Subclinical hypothyroidism is common in pregnant women and often related to adverse pregnancy outcomes, but its relationship with gestational diabetes remains controversial. In particular, the impact of thyroperoxidase antibodies status on the relationship between subclinical hypothyroidism and gestational diabetes is not clear. We investigated the association between combined thyroid stimulating hormone (TSH) level and thyroperoxidase antibodies status in early pregnancy (<20 weeks of gestation) and gestational diabetes mellitus. A total of 7084 pregnant women met the inclusion criteria, which included thyroperoxidase antibodies-positive subclinical hypothyroidism [TSH(H)TPOAb(+)] (n = 78), thyroperoxidase antibodies-negative subclinical hypothyroidism [TSH(H)TPOAb(−)] (n = 281), thyroperoxidase antibodies-positive euthyroidism [TSH(N)TPOAb(+)] (n = 648), and thyroperoxidase antibodies-negative euthyroidism [TSH(N)TPOAb(−)] (n = 6077). Of the 7084 cases included in our study, 1141 cases were diagnosed with gestational diabetes mellitus at 24–28 weeks of pregnancy. The prevalence of gestational diabetes mellitus in TSH(N)TPOAb(−), TSH(H)TPOAb(−), TSH(N)TPOAb(+), and TSH(H)TPOAb(+) was 14.65, 19.57, 24.85, and 46.15 %, respectively. Compared with TSH(N)TPOAb(−) women, the risk of gestational diabetes mellitus was increased in all other groups of women in early pregnancy. After dividing early pregnancy into first and second trimesters, we found that TSH(H)TPOAb(−) women in the first trimester do not show this increase. Our study suggests that subclinical hypothyroidism and thyroperoxidase antibodies-positive euthyroidism in early pregnancy are associated with an increased risk of gestational diabetes mellitus.

OBJECTIVE:To analyze clinical characteristics of children with 45, X/46, XY mosaicism and explore effective managements for them.METHOD:Five children with 45, X/46, XY mosaicism were all in puberty period, of whom, three were female and two male. The standing height, weight and sexual development were measured. The levels of sex hormones, other endocrine parameters were also determined, and imaging examinations were performed.RESULT:All the patients had disorders of sex development, of whom, 4 had short stature, and the HtSDs was -2.8 ± 1.1. The results of laboratory indexes suggested that 4 had hypergonadotropic hypogonadism, with the average level of LH (13.5 ± 5.8) IU/L and FSH (56.8 ± 37.4) IU/L. Imaging examinations revealed that 2 cases had cryptorchidism, 1 had immature uterus, 1 had testicular dysgenesis and 1 had normal testis. Three patients received rhGH treatment and 1 took gender assignment into account.CONCLUSION:Patients with mosaic 45, X/46, XY karyotypes had a wide range of phenotypic manifestations, and disorders of sex development and short stature were the main clinical features. However, the disorders of sex development varied among these patients. And the management for them depends upon many factors and needs to be individualized based on the cooperation with different clinical departments.

克氏综合征(Klinefelter's syndrome)即先天性睾丸发育不全,是常见的性染色体异常疾病[1],主要表现为小睾丸,小阴茎,乳房女性化.常见的核型为47,XXY或46,XY/47,XXY嵌合体型,有多种变型如XXYY,XXXY,XXXYY.我院儿科实验室自1981～2003年共检出89例.现将其染色体核型及临床表现分析于后.

OBJECTIVE:To assess the state of glucose metabolism and beta-cell function in obese and overweight children.METHODS:Levels of glucose and insulin were detected during oral glucose tolerance test in 52 obese and overweight children aged 11.3 +/- 1.8 years with body mass index (BMI) 30.2 +/- 19.2 kg/m(2). Insulin resistance index (IR = FIN x FPG/22.5), insulin sensitivity index (IS = 1/FIN x FPG) and ratio of insulin increment to glucose increment at 30' (I(30)-I(0)/G(30)-G(0)) post oral glucose were measured. (FIN = fasting insulin. FPG = fasting plasma glucose). The IR, IS and the ratio post oral glucose were compared among groups with varying BMI and between groups of impaired glucose tolerance (IGT) and control. Serum triglyceride determination and B ultrasonography of liver were performed.RESULTS:(1) one patient with type 2 diabetes (1.9%) and 5 patients with IGT (9.6%) were found. (2) IR (> or = 2.8) was observed in 76.9% of the cases. (3) The IR, IS and their ratio showed no difference between the compared groups. (4) IR and IS did not show significant difference but there was significant difference in ratio between the IGT and control group. (5) Increased serum triglyceride and fatty liver were noted in 36.5% and 53.3% of the cases, respectively.CONCLUSION:The results indicated that insulin resistance and reduced insulin sensitivity in obese and overweight children are common, and these changes seemed not to correlated with the varying degree of BMI. Beta-cells function was obviously impaired in obese children with IGT and disorder of lipid metabolism exists in many obese and overweight children revealed.

