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生长激素治疗糖皮质激素诱导的生长抑制。全国合作生长研究。

Treatment of glucocorticoid-induced growth suppression with growth hormone. National Cooperative Growth Study.

作者信息

Allen D B, Julius J R, Breen T J, Attie K M

机构信息

Department of Pediatrics, University of Wisconsin School of Medicine, Madison, USA.

出版信息

J Clin Endocrinol Metab. 1998 Aug;83(8):2824-9. doi: 10.1210/jcem.83.8.5036.

Abstract

Growth failure is common during long term treatment with glucocorticoids (GC) due to blunting of GH release, insulin-like growth factor I (IGF-I) bioactivity, and collagen synthesis. These effects could theoretically be reversed with GH therapy. The National Cooperative Growth Study database (n = 22,005) was searched for children meeting the following criteria: 1) pharmacological treatment with GC and GH for more than 12 months, 2) known type and dose of GC, and 3) height measurements for more than 12 months. A total of 83 patients were identified. Monitoring of glucose, insulin, IGF-I, IGF-binding protein-3, type 1 procollagen, osteocalcin, and glycosylated hemoglobin levels was performed in a subset of patients. Stimulated endogenous GH levels were less than 10 microg/L in 51% of patients and less than 7 microg/L in 37% of patients. The mean GC dose, expressed as prednisone equivalents, was 0.5 +/- 0.6 mg/kg day. Baseline evaluation revealed extreme short stature (mean height SD score = -3.7 +/- 1.2), delayed skeletal maturation (mean delay, 3.1 yr), and slowed growth rates (mean, 3.0 +/- 2.5 cm/yr). After 12 months of GH therapy (mean dose, 0.29 mg/kg x weeks), mean growth rate increased to 6.3 +/- 2.6 cm/yr, and height SD score improved by 0.21 +/- 0.4 (P < 0.01). During the second year of GH therapy (n = 44), the mean growth rate was 6.3 +/- 2.0 cm/yr. Prednisone equivalent dose and growth response to GH therapy were negatively correlated (r = -0.264; P < 0.05). Plasma concentrations of IGF-I, IGF-binding protein-3, procollagen, osteocalcin, and glycosylated hemoglobin increased with GH therapy, whereas glucose and insulin levels did not change. The following conclusions were reached. The growth-suppressing effects of GC are counterbalanced by GH therapy; the mean response is a doubling of baseline growth rate. Responsiveness to GH is negatively correlated with GC dose. Glycosylated hemoglobin levels increased slightly, but glucose and insulin levels were not altered by GH therapy.

摘要

长期使用糖皮质激素(GC)治疗期间生长发育迟缓很常见,这是由于生长激素(GH)释放受抑制、胰岛素样生长因子I(IGF-I)生物活性降低以及胶原蛋白合成减少所致。从理论上讲,这些影响可以通过GH治疗得到逆转。检索国家合作生长研究数据库(n = 22,005),寻找符合以下标准的儿童:1)接受GC和GH药物治疗超过12个月;2)已知GC的类型和剂量;3)有超过12个月的身高测量数据。共识别出83例患者。对部分患者进行了血糖、胰岛素、IGF-I、IGF结合蛋白-3、I型前胶原、骨钙素和糖化血红蛋白水平的监测。51%的患者刺激后内源性GH水平低于10μg/L,37%的患者低于7μg/L。以泼尼松等效剂量表示的平均GC剂量为0.5±0.6mg/kg·天。基线评估显示患者身材极度矮小(平均身高标准差评分=-3.7±1.2)、骨骼成熟延迟(平均延迟3.1年)且生长速度减慢(平均3.0±2.5cm/年)。GH治疗12个月后(平均剂量0.29mg/kg×周),平均生长速度增至6.3±2.6cm/年,身高标准差评分提高了0.21±0.4(P<0.01)。在GH治疗的第二年(n = 44),平均生长速度为6.3±2.0cm/年。泼尼松等效剂量与GH治疗的生长反应呈负相关(r = -0.264;P<0.05)。GH治疗后,血浆IGF-I、IGF结合蛋白-3、前胶原、骨钙素和糖化血红蛋白浓度升高,而血糖和胰岛素水平未改变。得出以下结论。GC的生长抑制作用可通过GH治疗得到平衡;平均反应是基线生长速度翻倍。对GH的反应性与GC剂量呈负相关。糖化血红蛋白水平略有升高,但GH治疗未改变血糖和胰岛素水平。

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