中华儿科杂志
中華兒科雜誌
중화인과잡지
Chinese Journal of Pediatrics
2009年
1期
48-52
,共5页
候凌%罗小平%杜敏联%马华梅%巩纯秀%李豫川%沈水仙%赵诸慧%梁黎%董关萍%严超英%杜宏伟
候凌%囉小平%杜敏聯%馬華梅%鞏純秀%李豫川%瀋水仙%趙諸慧%樑黎%董關萍%嚴超英%杜宏偉
후릉%라소평%두민련%마화매%공순수%리예천%침수선%조제혜%량려%동관평%엄초영%두굉위
生长激素%溶液%侏儒症%垂体性%胰岛索样生长因子Ⅰ%胰岛素样生长因子结合蛋白质3
生長激素%溶液%侏儒癥%垂體性%胰島索樣生長因子Ⅰ%胰島素樣生長因子結閤蛋白質3
생장격소%용액%주유증%수체성%이도색양생장인자Ⅰ%이도소양생장인자결합단백질3
Growth hormone%Solution%Dwarfism pituitary%Insulin-like growth factor Ⅰ%Insulin-like growth factor binding protein 3
目的 生长激素缺乏症(GHD)有赖于生长激素替代治疗.生长激素注射液可简化注射过程,提高依从性.进一步评价中国重组人生长激素注射液治疗儿童GHD的疗效和安全性.方法 采用多中心、前瞻性、随机开放的研究方法 ,对31例[男20例,女11例,年龄(10.5±4.1)岁]确诊为完全件GHD的患儿,给予重组人生长激素注射液,0.25 mg/(kg·周)[0.107 U/(kg·d)],每晚睡前皮下注射1次,治疗3、6、9、12个月后进行随访,疗程12个月.比较治疗前后的身高增长量(△HT)、年生长速率(growth velocity,GV)、身高均值标准差积分(HT SDS)、血胰岛素样生长因子Ⅰ(IGF-1)、胰岛素样生长因子结合蛋白质3(IGFBP-3)、抗生长激素抗体和骨成熟情况的变化,并评估药物治疗的安全性.结果 (1)治疗3、6、9、12个月后△HT(cm)分别为4.0±1.3、7.0±2.0、10.3±2.6和12.9±3.3(P<0.01),显示治疗后呈良好线性生长;GV(cm/年)治疗前为2.7±0.9,治疗后分别升至16.0±5.1、14.1±4.0、13.7±3.5和12.9±3.3,显示治疗后追赶生长明显,治疗前后比较,差异有统计学意义(P<0.01);HT SDS治疗前为-4.62±1.46,治疗后分别为-3.80±1.53、-3.28±1.60、-2.86±1.75和-2.47±1.86,显示治疗后身高与同年龄同性别正常儿童差距逐步缩小,与治疗前相比差异有统计学意义(P<0.01);(2)血IGF-1(ug/L)治疗前为41±64,治疗后分别为179±155、202±141、156±155和159±167;IGFBP-3(mg/L)治疗前为1540±1325,治疗后分别为3891±1815、4051±1308、3408±1435和3533±1413,显示随着身高增长,IGF-1、IGFBP-3被药物激活到较高水平,治疗前后差异均有统计学意义(P<0.01);(3)在治疗6个月、12个月后进行骨龄评估,骨成熟程度(△BA/△CA)分别为1.01±0.57、1.07±0.75,显示骨龄无加速发展;(4)治疗期间未发生严重不良事件,与药物有关的伴随反应主要表现为甲状腺功能减低.结论重组人生长激素注射液足一种安全有效治疗儿童GHD的药物.