患儿女,7岁4个月.因肥胖7年,加重两年就诊.系G1P1,出身体重4.2 kg,混合喂养.患儿生后1～6月体重每月增加2 kg,之后每年增加2～3 kg,近两年每年增加6～7 kg,呈匀称性肥胖.4岁半时在当地医院诊断为"甲状腺机能减退",临床无相应症状.韦氏智力测定50分.患儿饮食正常,运动能力、语言能力与同龄正常儿童相比略差,性格较温顺.病程中无多饮、多尿,无头痛、头晕、昏厥史.

近年克隆了定位于性染色体Xp22.32和Yp11.3的矮小同源盒基因(SHOX基因),其由6个外显子组成,全长35kb,编码表达两种蛋白异构体.SHOX基因异常与三种疾病的骨骼异常有关:特发性矮小、特纳综合征和Leri-Weill软骨骨生成障碍.该文就SHOX基因缺失和突变发生率与人体生长障碍不同表型间的关系作一分析,同时阐明SHOX基因研究对明确人体生长的生理病理过程有重要意义.

Objective: To research change the terminal height , the level of growth hormone, sexual development and record of formal schooling in Turner syndrome(TS).Methods: Karyotyping, growth hormone provocation tests, follow -up observations of schooling record and sexual development were studied. Results: 239 TS were karyotyped in 4 groups: I, 45,X,95; II, mosaicism ,64; III, with various aberrations of structure of X chromosome, 74; IV, with Y chromosome, 6. Terminal heights were 139.2±8.3cm, 68 growth hormone tests, Growth hormone deficiency 18, part of deficiency 34 and normal 16. In the follow -up survey of 45 TS, record of formal schooling were mainly junior middle school, skill school and special school. 19 had various of degree sexual development and 26 had no. Conclusion: The terminal heights of TS were marked lower than normal, Growth hormone was deficiency, learning ability decline, hypoplasia of sex gland.

特发性矮小症(ISS)的病因具有异质性及复杂性,不仅涉及生长激素(GH)—胰岛素样生长因子(IGF)轴,又涉及诸多与生长板调控软骨细胞增殖、凋亡有关的激素及局部因子。近年来,ISS已被批准为GH治疗的适应证,由于其病因难以明确,疗效又难预测,因此为追求促生长效应,大剂量、长疗程的治疗原则已被认可。但应引起关注的是潜在的某些副作用或风险势必增大。目前,对少数偏矮实属非矮小的正常儿童有扩大应用GH治疗的趋势,故临床医师应严格掌握GH治疗的指征,警惕滥用导入误区。

目的 以临床诊断作为矮小症患儿(可疑GHD)诊断标准,评估生长激素激发试验、胰岛素样生长因子Ⅰ(IGF-Ⅰ)及IGF结合蛋白3(IGFBP-3)对GHD的诊断价值.方法放免方法检测84例可疑GHD患者及63例非GHD患者GH峰值、IGF-Ⅰ及IGFBP-3,运用ROC曲线方法选定各生化检测的最佳截定值,并计算各最佳截定值的敏感性(sensitivity, S)、特异性(specificity, Sp)及诊断有效率(diagnostic efficiency, DEf).结果 ROC曲线显示GH激发试验GH峰值7.65 μg/L为最佳截定值, DEf达84.4%, S为75.9%,Sp达94.9%; IGF-Ⅰ SDS最佳截定值为-1.85,S为70.2%、 Sp为83.1%、DEf为70.2%; IGFBP-3 SDS最佳截定值为-1.55,比传统-2SD高,DEf为64.3%, Sp较高(89.8%),但S仅为45.8%.联合使用上述3种测定有较佳的DEf(91.2%), S(89.3%)和Sp(93.7%).结论 GH激发试验如选取一个好的截定值(本研究为GH峰值7.65 μg/L),则该试验对GHD具有较高诊断价值;单个IGF-Ⅰ检测则逊于GH激发试验; IGFBP-3单独诊断GHD价值不大.三者联合使用诊断率及准确率皆很高,最具诊断价值。

Turner 综合征主要表现为矮小和性发育幼稚,使用药物进行早期干预以改善其终身高尤为重要.自20世纪80年代中期基因重组人生长激素(recombinant human growth hormone,rhGH)问世以来,对本病的治疗已成为国内外学者关注的热点.1994~2001年,我院儿科内分泌组应用rhGH治疗Turner综合征20例,观察其用药前后身高增长速率的变化.

