Sas T C, de Muinck Keizer-Schrama S M, Stijnen T, Aanstoot H J, Drop S L
Department of Pediatrics, Sophia Children's Hospital/Erasmus University, Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2000 Feb;85(2):769-75. doi: 10.1210/jcem.85.2.6334.
To assess possible side-effects of GH treatment with supraphysiological doses on carbohydrate (CH) metabolism in girls with Turner syndrome (TS) during long term GH treatment and after discontinuation of GH treatment, the results of oral glucose tolerance tests and hemoglobin A1c measurements were analyzed in 68 girls with TS participating in a randomized dose-response trial. These previously untreated girls, aged 2-11 yr, were randomly assigned to 1 of 3 GH dosage groups: group A, 4 IU/m2 x day (-0.045 mg/kg x day); group B, first year ,4 IU/m2 day; thereafter, 6 IU/m2 x day (approximately 0.0675 mg/kg x day); group C, first year, 4 IU/m2 x day; second year, 6 IU/m2 x day; thereafter, 8 IU/m2 x day (approximately 0.090 mg/kg x day). After the first 4 yr, girls 12 yr of age or older started with 5 microg/kg BW-day 17beta-estradiol for induction of puberty. To assess the effects of long term high dose GH treatment on CH metabolism, the 7-yr data from the oral glucose tolerance tests in 9 girls of group C were evaluated (group C1). To determine whether the changes in CH metabolism during GH treatment would persist after discontinuation of GH treatment, the data for 28 girls who had reached adult height (group A, n = 9; group B, n = 10; group C, n = 9) were evaluated at baseline, after 4 yr of GH treatment, and 6 months after discontinuation of GH. Seven-year data for group C1 showed that glucose levels did not significantly change during GH treatment, whereas fasting insulin levels as well as glucose-induced insulin levels increased significantly. The data for the 28 girls who were treated with GH for a mean (SD) period of 85.3 (13.3) months demonstrated that the GH-induced higher insulin levels decreased to values close to or equal to pretreatment values after discontinuation of GH treatment. Changes in CH variables were not significantly related to the GH dose. Hemoglobin A1c levels never showed an abnormal value. The prevalence of impaired glucose tolerance was low, and none of the girls developed diabetes mellitus. In conclusion, long term GH treatment with dosages up to 8 IU/m2 x day in girls with TS has no adverse effects on glucose levels, but induced higher levels of insulin, indicating relative insulin resistance. The increased insulin levels during long term GH treatment decreased after discontinuation of GH treatment to values close to or equal to pretreatment values. Although the reversibility of the effects of long term GH is reassuring, the consequence of long term hyperinsulinism is still unknown.
为评估超生理剂量生长激素（GH）治疗对特纳综合征（TS）女孩长期GH治疗期间及GH治疗停药后碳水化合物（CH）代谢的可能副作用，分析了参与一项随机剂量反应试验的68例TS女孩的口服葡萄糖耐量试验结果和糖化血红蛋白A1c测量值。这些之前未接受过治疗的女孩年龄在2至11岁，被随机分配到3个GH剂量组中的1组：A组，4IU/m²·天（-0.045mg/kg·天）；B组，第1年4IU/m²·天，此后6IU/m²·天（约0.0675mg/kg·天）；C组，第1年4IU/m²·天，第2年6IU/m²·天，此后8IU/m²·天（约0.090mg/kg·天）。在最初4年之后，12岁及以上的女孩开始使用5μg/kg体重·天的17β-雌二醇诱导青春期。为评估长期高剂量GH治疗对CH代谢的影响，对C组9名女孩口服葡萄糖耐量试验的7年数据进行了评估（C1组）。为确定GH治疗期间CH代谢的变化在GH治疗停药后是否会持续存在，对28名已达到成人身高的女孩（A组，n = 9；B组，n = 10；C组，n = 9）在基线、GH治疗4年后以及停药6个月后的数据进行了评估。C1组的7年数据显示，GH治疗期间血糖水平无显著变化，而空腹胰岛素水平以及葡萄糖诱导的胰岛素水平显著升高。接受GH治疗平均（标准差）85.3（13.3）个月的28名女孩的数据表明，GH诱导的较高胰岛素水平在GH治疗停药后降至接近或等于治疗前值。CH变量的变化与GH剂量无显著相关性。糖化血红蛋白A1c水平从未显示异常值。葡萄糖耐量受损的患病率较低，且没有女孩患糖尿病。总之，TS女孩长期使用高达8IU/m²·天剂量的GH治疗对血糖水平无不良影响，但会诱导较高的胰岛素水平，表明存在相对胰岛素抵抗。长期GH治疗期间升高的胰岛素水平在GH治疗停药后降至接近或等于治疗前值。尽管长期GH作用的可逆性令人安心，但长期高胰岛素血症的后果仍不清楚。
