Völkl Thomas M K, Rauh Manfred, Schöfl Christof, Dörr Helmuth G
Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics and Adolescent Medicine, First Department of Internal Medicine, Friedrich-Alexander University of Erlangen-Nuremberg, Germany.
Growth Horm IGF Res. 2011 Aug;21(4):191-8. doi: 10.1016/j.ghir.2011.05.001. Epub 2011 Jun 1.
It has been shown that changes in IGF-I and IGFBP levels in children with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) are correlated with different states of metabolic control. Our approach was to analyze the serum levels of IGF-I, IGFBP-3, their molar ratio IGF-I:IGFBP-3 (MR), and ALS in a cohort of CAH children and adolescents, and their associations with different clinical and biochemical parameters.
56 patients, aged between 5.6 and 19.0 years were studied cross-sectionally. All patients had genetically proven CAH and received standard steroid substitution therapy. We measured serum levels of IGF-I, IGFBP-3, and ALS by commercial ELISA and calculated MR and assigned population-based SD scores (SDS).
(median, quartiles) Overall IGF-I was not significantly altered (0.05 SDS, -1.21, 0.92), whereas IGFBP-3 was significantly elevated (1.50 SDS; 0.58, 1.95, p<0.0001) compared to the reference population. Consecutively, MR was decreased (-0.64 SDS; -1.38, 0.32; p=0.0017). ALS was clearly decreased (-1.95 SDS; -3.075, -1.00; p<0.0001). ALS, IGF-I, MR, and IGFBP-3 SDS were lower in pubertal than in prepubertal patients (p<0.05). ALS SDS were lower in girls (p=0.0038). Correlation analyses (r(s), p) revealed correlations between MR/ALS and chronological age (-0.583, <0.0001/-0.428, 0.0010), MR/ALS and Tanner stages (-0.500, <0.0001/-0.334, 0.0118), MR/ALS and bone age (0.407, 0.0075/0.426, 0.0049), and between MR and ALS (0.405, 0.0020), respectively. For MR and ALS, we found no significant correlations for BMI, HOMA-IR, hydrocortisone and fludrocortisone dosage, or parameters of metabolic control.
Our data provide evidence that the components of the trimeric IGF-I-IGFBP-3-ALS complex are altered in CAH children with possible implications on pubertal growth and final height.
已有研究表明，21 - 羟化酶缺乏所致经典型先天性肾上腺皮质增生症（CAH）患儿的胰岛素样生长因子 - I（IGF - I）和胰岛素样生长因子结合蛋白（IGFBP）水平变化与不同的代谢控制状态相关。我们的研究方法是分析一组CAH儿童和青少年的血清IGF - I、IGFBP - 3水平、它们的摩尔比IGF - I:IGFBP - 3（MR）以及酸性不稳定亚基（ALS），并研究它们与不同临床和生化参数之间的关联。
对56例年龄在5.6至19.0岁之间的患者进行横断面研究。所有患者均经基因检测确诊为CAH，并接受标准的类固醇替代治疗。我们采用商用酶联免疫吸附测定法（ELISA）测量血清IGF - I、IGFBP - 3和ALS水平，并计算MR，同时赋予基于人群的标准差评分（SDS）。
（中位数，四分位数）总体而言，与参考人群相比，IGF - I无显著变化（0.05 SDS，-1.21，0.92），而IGFBP - 3显著升高（1.50 SDS；0.58，1.95，p<0.0001）。随后，MR降低（-0.64 SDS；-1.38，0.32；p = 0.0017）。ALS明显降低（-1.95 SDS；-3.075，-1.00；p<0.0001）。青春期患者的ALS、IGF - I、MR和IGFBP - 3 SDS低于青春期前患者（p<0.05）。女孩的ALS SDS较低（p = 0.0038）。相关性分析（r(s)，p）显示MR/ALS与实际年龄（-0.583，<0.0001/-0.428，0.0010）、MR/ALS与坦纳分期（-0.500，<0.0001/-0.334，0.0118）、MR/ALS与骨龄（0.407，0.0075/0.426，0.0049）以及MR与ALS（0.405，0.0020）之间存在相关性。对于MR和ALS，我们未发现它们与体重指数（BMI）、稳态模型评估的胰岛素抵抗指数（HOMA - IR）、氢化可的松和氟氢可的松剂量或代谢控制参数之间存在显著相关性。
我们的数据表明，三聚体IGF - I - IGFBP - 3 - ALS复合物的成分在CAH儿童中发生改变，这可能对青春期生长和最终身高产生影响。