目的:观察促性腺素释放素类似物(GnRH-A)治疗特发性中枢性性早熟(ICPP)的临床疗效.方法: 用GnRH-A缓释剂治疗18例(男性1例,女性17例) ICPP病人,疗程为6～12 mo,观察第二性征变化,男性睾丸,女性乳房、子宫、卵巢容积,骨龄,生长速率,促黄体素释放素(LHRH)激发试验.结果: 经治疗男性睾丸、女性卵巢、子宫容积及乳房均缩小,子宫容积和乳房分期治疗6 mo与治疗前比较分别为[(2.4±s 0.3)cm3 vs (5.9±0.9)cm3,P<0.01]和[(1.8±0.7) vs (2.80±0.10)], P<0.01].骨龄延缓,BA / CA值随疗程而缩小.治疗后身高、骨龄及实际年龄三者间的差距逐步改善, 治疗12 mo预测成人终身高(PAH)从(154.7±1.7)cm提高到(158±3)cm. 结论: GnRH-A缓释剂治疗ICPP可有效抑制性征发育,延缓骨龄成熟,并随疗程延长而改善成人终身高.

OBJECTIVE:To evaluate the therapeutic effect of China-made recombinant human growth hormone (r-hGH) in children with growth hormone deficiency (GHD) and to investigate the utilities of various biochemical parameters in GHD diagnosis and treatment.METHODS:Our study comprises of 30 normal children and 71 GHD children treated with China-made r-hGH substitution therapy 0.1 IU x kg(-1) x d(-1) for 6 months. Serum insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), bone turnover markers (Ost, ICTP), and anti-growth hormone antibody (GHAb) were detected before and after r-hGH treatment.RESULTS:After the first 3 and 6 months of treatment, growth velocities of GHD children were significantly increased (13.1 +/- 3.7 and 12.6 +/- 3.6 cm/year) compared with pretreatment values (2.9 +/- 0.8 cm/year, P < 0.01). GHD Children had obviously reduced serum levels of IGF-1, IGFBP-3, and bone turnover markers (Ost, ICTP) compared with normal controls (P < 0.01), and these biochemical parameters improved significantly after treatment (P < 0.01). Growth hormone antibodies were positive in 17 of 45 cases after treatment by binding capacity detection. The binding percentage of growth hormone antibody which was increased more than 30% after the treatment showed a negative correlation with growth velocity (P < 0.01).CONCLUSIONS:(1) The growth stimulating effect and safety were confirmed in using China-made r-hGH in the treatment of GHD children for 6 months. (2) The measurements of serum IGF-1 and IGFBP-3 may serve as useful parameters in the diagnosis of GHD. (3) Serum Ost and ICTP are useful laboratory criteria for evaluating the effect of r-hGH therapy in the early stage. (4) It is necessary to monitor serum levels of GHAb during r-hGH therapy.

目的比较两种预测遗传终身高度的方法在中国上海青年的正确性.方法中国上海青年,男＞20岁(n=160),女＞18岁(n=160).以中国上海青年的终身高和他们双亲的平均身高对FPH(the Final Heightfor Parental Height)和CMH(the Corrected Midparental Height)方法进行统计分析.结果中国上海和瑞典的研究人群的身材是不同的(P＜0.001).中国上海人比相对应的瑞典人都矮.瑞典人的父母分别比中国上海人的父母高7cm和6cm.瑞典人的男女青年的终身高比中国上海人男女青年都高5cm.这两组人群位于人类发展趋势的不同阶段.中国上海二代人身高男女分别增加3.5cm和2.2cm,而瑞典人仅增加0.7和1.0cm.FPH方法的平均剩余终身高接近于0(0.04cm,P=0.85),而CMH方法的平均剩余终身高明显的高于期望值0(2.87cm,P＜0.00).中国上海青年的实际终身高平均值和FPH靶身高的平均值基本一致,无显著性差异(男P=0.58,女P=0.74).而CMH方法则实际终身高高于靶身高(男3.1cm,女2.6cm),并且两者有高度显著差异(P＜0.001).结论 FPH公式优于CMH方法.

目的研究Turner综合征的终身高、生长激素水平、学历和性发育的变化.方法230例Turner综合征进行染色体检查,66例行生长激素激发试验,43例随访学历和性发育的情况.结果染色体核型分四组:第1组45,X,89例;第2组嵌合型,62例;第3组X染色体结构畸变,73例;第4组伴有Y染色体,6例.终身高139.3±8.3cm.生长激素完全缺乏18例,部分缺乏33例,正常15例.随访43例中,学历大部分在初中、技校和中专,18例有不同程度的性发育,25例无性发育.结论Turner征患者终身高明显低于正常人群,生长激素分泌低下,学习能力降低,性发育不全.

