Association between dietary patterns and central precocious puberty in girls / 中国学校卫生

Objective@#To explore the relationship between dietary patterns and central precocious puberty in children, and to provide a scientific basis for dietary prevention of precocious puberty.@*Methods@#A case-control study was conducted, among 35 newly diagnosed central precocious puberty girls from May to December 2019 as the case group, and 70 healthy girls with normal development as the control group. Physical development examination, parent questionnaire survey and child interview were carried out. Dietary information was assessed using a simplified food frequency questionnaire(FFQ). Principal component analysis was used to identify children s dietary patterns, and multiple Logistic regression was used to assess the association between dietary patterns and precocious puberty.@*Results@#Three different dietary patterns have been established, namely "snack and processed food type", "animal protein type" and "nutritional tonic type" dietary patterns, respectively. After adjusting for covariates such as age and BMI, Logistic regression analysis showed that the "snack and processed food type" dietary pattern was positively correlated with precocious puberty(OR=10.81, 95%CI=2.59-45.15, P<0.01). There was a negative correlation between "animal protein type" and precocious puberty(OR=0.24, 95%CI=0.06-0.91, P=0.04), while the association between "nutritive tonic" and precocious puberty was not statistically significant(OR=0.28, 95%CI=0.07-1.05, P=0.06).@*Conclusion@#Children s dietary patterns were related to precocious puberty." Snack and processed food "dietary pattern with a high intake of fried foods, puffed foods, foods containing preservatives or pigments, western fast foods, chocolate and products, was closely related to central precocious puberty.

Efecto sobre la talla en niñas con pubertad precoz central de diagnóstico tardío tratadas con análogos de GnRH / Effect of GnRH analogs on girls height with late diagnosis central precocious puberty

RESUMEN Objetivo: evaluar el efecto de los análogos de GnRH sobre la predicción de talla final adulta en niñas con pubertad precoz central de diagnóstico tardío. Materiales y métodos: estudio descriptivo, retrospectivo. Se incluyeron niñas atendidas entre 2012 y 2018 en la Unidad de Endocrinología Pediátrica del Hospital Cayetano Heredia con diagnóstico de pubertad precoz central idiopática de diagnóstico tardío. Se realizó evaluación antropométrica, evaluación de estadío Tanner y determinación de edad ósea con el método de Greulich y Pyle, estimando la predicción de talla final adulta mediante el método de Bayley Pinneau antes y después del tratamiento con análogos de GnRH. Se realizó t de student para comparar la predicción de talla antes y después del tratamiento. Se consideró significativo un p< 0,05. Resultados: se incluyeron 23 niñas con edad cronológica media de 8,4 ± 0,4 años y una edad ósea de 10,7 ± 0,8 años al ingreso. El 83,9% de las pacientes tuvieron exceso de peso y el 74,0% estadio Tanner 3 al diagnóstico. El tiempo promedio de tratamiento con análogos de GnRH fue de 20,5 ± 8,4 meses. El efecto del tratamiento calculado con la diferencia de predicción de talla final adulta menos predicción de talla inicial fue de 2,5 ± 4,1 cm (p<0,01). Conclusión: las niñas con diagnóstico de pubertad precoz central de diagnóstico tardío muestran un discreto beneficio sobre la predicción de talla final adulta, por lo que la terapia a esta edad debe ser individualizada.

ABSTRACT Objective: to assess the effect of GnRH analogues on predicted adult final height in girls with a late diagnosis of central precocious puberty. Material and Methods : this is a descriptive and retrospective study. Girls seen between 2012 and 2018 in the Pediatric Endocrinology Unit of Hospital Nacional Cayetano Heredia with a late diagnosis of idiopathic precocious central puberty were included. Anthropometric assessments were performed, Tanner stage assessment and bone age determination using the Greulich and Pyle method were performed, and the final adult height was predicted using the Bailey Pinneau method before and after therapy. A Student-t test was used for comparing the height prediction before and after therapy. A p<0.05 value was considered as significant. Results : twenty-three girls with mean chronological age 8.4 ± 0.4 years were included. Their bone age was 10.7 ± 0.8 on admission. Most of the patients (83.9%) were overweight and 74.3% were Tanner 3 at the time of diagnosis. The average time using GnRH analogues therapy was 20.5 ± 8.4 months. The effect of therapy, which was calculated using the prediction difference for the final adult height minus the initial height prediction was 2.5 ± 4.1 cm (p<0.001). Conclusion : girls with a diagnosis of late diagnosis central precocious puberty show a discrete benefit on the prediction of the final adult height, so therapy at this age should be individualized.