目的 生長激素缺乏癥(GHD)有賴于生長激素替代治療.生長激素註射液可簡化註射過程,提高依從性.進一步評價中國重組人生長激素註射液治療兒童GHD的療效和安全性.方法 採用多中心、前瞻性、隨機開放的研究方法 ,對31例[男20例,女11例,年齡(10.5±4.1)歲]確診為完全件GHD的患兒,給予重組人生長激素註射液,0.25 mg/(kg·週)[0.107 U/(kg·d)],每晚睡前皮下註射1次,治療3、6、9、12箇月後進行隨訪,療程12箇月.比較治療前後的身高增長量(△HT)、年生長速率(growth velocity,GV)、身高均值標準差積分(HT SDS)、血胰島素樣生長因子Ⅰ(IGF-1)、胰島素樣生長因子結閤蛋白質3(IGFBP-3)、抗生長激素抗體和骨成熟情況的變化,併評估藥物治療的安全性.結果 (1)治療3、6、9、12箇月後△HT(cm)分彆為4.0±1.3、7.0±2.0、10.3±2.6和12.9±3.3(P<0.01),顯示治療後呈良好線性生長;GV(cm/年)治療前為2.7±0.9,治療後分彆升至16.0±5.1、14.1±4.0、13.7±3.5和12.9±3.3,顯示治療後追趕生長明顯,治療前後比較,差異有統計學意義(P<0.01);HT SDS治療前為-4.62±1.46,治療後分彆為-3.80±1.53、-3.28±1.60、-2.86±1.75和-2.47±1.86,顯示治療後身高與同年齡同性彆正常兒童差距逐步縮小,與治療前相比差異有統計學意義(P<0.01);(2)血IGF-1(ug/L)治療前為41±64,治療後分彆為179±155、202±141、156±155和159±167;IGFBP-3(mg/L)治療前為1540±1325,治療後分彆為3891±1815、4051±1308、3408±1435和3533±1413,顯示隨著身高增長,IGF-1、IGFBP-3被藥物激活到較高水平,治療前後差異均有統計學意義(P<0.01);(3)在治療6箇月、12箇月後進行骨齡評估,骨成熟程度(△BA/△CA)分彆為1.01±0.57、1.07±0.75,顯示骨齡無加速髮展;(4)治療期間未髮生嚴重不良事件,與藥物有關的伴隨反應主要錶現為甲狀腺功能減低.結論重組人生長激素註射液足一種安全有效治療兒童GHD的藥物.
목적 생장격소결핍증(GHD)유뢰우생장격소체대치료.생장격소주사액가간화주사과정,제고의종성.진일보평개중국중조인생장격소주사액치료인동GHD적료효화안전성.방법 채용다중심、전첨성、수궤개방적연구방법 ,대31례[남20례,녀11례,년령(10.5±4.1)세]학진위완전건GHD적환인,급여중조인생장격소주사액,0.25 mg/(kg·주)[0.107 U/(kg·d)],매만수전피하주사1차,치료3、6、9、12개월후진행수방,료정12개월.비교치료전후적신고증장량(△HT)、년생장속솔(growth velocity,GV)、신고균치표준차적분(HT SDS)、혈이도소양생장인자Ⅰ(IGF-1)、이도소양생장인자결합단백질3(IGFBP-3)、항생장격소항체화골성숙정황적변화,병평고약물치료적안전성.결과 (1)치료3、6、9、12개월후△HT(cm)분별위4.0±1.3、7.0±2.0、10.3±2.6화12.9±3.3(P<0.01),현시치료후정량호선성생장;GV(cm/년)치료전위2.7±0.9,치료후분별승지16.0±5.1、14.1±4.0、13.7±3.5화12.9±3.3,현시치료후추간생장명현,치료전후비교,차이유통계학의의(P<0.01);HT SDS치료전위-4.62±1.46,치료후분별위-3.80±1.53、-3.28±1.60、-2.86±1.75화-2.47±1.86,현시치료후신고여동년령동성별정상인동차거축보축소,여치료전상비차이유통계학의의(P<0.01);(2)혈IGF-1(ug/L)치료전위41±64,치료후분별위179±155、202±141、156±155화159±167;IGFBP-3(mg/L)치료전위1540±1325,치료후분별위3891±1815、4051±1308、3408±1435화3533±1413,현시수착신고증장,IGF-1、IGFBP-3피약물격활도교고수평,치료전후차이균유통계학의의(P<0.01);(3)재치료6개월、12개월후진행골령평고,골성숙정도(△BA/△CA)분별위1.01±0.57、1.07±0.75,현시골령무가속발전;(4)치료기간미발생엄중불량사건,여약물유관적반수반응주요표현위갑상선공능감저.결론중조인생장격소주사액족일충안전유효치료인동GHD적약물.
