促性腺激素释放激素类似物(曲普瑞林)治疗女童特发性中枢性性早熟23例疗效观察

目的观察促性腺激素释放激素类似物(曲普瑞林)治疗女童特发性中枢性性早熟(ICPP)的临床疗效。方法应用曲普瑞林治疗23例ICPP女童6个月,观察治疗前后第二性征、子宫、卵巢、骨龄(BA)、血清雌二醇(E2)、促性腺激素释放激素(GnRH)激发试验激素水平、预测成人终身高的变化及药物副反应。结果治疗后患儿乳房、子宫、卵巢体积均有缩小,E2、促黄体生成激素(LH)、卵泡刺激素(FSH)峰值均显著降低,骨龄成熟延迟,骨龄/实际生活年龄(BA/CA)值下降,预测成人终身高治疗前为(155.5±0.81)cm,治疗后为(157.0±0.81)cm,较治疗前有改善,差异具有统计学意义(P<0.01)。结论曲普瑞林治疗ICPP能够抑制性腺轴及性腺发育,延缓BA成熟,最终对改善成人终身高有意义。     

先天性肾上腺皮质增生症合并中枢性性早熟临床分析

目的分析先天性肾上腺皮质增生症(CAH)患儿合并中枢性性早熟的临床表现。方法通过回顾性分析和临床随访,在12例21羟化酶缺乏患儿中发现20例合并中枢性性早熟。根据治疗和非治疗情况分为A组(9例)和B组(11例),分析其发生的年龄、骨龄以及与激素替代治疗的关系。结果A组中发生中枢性性早熟的实际年龄平均为(5.6±2.1)岁,骨龄平均为(12.0±3.2)岁;B组中诊断中枢性性早熟平均年龄在(6.8±1.1)岁;骨龄平均值在(11.7±2.0)岁,两组在统计学上差异无显著性。B组应用氢化可的松治疗后平均2.3年出现中枢性性早熟。结论CAH患儿骨龄发育提前是发生性早熟的主要原因,早诊断和早治疗可改善预后。     

醋酸甲羟孕酮和醋酸亮丙瑞林治疗女童性早熟疗效比较

目的　观察醋酸甲羟孕酮、醋酸亮丙瑞林治疗女童真性性早熟的疗效。方法　分别采用醋酸甲羟孕酮 4～ 2 0mg/d口服和醋酸亮丙瑞林 6 0～ 90 μg/ (kg·月 ) ,每 4周 1次 ,皮下注射治疗女童性早熟 74例。 结果　两种药物均可使乳房变软、缩小。醋酸甲羟孕酮组治疗后 2 0例第二性征均发育减退 ,对骨龄及子宫、卵巢发育无明显的抑制作用 ,治疗前后血清雌二醇 (E2 )水平有明显差异 (P <0 .0 5 ) ;醋酸亮丙瑞林组所有患儿治疗后第二性征发育减退、骨龄增长速度及卵巢、子宫发育减慢 ,E2 、睾丸素 (T)及卵泡刺激素 (FSH)和血清促黄体素(LH)明显下降 (P <0 .0 5 )。结论　醋酸亮丙瑞林较醋酸甲羟孕酮更能有效地抑制垂体促性腺激素和性腺激素分泌 ,控制性征发育和延缓骨龄     

促性腺激素释放激素类似物治疗儿童中枢性性早熟短期疗效

为了解短效促性腺激素释放激素类似物(GnRH_a)治疗儿童中枢性性早熟(CPP)的疗效 ,我们总结了近2年来用GnRH_a治疗8例女性CPP患儿的疗效 ,现报告如下。资料与方法一、资料自1997年2月～1999年1月我院小儿内分泌专科门诊收治8例女性CPP患儿 ,发病年龄3～7岁6月 ,平均5岁8月 ;治疗前的生长速度3.5～5.0cm/半年 ,平均4.25cm/半年 ;身高在同年龄、同性别的第90百分位数以上 ;乳房发育按Tanner's标准为Ⅱ～Ⅳ ;阴毛生长6例 ;出现白带4例 ,月经2例。骨龄均大于实际年龄1年以上 ,其中5例大于2个标准差 ;盆腔B超显示子宫和卵巢有不同程度的发…     