Association of PLCB1 gene polymorphism with the risk of central precocious puberty in Chinese Han girls / 中国学校卫生

Objective@#To investigate the association between mutation of PLCB1, the downstream gene of KISS1/GPR54 pathway, and the risk of central precocious puberty (CPP) in Chinese Han girls.@*Methods@#Totally 169 pairs of CPP girls on their first visit to hospital and age-matched controls (± 3 months) were recruited. The genotypes of rs6140544, rs11476922, rs3761170 and rs2235613 were determined and the effect of loci variations on CPP was investigated.@*Results@#After adjusting for confounding factors (BMI, maternal age at menarche, maternal age at birth, and time for bed), rs2235613 variation was significantly negative associated with CPP in recessive models(OR=0.46，95%CI=0.24-0.91), and mutation in rs3761170 increased the risk of CPP in dominant models (OR=1.99，95%CI=1.01-3.93).@*Conclusion@#The study suggests that mutation in rs3761170 increases the risk of CPP and rs2235613 variation may have a protective effect on the risk of CPP.

Investigation on intelligence, self-concept and psychosocial adaptation of precocious girls / 中国学校卫生

Objective@#To explore the intelligence, self-concept and psychosocial adaptability among girls with precocious puberty,and to provide theoretical basis for the prevention and treatment of precocious puberty in girls.@*Methods@#Performed the Wechsler Preschool and Primary Scale of Intelligence, the Piers-Harris Children’s Self-concept Scale and the Social Adaptive Quotient for evaluating the intelligence quotient (IQ), self-concept and psychosocial adaptability of 45 precocious girls and 90 normal girls,respectively. The differences between these two groups of girls were analyzed.@*Results@#The level of intelligence of precocious girls (119.80±16.37) was higher than that of normal girls (109.96±17.13)(t=3.19, P<0.01). The total score of self-concept of precocious girls (57.98±6.14) was lower than that of girls in the normal group (61.68±5.16)(t=3.68, P<0.01). Furthermore, the independent functional factors, cognitive functional factors, social self-control factors and ADQ of precocious girls were lower than those of normal girls (P<0.01), and 24.4% of them were at the lower limit of psychosocial adaptability, lower than those of normal girls(U=4.84，P<0.01).@*Conclusion@#Girls with precocious puberty show impairments on the development of intelligence, self-concept and psychosocial adaptability.

Application of three-dimensional ultrasound imaging in diagnosis of precocious puberty in girls / 中国医学影像技术

Objective: To investigate the value of three-dimensional ultrasonography (3D-US) in diagnosis of precocious puberty in girls. Methods: Totally 32 girls diagnosed as central precocious were enrolled. Two-dimensional ultrasonography (2D-US) and 3D-US of pelvis were performed, and the volume of uterus and ovary, the number of follicles, the maximum follicle diameter and ovarian blood flow parameters were recorded. At the same time, the basic levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2) were detected. The parameters measured with 2D-US and 3D-US were compared, and the correlation between ultrasonic measurement parameters and hormone level was also analyzed. Results: 3D-US could clearly show the internal structure of uterus and ovary. The number of follicles larger than 4 mm and the maximum follicle diameter measured with 3D-US were all greater than those with 2D-US (both P0.05). The color blood flow display rate of ovary in 3D-US was 87.50% (28/32), significantly better than that of 2D-US (28.12% [9/32], P<0.01). 3D-US energy Doppler vascular index (VI), blood flow index (FI), blood vessel-blood flow index (VFI) were positively correlated with the maximum follicle diameter (r=0.43, 0.44, 0.54, all P<0.05). 3D-US measurements of ovarian volume and maximum follicle diameters were positively correlated with the serum LH (r=0.39, 0.72) and FSH (r=0.38, 0.64, all P<0.05). Conclusion: 3D-US is superior to 2D-US in counting follicles, measuring the maximum follicle diameter and showing ovarian blood supply in precocious girls, and is expected to play an important role in the diagnosis of precocious puberty in girls.

