促性腺激素釋放激素類似物與生長激素聯(lián)用治療中樞性性早熟的療效觀察
發(fā)布時間：2019-01-10 08:05
【摘要】：目的中樞性性早熟(CPP)又稱為促性腺激素釋放激素(GnRH)依賴性性早熟,是由于下丘腦—垂體一性腺軸(HPGA))過早啟動,提前分泌GnRH,激活性腺軸,使垂體分泌促性腺激素以致性腺發(fā)育,進(jìn)而引起內(nèi)、外生殖器發(fā)育和第二性征呈現(xiàn)。促性腺激素釋放激素類似物(GnRHa)能有效抑制下丘腦-垂體-性腺軸(HPGA)的活動、抑制性激素分泌、減緩骨齡(B A)進(jìn)展、改善最終成年身高(FAH),是目前國際上治療中樞性性早熟(CPP)的標(biāo)準(zhǔn)藥物。對于大多數(shù)患兒來說,早期及充足療程的GnRHa治療對于改善患兒的身高較為明顯。然而,仍有些患兒骨齡進(jìn)展迅速,導(dǎo)致生長潛能受損,預(yù)測成年身高常不理想。因此,如何更好的改善患兒的身高顯得尤為重要。本研究觀察單用GnRHa以及GnRHa和基因重組人生長激素(rhGH)聯(lián)用治療中樞性性早熟女孩的療效。方法選取2008年9月—2012年2月在我院就診的中樞性性早熟患兒,所有患兒均為女孩。入選標(biāo)準(zhǔn)：1.在8歲前出現(xiàn)第二性征；2.血清促性腺激素水平升高達(dá)青春期水平；3.性腺增大；4.線性生長加速；5.骨齡大于實際年齡1年以上；6.排除其他器質(zhì)性病變。同時患兒骨齡進(jìn)展迅速,生長潛能受損,預(yù)測成年身高未能達(dá)到遺傳靶身高或理想身高,符合GnRHa的治療適應(yīng)癥。入選病例為40例,GnRHa和rhGH聯(lián)用組為20例,同時選擇GnRHa單用組20例,兩組患兒就診時年齡、骨齡及身高等資料均匹配,差異無統(tǒng)計學(xué)意義。所有患兒均排除生長激素缺乏,簽署知情同意書。單用組治療為GnRHa100μg/(kg·次),每28-32d皮下注射,聯(lián)用組在GnRHa治療的基礎(chǔ)上加用rhGH0.3mg/(kg·week),以觀察兩組不同用藥的療效。兩組患兒治療療程均達(dá)—年,分別為1.45±0.32和1.68±0.40年。結(jié)果1.聯(lián)合用藥組的預(yù)測成年身高治療后較治療前有明顯改善(158.45±3.55cmVS150.76±2.42cm),差異也有統(tǒng)計學(xué)意義(P0.05),并且達(dá)到遺傳靶身高158.18cm。單用GnRHa組治療后的預(yù)測成年身高較治療前也有增加(154.68±2.83cmVS151.41±1.95cm),差異也有統(tǒng)計學(xué)意義(P0.05),但是未能達(dá)到遺傳靶身高159.29cm。2.聯(lián)合用藥組及單用組治療前后按骨齡的身高標(biāo)準(zhǔn)差分值(HtSDSBA)均有統(tǒng)計學(xué)意義,但聯(lián)用組的HtSDSBA增加更為顯著,由-1.89±0.42增加為-1.05±0.46,單用組僅由-1.89±0.29增加為-1.64±0.28。3.聯(lián)合用藥組的生長速度為7.53±0.73cm/年快于單用組的生長速度4.92±0.41cm/年,但兩組的△骨齡/Δ年齡無統(tǒng)計學(xué)差異。4.兩組患兒治療后體重指數(shù)(BMI)均有增加,單用組增加較聯(lián)合用藥組明顯,ΔBMI分別為1.01±1.20kg/m2和0.61±1.17kg/m2,但差異無統(tǒng)計學(xué)意義(P0.05),均在同齡兒的正常范圍,兩組治療期間均未觀察到不良反應(yīng)。結(jié)論對于就診時生長潛能受損,預(yù)測成年身高不理想的特發(fā)性中樞性性早熟的患兒,GnRHa聯(lián)用rhGH治療對患兒的預(yù)測成年身高改善比單用GnRHa更明顯。聯(lián)合用藥后患兒按骨齡的身高標(biāo)準(zhǔn)差分值改善明顯,生長速度加快,同時骨齡無明顯增加。短期的聯(lián)合用藥對患兒的BMI無明顯影響,也未觀察到不良反應(yīng)。
[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.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R725.8
本文編號：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.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R725.8
【引證文獻(xiàn)】
相關(guān)期刊論文 前1條
1 蔡正維;謝宗蘭;劉孝橋;;GnRHa治療中樞性性早熟的新進(jìn)展[J];臨床和實驗醫(yī)學(xué)雜志;2013年15期
，本文編號：2406081
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