为了研究GH剂量和年龄在GH开始时对特纳综合征(TS)女孩的影响,针对青春期开始(PO)和成年身高(AH)的正常身高和年龄。然而,诊断年龄将限制治疗的可能性。
国家多中心研究者发起的TS女孩研究(TNR87-052-01和TNR88-072),GH年龄3-16岁在1987-1998年开始,AH在2003-2011年开始。在144名患有TS的青春期前女孩中,132名女孩被跟踪到AH(意向治疗),43名女孩过早减少剂量或停止治疗,使每议定书人口n=89。GH开始的年龄为3-9岁(年轻;n=79)或9-16岁(年龄;n=53)。给予重组人(rh)GH(Genotropin®Kabi肽激素,瑞典)33或67微克/千克/天,口服乙炔-雌二醇(2/3)或经皮17β-雌二醇(1/3),and,11岁以后,主要是奥德罗酮.在高度SDS中获得,AHSDS,评估PO和AH的年龄。
在GH开始时,所有亚组的身高SDS为-2.8(与非TS女孩相比),年轻人的平均年龄为5.7岁,老年人的平均年龄为11.6岁。年轻和老年TS女孩都有明显的剂量反应;平均差异为(95CI)0.66(-0.91至-0.26)和0.57(-1.0至-0.13),分别。青春期前增益SDS(1.3-2.1)在青春期期间部分丢失(-0.4至-2.1)。PO时的年龄/身高SDS范围从GH67young的13岁/-0.42到GH33old的15.2岁/-1.47。在AH,GH67old组最高(17.2岁;159.9厘米;-1.27SDS;总收益SDS,1.55)与GH67年轻组相比延迟最少(16.1岁;157.1厘米;-1.73SDS;总计,1.08).最短的是GH33young组(17.3岁;153.7厘米:-2.28SDS;总收益SDS,0.53),最迟的是GH33old小组,(18.5年;156.5厘米;-1.82SDS;总收益SDS,0.98)。
对于年轻和年老的TS女孩,有GH剂量的生长反应,对于年轻人来说,PO和AH的延迟年龄较少。四组都达到了正常范围的AH,尽管在青春期部分失去了青春期前的收获。根据诊断时的年龄,较高GH剂量的低年龄开始导致更大的青春期前身高增加,允许雌激素在正常年龄更早开始,并在正常年龄达到正常AH,有利于生理治疗,也可能有利于骨骼健康,听力,子宫生长和生育,青春期的社会心理健康,以及向成年的过渡。
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 heightSDS, AHSDS, and age at PO and at AH were evaluated.
At GH start, heightSDS 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 gainSDS (1.3-2.1) was partly lost during puberty (-0.4 to -2.1). Age/heightSDS at PO ranged from 13 years/-0.42 for GH67young to 15.2 years/-1.47 for GH33old. At AH, GH67old group became tallest (17.2 years; 159.9 cm; -1.27 SDS; total gainSDS, 1.55) compared to GH67young group being least delayed (16.1 years; 157.1 cm; -1.73 SDS; total, 1.08). The shortest was the GH33young group (17.3 years; 153.7 cm: -2.28 SDS; total gainSDS, 0.53), and the most delayed was the GH33old group, (18.5 years; 156.5 cm; -1.82 SDS; total gainSDS, 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.