Van Pareren Yvonne K, De Muinck Keizer-Schrama Sabine M P F, Stijnen Theo, Sas Theo C J, Drop Stenvert L S
Department of Pediatrics, Division of Endocrinology, Erasmus Medical Centre/Sophia Children's Hospital, 3015 GJ Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2002 Dec;87(12):5442-8. doi: 10.1210/jc.2002-020789.
GH treatment increases insulin levels in girls with Turner syndrome (TS), who are already predisposed to develop diabetes mellitus and other risk factors for developing cardiovascular disease. Therefore, in the present study, we investigated carbohydrate metabolism and several other risk factors that may predict development of cardiovascular disease in girls with TS after discontinuation of long-term GH treatment. Fifty-six girls, participating in a randomized dose-response study, were examined before, during, and 6 months after discontinuing long-term GH treatment with doses of 4 IU/m(2).d ( approximately 0.045 mg/kg.d), 6 IU/m(2).d, or 8 IU/m(2).d. After a minimum of 4 yr of GH treatment, low-dose micronized 17beta-estradiol was given orally. Mean (SD) age at 6 months after discontinuation of GH treatment was 15.8 (0.9) yr. Mean duration of GH treatment was 8.8 (1.7) yr. Six months after discontinuation of GH treatment, fasting glucose levels decreased and returned to pretreatment levels. The area under the curve for glucose decreased to levels even lower than pretreatment level (P < 0.001). Fasting insulin levels and the area under the curve for insulin decreased to levels just above pretreatment level (P < 0.001 for both), although being not significantly different from the control group. No dose-dependent differences among GH dosage groups were found. At 6 months after discontinuation, impaired glucose tolerance was present in 1 of 53 girls (2%), and none of the girls developed diabetes mellitus type 1 or 2. Compared with pretreatment, the body mass index SD-score had increased (P < 0.001), and the systolic and diastolic blood pressure SD-score had decreased significantly at 6 months after discontinuation of GH treatment (P < 0.001 for both) although remaining above zero (P < 0.001, P < 0.05, and P < 0.005, respectively). Compared with pretreatment, total cholesterol (TC) did not change after discontinuation of GH treatment, whereas the atherogenic index [AI = TC/high-density lipoprotein cholesterol (TC/HDL-c)] and low-density lipoprotein cholesterol (LDL-c) had decreased; and both HDL-c and triglyceride levels increased (P < 0.001 for AI, LDL-c, and HDL-c; P < 0.05 for triglyceride). Compared with the control group, AI, serum TC, and LDL-c levels were significantly lower (P < 0.001 for all), whereas HDL-c levels were significantly higher (P < 0.05). In conclusion, after discontinuation of long-term GH treatment in girls with TS, the GH-induced insulin resistance disappeared, blood pressure decreased but remained higher than in the normal population, and lipid levels and the AI changed to more cardio-protective values.
生长激素（GH）治疗可提高特纳综合征（TS）女孩的胰岛素水平，而这些女孩本身就易患糖尿病及其他心血管疾病风险因素。因此，在本研究中，我们调查了碳水化合物代谢以及其他一些可能预测长期GH治疗停药后TS女孩心血管疾病发生的风险因素。56名参与随机剂量反应研究的女孩，在接受4 IU/m²·d（约0.045 mg/kg·d）、6 IU/m²·d或8 IU/m²·d的长期GH治疗前、治疗期间及停药后6个月接受了检查。在至少4年的GH治疗后，口服低剂量微粉化17β-雌二醇。GH治疗停药后6个月时的平均（标准差）年龄为15.8（0.9）岁。GH治疗的平均持续时间为8.8（1.7）年。GH治疗停药后6个月，空腹血糖水平下降并恢复到治疗前水平。葡萄糖曲线下面积降至甚至低于治疗前水平（P<0.001）。空腹胰岛素水平及胰岛素曲线下面积降至略高于治疗前水平（两者均P<0.001），尽管与对照组无显著差异。未发现GH剂量组间存在剂量依赖性差异。停药后6个月时，53名女孩中有1名（2%）存在糖耐量受损，且无女孩发生1型或2型糖尿病。与治疗前相比，体重指数标准差评分升高（P<0.001），GH治疗停药后6个月时收缩压和舒张压标准差评分显著下降（两者均P<0.001），尽管仍高于零（分别为P<0.001、P<0.05和P<0.005）。与治疗前相比，GH治疗停药后总胆固醇（TC）未改变，而致动脉粥样硬化指数[AI = TC/高密度脂蛋白胆固醇（TC/HDL-c）]和低密度脂蛋白胆固醇（LDL-c）下降；高密度脂蛋白胆固醇（HDL-c）和甘油三酯水平均升高（AI、LDL-c和HDL-c均P<0.001；甘油三酯P<0.05）。与对照组相比，AI、血清TC和LDL-c水平显著更低（均P<0.001），而HDL-c水平显著更高（P<0.05）。总之，TS女孩长期GH治疗停药后，GH诱导的胰岛素抵抗消失，血压下降但仍高于正常人群，血脂水平和AI转变为更具心脏保护作用的值。
