Effects of obesity on peak level of luteinizing hormone in gonadotropin-releasing hormone agonist test and obesity-related hormones in girls with central precocious puberty / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the effects of obesity on the peak level of luteinizing hormone (LH) in the gonadotropin-releasing hormone (GnRH) agonist test and obesity-related hormones in girls with central precocious puberty (CPP).</p><p><b>METHODS</b>Three hundred and thirty-three girls with CPP who underwent the GnRH agonist test between 2012 and 2014 were classified into three groups: normal weight (n=123), overweight (n=108), and obesity (n=102), according to body mass index (BMI). The sexual development indices were compared between the three groups. Twenty girls were randomly selected from each group for evaluation of the serum levels of leptin, sex hormone binding globulin (SHBG), neurokinin B, and kisspeptin. The correlation of BMI with the levels of various hormones was assessed using Pearson correlation analysis.</p><p><b>RESULTS</b>There was no significant difference in mean age at diagnosis between the three groups; however, the bone age was significantly higher in the overweight and obesity groups than in the normal weight group (P<0.05). The peak level of LH in the GnRH agonist test and SHBG level in the normal weight group were significantly higher than those in the overweight and the obesity groups, while the serum levels of leptin and neurokinin B were significantly lower in the normal weight group than in the overweight and the obesity groups (P<0.05). BMI was negatively correlated with the peak level of LH in the GnRH agonist test and SHBG level (P<0.05), and positively correlated with the levels of leptin and neurokinin B (P<0.05).</p><p><b>CONCLUSIONS</b>The effects of BMI on the result of the GnRH agonist test and levels of obesity-related hormones should be taken into account in girls with precocious puberty.</p>

Relationship of plasma ghrelin and adenohypophyseal hormone levels in female precocious puberty / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the relationship of plasma ghrelin and adenohypophyseal hormone levels in female precocious puberty.</p><p><b>METHODS</b>A total of 84 patients aged from 6 to 9 years were enrolled in this study. They were divided into idiopathic central precocious puberty (ICPP) and premature thelarche(PT)groups according to their secondary sexual characteristics, bone age, volumes of uterus and ovary, and results of GnRH test. Plasma ghrelin levels were measured by radioimmunoassay. ACTH, TSH, PRL, GH, LH and FSH were measured by chemoluminescence technique.</p><p><b>RESULTS</b>Ghrelin levels in ICPP group were Log (2.42+/-0.26) ng/L, which were significantly lower than those in PT group and controls [Log (2.62+/-0.21) ng/L and Log (2.58+/-0.44) ng/L, respectively, P<0.05]. However there was no significant difference between PT group and controls(P>0.05). Ghrelin levels of ICPP girls with Tanner III were Log (2.31+/-0.24) ng/L, significantly lower than those of ICPP girls with Tanner II [Log (2.53+/-0.24) ng/L, P<0.05]. By bivariate correlation analysis, ghrelin levels in precocious puberty girls were negatively correlated with ACTH, PRL and LH15, LH30 and LH60 in GnRH test(r=-0.248, -0.235, -0.445, 0.405, 0.398, respectively, P<0.05). No significant correlation was found between ghrelin and GH, LH0(-2), FSH0(-2), and FSH15, FSH30 and FSH60 in GnRH test.</p><p><b>CONCLUSION</b>ICPP girls have lower plasma ghrelin levels, which are decreased with the development of Tanner stage. The plasma ghrelin levels are negatively correlated with ACTH, PRL and LH.</p>

