中西医结合治疗矮小症的进展及生长激素的安全性研究

【作者】 杨晔；

【导师】 张知新；

【作者基本信息】 北京中医药大学 ， 中西医结合临床， 2012， 硕士

【摘要】 研究背景：矮小症是一种以身材矮小为主要症状的疾病,是由内分泌代谢异常、遗传性疾病、营养不良、精神心理障碍或其他原因导致的一种身高异常的疾病。矮小症目前在我国的发病率为男性4.87%,女性4.19%。[1]可导致患者成年终身高受损、自卑等心理障碍,根据病因的不同还可有其他伴发症状,对患者的健康造成重要影响。目前对矮小症的治疗,主要是对因治疗。生长激素为促进人体线性生长的重要激素,重组人生长激素(Recombinant human growth hormone,rhGH)是治疗矮小症的主要药物。美国药品食品管理局(Food and Drug Administration, FDA)批准的生长激素适应症包括：儿童生长激素缺乏症(Children’s growth hormone deficiency)、特纳综合征(Turner syndrome,TS)、成人生长激素缺乏(Adults with growth hormone deficiency)、 Prader-Willi综合征、小于胎龄儿(Small for gestational age infant,SGA)、特发性矮身材(Idiopathic short stature,ISS)、SHOX基因缺少但不伴GHD患儿。随着rhGH在临床中的广泛应用,rhGH长期治疗中存在的安全性问题,也逐渐引起了人们的重视。中医治疗矮小症缺乏系统研究,目前仅有复方制剂、针灸方法小样本应用于临床,未见大样本的有效性研究。因此,进一步研究中西医结合改善矮小症十分重要。本研究拟选择重组人生长激素,监测治疗前后血小板参数的变化,为矮小症患儿安全用药提供数据支持。目的：通过临床病例分析,观察矮小症患儿使用重组人生长激素(rhGH)(?)台疗后血小板参数的变化,监测生长激素在矮小症患儿的替代治疗中对血小板的影响,评估rhGH治疗的安全性。方法：在中日友好医院小儿内分泌专科门诊中,随机选择生长激素缺乏症(GHD)患儿18例,特发性矮小症患儿(ISS)10例,Turner综合征患儿(TS)5例,给予rhGH皮下注射治疗,疗程6个月。采集rhGH治疗前后患儿空腹静脉血,检测血常规,进行统计分析,评价rhGH治疗对血小板计数(platelet count,PLT)、血小板分布宽度(platelet distribution width, PDW)、平均血小板体积(mean platelet volume, MPV)、大血小板比率(Big platelet ratio,P-LCR)、血小板压积(Platelet deposited, PCT)5个参数的影响,得出结论。结果：治疗后33例矮小患儿血小板计数(PLT)升高,较治疗前有统计学意义(P<0.01),但血小板分布宽度(platelet distribution width, PDW).平均血小板体积(mean platelet volume, MPV)、大血小板比率(Big platelet ratio, P-LCR)、血小板压积(Plateletdeposited, PCT)变化无统计学意义。rhGH治疗6个月后,其中6例ISS患儿和4例TS患儿治疗后PLT升高、大于正常范围,且有显著性差异(P<0.05),而9例GHD患儿治疗前后PLT升高、大于正常范围,但无统计学意义。33例患儿中19例患儿PLT升高大于正常范围,GHD组9例,ISS组6例,TS组4例。三组患儿PLT升高、大于正常范围的发生率无显著性差异。治疗前后血小板分布宽度(PDW)、平均血小板体积(MPV)、大血小板比率(P-LCR)、血小板压积(PCT)变化无统计学意义。结论：通过统计分析得出,6个月的rhGH治疗可促进矮身材患儿PLT升高,部分可高出正常范围,可能导致血液高凝状态,血栓形成风险增加,监测血小板计数的变化对监测重组人生长激素的安全性具有重要意义。推测rhGH治疗后导致矮小患儿血小板生成增加的机制可能与rhGH治疗调节了糖脂代谢有关,但确切机制有待进一步研究。更多还原

【Abstract】 Background:Short disease is a disease of abnormal height, whose main symptom is short stater, caused by the endocrine metabolic abnormalities, hereditary disease, poor nutrition, mental disorders or other reasons. The incidence of short disease is for4.87%male and4.19%female at present in our country. It can cause final height loss,and psychological barriers such as inferiority. There would be other comorbid symptoms according to different causes,which influent patients health seriously. At present the main treatment of short disease is to eliminate reasons. Growth hormone is an important hormone promoting the linear growth of human body. Recombinant human growth hormone (rhGH) is the main drug to treat short disease. The indications of rhGH approvaled by the United States food and drug administration FDA include children’s growth hormone deficiency (GHD), Turner syndrome(TS), adult GHD replacement therapy, Prader-Willi syndrome, and less than gestational age (SGA), idiopathic short stature (ISS), SHOX gene but not with GHD lack of children. With rhGH widely applicated in clinical, people pay more attention to the safety problem of rhGH long-term treatment.Traditional Chinese medicine treatment on short disease is lack in systematic research.There are only compound preparations, acupuncture methods used in clinical as small samples, no large sample or effective research including control. Therefore, it is very important of further study of traditional Chinese medicnine and western morden medicine combined treatments for short disease. This study was to choose to promote the growth of children of the small clinical the most effective, one of the most widely applied recombinant human growth hormone, monitoring the change of platelet parameters before and after treatment, maintenance of small children to provide data to support health disease.Objective:the clinical case analysis, to observe short stater children using recombinant human growth hormone (rhGH) after treatment, the change of platelet parameters, monitoring growth hormone treatment short disease promote the growth of effective treatment of children of the side effects, to observe the safety of rhGH treatment.Methods:18pediatric patients with growth hormone deficiency (GHD),10with idiopathic short stature (ISS) and5with Turner syndrome (TS)were selected in random. Each of them was treated with rhGH for6months. Collected Fasting vein blood before and after6months of rhGH therapy, evaluat the rhGH therapy effects of parameters of platelets Results:The platelet count (PLT) in33children with short stature increased in a statistically significant (P<0.01) after treatment. PLT increased greater than the normal range in a significant difference (P<0.05) in six cases of ISS children and4cases of TS children after treatment. And PLT increased greater than the normal range after treatment in9cases of GHD, but there was no statistically significant. The incidence of PLT increasing greater than the normal range between three groups of patients after treatment had no significant differences. Before and after treatment, platelet distribution width,(PDW), average platelet volume (MPV), big platelet ratio (P-LCR), platelet deposited (PCT) changes had no statistically significant.Conclusion:PLT of short stature children was increased after six months of rhGH treatment, part of them PLT was increased above the normal range, which may cause blood high pour-point state and increase the thrombosis risk. Monitoring changes of platelet count have an important significance in improving the safety application to growth hormone. The mechanism of rhGH increasing platelet production in children with short stature after treatment may related to the remedial adjustment on glucose and lipid metabolism, but the exact mechanism needs further research.更多还原