Short stature and failure of pubertal development in thalassaemia major: evidence for hypothalamic neurosecretory dysfunction of growth hormone secretion and defective pituitary gonadotropin secretion
Short stature and failure of pubertal development in thalassaemia major: evidence for hypothalamic neurosecretory dysfunction of growth hormone secretion and defective pituitary gonadotropin secretion
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DOI：
10.1007/s004310050711
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发表时间：
1997-10-01
影响因子：
3.6
通讯作者：
Schroter, W
中科院分区：
文献类型：
--
作者：
Roth, C;Pekrun, A;Schroter, W
在重型β地中海贫血患者中，频繁输血联合去铁胺螯合治疗可提高生存率。与继发性含铁血黄素沉着症相关的内分泌紊乱，如身材矮小、青春期延迟和性腺功能减退是青少年和成人患者的主要问题。总共有32例患者P-地中海贫血严重接受治疗的儿童医院，哥廷根大学进行了检查。其中14人身材矮小。生长激素（GH）的分泌进行了研究，在13例患者表现出身材矮小或生长速度降低。本组10例患者的刺激GH分泌均在正常范围内。对他们夜间自发GH分泌的研究显示，这些患者的平均GH显著降低，GH峰值幅度降低。低胰岛素样生长因子（IGF）-I水平被认为是在生长迟缓的地中海贫血患者。八个进行了IGF生成测试，并显示IGF-I和胰岛素样生长因子结合蛋白（IGFBP）-3水平的强烈增加，表明肝脏完整的IGF-I生成。低促性腺激素性腺功能减退症被发现存在于男性和女性患者性发育受损。在2名女性和5名男性患者中，每个泵用LH释放激素（GnRH）预充后，未观察到血清雌二醇或睾酮水平或LH/FSH对GnRH的反应发生变化，表明他们患有严重的垂体促性腺激素不足。三名青春期男性患者，但表现出身材矮小，低GH，低IGF-I和性腺功能减退症，接受低剂量长效睾酮。治疗3-12个月后，患儿生长突增明显，夜间GH水平升高，IGF-I和IGFBP-3水平均升高。结论地中海贫血患儿GH分泌减少和IGF-I水平降低与铁超载引起的神经分泌功能紊乱有关，与肝功能损害无关。低促性腺激素性性腺功能减退症是由垂体促性腺激素功能的选择性丧失引起的。在GH缺乏和性腺功能减退的患者中，在开始GH治疗之前，应考虑将低剂量性类固醇治疗作为替代或附加治疗。
In patients with beta-thalassaemia major, frequent blood transfusions combined with desferrioxamine chelation therapy lead to an improved rate of survival. Endocrine disorders related to secondary haemosiderosis such as short stature, delayed puberty and hypogonadism are major problems in both adolescent and adult patients. A total of 32 patients with P-thalassaemia major undergoing treatment at the Children's Hospital, University of Gottingen were examined. Fourteen of these were short in stature. Growth hormone (GH) secretion was investigated in 13 patients exhibiting either a short stature or reduced growth rate. The stimulated GH secretion of 10 patients in this subgroup lay within the normal range. Studies of their spontaneous GH secretion during the night revealed that these patients had a markedly reduced mean GH and reduced amplitudes in their GH peaks. Low insulin-like growth factor (IGF)-I levels were seen in the growth-retarded thalassaemic patients. Eight were subjected to an IGF generation test and showed a strong increase in both IGF-I and insulin-like growth factor binding protein (IGFBP)-3 levels indicating intact IGF-I generation by the liver. Hypogonadotropic hypogonadism was found to be present in both the male and female patients with impaired sexual development. After priming with LH-releasing hormone (GnRH) per pump in 2 female and 5 male patients, no change in either their serum oestradiol or testosterone levels or in LH/FSH response to GnRH was observed suggesting that they were suffering from a severe pituitary gonadotropin insufficiency. Three male patients at the age of puberty but exhibiting short stature, low GH, low IGF-I and hypogonadism received low dose long-acting testosterone. After 3-12 months of therapy there was a marked growth spurt, higher nocturnal GH levels and an increase in both IGF-I and IGFBP-3.Conclusion Reduced GH secretion and low IGF-I in thalassaemic patients are related to a neurosecretory dysfunction due to iron overload rather than to liver damage. Hypogonadotropic hypogonadism is caused by the selective loss of pituitary gonadotropin function. In patients with both GH deficiency and hypogonadism, low dose sexual steroid treatment should be considered either as an alternative or an additional treatment before starting GH therapy.