Psychological behavior of girls with idiopathic central precocious puberty before and after treatment with gonadotropin-releasing hormone analogue / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To observe the psychological behavior of girls with idiopathic central precocious puberty (ICPP) before and after treatment by gonadotropin-releasing hormone analogue (GnRHa).</p><p><b>METHODS</b>Raven's Standard Progressive Matrices(SPM), Achenbach's Child Behavior Checklist (CBCL), Self-Esteem Scale (SES), and Body-Esteem Scale (BES) were used to assess the psychological behavior in the ICPP girls before and after GnRHa treatment, as well as in control girls. The serum levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) were measured by ELISA before and after GnRHa treatment.</p><p><b>RESULT</b>(1) The SES and BES scores in ICPP were significantly lower than those of controls(P <0.05). The CBCL scores in depressed, withdrawn,aggressive and somatic complaint assessment were significantly higher in ICPP group than those of control group. (2) The SES score, the body strength scores for BES 12 months after treatment were significantly higher than those pretreatment (P <0.05). Serum DHEA levels in ICPP group and control group were Log(0.77 +/-0.36)microg/L and Log (0.28 +/-0.22) microg/L respectively, with a significant difference (P <0.01). Serum DHEA and DHEAS of ICPP 3 months after treatment were decreased from Log(0.83 +/-0.35)microg/L and Log(2.27 +/-0.30)microg/L to Log(0.68 +/-0.44)microg/L and Log (2.11 +/-0.43)microg/L (both P <0.05). The serum DHEA and DHEAS levels 12 months after treatment were Log(0.78 +/-0.30)microg/L and Log(2.40 +/-0.34)microg/L, there was no significant difference before and after treatment (P >0.05). (3) The SES score,the weight concern and body strength scores for BES were negatively correlated with serum DHEA and DHEAS levels in precocious puberty girls (r=-0.492,-0.356,-0.202 and -0.216, all P <0.05). The nine CBCL factors were not correlated with serum DHEA levels.</p><p><b>CONCLUSION</b>Precocious puberty girls are prone to lower self-esteem and less confidence, which are correlated with the increase of serum DHEA levels. There is more frequency to be depressed, withdrawn, aggressive and complaining in these girls, however, which are not correlated with serum DHEA levels. GnRHa may reverse the problem of psychological behavior in ICPP girls.</p>

Long-acting gonadotropin-releasing hormone analogue in treatment of idiopathic central precocious puberty in girls / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the efficacy and side-effects of long-acting gonadotropin-releasing hormone analogue (GnRHa) in treatment of idiopathic central precocious puberty (ICPP) in girls.</p><p><b>METHODS</b>Thirty six ICPP girls were treated with GnRHa. The secondary sexual characteristics, uterus volume, ovary volume, follicle development, bone age/chronological age (BA/CA), predicted adult height (PAH), serum inhibitor A (INHA) and inhibitor B (INHB), body mass index (BMI) and growth rate were compared before and after treatment. Bone age was assessed using the Greulich-Pyle method, PAH was calculated by the Payley-Pinneau method, serum INHA and INHB were measured by ELISA, and serum LH and FSH were measured by chemoluminescence.</p><p><b>RESULT</b>(1) Breast development was reduced after 3 to approximately 6 months of treatment, and no continued development were observed. In 12 girls the breast development returned from Tanner II to B1. (2) Both uterus and ovary volume were decreased after 6 months [(3.28 +/-2.20)ml comrade with (1.27 +/-0.69)ml and (3.62 +/-1.94)ml compared with (1.24 +/-0.50)ml, respectively]; the follicle was reduced or even disappeared; and the serum INHA and INHB were decreased from Log(0.93 +/-0.35)ng/L and Log(1.95 +/-0.37)ng/L to Log(0.60 +/-0.32)ng/L and Log(1.46 +/-0.32)ng/L, respectively. (3) BA/CA was decreased from 1.40 +/-0.20 to 1.26 +/-0.15; PAH was increased from (149.12 +/-4.04)cm to (152.84 +/-3.72)cm after one-year treatment; BMI showed no significant changes (16.04 +/-1.68 compared with 15.93 +/-1.69).</p><p><b>CONCLUSION</b>GnRHa can effectively inhibit the development of sex gland and the secondary sexual characteristics, stabilize or delay bone maturation, improve the predicted adult height, and has no observed side-effects in the short-term treatment for ICPP girls.</p>

