不同治疗方案对先天性卵巢发育不全症患儿身高增长的疗效比较

目的比较不同治疗方案对先天性卵巢发育不全症（Ｔｕｒｎｅｒ综合征,ＴＳ）患儿身高增长的疗效。方法回顾性分析两组ＴＳ患儿的疗效：一组（６例）接受小剂量康力龙治疗５～１６个月,另一组（１２例）接受同样剂量的康力龙与生长激素（ＧＨ）联合治疗６～１４个月。结果单用康力龙组生长速度（ＧＶ）达到（５５４±１４６）ｃｍ／ａ,身高Ｚ评分（ＨｔＳＤＳ）由－３９１±１３４提高到－３５３±１４３。联合治疗组生长速度为（８５３±２５７）ｃｍ／ａ,ＨｔＳＤＳ由－３３６±１１６提高到－２６１±１０４。联合治疗组疗效较单用康力龙组为优（Ｐ＜００５）,其治疗期间ＧＶ与患儿年龄呈负相关（ｒ＝－０８０,Ｐ＜００１）。结论联合应用ＧＨ与小剂量康力龙治疗ＴＳ疗效确切,适宜临床应用。     

促性腺激素释放激素拟似剂与儿童真性性早熟

促性腺激素释放激素拟似剂（ＧｎＲＨａ）是目前治疗儿童真性性早熟的首选药物，它通过垂体的降调节作用抑制青春期的提前出现。临床需根据患儿病情确定是否应用及何时应用ＧｎＲＨａ，并监测疗效。ＧｎＲＨａ可有效改善最终身高且无明显不良影响。     

促性腺激素释放激素类似物治疗儿童真性性早熟10例报告

为观察促性腺激素释放激素类似物 (GnRH_A)治疗儿童性早熟的疗效 ,以GnRH_A每次100μg/kg,每28d应用1次 ,对10例真性性早熟患儿进行治疗。治疗3个月后所有患儿第二性征明显退缩 ;治疗6个月后所有患儿性激素水平下降 ,BA/CA下降 ,预测成年身高[按骨龄预测成年身高 (Bayley_pinneau法 )]由治疗前 (156.4±6.2)cm升至(159.4±7.4)cm(P<0.01)。治疗过程中无明显不良反应。GnRH_A能抑制下丘脑 -垂体 -性腺轴的活动 ,使性激素分泌减少 ,从而使真性性早熟患儿第二性征逐渐退缩 ,骨龄生长减慢 ,改善最终身高 ,而且GnRH_A临床使用安全。     

女童乳房早发育的临床鉴别

目的：探讨乳房早发育与真性和假性早熟的关系。方法采用回顾性研究的方法,对３６名乳房早发育患者的临床表现、盆腔Ｂ超、血激素、骨龄、身高等指标进行对照分析。结果真性性早熟１７例,假性性早熟１９例,两组临床表现无明显差异;真性性早熟组骨龄／身高年龄高于假性性性早熟组;９４．７４％的真性性早熟腹部Ｂ超检查卵巢有发育;两组大部分患者黄体生成素（ＬＨ）和卵泡刺激素（ＦＳＨ）正常,而促性腺激素释放激素（ＬＨ）和     

吡唑甲氢龙对青春期前矮身材儿童的促生长作用：附38例报告

７０例青春期前生长落后患儿，随机分为两组，分另紧吡唑甲氢龙和可乐定（Ａ组），或单一可乐定治疗（Ｂ组）。Ａ组身高增长速率由治疗前３．０±０．９ｃｍ／年增至８．６±１．７ｃｍ／年；Ｂ组身高增长率由治疗前２．７±１．０ｃｍ／年增至６．３±１．７ｃｍ／年。结果表明：吡唑甲氢龙对青春期前生长落后患儿有明显的促生长作用。     