中枢性性早熟患儿5种骨龄测定方法的比较研究

目的探讨CHN法、TW2法中日英3种标准、TW3法5种骨龄测定方法对中枢性性早熟(CPP)患儿的诊断价值及正常值临界点的确定。方法由两名医师采用盲法回顾性分析CPP患儿61例(病例组),与每一个CPP患儿性别相同,年龄、身高、体质量基本一致的同期体检者61例、8岁以后出现乳房发育的女童6例(均为对照组)治疗前左手腕部X线片,用CHN法、TW2法中英日3种标准和TW3法进行骨龄判定,计算骨龄与年龄的差值,用SPSS13.0统计软件进行受试者工作特征(ROC)分析。结果 (1)两名医师骨龄测定结果的Kappa值为0.776(u=16.128,P<0.05);(2)5种骨龄测定方法的ROC曲线下面积分别为:CHN法0.921±0.024,95%可信区间为0.875～0.967;TW2法中国南方人标准为0.947±0.019(0.910～0.983);TW2法日本人标准为0.937±0.023(0.892～0.982);TW2法英国人标准为0.931±0.022(0.888～0.975);TW3骨龄测定法为0.924±0.023(0.879～0.969);5种方法的诊断价值差异无统计学意义(Z=0.85,P>0.05...     

内分泌系统疾病

940928儿童性早熟35例临床分析娜宾如…刀实用儿科临床杂志一1993,8(5、6)一484 35例中真性性早熟11例,女8例,男3例。其中特发性6例,CT证实为垂体瘤男!例,女2例,Mccune一月bngh综合征女孩l例,病脑后遗症女孩之例。11例均有乳房发育.假性性早熟24例,男9例,女15例。其中乳房发育4例,内源性性激素增加16例。11例真性性早熟其身高体重及骨龄测定均大于实际年龄,其中8例不同程度子宫增大。性激素测定11例中,4例真性其促性腺激素(FSH、LH)增高,同时性腺激素(EZ、T)也增高.7例假性仅性腺激素增高,1例LH轻度增加。阴道粘膜脱落细胞学检查13例,…     

不同剂量促性腺激素释放激素类似物治疗女童特发性中枢性性早熟的临床观察

目的　观察不同剂量促性腺激素释放激素类似物 (GnRHa)缓释剂治疗特发性中枢性性早熟女童(ICPP)的疗效。方法　以达菲林针 1 0 0 μg/ (2 8d·kg)肌注两次 ,随机改用 40～ 50 μg/ (2 8d·kg) ;与随机改用 80～ 1 0 0 μg/ (2 8d·kg)治疗ICPP女童各 1 0例 ,每例共 1 2次 ,疗程 1年。起始年龄 (8.3± 0 .9)岁 ;观察治疗前后两组性征、身高、骨龄及预测成年身高及性激素、生长激素 (GH)变化。结果　两组治疗后性征均减退 ,性激素水平下降 ,骨龄增长受抑 ;两组预测成年身高改善相似。结论　小剂量达菲林治疗ICPP能有效抑制中枢性性早熟 ,改善患儿成年身高 ,较大剂量具有更实用、经济的优点     

