促性腺激素释放激素类似物与生长激素联用治疗中枢性性早熟的疗效观察
发布时间：2019-01-10 08:05
【摘要】：目的中枢性性早熟(CPP)又称为促性腺激素释放激素(GnRH)依赖性性早熟,是由于下丘脑—垂体一性腺轴(HPGA))过早启动,提前分泌GnRH,激活性腺轴,使垂体分泌促性腺激素以致性腺发育,进而引起内、外生殖器发育和第二性征呈现。促性腺激素释放激素类似物(GnRHa)能有效抑制下丘脑-垂体-性腺轴(HPGA)的活动、抑制性激素分泌、减缓骨龄(B A)进展、改善最终成年身高(FAH),是目前国际上治疗中枢性性早熟(CPP)的标准药物。对于大多数患儿来说,早期及充足疗程的GnRHa治疗对于改善患儿的身高较为明显。然而,仍有些患儿骨龄进展迅速,导致生长潜能受损,预测成年身高常不理想。因此,如何更好的改善患儿的身高显得尤为重要。本研究观察单用GnRHa以及GnRHa和基因重组人生长激素(rhGH)联用治疗中枢性性早熟女孩的疗效。方法选取2008年9月—2012年2月在我院就诊的中枢性性早熟患儿,所有患儿均为女孩。入选标准：1.在8岁前出现第二性征；2.血清促性腺激素水平升高达青春期水平；3.性腺增大；4.线性生长加速；5.骨龄大于实际年龄1年以上；6.排除其他器质性病变。同时患儿骨龄进展迅速,生长潜能受损,预测成年身高未能达到遗传靶身高或理想身高,符合GnRHa的治疗适应症。入选病例为40例,GnRHa和rhGH联用组为20例,同时选择GnRHa单用组20例,两组患儿就诊时年龄、骨龄及身高等资料均匹配,差异无统计学意义。所有患儿均排除生长激素缺乏,签署知情同意书。单用组治疗为GnRHa100μg/(kg·次),每28-32d皮下注射,联用组在GnRHa治疗的基础上加用rhGH0.3mg/(kg·week),以观察两组不同用药的疗效。两组患儿治疗疗程均达—年,分别为1.45±0.32和1.68±0.40年。结果1.联合用药组的预测成年身高治疗后较治疗前有明显改善(158.45±3.55cmVS150.76±2.42cm),差异也有统计学意义(P0.05),并且达到遗传靶身高158.18cm。单用GnRHa组治疗后的预测成年身高较治疗前也有增加(154.68±2.83cmVS151.41±1.95cm),差异也有统计学意义(P0.05),但是未能达到遗传靶身高159.29cm。2.联合用药组及单用组治疗前后按骨龄的身高标准差分值(HtSDSBA)均有统计学意义,但联用组的HtSDSBA增加更为显著,由-1.89±0.42增加为-1.05±0.46,单用组仅由-1.89±0.29增加为-1.64±0.28。3.联合用药组的生长速度为7.53±0.73cm/年快于单用组的生长速度4.92±0.41cm/年,但两组的△骨龄/Δ年龄无统计学差异。4.两组患儿治疗后体重指数(BMI)均有增加,单用组增加较联合用药组明显,ΔBMI分别为1.01±1.20kg/m2和0.61±1.17kg/m2,但差异无统计学意义(P0.05),均在同龄儿的正常范围,两组治疗期间均未观察到不良反应。结论对于就诊时生长潜能受损,预测成年身高不理想的特发性中枢性性早熟的患儿,GnRHa联用rhGH治疗对患儿的预测成年身高改善比单用GnRHa更明显。联合用药后患儿按骨龄的身高标准差分值改善明显,生长速度加快,同时骨龄无明显增加。短期的联合用药对患儿的BMI无明显影响,也未观察到不良反应。
[Abstract]:Objective Central precocious puberty (CPP), which is also called the gonadotropin-releasing hormone (GnRH)-dependent precocious puberty, is due to the early initiation of the hypothalamic pituitary-gonad axis (HPGA), the release of GnRH in advance, the activation of the gonad axis, the secretion of the gonadotrophin in the pituitary, and the development of the gonad. resulting in the development of internal, external genitalia and the presence of a second sign. Gonadotropin-releasing hormone analogues (GnRHa) can effectively inhibit the activity of the hypothalamic-pituitary-gonad axis (HPGA), inhibit the secretion of sex hormones, slow the progression of bone age (B A), and improve the final adult height (FAH), is a standard medicine for treating central precocious puberty (CPP) at present. For most children, the early and adequate treatment of GnRHa therapy is more pronounced for children with improved height. However, some children still have a rapid progression of bone age, which leads to impaired growth potential and is often not ideal for predicting adult height. Therefore, it is very important to improve the height of the child better. In this study, the efficacy of GnRHa and the combination of GnRHa and recombinant human growth hormone (rhGH) in the treatment of central precocious girls was observed. Methods The central precocious puberty in our hospital from September 2008 to February 2012 was selected, and all the children were girls. Inclusion Criteria: 1. a second sign before the age of 8;. The level of serum gonadotropin is elevated to the level of puberty; 3. an increase in the gonad; 4. Linear growth acceleration; 5. the bone age is more than 1 year or more than the actual age; and 6. Other organic lesions were excluded. At the same time, the bone age of the child is rapid, the growth potential is damaged, the height or the ideal height of the adult body is predicted to be unable to reach the height of the genetic target or the ideal height, and the treatment indication of the GnRHa can be met. The selected cases were 40 cases, 20 cases in the combination group of GnRHa and rhGH, 20 cases of GnRHa single-use group and 20 cases of GnRHa single-use group. The age, age, age and height of the two groups were matched, and the difference was not statistically significant. All children excluded growth hormone deficiency and signed informed consent. The single-use group was treated with GnRHa 100. m u.g/ (kg 路 times) and injected subcutaneously at 28-32d, and the combined group was treated with rhGH-0.32mg/ (kg. wek) on the basis of GnRHa treatment to observe the efficacy of two groups of different drugs. The treatment course of the two groups was 1. 