Effect of maternal autoimmune thyroid disease on intellectual development of infants / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the effect of maternal Hashimoto's disease (an autoimmune thyroid disease) on intellectual development of infants.</p><p><b>METHODS</b>From July 2001 to June 2003, 21 infants born by mothers suffered from Hashimoto's disease were followed up with provincial neonatal disease screening network system. Their thyroid function was assessed and their mental development was evaluated with Gesell development schedules.</p><p><b>RESULT</b>(1) Among the 21 infants, 8 showed normal thyroid function, 11 showed hyperthyrotropinemia, 2 cases had congenital hypothyroidism, which showed significant differences from those born by healthy mothers. (2) The mental and psychomotor development of infants whose mothers suffered from Hashimoto's disease lagged behind those with the healthy mothers (P <0.05).</p><p><b>CONCLUSION</b>Maternal Hashimoto's disease may affects infants' thyroid function and mental development.</p>

Effect of recombinant human growth hormone on glucose metabolism in children with growth hormone deficiency / 中华儿科杂志

<p><b>OBJECTIVE</b>Numerous studies in children with growth hormone deficiency (GHD) show that recombinant human growth hormone (rhGH) treatment results in significant catch-up growth, but some papers reported that the children who underwent rhGH therapy might be at increased risk of diabetes. The aim of this study was to investigate the effects of rhGH treatment on blood glucose and insulin metabolism in children with GHD and the relationship between growth hormone (GH) and glucose homeostasis.</p><p><b>METHODS</b>In this study, 44 children with GHD treated with rhGH [0.1 U/(kgxd)] and age- and sex-matched 20 healthy children were enrolled. The GHD group included 28 males and 16 females aged from 4.5 to 16.5 years (mean 10.4 +/- 2.6 years), including 18 cases of complete GHD and 26 cases of partial GHD. The sexual development stage of all subjects was in Tanner I. Oral glucose tolerance tests (OGTT) were done, and body mass index (BMI), serum insulin-like growth factor-1 (IGF-1) level and insulin resistance by homeostasis model (HOMA-IR) were measured at the time of diagnosis and every 3 months after rhGH therapy. Continuous glucose monitoring system (CGMS) was applied for two cases with hyperglycemia.</p><p><b>RESULTS</b>(1) Fasting glucose and IGF-1 levels increased since 3 months of treatment and did not decrease since then. The levels of fasting glucose and IGF-1 at every time points of rhGH therapy were higher than the levels at the time of diagnosis (F = 6.81, P < 0.01; F = 7.31, P < 0.01, respectively). HOMA-IR and fasting insulin levels were increased since 3 and 9 months of treatment (P = 0.001 and P = 0.021, respectively). They decreased after 12 months of therapy and the levels at 18 months of therapy were similar to that at diagnosis. (2) Pearson correlation analysis showed that HOMA-IR was positively correlated with BMI, IGF-1 and the duration of treatment (r = 0.251, 0.437, 0.281, P < 0.01, respectively). The curve between HOMA-IR and duration of therapy was similar with parabola and the quadratic equation obtained was as follows: HOMA-IR = 1.5048 + 0.2177 x duration of therapy (months)-0.0103 x duration of therapy (months)(2) (r(2) = 0.147, F = 14.16, P < 0.01). (3) Two cases had transitory hyperglycemia. Their fasting glucose levels were all higher than 7.1 mmol/L. The glucose levels returned to normal after 1 month and 5 days respectively. OGTT and CGMS showed that their plasma glucose levels were normal after rhGH therapy was applied again.</p><p><b>CONCLUSION</b>The children who underwent rhGH therapy may be at increased risk of insulin resistance (especially during the first year) and the therapy may even induce transitory glucose metabolic disorder in a very small proportion of patients. Circulating IGF-1 may participate in the control of insulin sensitivity and play an important role in the hormonal balance between GH and insulin. It may be necessary to monitor glucose metabolism and IGF-1 for all children who are treated with rhGH therapy.</p>