乳房早发育患儿去氢异雄酮的变化及意义

乳房早发育为儿科常见内分泌疾病 ,部分患儿可发展成中枢性性早熟 ,使青春期发育时间提前 ,目前其发病机制尚不清楚 ,我们对 5 0例乳房早发育患儿多种性激素水平进行检测 ,现报道如下。临床资料 :选自 1996年 6月至1999年 12月儿科门诊按Ｗｉｌｋｉｎｓ标准诊断乳房早发育患儿 5 0例 ,年龄 2 1～ 7 8岁 ,平均 (5 92± 1 41)岁。对照组选自儿童保健体检正常发育儿童 30例 ,年龄 2 6～ 7 3岁 ,平均 (5 98±1 45 )岁。方法 :两组均抽取清晨空腹静脉血3ｍＬ ,分离血清后置 - 2 0℃冰箱待测 ,血清雌二醇 (Ｅ2 )、睾酮 (Ｔ )、泌乳素(ＰＲＬ)…     

内分泌系统疾病

023,47不同荆,促性腺激素释放激素类似物治疗女童特发性中枢性性早熟的临床观察/杨立础…//实用儿科临床杂志一2002,17(3)一200一201 以达菲林针10。陀/(28d·kg)肌注2次,随机改用40一50拜g/(28d·kg)。与随机改用80~100拜g/(28d·kg)治疗特发性中枢性性早熟女童各10例,每例共12次,疗程1年。起始年龄(8.3士0.9)岁;观察治疗前后两组性征、身高、骨龄及预测成年身高及性激素、生长激素变化。结果:两组治疗后性征均减退,性激素水平下降,骨龄增长受抑;两组预测成年身高改善相似。表1参4(李瑛) 023948先天性肾上腺皮质增生症的治疗与随访/祝国红…     

性早熟女童骨代谢特点研究

目的探讨性早熟女童骨代谢水平的变化及临床意义。方法对35例中枢性性早熟(CPP)女童(其中A1组16例,年龄6.0～7.9岁;A2组19例,年龄8.0～9.0岁)及21例单纯性乳房早发育(PT)女童(年龄6.0～7.9岁)的血清骨代谢生化指标、胰岛素样生长因子_1(IGF_1)和桡骨远端1/3处骨超声强度(SOS)值进行检测,并与年龄匹配的正常对照组进行比较。结果CPP及PT女童桡骨远端SOS、SDS值均明显升高。A1组Ⅰ型胶原交联羧基末端肽(OC)、骨碱性磷酸酶(BAP)显著高于正常对照组,Ⅰ型胶原交联羧基末端肽(ICTP)、IGF_1有升高趋势;A2组骨钙素(OC)、BAP、ICTP、IGF_1均显著高于正常对照组。PT组女童与同年龄对照组比较OC、BAP明显升高,ICTP、IGF_1差异无显著性;与A1组比较各指标差异无显著性。CPP女童IGF_1水平与LH峰值、LH/FSH比值、骨龄间呈正相关(r=0.38～0.54,P均<0.05);CPP女童骨代谢指标BAP与骨龄、IGF_1值间呈正相关(r=0.35、0.35,P均<0.05)。结论性早熟女童在发育早期即有明显骨代谢改变,骨密度增高、骨形成和骨吸收增加,以骨形成增加为主;血清OC、BAP、ICTP和IGF_1水平与性发育关系密切,其变化是性早熟的早期信号。     

Accelerated versus slowly progressive forms of puberty in girls with precocious and early puberty. Gonadotropin suppressive effect and final height obtained with two different analogs

