Zhou X, Loke K Y, Pillai C C, How H K, Yap H K, Lee K O
Department of Medicine, National University of Singapore, Singapore 119074.
Eur J Endocrinol. 2001 Mar;144(3):237-43. doi: 10.1530/eje.0.1440237.
Children with steroid-dependent nephrotic syndrome (SDNS), despite being in remission on glucocorticoids, continue to have growth retardation and short stature. The mechanism is uncertain as both chronic glucocorticosteroids and the nephrotic syndrome may independently affect growth. We investigated the changes in the IGFs and IGF-binding proteins (IGFBPs) in a group of short SDNS children, and studied the changes prospectively with 1 year's treatment with GH.
Total and 'free' IGF-I, IGFBP-3 and acid-labile subunit (ALS) were studied in eight SDNS boys (mean age=12.6 years; mean bone age=9.1 years) on long term oral prednisolone (mean dose 0.46 mg/kg per day) before, during, and after, 1 year's treatment with GH (mean dose 0.32 mg/kg per week). Pretreatment comparisons were made with two control groups, one matched for bone age (CBA; mean bone age=9.2 years), and another for chronological age (CCA; mean chronological age=13 years). Subsequently, three monthly measurements of serum and urine IGFBPs were carried out in the GH-treated SDNS patients using Western ligand blot and Western immunoblot.
Pre-treatment serum total IGF-I levels and the IGF-I/IGFBP-3 ratio were elevated significantly in SDNS compared with CBA, and were similar to CCA. Serum free IGF-I levels were elevated significantly compared with both control groups, but serum IGFBP-3 did not differ significantly. Urinary IGFBP-2, IGFBP-3 and ALS were detectable in the SDNS children only. With GH treatment, IGF-I and IGFBP-3, but not IGF-II, increased significantly compared with pre-treatment values, and returned to baseline after cessation of GH treatment. Urinary IGFBPs did not change significantly with GH treatment.
There is persistent urinary loss of IGFBP-2, IGFBP-3 and ALS in children with SDNS in remission with growth retardation. However, the significant elevation in serum IGF-I suggests that glucocorticoid-induced resistance to IGF is the main factor responsible for the persistent growth retardation in these children. Exogenous GH was able to overcome this resistance by further increasing serum IGF-I.
患有类固醇依赖型肾病综合征（SDNS）的儿童，尽管使用糖皮质激素处于缓解期，但仍持续存在生长发育迟缓及身材矮小的问题。其机制尚不确定，因为长期使用糖皮质激素和肾病综合征可能各自独立影响生长。我们研究了一组身材矮小的SDNS儿童中胰岛素样生长因子（IGFs）和胰岛素样生长因子结合蛋白（IGFBPs）的变化，并前瞻性地研究了生长激素（GH）治疗1年期间的变化情况。
对8名接受长期口服泼尼松龙（平均剂量0.46mg/kg/天）治疗的SDNS男孩（平均年龄12.6岁；平均骨龄9.1岁），在接受GH治疗（平均剂量0.32mg/kg/周）前、治疗期间及治疗后，检测其总IGF-I、“游离”IGF-I、IGFBP-3和酸不稳定亚基（ALS）。治疗前与两个对照组进行比较，一组按骨龄匹配（CBA；平均骨龄9.2岁），另一组按实际年龄匹配（CCA；平均实际年龄13岁）。随后，对接受GH治疗的SDNS患者每三个月进行一次血清和尿液IGFBPs的检测，采用Western配体印迹法和Western免疫印迹法。
与CBA组相比，SDNS组治疗前血清总IGF-I水平及IGF-I/IGFBP-3比值显著升高，与CCA组相似。与两个对照组相比，血清游离IGF-I水平显著升高，但血清IGFBP-3无显著差异。仅在SDNS儿童尿液中可检测到IGFBP-2、IGFBP-3和ALS。接受GH治疗后，与治疗前相比，IGF-I和IGFBP-3显著升高，但IGF-II未升高，停止GH治疗后恢复至基线水平。GH治疗后尿液IGFBPs无显著变化。
处于缓解期但生长发育迟缓的SDNS儿童持续存在IGFBP-2、IGFBP-3和ALS的尿中丢失。然而，血清IGF-I的显著升高表明糖皮质激素诱导的对IGF的抵抗是这些儿童持续生长发育迟缓的主要因素。外源性GH能够通过进一步升高血清IGF-I来克服这种抵抗。