Rapidly progressive puberty in a patient with mosaic Turner syndrome: a case report and literature review / 中华儿科杂志

Objective@#To explore the clinical characteristics of diagnosis and treatment in patients with Turner syndrome and rapidly progressive puberty.@*Method@#A rare case of rapidly progressive puberty in Turner syndrome with a mosaic karyotype of 45, X/46, X, del(X)(p21)(80%/20%)was diagnosed at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in January. 2015. Clinical characteristics and the related literature were reviewed. Original papers on precocious puberty or rapidly progressive puberty in Turner syndrome, published until Apr. 2016 were retrieved at PubMed and CNKI databases by the use of the key words "Turner syndrome" , "precocious puberty" and "rapidly progressive puberty" .@*Result@#The patient was born at term with birth weight of 2 450 g and was diagnosed with SGA at 3 years of age for the first evaluating of growth and development. Then recombined human growth hormone (rhGH )was given at 4 years of age due to short stature (height<3 percentile) and low growth velocity(<5.0 cm/year) as well. However, rhGH treatment was discontinued after 9 months because of economic burdens. Breast development was noted at 9 years and 3 months. The patient was followed up at 3 months intervals. Physical examination revealed a Tanner stage Ⅲ breast development at 10.33 years , the bone age was 11.6 years. Then, gonadotropin-releasing hormone analogs treatment was added to slow pubertal progression and to preserve maximum adult height. The growth rate decreased with therapy from 7.5 cm/year to 4.4 cm/year. The patient was reevaluated, and the chromosome analysis of peripheral blood revealed a mosaic karyotype 45, X/46, X, del(X)(p21)(80%/ 20%). To date, only 10 cases have been reported in the literature. Six of them showing mosaic TS, three karyotypes with structural abnormality of short arm of X chromosome, one with the karyotype 45, X.@*Conclusion@#It is the first time that rapidly progressive puberty in a 45, X/46, X, del(X)(p21) mosaic Turner syndrome is reported. Although short stature and ovarian dysgenesis are common in TS, precocious puberty may occur in TS, which is liable to cause delayed diagnosis and misdiagnosis. Careful examination is recommended for patients with unusual growth pattern, even though girls have normal height in accord with standard growth curve or spontaneous puberty. Evaluation for TS and subsequent investigation should be prompted.

Serum Anti-Müllerian Hormone Levels in Precocious Puberty Girls according to Stage of GnRH Agonist Treatment

Few studies have investigated the long-term effects of gonadotropin-releasing hormone (GnRH) agonist treatment on the reproductive function of central precocious puberty (CPP) girls. In this cross-sectional study, we assessed the ovarian function by analyzing the serum anti-Müllerian hormone (AMH) levels of CPP girls. Our study included 505 CPP girls subdivided into 5 groups according to the GnRH agonist treatment stage: group A (before treatment, n = 98), group B (3 months after initiation, n = 103), group C (12 months after initiation, n = 101), group D (24 months after initiation, n = 101), and group E (6 months after discontinuation, n = 102). We compared the serum AMH levels of the CPP girls with those of 100 bone age-matched controls (before treatment: n = 55; after discontinuation: n = 45). At baseline, the mean AMH level of the CPP girls was 5.9 ± 3.6 ng/mL. The mean AMH level after 3 months of the GnRH agonist treatment was lower (4.7 ± 3.2 ng/mL, P = 0.047) than that at baseline and recovered after 12 months of treatment. Six months after discontinuation, the AMH levels were similar to those at pre-treatment. Before and after the GnRH agonist treatment, the AMH levels were similar to those of the bone age-matched controls. In the precocious puberty girls, the AMH levels based on the GnRH agonist treatment stage were all within the normal reference range. The results of this study suggest that GnRH agonist treatment has no adverse effects on the reproductive function.