OBJECTIVES: To distinguish which children with precocious puberty (PP) and early puberty (EP) should be treated and which followed without therapy. To determine the effect of GnRH analog treatment on the final height of treated patients and compare the effect of two different analogs on gonadotropin suppression and final height. STUDY DESIGN: Sixteen females with PP or EP with a mean chronological age (CA) of 8.8 +/- 1.4 years and a mean bone age (BA) of 10.8 +/- 1.3 years were treated for a mean of 2.7 +/- 1.0 years with a GnRH analog (triptorelin or leuprolide acetate; group A), while 21 girls with a mean CA of 8.5 +/- 1.0 years, a mean BA of 9.7 +/- 1.4 years and a predicted adult height of >155 cm were followed without therapy (group B). Criteria for treatment were one of: a. predicted adult height (PAH) of <155 cm initially or at any time during follow up; b. PAH over 155 cm with a dramatic decrease in PAH over a 6-month follow-up period; c. advanced and rapidly progressing breast development for age (Tanner 3 before the age of 9 years). RESULTS: GnRHa therapy suppressed gonadotropins in group A, while gonadotropins increased gradually in group B. Height velocity (HV) decreased in group A, while it remained accelerated in group B; BA increased a mean of 1.7 +/- 0.5 years in group A and 3.2 +/- 0.3 years in group B. This resulted in a height increase in group A from a baseline PAH of 153.7 +/- 1.2 cm to a final height (FH) of 160.9 +/- 4.0 cm (p <0.001), clearly above their target height (TH) of 157.7 +/- 4.2 cm. The height of group B children did not change over time (164.1 +/- 4.1 cm before therapy and 166.0 +/- 6.0 cm at FH), both above their TH. The mean leuprolide acetate dose utilized in this study decreased during treatment, while both the initial and final triptorelin dose remained unchanged. Adequate gonadotropin suppression (peak level of LH and FSH of <2 IU/l after i.v. GnRH stimulation) was noted with both leuprolide acetate and triptorelin, although LH suppression was slightly more pronounced with triptorelin. BA advanced 1.8 +/- 0.4 years during leuprolide acetate treatment and 1.5 +/- 0.3 years with triptorelin, so that FH increased a mean of 5.5 +/- 1.3 cm with leuprolide acetate and 8.7 +/- 2.2 cm with triptorelin. CONCLUSIONS: PAH of <155 cm before or during therapy, PAH of >155 cm with a dramatic decrease in predicted height over a 6-month follow-up period and/or advanced and rapidly progressing breast development in girls with PP or EP were useful parameters in deciding which patients to treat. GnRHa therapy suppressed gonadotropins, HV and bone maturation in children with an accelerated form of PP or EP, resulting in a significant height increase. Final height remained stable over time in untreated patients. Adequate gonadotropin suppression was noted with both analogs, although with the doses of analog used in our study, LH and BA suppression were more pronounced with triptorelin, resulting in a larger height gain.     

Preserving adult height potential in girls with idiopathic true precocious puberty

We designed a prospective study of height potential in girls with idiopathic precocious puberty, comparing the presenting features of girls with and without evidence of reduced adult height potential. The 14 girls with impaired adult height prognoses (group 1) were reexamined after treatment with a gonadotropin releasing hormone agonist, nafarelin. The seven girls with the prognosis of unimpaired height (group 2) were followed without therapy. We found that the group could be distinguished at initial examination by the greater bone age/height age ratio of group 1 (mean +/- SEM: 1.4 +/- 0.06 vs 1.0 +/- 0.05; p less than 0.005) and by the greater difference between predicted height and target height in group 1. The mean predicted height in group 1 was significantly less than the mean target height (150.7 +/- 2.1 vs 165.4 +/- 3.0 cm; p less than 0.005), whereas the mean predicted and target heights in group 2 were similar (165.4 +/- 3.0 vs 164.3 +/- 2.1 cm). Initial estradiol levels were also greater in group 1 than in group 2 (21.6 vs 10.6 pg/ml; p less than 0.05), although this difference was not sustained during follow-up. In group 1, nafarelin therapy suppressed the pituitary-gonadal axis, and although there was a transient reduction in height potential in girls with the youngest bone ages during the first 6 months of therapy, 2 years of treatment slightly improved predicted heights from 150.7 +/- 2.1 to 152.7 +/- 2.0 cm (p less than 0.05). Height predictions also increased without therapy during the 2-year observation period in group 2, from 165.4 +/- 3.0 to 168.7 +/- 4.1 cm (p less than 0.05). Our data indicate that gonadotropin releasing hormone agonist therapy preserves height potential in girls with an initially impaired height prognosis, and that height potential is preserved without therapy in those with a good initial height prognosis.     