来曲唑治疗特发性中枢性性早熟男童的临床观察

目的 对骨龄大于13岁、身高偏矮小的中枢性性早熟（ICCP）男童应用来曲唑（letrozole）治疗,观察该治疗方案对延缓骨龄老化和改善成年预测身高的效果和不良反应。方法 将骨龄大于13岁的ICCP男童20例随机分为2组,每组10例,一组予来曲唑口服治疗6个月[2.5 mg/（m2·d）,Qd];另一组为对照组,定期观察,不予特殊治疗。观察两组男童骨龄、生长速度、身高标准差积分、预测成年身高标准差积分、性征发育情况及性激素水平的变化。并观察来曲唑治疗相关不良反应。结果 试验开始6个月后,来曲唑组和对照组男童骨龄均显著增加,但来曲唑组男童骨龄增长（13.82±0.23岁）较对照组男童（14.47±0.30岁）明显缓慢（PPP结论 对骨龄超过13岁、身高受损显著的ICCP男童应用来曲唑能够有效减缓骨龄老化,改善预测成年身高,且未见明显不良反应。     

女童性早熟38例

目的探讨女童真性性早熟和假性性早熟的早期鉴别及预防。方法对38例女童性早熟患儿详细询问病史,测身高、体质量,摄左腕正位X线片进行骨龄评价(Gmelich-Pyle法),B超检查,促性腺激素释放激素(LHRH)刺激试验:静脉注射戈那瑞林2.5μg.kg-1,分别于注射后0min、30min、60min静脉采血查血卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)水平。结果38例中真性性早熟18例,其中17例为原发性;假性性早熟20例,均原因不明,但对各种儿童饮料、滋补保健品经常食用及各种肉类在饮食中比例较大者假性性早熟组明显高于真性性早熟组。LHRH刺激试验LH、FSH和E2的峰值升高均明显,其中以LH峰值升高最明显。2组比较,骨龄/身高年龄差异显著,骨龄/实际年龄无统计学差异。结论LH和骨龄/身高年龄是真假性早熟最重要的鉴别指标,性早熟应以早预防、早诊断、早治疗为主,同时应对其进行心理行为干预治疗。     

快进展型青春期威廉姆斯综合征女童1例GnRHa治疗分析

目的探讨威廉姆斯综合征(WBS)患儿性早熟的治疗。方法回顾分析1例快进展型青春期WBS女童的临床资料,并复习相关文献。结果女性患儿,9岁5个月,因乳腺发育1年余、月经来潮3次就诊。根据患儿特殊面容、主动脉瓣上狭窄、智能发育落后、性早熟及医学外显子测序,WBS诊断明确。患儿骨龄提前2岁,子宫长径37 mm,内膜5 mm,双侧卵巢均有数个>4 mm的卵泡,卵巢容积3~4 mL,随机促黄体生成素(LH)3.43mIU/mL,骨龄身高SDS为-1.92,符合快进展型青春期的诊断标准,给予促性腺激素释放激素类似物(GnRHa)治疗。治疗1年后复查,患儿性激素处于青春期前水平,年身高增长速率5.3 cm,骨龄身高SDS为-1.55。结论WBS患儿可出现性早熟(快进展型青春期),应用GnRHa干预可改善患儿成年终身高,同时缓解家长的焦虑。     

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     

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,…     

GnRHa治疗中枢性性早熟女童对终身高的影响

目的：观察促性腺激素释放激素类似物（GnRHa）对治疗中枢性性早熟（central precocious puberty,CPP）女童终身高的作用及相关因素。方法：对26例CPP女童应用GnRHa治疗前后预测身高、骨龄的标准差分值［HtSDS(BA)］、终身高、体重指数（BMI）、初潮情况等进行评价,分析它们与终身高的相关性。结果：治疗前预测身高为151.5±5.7 cm;停药时预测身高为158.4±5.2 cm;终身高为158.0±4.0 cm,高于靶身高155.3±4.4 cm (P<0.01)。终身高与初始身高、预测身高、HtSDS(BA)正相关。治疗前BMI为17.1±2.1、治疗后BMI为19.9±3.2,两者呈正相关。停药后平均13.2±6.1个月后初潮,平均初潮年龄为12.2±0.7岁。结论：GnRHa治疗CPP可有效地改善终身高,终身高与治疗前身高及预测身高等密切相关,停药后患儿青春发育与正常儿童相似。［中国当代儿科杂志,2009,11（5）：374-376］     

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。     

Gonadotrophin-Releasing Hormone Analogues as Therapeutic Probes in Human Growth and Development: Evidence from Children with Central Precocious Puberty

