Low L C, Kwan E Y, Lim Y J, Lee A C, Tam C F, Lam K S
Department of Paediatrics, Queen Mary Hospital, University of Hong Kong.
Clin Endocrinol (Oxf). 1995 Apr;42(4):359-63. doi: 10.1111/j.1365-2265.1995.tb02643.x.
Despite regular transfusion and desferrioxamine treatment, growth failure is commonly seen in adolescent children with beta-thalassaemia major. The growth failure has been thought to be due to GH resistance rather than GH deficiency. We investigated the effect of GH on short non-GH deficient children with beta-thalassaemia.
Recombinant human GH was given in a dose of 0.14 IU/kg/day subcutaneously in an open study.
Fifteen prepubertal Chinese children with beta-thalassaemia major (ranging from 7.16 to 14.7 years in age) with height -1.5 SD or more below the population mean for age and a growth velocity of less than 5 cm/year were treated with growth hormone for one year. All children had peak GH response > 15mlU/l to insulin induced hypoglycaemia and normal thyroid function and adrenal reserve.
Anthropometric measurements were performed every 3 months. Morning urine was tested twice weekly for glycosuria. Blood count, renal and liver function tests, fasting blood glucose, IGF-I and fructosamine levels were assessed at entry and every 3 months during treatment. Fasting insulin was measured before and after 3 and 12 months of GH treatment. Skeletal maturity was assessed before and after one year of treatment.
Treatment was stopped in two children after 6 months because of poor growth response and noncompliance with treatment and in one child at 9 months because of bone marrow transplantation. In the 13 children, the growth velocity increased from 3.6 +/- 0.7 cm/year to 8 +/- 1.2 cm/year after one year of GH treatment (P < 0.001). IGF-I was low before treatment (10.1 +/- 2.7 nmol/l), rising significantly to 15.8 +/- 4.8, 18.4 +/- 4.6, 19.3 +/- 6.4 and 21.9 +/- 7.5 nmol/l at 3, 6, 9 and 12 months of treatment (P < 0.005). The mean pretreatment bone age in the 13 children was 9.58 +/- 1.41 years and increased to 10.53 +/- 1.43 years after one year of treatment (delta BA/CA 0.95 +/- 0.3 years). None of the patients developed glycosuria or hypertension. There was no significant change in blood count, renal and liver function, thyroid function, fasting blood glucose or insulin concentrations during treatment.
Growth failure in these children with normal GH reserve and low serum IGF-I concentrations would suggest GH insensitivity. Supraphysiological doses of exogenous GH can cause a significant increase in serum IGF-I levels and a significant improvement in short-term growth of short children with beta-thalassaemia major.
尽管进行了定期输血和去铁胺治疗，但重型β地中海贫血青少年儿童生长发育迟缓仍很常见。人们认为生长发育迟缓是由于生长激素抵抗而非生长激素缺乏所致。我们研究了生长激素对非生长激素缺乏的重型β地中海贫血矮小儿童的影响。
在一项开放性研究中，以0.14 IU/kg/天的剂量皮下注射重组人生长激素。
15名青春期前的中国重型β地中海贫血儿童（年龄7.16至14.7岁），身高低于同年龄人群均值1.5标准差或更多，生长速度小于5厘米/年，接受生长激素治疗一年。所有儿童对胰岛素诱发的低血糖的生长激素峰值反应>15 mIU/l，甲状腺功能和肾上腺储备正常。
每3个月进行人体测量。每周两次检测晨尿中的糖尿。在入组时以及治疗期间每3个月评估血常规、肝肾功能、空腹血糖、胰岛素样生长因子-I（IGF-I）和果糖胺水平。在生长激素治疗3个月和12个月前后测量空腹胰岛素。在治疗一年前后评估骨骼成熟度。
2名儿童在6个月后因生长反应不佳和不依从治疗而停止治疗，1名儿童在9个月时因骨髓移植而停止治疗。在13名儿童中，生长激素治疗一年后生长速度从3.6±0.7厘米/年增加到8±1.2厘米/年（P<0.001）。治疗前IGF-I较低（10.1±2.7 nmol/l），在治疗3、6、9和12个月时显著升高至15.8±4.8、18.4±4.6、19.3±6.4和21.9±7.5 nmol/l（P<0.005）。13名儿童治疗前的平均骨龄为9.58±1.41岁，治疗一年后增加到10.53±1.43岁（骨龄/年龄差值0.95±0.3岁）。没有患者出现糖尿或高血压。治疗期间血常规、肝肾功能、甲状腺功能、空腹血糖或胰岛素浓度没有显著变化。
这些生长激素储备正常且血清IGF-I浓度低的儿童生长发育迟缓提示生长激素不敏感。超生理剂量的外源性生长激素可使血清IGF-I水平显著升高，并使重型β地中海贫血矮小儿童的短期生长显著改善。