Mutações inativadoras no gene MKRN3 são causa de puberdade precoce central familial / Inactivating mutations in the MKRN3 gene are cause of familial central precocious puberty

A maioria dos casos de puberdade precoce central (PPC) em meninas permanece idiopática. A hipótese de uma causa genética vem se fortalecendo após a descoberta de alguns genes associados a este fenótipo, sobretudo aqueles implicados com o sistema kisspeptina (KISS1 e KISS1R). Entretanto, apenas casos isolados de PPC foram relacionados à mutação na kisspeptina ou em seu receptor. Até recentemente, a maioria dos estudos genéticos em PPC buscava genes candidatos selecionados com base em modelos animais, análise genética de pacientes com hipogonadismo hipogonadotrófico, ou ainda, nos estudos de associação ampla do genoma. Neste trabalho, foi utilizado o sequenciamento exômico global, uma metodologia mais moderna de sequenciamento, para identificar variantes associadas ao fenótipo de PPC. Trinta e seis indivíduos com a forma de PPC familial (19 famílias) e 213 casos aparentemente esporádicos foram inicialmente selecionados. A forma familial foi definida pela presença de mais de um membro afetado na família. DNA genômico foi extraído dos leucócitos do sangue periférico de todos os pacientes. O estudo de sequenciamento exômico global realizado pela técnica ILLUMINA, em 40 membros de 15 famílias com PPC, identificou mutações inativadoras em um único gene, MKRN3, em cinco dessas famílias. Pesquisa de mutação no MKRN3 realizada por sequenciamento direto em duas famílias adicionais (quatro pacientes) identificou duas novas variantes nesse gene. O MKRN3 é um gene de um único éxon, localizado no cromossomo 15 em uma região crítica para a síndrome de Prader Willi. O gene MKRN3 sofre imprinting materno, sendo expresso apenas pelo alelo paterno. A descoberta de mutações em pacientes com PPC familial despertou o interesse para a pesquisa de mutações nesse gene em 213 pacientes com PPC aparentemente esporádica por meio de reação em cadeia de polimerase seguida de purificação enzimática e sequenciamento automático direto (Sanger). Três novas mutações e duas...

Most cases of central precocious puberty (CPP) in girls remain idiopathic. The hypothesis of a genetic cause has been strengthened after the discovery of some genes associated with this phenotype, particularly those involved with the kisspeptin system (KISS1 and KISS1R). However, genetic defects in KISS1 and its receptor are rare and have been identified in only a few patients with CPP.over the past years. To date, most genetic studies in CPP was based mainly on a candidate gene approach, including genes selected in animal studies, human models of patients with hypogonadotropic hypogonadism or in genome wide association studies. In the present study, we used whole exome sequencing, a more advanced method of sequencing, to identify variants associated with CPP. Thirty-six patients with the familial form of CPP (19 families) and 213 apparently sporadic cases were initially selected. The familial form was defined by the presence of more than one member affected in the family. Genomic DNA was extracted from peripheral blood leukocytes in all patients. Whole exome sequencing performed by ILLUMINA technique in 40 members of 15 families with CPP, identified inactivating mutations in a single gene, MKRN3, in five out of these families. Analysis of MKRN3 mutations performed by automatic sequencing in two additional families (four patients) identified two novel mutations. MKRN3 is an introless gene located on chromosome 15, in the Prader Willi syndrome critical region, and it is expressed only by the paternal allele due to the maternal imprinting. Following the initial findings, we searched for MKRN3 mutations in 213 patients with apparently sporadic CPP using polymerase chain reaction followed by direct enzymatic purification and automated sequencing (Sanger). Three new mutations and two previously reported, including four frameshifts and one missense variant was identified in six unrelated girls with CPP. All variants were not described in...