Objective Human growth hormone (hGH) is an essential therapeutic drug for the treatment of growth hormone (GH) deficiency (GHD). However, the process of dissolving hGH of the powder form is complicated and potentially hazardous. In the present study, we evaluated the efficacy and safety of preparation in the replacement therapy for children with GH deficiency. Methods A 12-month randomized, open-label, multicenter trial was conducted in 31 previously untreated children with growth failure secondary to GH deficiency [20 boys and 11 girls,mean age (10.5±4.1)years]. An recombined human growth hormone (rhGH) solution (Jintropin AQ) was given via subcutaneous injection daily in every evening at a weekly dose of 0.25 mg/kg. The patients were followed up at 3, 6, 9, and 12 months of the treatment, and the course of treatment was 12 months. Body height was measured 3-monthly and height velocity (HV) and mean height standard deviation score (HT SDS) were calculated. Serum Insulin-like growth factor Ⅰ (IGF-1), Insulin-like growth factor binding protein 3 (IGFBP-3), GH antibodies and safety parameters were assessed at the baseline and at 3-month intervals. Bone age (BA) was assessed at the baseline and the rate of skeletal maturation (△BA/△CA) was calculated after 6 and 12 months of rhGH treatment by a central bone age reader. Moreover, the safety of rhGH solution treatment was assessed. Results After 12 months of liquid rhGH therapy, growth parameters were significantly increased over baseline. (1) The mean (±SD) height increment △HT (cm) was 4.0±1.3, 7.0±2.0, 10.3±2.6 and 12.9±3.3 after 3, 6, 9, and 12 months of treatment, respectively (P<0.01), which indicated linear growth after treatment. The GV (cm/years) was 2.7±0.9 before treatment and increased to 16.0±5.1, 14.1±4.0, 13.7±3.5, and 12.9±3.3 after treatment, suggesting that catch-up growth was significant after treatment as compared to the pre-treatment status (P<0.01). Accordingly, pest-treatment catch-up growth was obvious, significent differences were observed in HT SDS, which was -4.62±1.46 at the onset of therapy and increased significantly after the treatment to - 3.80±1.53, - 3.28±1.60, - 2.86±1.75 and -2. 47±1.86, respectively (P<0.01). The height difference between GH deficient children and unimpaired children of the same age and gender gradually decreased after treatment, which was significantly different from that seen before treatment (P<0.01). (2) The levels of serum IGF-1 and IGFBP-3 were increased comparably for the treatment. IGF-1 level (ug/L) was 41±64 at baseline and increased to 179± 155,202±141, 156±155 and 159±167 after 3, 6, 9, 12 months of treatment. IGFBP-3 level (mg/L) was 1540±1325 at baseline, and increased to 3891±1815,4051±1308,3408±1435 and 3533±1413, respectively, suggesting that with the increases in height, IGF-1, and IGFBP-3 were significantly activated to relatively high levels by the medication and reached peak values between 3 and 6 months of treatment. The levels of IGF-1 and IGFBP-3 were significantly different before and after treatment (P<0.01). The IGF-1/ IGFBP-3 molar ratio significantly increased during GH therapy (0.143±0.013 pre-therapy up to 0.240± 0.055 post-therapy, P<0.01). The IGF-1/IGFBP-3 molar ratio tended to stabilize after 3-month GH therapy. (3) The bone age assessment carried out 6 and 12 months after treatment showed that the bone maturity (△BA/△CA) was 1.01±0.57 and 1.07±0.75, respectively, suggesting that there was no speed-up development in the bone age. No severe adverse events were observed during the trial and the most frequent accompanying event was mild hypothyroidism. Conclusions rhGH solution (Jintropin AQ) is a safe and effective preparation in the replacement therapy for children with GH deficiency.