45, 0. 32 and 1.68 for 0. 40 years. Results 1. The combined treatment group had a significant improvement in the treatment of adult height (158.45, 3.55cmV150. 76 and 2.42cm), and the difference was also significant (P0.05), and the height of the genetic target was 158.18cm. The prediction of adult height after treatment with GnRHa group was also increased (154.68, 2.83cmV151.41 and 1.95cm), and the difference was also of statistical significance (P <0.05), but could not reach the target height of 159.29cm. The mean height standard deviation score (HtSDSBA) of the combined treatment group and the single-use group was statistically significant before and after treatment, but the HtSDSBA of the combined group was more significant, increased from-1.89 to-0.42 to-1.05-0.46, and the single-use group was increased from-1.89-0.29 to-1.64-0.28.3. The growth rate of the combined treatment group was 7.53-0.73cm/ year, and the growth rate was 4.92-0.41cm/ year in the single-use group, but there was no statistical difference between the two groups. After the treatment, the body mass index (BMI) of the two groups was increased, and the single-use group was more obvious than that of the combined group. The BMI was 1.01-1.20kg/ m2 and 0.61-1.17kg/ m2, but the difference was not significant (P0.05). The adverse reactions were not observed in the normal range of the same age group and the two groups of treatment. Conclusion For children with idiopathic central precocious puberty with impaired growth potential at the time of treatment, it is more obvious that GnRHa combined with rhGH in the treatment of children with idiopathic central precocious puberty is more obvious than that of single-use GnRHa in the treatment of children with idiopathic central precocious puberty. After combined use, the standard deviation of the height of bone age was improved, the growth rate was increased, and the bone age was not significantly increased. The short-term combined use had no significant effect on the BMI of the child, and no adverse reaction was observed.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R725.8
本文编号：2406081
[Abstract]:Objective Central precocious puberty (CPP), which is also called the gonadotropin-releasing hormone (GnRH)-dependent precocious puberty, is due to the early initiation of the hypothalamic pituitary-gonad axis (HPGA), the release of GnRH in advance, the activation of the gonad axis, the secretion of the gonadotrophin in the pituitary, and the development of the gonad. resulting in the development of internal, external genitalia and the presence of a second sign. Gonadotropin-releasing hormone analogues (GnRHa) can effectively inhibit the activity of the hypothalamic-pituitary-gonad axis (HPGA), inhibit the secretion of sex hormones, slow the progression of bone age (B A), and improve the final adult height (FAH), is a standard medicine for treating central precocious puberty (CPP) at present. For most children, the early and adequate treatment of GnRHa therapy is more pronounced for children with improved height. However, some children still have a rapid progression of bone age, which leads to impaired growth potential and is often not ideal for predicting adult height. Therefore, it is very important to improve the height of the child better. In this study, the efficacy of GnRHa and the