The Diagnostic Value of Pelvic Ultrasound in Girls with Central Precocious Puberty / 전남의대학술지

The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for differentiating central precocious puberty (CPP) from exaggerated thelarche (ET). Because of this test's limitations, previous studies have clarified the clinical and laboratory factors that predict CPP. The present study investigated the early diagnostic significance of pelvic ultrasound in girls with CPP. The GnRH stimulation test and pelvic ultrasound were performed between March 2007 and February 2015 in 192 girls (aged <8 years) with signs of early puberty and advanced bone age. Ninety-three of 192 patients (48.4%) were diagnosed as having CPP and the others (51.6%) as having ET. The CPP group had higher uterine volumes (4.31+/-2.79 mL) than did the ET group (3.05+/-1.97 mL, p=0.03). No significant differences were found in other ultrasonographic parameters. By use of receiver operating characteristic curve analysis, the most predictive parameter for CPP was a uterine volume of least 3.30 mL, with an area under the curve of 0.659 (95% confidence interval: 0.576-0.736). The CPP group had significantly higher uterine volumes than did the ET group, but there were no reliable cutoff values in pelvic ultrasound for differentiating between CPP and ET. Pelvic ultrasound should be combined with clinical and laboratory tests to maximize its diagnostic value for CPP.

The Diagnostic Value of Pelvic Ultrasound in Girls with Central Precocious Puberty / 전남의대학술지

The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for differentiating central precocious puberty (CPP) from exaggerated thelarche (ET). Because of this test's limitations, previous studies have clarified the clinical and laboratory factors that predict CPP. The present study investigated the early diagnostic significance of pelvic ultrasound in girls with CPP. The GnRH stimulation test and pelvic ultrasound were performed between March 2007 and February 2015 in 192 girls (aged <8 years) with signs of early puberty and advanced bone age. Ninety-three of 192 patients (48.4%) were diagnosed as having CPP and the others (51.6%) as having ET. The CPP group had higher uterine volumes (4.31+/-2.79 mL) than did the ET group (3.05+/-1.97 mL, p=0.03). No significant differences were found in other ultrasonographic parameters. By use of receiver operating characteristic curve analysis, the most predictive parameter for CPP was a uterine volume of least 3.30 mL, with an area under the curve of 0.659 (95% confidence interval: 0.576-0.736). The CPP group had significantly higher uterine volumes than did the ET group, but there were no reliable cutoff values in pelvic ultrasound for differentiating between CPP and ET. Pelvic ultrasound should be combined with clinical and laboratory tests to maximize its diagnostic value for CPP.

Etiological analysis of vaginal bleeding in girls / 中华实用儿科临床杂志

Objective To investigate the etiological factors fc,r abnormal vaginal bleeding in girls.Methods Data of 65 female children aged from 3 months and 10 years old with abnormal vaginal bleeding,who were treated in Department of Endocrinology,Wnhan Children's Hospital from March 2009 to October 2013 were collected by using medical records and follow-ups.By means of pelvic ultrasound,bone age assessment,hysteroscope,hormone level and genetic testing,the causes of the disease were analyzed.Results Of 65 patients,37 cases had breast developed,21 ca-ses had nipple,areola and vulva pigmentation increased,16 cases with genital secretions increasing and odor,the height growth in 21 cases accelerated,abdominal pain was presented in 5 cases,and 6 cases had skin milk coffee spots.The leading etiological factors for vaginal hemorrhage in these girls were sexual precocity.The peripheral precocious puberty accounted for the first place (30/65 cases,46.2％),and followed by the central precocious puberty (20/65 cases,30.8 ％).Hyperphlogosis accounted for 12.3 ％ (8/65 cases),vaginal foreign body accounted for 6.2 ％ (6/65 cases),and genital tract tumors accounted for 4.6％ (3/65 cases).In the 30 peripheral precocious puberty cases,exogenous precocious puberty accounted for 16.9％ (11 cases),8 cases(12.3％) were of solitary ovarian cyst,8 cases(12.3％) of McCune-Albright syndrome,and 3 cases of ovarian tumors.In the 20 central precocious puberty cases,idiopathic central precocious puberty accounted for 18.5％ (12 cases),4 cases(6.2％) were of organic disease of central nervous system,and 4 cases (6.2％) of hypothyroidism.Of 65 children,12 cases lost follow-up and 1 case abandoned treatment.The rests received appropriate treatment according to different causes,and the vaginal bleeding were effectively controlled after 3 months to 2.5 years of follow-ups without recurrence of bleeding.But there were 2 cases of isolated ovarian cyst and 3 cases of McCune-Albright syndrome turned into central precocious puberty.Conclusions Endocrine diseases are the common factors for children's vaginal bleeding.Neoplasm is not rare in girl's abnormal vaginal hemorrhage.