多囊卵巢综合征(PCOS)常见于育龄期妇女,发生率约为5%～10%.围青春期少女中PCOS的发生率不详.不少迹象示妇女PCOS大多可追溯自少女期.

OBJECTIVEPrader-Willi syndrome (PWS) is an example of a human genetic disorder that involves imprinting genes on the proximal long arm of chromosome 15 and SNRPN gene as a candidate gene for this syndrome. The purpose of this study was to show the molecular genetic defects and genomic imprinting basis in Chinese PWS patients and to evaluate the clinical applications of a differential diagnostic test for PWS.METHODSFluorescence in situ hybridization (FISH) and methylation-specific PCR (MSPCR) techniques were applied for 4 clinically suspected PWS patients. Using three probes, including SNRPN probe for identification of the critical locus in PWS region, D15Z1 and PML control probes for identification of the 15p arm and 15q arm, the authors detected the deletions 15q in PWS. MSPCR was based on sodium bisulfite treatment of DNA and PCR primers specific for the maternal and paternal allele.RESULTSWhen hybridized with mixed probes, it was found in 2 patients that the central specific signal was absent, but both the flanking control signals were retained, indicating SNRPN gene deletion of chromosome 15q11-13. Bisulfite-modified DNA from all PWS children amplified with methylated allele-specific primer pair showed only maternal 131bp PCR product, indicating the maternal uniparental disomy (UPD15).CONCLUSIONGenomic imprinting plays an important role in the molecular pathogenesis of PWS that caused by paternal microdeletions of 15q11-q13 or maternal UPD of chromosome 15. The basic defect seemed to be an absence of function of PWS genes that are normally expressed only from the paternal chromosome 15. MSPCR is a rapid and simple PCR-based assay compared with other cyto-molecular tests and its results were consistent with the clinical diagnosis of PWS, so it seems to be a reliable diagnostic method for PWS patients who show abnormal methylation at SNRPN. The genetic differential tests for PWS are important in determining familial recurrence risk.

Objective To explore the effect of androgen on antimullerian hormone (AMH) and to evaluate clinical significance of AMH assay. Methods Ten boys aged 12～20 years old with primary growth hormone deficiency (GHD) and hypogonadotropic hypogonadism (patient group) and 48 healthy adolescent boys in various Tanner stages from G 1～G 4～5 (control group) were assayed for serum AMH, testosterone. All patients received recombinant human GH (0.1 U·kg -1·d -1) for 2 years with combined human chorionic gonadotrophin (1000 U b.i.w) or testosterone enanthate (50～100 mg/month) treatment during the second year. Blood samples were collected at the start and then every 6 months. Results (1) In control group, serum AMH level was highest before puberty and declined subsequently as pubertal stage advanced, and the lowest level occurred at stage G 4～5, and serum AMH level was negatively correlated with the testosterone level. (2) The serum AMH of patient group was (318.0±34.7)pmol/L before treatment, significantly higher than the controls 〔(41.6±6.7)pmol/L (P0.001)〕. After the first year of GH therapy, serum AMH declined to (195.4±61.2)pmol/L (P0.01). A further decrease in serum AMH levels was observed at the end of the 2nd year after combined treatment for 1 year (P0.001). Serum testosterone level was elevated in contrast to the decreased AMH concentration. Conclusion (1) Serum AMH level shows a negative correlation with serum testosterone concentration in healthy adolescent boys. (2) Serum AMH level in GHD patients with hypogonadotropic hypogonadism shows higher value, and declines with the treatment of GH and sex hormone, with concomitant elevation of serum testosterone level. (3) Serum AMH assay may provide an additional information of testicular functions.

OBJECTIVE [corrected] To investigate the mutation at the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) nucleotide 1138 site for identifying the major pathologic mechanism of achondroplasia (ACH) and to evaluate the efficacy of denaturing gradient gel electrophoresis(DGGE) method for screening the point mutations. METHODS The genomic DNA from 17 clinically diagnosed ACH patients where analysed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) with Sfc I and Msp I restriction endonucleases and by PCR-DGGE technique for screening. RESULTS G to A transition mutation at nucleotide 1138 was detected in 14/17 of the ACH patients as heterozygotes by PCR-RFLP with Sfc I digestion. No 1138 G to C transition was detected by Msp I digestion. All of the 14 samples with G to A mutation were also found to be positive for point mutation by PCR-DGGE. No mutation was detected in 3 negative samples by PCR-RFLP, implying that there was actually no point mutation in this amplified region. CONCLUSION Nucleotide 1138 in transmembrane domain of FGFR3 gene is the hot point for mutation in ACH and hence its major pathologic cause. PCR-DGGE is a sensitive and reliable technique for point mutation screening, especially for the heterozygotes.