Relationship between serum dehydroepiandrosterone levels and female precocious puberty / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the relationship of serum dehydroepiandrosterone (DHEA) levels and female precocious puberty.</p><p><b>METHODS</b>The serum levels of DHEA and dehydroepiandrosterone sulfate (DHEAS) were measured by ELISA in 60 idiopathic central precocious puberty (ICPP) girls, 62 premature thelarche (PT) girls and 31 age-matched health prepuberty girls. Bone age,volume of uterus and ovary, DHEA and DHEAS were re-measured in 3, 12 months after treatment with Diphereline in ICPP girls.</p><p><b>RESULT</b>(1) The Log(DHEA) and Log(DHEAS) were (0.81 +/-0.36)microg/L and (2.31 +/-0.31)microg/L in ICPP group, (0.72 +/-0.30)microg/L and (2.31 +/-0.28)mg/L in PT group, and (0.32 +/-0.26)microg/L and (2.16+/-0.27)microg/L in controls (P <0.05). However, no significant differences were found between ICPP and PT group (P >0.05). Moreover, the serum levels of DHEA and DHEAS in precocious puberty girls with Tanner III stage were significant higher than those with Tanner II stage (P <0.05). (2) With bivariate correlation analysis, Log(DHEA) was positively correlated with height, bone age, volume of uterus and ovary (r=0.429, 0.339, 0.217, 0.282; all P<0.05), while no significant correlation with Log(LH peak), Log(FSH peak) and BMI (r=0.135, -0.165, 0.059). Log(DHEAS) was positively correlated with height,bone age and volume of ovary (r=0.319, 0.210, 0.181; P <0.05), while no correlated with Log(LH peak), Log(FSH peak), volume of uterus and BMI (r=0.012, -0.173, 0.146 and 0.081 respectively). (3) Serum Log (DHEA) and Log(DHEAS) of 32 ICPP were decreased from (0.83 +/-0.35) microg/L and (2.27 +/-0.30)microg/L to (0.68 +/-0.44)microg/L and (2.11 +/-0.43)microg/L (P<0.05) 3 months after treatment. The serum Log(DHEA) and Log(DHEAS) in 12 months after treatment were (0.78 +/-0.30)microg/L and (2.40+/-0.34)microg/L, which was not significantly different with that before treatment (P>0.05). However, the volume of uterus and ovary, bone age/age in 12 months after treatment were significantly different with those before treatment (2.82 +/-1.52 compared with 1.09 +/-0.50 ml, 3.15 +/-1.13 compared with 1.18 +/-0.42 ml, 1.43 +/-0.23 compared with 1.25 +/-0.12, all P<0.05).</p><p><b>CONCLUSION</b>(1) The serum levels of DHEA and DHEAS are increased in precocious puberty girls with the development of Tanner stage. (2) Serum levels of DHEA and DHEAS are declined transiently when the hypothalamic-pituitary-gonadal axis is inhibited. (3) Serum DHEA is associated with the acceleration of growth and bone age in precocious puberty girls.</p>