Puberdade precoce: condições associadas / Precocious puberty: associated conditions / Pubertad precoz: condiciones asociadas

Analisar as características das crianças com puberdade precoce central (PPC), identificando-se tanto suas características clínico-epidemiológicas como os fatores determinantes para o recebimento de uma atenção à saúde oportuna. Métodos: Estudo retrospectivo e analítico de 342 prontuários, entre 1994 e 2010, de crianças de 1 a 11 anos com PPC, provenientes do ambulatório de endocrinologia de um hospital de referência. Analisaram-se as variáveis biológicas, econômicas, familiares e nutricionais de forma uni e bivariada, utilizando-se o teste Qui-Quadrado na avaliação estatística das associações. Resultados: Identificaram-se como principais características: 25 (7,3%) eram adotadas, 92(27,1%) estavam com sobrepeso, 85 (25,1%) estavam com obesidade, e 205 (60,3%) tiveram início da puberdade antes dos 6 anos. Crianças com PPC atendidas tardiamente foram as que apresentaram sinais da puberdade mais cedo (p<0,001) e pertenciam a famílias de menor renda (p<0,002). Conclusão: Elevadas proporções de crianças com PPC eram adotadas e portadoras de sobrepeso/obesidade. Crianças com aparecimento excessivamente precoce dos sinais de puberdade e de baixa renda familiar sofreram significativo retardo na obtenção da atenção especializada...

To analyze the characteristics of children with central precocious puberty (CPP), identifying both their clinical and epidemiological characteristics, as well as the determinants for receiving timely specialized health care. Methods: Cross-sectional retrospective study with analytical approach of 342 medical records of children aged 1 to 11 years with CPP, from the Endocrinology Outpatient Clinic of a reference hospital. Biological, socio-economic, family and nutritional data of the 1994 to 2010 period was submitted to univariate and bivariate analysis, using the chi-square test for the statistical evaluation of the associations. Results: The main features of children with CPP were: being adopted, 25 (7.3%); being overweight, 92 (27.1%); being obese, 85 (25.1%); initiating puberty before six years of age, 205 (60.3%). Children with PPC who received late specialized care were the ones who most precociously presented signs of puberty (p<0.001), and belonged to families with lower income (p<0.002). Conclusion: High proportions of children with CPP were adopted and presented overweight/obesity. Children with excessively early onset of puberty signs, and belonging to low income families, suffered significant delay in obtaining specialized care...

Analizar las características de los niños con pubertad precoz central (PPC)identificando sus características clínico-epidemiológicas como factores determinantespara el recibimiento de una atención a la salud oportuna. Métodos: Estudio transversal, retrospectivo y analítico de 342 historiales clínicos de niños entre 1 y 11 años con PPC del ambulatorio de endocrinología de un hospital de referencia entre 1994 y 2010. Las variables biológicas, económicas, familiares y nutricionales fueron analizadas de forma uni y bivariada utilizando la prueba del Chi-cuadrado en la evaluación estadística de lãs asociaciones. Resultados: Las principales características identificadas fueron: 25 (7,3%) eran adoptados, 92 (27,1%) tenían sobrepeso, 85 (25,1%) eran obesos y 205 (60,3%)iniciaron la pubertad antes de los 6 años. Niños con PPC com retraso en la asistencia presentaron señales de pubertad más precoz (p<0,001) y pertenecían a familias con menor renta (p<0,002). Conclusión: Elevadas proporciones de niños con PPC eran adoptados y portadores de sobrepeso/obesidad. Niños con El surgimiento excesivamente precoz de señales de pubertad y baja renta familiar sufrieron retraso significativo en la obtención de La asistencia especializada...