combination of GnRHa and recombinant human growth hormone (rhGH) in the treatment of central precocious girls was observed. Methods The central precocious puberty in our hospital from September 2008 to February 2012 was selected, and all the children were girls. Inclusion Criteria: 1. a second sign before the age of 8;. The level of serum gonadotropin is elevated to the level of puberty; 3. an increase in the gonad; 4. Linear growth acceleration; 5. the bone age is more than 1 year or more than the actual age; and 6. Other organic lesions were excluded. At the same time, the bone age of the child is rapid, the growth potential is damaged, the height or the ideal height of the adult body is predicted to be unable to reach the height of the genetic target or the ideal height, and the treatment indication of the GnRHa can be met. The selected cases were 40 cases, 20 cases in the combination group of GnRHa and rhGH, 20 cases of GnRHa single-use group and 20 cases of GnRHa single-use group. The age, age, age and height of the two groups were matched, and the difference was not statistically significant. All children excluded growth hormone deficiency and signed informed consent. The single-use group was treated with GnRHa 100. m u.g/ (kg 路 times) and injected subcutaneously at 28-32d, and the combined group was treated with rhGH-0.32mg/ (kg. wek) on the basis of GnRHa treatment to observe the efficacy of two groups of different drugs. The treatment course of the two groups was 1. 45, 0. 32 and 1.68 for 0. 40 years. Results 1. The combined treatment group had a significant improvement in the treatment of adult height (158.45, 3.55cmV150. 76 and 2.42cm), and the difference was also significant (P0.05), and the height of the genetic target was 158.18cm. The prediction of adult height after treatment with GnRHa group was also increased (154.68, 2.83cmV151.41 and 1.95cm), and the difference was also of statistical significance (P <0.05), but could not reach the target height of 159.29cm. The mean height standard deviation score (HtSDSBA) of the combined treatment group and the single-use group was statistically significant before and after treatment, but the HtSDSBA of the combined group was more significant, increased from-1.89 to-0.42 to-1.05-0.46, and the single-use group was increased from-1.89-0.29 to-1.64-0.28.3. The growth rate of the combined treatment group was 7.53-0.73cm/ year, and the growth rate was 4.92-0.41cm/ year in the single-use group, but there was no statistical difference between the two groups. After the treatment, the body mass index (BMI) of the two groups was increased, and the single-use group was more obvious than that of the combined group. The BMI was 1.01-1.20kg/ m2 and 0.61-1.17kg/ m2, but the difference was not significant (P0.05). The adverse reactions were not observed in the normal range of the same age group and the two groups of treatment. Conclusion For children with idiopathic central precocious puberty with impaired growth potential at the time of treatment, it is more obvious that GnRHa combined with rhGH in the treatment of children with idiopathic central precocious puberty is more obvious than that of single-use GnRHa in the treatment of children with idiopathic central precocious puberty. After combined use, the standard deviation of the height of bone age was improved, the growth rate was increased, and the bone age was not significantly increased. The short-term combined use had no significant effect on the BMI of the child, and no adverse reaction was observed.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R725.8
【引证文献】
相关期刊论文 前1条
1 蔡正维;谢宗兰;刘孝桥;;GnRHa治疗中枢性性早熟的新进展[J];临床和实验医学杂志;2013年15期
，本文编号：2406081
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