Multifactorial analysis of effects of mothers' autoimmune thyroid disease on their infants' intellectual development / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze factors relevant to retarded intellectual development in infants born to mothers with autoimmune disease of thyroid.</p><p><b>METHODS</b>All the term newborns born to mothers with autoimmune thyroid disease (selection criteria) without asphyxia in all county, city, and provincial hospitals in Zhejiang province (except for Ningbo City) from July 2001 to June 2003 were enrolled through Zhejiang provincial neonatal disease screening network system. The control group was consisted of the neonates who were born to mothers without thyroid disease in these hospitals during the same period. Heel capillary blood samples were collected from the neonates older than 3 days in local hospitals and sent to the center of Zhejiang provincial neonatal disease screening network system. TSH levels were measured by Time Difference Fluorescent Analysis Device (1420 II type, EGG Company, US). If the level of TSH was higher than 9 mU/L, their mothers were called back to the center with their infants within 3 days. If the level of TSH was normal, they were called back to hospitals at age of 28 - 35 days of infants. The pattern of maternal thyroid disease, duration, thyroid function, the history of maternal drug administration, maternal age, gestational age and body weight of the neonates were recorded. The neonatal and maternal serum thyroid function tests were re-performed and the serum TPOAb, TGAb, TRAb and TSAb levels in both neonates and their mothers were measured as well. A 1-year follow-up study was done and all these subjects were investigated by means of Gesell development schedules by special investigators at the age of 1, 3, 6 and 12 months. The results were expressed as developmental quotient. Case-sectional study was performed. Statistical analyses were conducted using SPSS software. The multiple logistic regression analysis was used to analyze factors which might have effect on infantile personal-social ability, adaptive ability, gross motor ability or the fine-motor ability. One-way ANOVA was used to compare those five subfields ability followed by LSD multiple comparisons and Dunnet's C test was used when variances were not equal. Correlation analysis was used to compare the anti-thyroid antibody between neonates and their mothers.</p><p><b>RESULTS</b>Poor personal-social ability, adaptive ability, gross motor ability and fine motor ability of infants born to mothers with autoimmune thyroid diseases were found as compared to the infants born to healthy mothers (P < 0.01). Moreover, the infants born to mothers with Hashimoto's thyroiditis had significantly poorer fine motor ability and adaptive ability than those born to mothers with Grave's disease (P < 0.05). The Spearman correlation coefficients of TPOAb, TGAb, TRAb and TSAb were 0.636, 0.574, 0.619 and 0.473, respectively, and all the P values were lower than 0.01.The multifactor logistic regression analysis showed that infantile TPOAb levels and maternal TRAb levels were associated with infantile personal-social ability, adaptive ability, and gross motor; while maternal TPOAb levels and thyroid function during gestation were associated with infantile fine-motor ability (P < 0.05).</p><p><b>CONCLUSION</b>Maternal autoimmune thyroid diseases during pregnancy had adverse effects on intellectual development of infants. The maternal levels of TPOAb, TRAb and thyroid status were associated with the infantile personal-social ability, adaptive ability, gross motor and fine motor development. In order to reduce the effect on infant, it is necessary to treat adequately the maternal autoimmune thyroid diseases during pregnancy.</p>

Simplified gonadorelin stimulation test in diagnosis of precocious puberty / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To assess the diagnostic value of the simplified gonadorelin stimulation test for precocious puberty.</p><p><b>METHODS</b>Two hundred and ninety-two girls with signs of advanced breast development received the gonadorelin stimulation test. According to the result of gonadorelin stimulation test, the girls were divided into 3 groups: 151 with central precocious puberty (CPP),119 with premature thelarche (PT) and 22 with peripheral precocious puberty (PPP).</p><p><b>RESULTS</b>LH or FSH levels at 15 min, 30 min, 60 min in PPP group were not significantly different (P>0.05). Those were significantly different in PT group (P<0.01). The highest levels of LH were at 30 min and the highest levels of FSH were at 60 min. LH or FSH levels at 15 min, 30 min, 60 min in CPP group were significantly different (P<0.01) with the highest levels at 30 min. The ratio of basal LH and FSH >0.2 had a diagnostic sensitivity of 48.3 % and specificity of 69.7%. Taking the LH/FSH ratio >0.9 at 15 min, 30 min, 60 min as cut-off value, the diagnostic sensitivity was 80.1%, 68.9% and 38.4%, and the specificity was 90.8%, 96.6% and 69.7%, respectively.</p><p><b>CONCLUSION</b>The LH/FSH ratio>0.9 at 15 min after gonadorelin stimulation test can be used as a cut-off value to differentiate CPP from PT and blood sample at 60 min were not necessary.</p>