ABSTRACT. Statural growth and skeletal development were assessed in 87 girls with idiopathic central precocious puberty (CPP) during gonadotrophin-releasing hormone analogue (GnRHa)-induced suppression of gonadarche. Before the start of therapy, mean chronological age (CA) was 6.3 years and mean bone age (BA) was 10.6 years. During up to 6 consecutive years of complete suppression of gonadal sex steroid secretion, the mean height velocity decreased from 10.8 cm/year to prepubertal rates. At each interval height velocity was found to be inversely and negatively correlated with BA such that girls with advanced BAs grew at rates well below prepubertal norms but appropriately for their degree of skeletal maturation. Skeletal maturation similarly slowed during prolonged GnRHa administration (ABA/ACA = 0.6 ± 0.1 over 3 years, mean ± SD, n = 66) and was also negatively correlated with the BA before the start of therapy. Predicted adult height increased progressively during therapy; however, when analysed as changes in height SDS(BA), the impact of treatment was variable and correlated positively with the initial degree of skeletal maturation. The effect of GnRHa therapy on growth in children with CPP requires long-term study and is best analysed by employing a developmental perspective.     

Effects of combined gonadotropin-releasing hormone agonist and growth hormone therapy on adult height in precocious puberty: a further contribution

Out of 35 girls with idiopathic central precocious puberty (CPP) treated with gonadotropin-releasing hormone agonist (GnRHa) (depot-triptorelin) at a dose of 100 microg/kg every 21 days i.m. for at least 2-3 years whose growth velocity fell below the 25th percentile for chronological age (CA), 17 received growth hormone (GH) in addition at a dose of 0.3 mg/kg/week, s.c., 6 days per week, for 2-4 years. The other 18, matched for bone age (BA), CA and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, remained on GnRHa alone, and were used as a control group to evaluate GH efficacy. No patient was GH deficient. Both groups discontinued treatment at a comparable BA (mean +/- SD): BA 13.4 +/- 0.6 in GnRHa plus GH group vs 13.0 +/- 0.5 years in the GnRHa alone group. The 35 patients have reached adult height (i.e. growth during the preceding year was less than 1 cm, with a BA of over 15 years). Patients of the group treated with GH plus GnRHa showed an adult height (161.2 +/- 4.8 cm) significantly higher (p < 0.001) than pre-treatment predicted adult height (PAH) calculated according to tables either for accelerated girls (153.2 +/- 5.0 cm) or for average girls (148.6 +/- 4.3 cm). The adult height of the GnRH alone treated group (156.6 +/- 5.7) was not significantly higher than pre-treatment PAH if calculated on Bayley and Pinneau tables for accelerated girls (153.9 +/- 3.8 cm), whilst it remained significantly higher if calculated on tables for average girls (149.6 +/- 4.0 cm) (p < 0.001). The gain between pre-treatment PAH and final height was 8.2 +/- 4.8 cm according to tables for accelerated girls and 12.7 +/- 4.8 cm according to tables for average girls in patients treated with GH plus GnRHa; while in patients treated with GnRH alone the gain calculated between pre-treatment PAH for accelerated girls was just 2.3 +/- 2.9 cm and 7.1 +/- 2.7 cm greater than pre-treatment PAH for average girls. The difference between the gain obtained in the two groups (about 6 cm) remained the same, however PAH was calculated. The addition of GH to GnRHa in a larger cohort of patients with CPP with a longer follow-up confirms the safety of the combined treatment and the still significant but more variable gain in the group with the combined treatment, probably due to the larger number of patients analyzed. Caution is advised in using such an invasive and expensive treatment, and there is need for further studies before widespread clinical use outside a research setting.     

Height prognosis of children with true precocious puberty and growth hormone deficiency: effect of combination therapy with gonadotropin releasing hormone agonist and growth hormone.