促性腺激素释放激素类似物联合重组人生长激素对中枢性性早熟女童身高的影响

目的 研究促性腺激素释放激素类似物（GnRHa）与重组人生长激素（rhGh）联合治疗以及GnRHa单用对骨龄≥10岁的特发性中枢性性早熟（ICPP）女童成年身高的改善情况。方法 将6个医学中心确诊为ICPP符合研究条件的80例女童（年龄9.0±0.7岁,骨龄≥10岁）根据治疗方法分为GnRHa与rhGh联合治疗组（31例）及GnRHa单用组（49例）。观察治疗前后的预测成年身高、接近成年身高和身高净获等各项指标的变化。结果 两组在治疗后按骨龄的身高标准差分值均较治疗前有显著改善（P<0.01）,其中GnRHa与rhGh联合治疗组明显优于GnRHa单用组（P<0.01）。联合用药组接近成年身高（157±6 cm vs 157±4 cm）、身高净获（4.68 cm vs 3.89 cm）、停药时预测成年身高（161±5 cm vs 158±5 cm）、接近成年身高与遗传靶身高差值等指标均略高于GnRHa单用组,但差异无统计学意义（均P >0.05）。结论 GnRHa与rhGh联合治疗或GnRHa单用组均能改善骨龄≥10岁ICCP女童的成年身高,但两药联用优势不明显。对ICPP患儿预测成年身高的评估需要慎重,停药时的预测值偏高。     

Final height in central precocious puberty after long term treatment with a slow release GnRH agonist

OBJECTIVE: To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. PATIENTS: 31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were treated for a mean (SD) of 3.4 (1.0) years and were followed up for 4.0 (1.2) years after the treatment was stopped. RESULTS: The rate of bone maturation decreased during treatment and the predicted adult height increased from 158.2 (7.4) cm to 163.9 (7.5) cm at the end of treatment (p < 0.001). When treatment was stopped bone maturation accelerated, resulting in a final height of 161.6 (7.0) cm, which was higher than the predicted adult height at the start of treatment (p < 0.001). Height at the start of treatment was the most important factor positively influencing final height (r = 0.75, p < 0.001). Bone age at cessation of treatment negatively influenced final height (r = -0.52, p = 0.03). A negative correlation between bone age and height increment after discontinuation of treatment was observed (r = -0.85, p = 0.001). Residual growth capacity was optimal when bone age on cessation of treatment was 12 to 12.5 years. Body mass index increased during treatment and remained high on cessation. At final height, the ratio of sitting height to subischial leg length was normal. Menarche occurred at 12.3 (1.1) years, and at a median (range) of 1.1 (0.4 to 2.6) years after treatment was stopped. The ovaries were normal on pelvic ultrasonography. CONCLUSIONS: Treatment of CPP with triptorelin increases final height, with normal body proportions, and seems to increase body mass index. The best results were achieved in girls who were taller at the start of treatment. Puberty was resumed after treatment, without the occurrence of polycystic ovaries.     

Treatment of central precocious puberty with triptorelin 11.25 mg depot formulation

A new triptorelin 11.25 mg long depot formulation is now available for the treatment of central precocious puberty (CPP). The aim of our study was to evaluate the efficacy of triptorelin 11.25 mg administered every 90 days to suppress gonadotropin and sex steroid secretion and pubertal signs in children with CPP during 2 years of treatment. Inclusion criteria were clinical pubertal development before the age of 8 years in girls or 9 years in boys, advanced bone age and a pubertal LH response (peak >5 mIU/ml) to GnRH. We studied 20 patients (19 girls and 1 boy), with a median age at entry into the study of 7.5 +/- 0.2 years for girls, and 9 years for the boy. The basal and GnRH-stimulated serum levels of LH and FSH decreased significantly from baseline to 3 months of therapy (p <0.0001). All patients had a GnRH-stimulated peak below 3 mIU/ml between 6 and 24 months of treatment. The pituitary-gonadal axis recovered adequately after discontinuation of therapy. These results suggest that 3-month depot triptorelin is a satisfactory alternative for the therapy of children with CPP. The longer interval between injections may increase acceptability and compliance with treatment.     

