）33 或 67μg/kg/天，口服乙炔雌二醇（2/3）或经皮 17β-雌二醇（1/3），并且在 11 岁后，主要使用氧雄龙。评估身高增长、AH、PO 和 AH 的年龄。
在 GH 开始时，所有亚组的身高均比非 TS 女孩低-2.8，年轻组的平均年龄为 5.7 岁，年长组的平均年龄为 11.6 岁。年轻和年长的 TS 女孩都有明显的剂量反应；平均差异分别为（95%CI）0.66（-0.91 至 -0.26）和 0.57（-1.0 至 -0.13）。青春期前的身高增长（1.3-2.1）在青春期期间部分丢失（-0.4 至-2.1）。PO 的年龄/身高范围为 GH 组的 13 岁/-0.42 到 GH 组的 15.2 岁/-1.47。在 AH 时，GH 组的身高最高（17.2 岁；159.9cm；-1.27 SDS；总增长，1.55），GH 组的延迟最小（16.1 岁；157.1cm；-1.73 SDS；总增长，1.08）。GH 组的身高最矮（17.3 岁；153.7cm：-2.28 SDS；总增长，0.53），GH 组的延迟最大（18.5 岁；156.5cm；-1.82 SDS；总增长，0.98）。
对于年轻和年长的 TS 女孩，都有 GH 剂量生长反应，而且对于年轻女孩，PO 和 AH 的年龄延迟较少。所有四个组都在正常范围内达到了 AH，尽管在青春期期间部分丢失了青春期前的身高增长。根据诊断时的年龄，较低的起始年龄和较高的 GH 剂量导致青春期前的身高增长更大，允许雌激素更早地在正常年龄开始，并在正常年龄达到正常的 AH，有利于生理治疗，可能还有骨骼健康、听力、子宫生长和生育、青春期期间的心理健康、以及向成年期的过渡。