We evaluated height prognosis and therapeutic efficacy of long-term, combination therapy with gonadotropin releasing-hormone agonist and growth hormone (GH) in five children (three girls) with coexistent precocious puberty and GH deficiency. Their clinical characteristics and growth response were compared with those of 12 girls with idiopathic true precocious puberty and eight prepubertal GH-deficient children (one girl). Precocious GH-deficient subjects were older than the precocious GH-sufficient children (9.5 +/- 1.8 years vs 6.5 +/- 1.3 years; mean +/- SD), but bone ages were comparable (12 +/- 3.7 years vs 10 +/- 0.9 years); their chronologic age was similar to that of the prepubertal GH-deficient children (9.6 +/- 2.1 years), but bone age was significantly more advanced (6.9 +/- 2.3 years). The mean height velocity of the prepubertal GH-deficient children (3.8 +/- 1.5 cm/yr) was lower than that of the precocious GH-deficient subjects (6.7 +/- 1.6 cm/yr) and the precocious GH-sufficient children (9.5 +/- 2.9 cm/yr). Baseline adult height prediction z scores were significantly lower in the precocious GH-deficient children (-3.7 +/- 1.0) than in either the precocious GH-sufficient children (-2.2 +/- 1.0) or the prepubertal GH-deficient subjects (-1.5 +/- 0.8). During therapy with gonadotropin releasing-hormone agonist, growth rates slowed to an average of 3.7 cm/yr in the precocious GH-deficient children but increased after the addition of GH to 7.4 cm during the first year of combination therapy. After 2 to 3 years of combination therapy, height predictions increased an average of 10 cm, compared with an increase of 2.8 cm in the precocious GH-sufficient group treated with gonadotropin releasing-hormone agonist alone. We conclude that combination treatment with gonadotropin releasing-hormone agonist and GH improves the height prognosis of children with coexistent true precocious puberty and GH deficiency, but falls short of achieving normal adult height potential.     

End results in central precocious puberty with GnRH analog treatment: the data of the Italian Study Group for Physiopathology of Puberty

We report some end results with GnRH agonist (GnRHa) treatment in central precocious puberty (CPP), in terms of final height (FH), ovarian function, peak bone mass, body composition and psychological problems. The two studies reported (Study I and II) are part of the activity of the Italian Study Group for Physiopathology of Puberty. Study L Growth data were analyzed of three groups of patients: treated with i.n. spray buserelin, i.m. triptorelin and untreated. Both GnRHa administration modes were effective in arresting pubertal development and all girls had complete recovery of the reproductive axis after therapy. Treated patients showed an improvement in final height in comparison with untreated patients and compared to predicted height at the start of treatment with both agonist treatments. However, patients treated with the long-acting slow release preparation had a better improvement in adult height and reached or exceeded the genetic height potential. Study II. In a retrospective evaluation of the outcome in 71 girls with idiopathic CPP treated with triptorelin, we found that FH fell within the population norm and the target range in 87.3% and 90% of the patients respectively. The tallest FH was recorded in the patients who started therapy at less than 6 years of age and in those who discontinued treatment at a bone age of 12.0-12.5 yr. Finally, we and other groups have recently found normal values of bone mineral density in girls at the end of GnRHa treatment in the great majority of patients.     

Treatment of central precocious puberty with an intranasal analogue of GnRH (Buserelin)

One boy and 13 girls with central precocious puberty were treated for 1 year using Buserelin, a GnRH analogue, given intranasally (0.3 mg, four times a day). After 1, 3 and 12 months of therapy, the gonadotropin responses to GnRH were abolished in all the patients whereas mean basal serum concentrations of luteinizing hormone (LH) remained similar to those of pubertal controls. During Buserelin treatment, genital development in the boy and breast development in the girls showed no further progress or some regression. In the boy, serum testosterone levels returned to prepubertal values. In the girls, serum oestradiol levels were variable and, in four of them, vaginal smears showed the persistence of a slight oestrogenic effect during therapy. Pelvic ultrasonography did not show any significant variation in ovarian and uterine lengths. Among the 14 patients, 3 had some progression of pubic hair development, irrespective of serum dehydroepiandrosterone sulphate (DHEAS) levels. In eight patients previously treated with cyproterone, elevated prolactin levels were observed before and during the first month of Buserelin administration. During treatment, mean height velocity was markedly reduced from 11.6 to 6.1 cm/year and mean bone age velocity (±1 SD) was 0.85±0.38 year/year. After 1 year of treatment, the differences in predicted adult height ranged between −0.74 and +1.04 SDS (standard deviation score). These differences were inversely related (r=−0.72) to the prognosis of adult height calculated before treatment. We conclude that, in central precocious puberty, intranasal administration of Buserelin, 1.2 mg/day, may arrest sexual development and reduce height velocity and bone maturation. Improvement of adult height prognosis may occur, especially when it was markedly impaired before treatment.     