Randomised trial of LHRH analogue treatment on final height in girls with onset of puberty aged 7.5-8.5 years.

OBJECTIVE: To study the effectiveness of luteinising hormone releasing hormone (LHRH) analogues in improving final height in girls affected by early puberty. PATIENTS: Forty six consecutive girls with onset of puberty aged 7.5-8.5 years randomly divided into two groups: one treated with 3.75 mg triptorelin intramuscularly every four weeks (group 1); and the other with no treatment (group 2). RESULTS: Mean (SD) chronological age at onset of menarche was significantly higher in group 1 than in group 2 (11.9 (1.0) v 10.8 (0.7) years). However, mean (SD) height at menarche (152.7 (7.2) v 152.5 (5.7) cm) and mean (SD) growth after menarche (4.9 (3.0) v 5.4 (2.2) cm) were similar in both groups. The mean (SD) final height was similar in the two groups (group 1, 158.1 (6.2) cm; group 2, 158. 6 (6.0) cm) and not significantly different from target height. Fourteen of 20 patients in group 1 and 12 of 18 patients in group 2 showed final height equal to or higher than target height. Final heights of girls with poor initial height prognosis were significantly lower than those of girls with good prognosis, but in patients with the same initial height prognosis, both groups showed final heights similar and not significantly different from their target heights. CONCLUSIONS: LHRH analogue has no apparent effect on final height in subjects with onset of puberty between 7.5 and 8.5 years.     

When and how to combine growth hormone with a luteinizing hormone-releasing hormone analogue

The effect of combined treatment with growth hormone (GH) and a luteinizing hormone-releasing hormone (LHRH) analogue, or GH alone, on pubertal height gain was assessed in an uncontrolled study in 15 boys and 10 girls with GH deficiency (GHD). Seven boys and six girls were treated with GH alone (group 1), and eight boys and four girls were treated with a combination of GH and an LHRH analogue during puberty (group 2). Mean ages (+/- SD) at the start of GH treatment and at the onset of puberty were significantly lower in group 2 (8.0 +/- 3.3 years and 11.2 +/- 0.8 years, respectively, in boys, and 6.3 +/- 1.6 years and 10.8 +/- 0.7 years in girls) than in group 1 (12.8 +/- 1.9 years and 13.7 +/- 1.4 years in boys, and 11.2 +/- 1.0 years and 12.5 +/- 1.2 years in girls). Height at the onset of puberty was less in group 2 than in group 1, but the difference was significant only for the boys. Combination treatment was started at a mean age of 11.7 +/- 1.2 years in boys and 11.5 +/- 1.0 years in girls. The duration of the combination treatment was 5.1 +/- 1.5 years in boys and 2.3 +/- 0.7 years in girls. The duration of the period between the onset of puberty and the end of GH treatment was significantly longer in group 2 (6.8 +/- 1.2 years in boys and 5.5 +/- 1.0 years in girls) than in group 1 (4.3 +/- 1.6 years in boys and 3.6 +/- 1.4 years in girls). The pubertal height gain was also significantly greater in group 2 (36.7 +/- 6.5 cm in boys and 29.0 +/- 8.3 cm in girls) than in group 1 (21.9 +/- 4.1 cm in boys and 18.6 +/- 4.1 cm in girls). Final height was significantly greater in group 2 than in group 1 in boys. Although there was no significant difference in final height between groups in the girls, the change in height SDS from the start of GH treatment until final height was significantly greater in group 2 (2.7 +/- 1.6 in boys and 4.5 +/- 0.5 SD in girls) than in group 1 (1.0 +/- 0.8 in boys and 1.8 +/- 0.9 SD in girls), in both boys and girls. In conclusion, it appears that combination of an LHRH analogue and GH may increase the pubertal height gain and the final height of children with GHD. The improvement is attributed to the prolongation of the treatment period, permitting slow bone maturation, and to the maintenance of height velocity. This combination treatment appears to be more effective in boys than girls. To fully assess this therapeutic approach, prospective controlled studies are needed.     