Obese children with benign acanthosis nigricans and insulin resistance: analysis of 19 cases / 中华儿科杂志

<p><b>OBJECTIVE</b>The prevalence of obesity and of type 2 diabetes mellitus in children have increased in the Chinese population over the past two decades, and thus diabetes prevention has become a major concern of public health agencies. Identification of individuals at risk for diabetes is an essential first step in designing and implementing intervention programs. Insulin resistance is the hallmark of the pathophysiology of type 2 diabetes mellitus. Subjects with hyperinsulinemia and impaired glucose tolerance are well accepted as being at high risk for diabetes. Acanthosis nigricans (AN) has been proposed as a reliable marker of hyperinsulinemia, but its utility for predicting hyperinsulinemia has not been systematically evaluated in obese children. In order to further explore the relationship between obese childhood with benign acanthosis nigricans and insulin resistance and type 2 diabetes mellitus, we examined 19 obese children with benign acanthosis nigricans.</p><p><b>METHODS</b>Nineteen of seventy six obese children (25%) with BMI over 25 enrolled in the Children' Hospital of Zhejiang University School of Medicine fromJune 1st to September 1st in 2003 were studied. Skin biopsies were performed in these 19 obese children with acanthosis nigricans for final diagnosis. Levels of glucose, insulin, and glucose/insulin ratio were measured on fasting blood specimens and anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index were examined. Oral glucose tolerance tests were also performed in these 19 children with benign acanthosis nigricans.</p><p><b>RESULTS</b>Anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index as well as fasting insulin level in acanthosis nigricans group were significantly higher than that of healthy controls (P < 0.01). Fasting glucose to insulin ratio (FGIR) of these 19 obese children with benign acanthosis nigricans was 4.27 +/- 0.53, indicating apparent insulin resistance. One of them was diagnosed as type 2 diabetes mellitus and ten of them showed impaired oral glucose tolerance.</p><p><b>CONCLUSION</b>Childhood benign acanthosis nigricans is tightly associated with obesity, hyperinsulinemia, insuline resistance and type 2 diabetes mellitus, and may be used as a reliable index of insulin resistance.</p>

Study for acid-base homeostasis in children with growth hormone deficiency / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the difference of plasma actual bicarbonate between the children with growth hormone deficiency (GHD) and idopathatic short stature (ISS) and to value the plasma bicarbonate standard deviation scores (SDS) in diagnosis of GHD.</p><p><b>METHODS</b>Forty-seven short stature children were divided into two groups (GHD and ISS) according to the peak GH response to provocative test. Plasma actual bicarbonate concentrations anion gap (AG), base excess and electrolytes were measured in 47 children with short stature before GH provocative tests.</p><p><b>RESULTS</b>The mean plasma actual bicarbonate concentrations, bicarbonate SDS were (22.60+/-1.29)mmol/L and -0.27+/-0.98 respectively in GHD children, which were significantly lower than those of ISS children (P<0.01), whereas AG was higher than that of ISS children [(11.73+/-4.52 vs 7.87+/-1.70) mmol/L], P<0.01. Seventy-two percent of patients with bicarbonate SDS<or=1 s were diagnosed as GHD.</p><p><b>CONCLUSION</b>Plasma actual bicarbonate concentrations and bicarbonate SDS are lower in patients with GHD than those in patients with idopathatic short stature. Evaluation of plasma bicarbonate SDS of short stature children can predict the probability of GHD, especially when bicarbonate SDS is less than 1 s.</p>

Study on plasma ghrelin level in girls with precocious puberty / 中华内分泌代谢杂志

Plasma ghrelin level was measured by RIA in 49 grids with idiopathic central precocious puberty(ICPP)and 35 girls with simple premature thelarche(PT).The results showed that the plasma ghrelin level was negatively correlated with Tanner stage,bone age,Lid at 15,30 and 60 min after GnRH activation, uterus and ovary volumes.The plasma ghrelin level in the ICPP group was remarkably lower than that in the PT and control groups(both P