Combined therapy with GnRH analog plus growth hormone in central precocious puberty

GnRH analogues (GnRHa) arrest pubertal development, and slow growth velocity (GV) and bone maturation, thus improving adult height in central precocious puberty (CPP). In some patients, however, GV decreases to such an extent that it compromises the improvement in predicted adult height (PAH) and therefore the addition of GH is suggested. Of 20 patients with idiopathic CPP (treated with GnRHa [depot-triptorelin] at a dose of 100 microg/kg every 21 days i.m. for at least 2-3 yr) whose GV fell below the 25th percentile for chronological age (CA), ten received, in addition to the GnRHa, GH at a dose of 0.3 mg/kg/wk, s.c. 6 days weekly, for 2-4 yr. Ten patients matched for BA, CA, and duration of GnRHa treatment who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of the addition of GH. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean +/- SEM): 13.2 +/- 0.2 yr in GnRHa + GH vs 13.0 +/- 0.1 yr in the control group. At the conclusion of the study all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH + GnRHa showed an adult height significantly higher (p<0.001) than pretreatment PAH (160.6 +/- 1.3 vs 152.7 +/- 1.7 cm). Height SDS for BA significantly increased from -1.5 +/- 0.2 at start of GnRHa to -0.21 +/- 0.2 at adult height (p<0.001). Target height was significantly exceeded. The GnRH alone treated group reached an adult height not significantly higher than pretreatment PAH (157.1 +/- 2.5 vs 155.5 +/- 1.9 cm). Height SDS for BA did not change (from -1.0 +/- 0.3 at start of GnRHa to -0.7 +/- 0.4 at adult height). Target height was just reached but not significantly exceeded. The gain in centimeters obtained calculated between pretreatment PAH and final height was 7.9 +/- 1.1 cm in patients treated with GH combined with GnRH analogue while in patients treated with GnRH analogue alone the gain was just 1.6 cm +/- 1.2 (p=0.001). Furthermore, no side effects, bone age progression, or ovarian cysts, were observed in GnRHa + GH treated patients. In conclusion, a gain of 7.9 cm in adult height represents a significant improvement which justifies the addition of GH for 2-3 yr to conventional treatment with GnRH analogues in patients with central precocious puberty, and with a decrease in growth velocity so marked as to impair predicted adult height to below the third percentile.     

Gonadotrophin-Releasing Hormone Agonist Treatment of Central Precocious Puberty: an Analysis of Growth Data in a Developmental Context

ABSTRACT. Growth and skeletal maturation was assessed in 83 girls with central precocious puberty (CPP) during pituitary—gonadal suppression induced by treatment with a gonadotrophin-releasing hormone agonist (GnRHa). The mean pretreatment chronological age (CA) was 6.3 years and the mean bone age (BA) was 10.6 years. During the suppression of gonadal sex steroid secretion, mean height velocity (HV) decreased from a pretreatment value of 10.8 cm/year to 5.9 (year 1, n = 83), 4.9 (year 2, n = 72), 4.2 (year 3, n = 49, and 4.4 (year 4, n = 23) cm/year. During each interval, there was a negative correlation between HV and the pretreatment BA. In addition, the rate of skeletal maturation was reduced during GnRHa treatment (ΔBA/ΔCA = 0.6 ± 0.1 over 3 years, n = 45). The rate of skeletal maturation during therapy was also negatively correlated with pretreatment BA. Predicted adult stature, based upon z -scores of height for BA, increased significantly and progressively during therapy but the changes in height SDS for BA varied significantly. Since HV, ΔBA/ΔCA, and the change in height SDS for BA (ΔHT SDS for BA) during pituitary—gonadal suppression all correlated with the initial degree of skeletal maturation, the effect of GnRHa therapy on Final adult height in children with CPP will be best understood if growth data are assessed within a developmental framework.