Final height in central precocious puberty after long term treatment with a slow release GnRH agonist.

OBJECTIVE: To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. PATIENTS: 31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were treated for a mean (SD) of 3.4 (1.0) years and were followed up for 4.0 (1.2) years after the treatment was stopped. RESULTS: The rate of bone maturation decreased during treatment and the predicted adult height increased from 158.2 (7.4) cm to 163.9 (7.5) cm at the end of treatment (p < 0.001). When treatment was stopped bone maturation accelerated, resulting in a final height of 161.6 (7.0) cm, which was higher than the predicted adult height at the start of treatment (p < 0.001). Height at the start of treatment was the most important factor positively influencing final height (r = 0.75, p < 0.001). Bone age at cessation of treatment negatively influenced final height (r = -0.52, p = 0.03). A negative correlation between bone age and height increment after discontinuation of treatment was observed (r = -0.85, p = 0.001). Residual growth capacity was optimal when bone age on cessation of treatment was 12 to 12.5 years. Body mass index increased during treatment and remained high on cessation. At final height, the ratio of sitting height to subischial leg length was normal. Menarche occurred at 12.3 (1.1) years, and at a median (range) of 1.1 (0.4 to 2.6) years after treatment was stopped. The ovaries were normal on pelvic ultrasonography. CONCLUSIONS: Treatment of CPP with triptorelin increases final height, with normal body proportions, and seems to increase body mass index. The best results were achieved in girls who were taller at the start of treatment. Puberty was resumed after treatment, without the occurrence of polycystic ovaries.     

Human growth hormone and gonadotropin releasing hormone analog combination therapy increases predicted height in short normal girls

The "short normal" child constitutes a real challenge for the pediatric endocrinologist. In a subgroup of short normal children, puberty starts at a normal age but with low height, and hence, the final height is expected to be quite compromised. Efforts to improve the outcome in this group have been made in the past with equivocal results. We present the growth data of 8 short girls with normal growth hormone values on provocative testing and low height at puberty initiation. At intervention the height and the stage of puberty were 129.3 +/- 5 cm and II to III, respectively, and the predicted height was 148.8 +/- 2.6 cm. Gonadotropin releasing hormone analog, triptorelin (3.6 +/- 0.5 microg/kg/day) and growth hormone (0.5 IU/kg/week) were used in different sequential order and simultaneously in each child. The mean total treatment period was 47.6 +/- 11.2 months. The mean predicted and the mean final height in the total group were 148.8 +/- 2.6 and 154.5 +/- 3.6 cm, respectively (p:0.028). The final height did not differ from the target height (154.8 +/- 8 cm versus 154.5 +/- 3.6 cm), while in 4 children, the final height was greater than the target height. The height gain (delta Final height - Predicted height) was 5.7 +/- 1.3 cm. If we analyze separately the girls in whom growth hormone was started first and gonadotropin releasing hormone analog followed versus those who started the analog first, the delta Final height - Predicted height was 8 +/- 3 cm in the former and 4.8 +/- 3.1 cm in the latter (p:0.03). It seemed that the difference was accounted for by duration of growth hormone therapy (51.3 +/- 10.6 months versus 28.6 +/- 10.6 months) (p:0.026), rather than by other factors. In conclusion, under the conditions of the present study, the combination of puberty arrest and growth hormone therapy significantly improved predicted height. The most significant determinant of the height gain was the duration of growth hormone therapy.