Value of color Doppler ultrasonography in the diagnosis of precocious puberty in girls / 中华超声影像学杂志

Objective To assess the role of pelvic ultrasound examination in discriminating between normal girls,isolated premature thelarche/pubarche /menarche and central precocious puberty (CPP).Methods Eighty-four isolated premature thelarche/pubarche /menarche cases,47 CPP cases,and 177 normal girls aged 0-10 years were recruited.All diagnoses were confirmed by the gonadotropin-releasing hormone-stimulation test.All subjects underwent pelvic ultrasound examination for the measurement of length,width,thickness,and volume of the uterine body,uterine cervix,and ovary,and the number of follicles with diameter≥ 4 mm.The groups were subdivided by age intervals when the difference in ultrasound measurements between CPP,isolated premature thelarche/pubarche/menarche,and normal girls were analyzed.Results 1) Differentiation between CPP and normal girls:for the 6-8 years,there were 11 variables elevated in CPP as compared to the normal girls.Uterine cervix thickness was the most efficient parameter as judged by the largest value of area under the ROC curve (0.958).The best cut-off,sensitivity,and specificity was 0.73 cm,93.30％,and 85.70％ respectively;for the 8-10 years,uterine body volume was the best parameter among the 10 elevated variables as judged by the largest area under the ROC curve (0.869),3.23 cm3 was the best cut-off limit with a sensitivity of 84.21％ and a specificity of 52.11％.2) Differentiation between isolated premature thelarche/pubarche/menarche and normal girls:for the 0-6 years,ovary thickness was the best variable as judged by the largest area under the ROC curve (0.806),0.98cm was the best cut-off limit with a sensitivity of 76.46％ and a specificity of 84.85 ％ ;for the 6-8 years,ovary width was the best variable among the 8 valuable variables for its largest area under the ROC curve (0.843),1.39 cm was the best cut-off limit with a sensitivity of 85.71％ and a specificity of 73.81％ respectively;for the 8-10 years,uterine cervix thickness was the best variable among the 5 valuable variables for its largest area under ROC curve (0.841),0.75 cm was the best cut-off limit with a sensitivity of 90.48％ and a specificity of 64.21％.3) Differentiation between CPP and isolated premature thelarche/ pubarche/menarche cases:for the 6-8 years,uterine cervix length and width were potential parameters.Uterine cervix length was the best variable for its largest area under the ROC curve(0.764),and 1.49 cm was the best cut-off limit,the corresponding sensitivity and specificity was 93.33％ and 55.17％ respectively;for the 8-10 years,3 variables could be used,among which uterine cervix length was the best variable for its largest area under the ROC curve (0.893),1.88 cm was the best cut-off limit with a sensitivity of 100％ and a specificity of 71.43％.Condusions Pelvic ultrasound examination is a valuable tool for the diagnosis and differentiation between CPP,isolated premature thelarche/pubarche /menarche and normal girls.

Effect of combined treatment with GnRHa and GH on linear growth in mid-and late pubertal girls at great bone ages with CPP or EFP and rela-tion to CNP signaling pathway / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the effect of combined treatment with gonadotropin-releasing hormone analogue ( GnRHa) and growth hormone ( GH) on the linear growth in mid-and late pubertal girls at great bone ages with central precocious puberty ( CPP) or early and fast puberty ( EFP) , and to determine the relation between C-type natriuretic pep-tide ( CNP) signaling pathway and the accelerative effect of GH on long bone growth in these girls.METHODS:Twenty-two girls were diagnosed as CPP or EFP, whose bone ages were older than 11.5 years with impaired predicted adult height ( PAH) , and divided into GnRHa treatment group ( treated with GnRHa alone, slow-release of triptorelin 60~80 μg/kg every 4 weeks, im) and combined treatment group ( treated with GnRHa and GH, 1 U/kg GH every week for 6~7 times, sc) .The height, weight and pubertal stage were determined every 3 months.At the beginning and after 6 months of the treatment, the bone age was evaluated and the serum concentrations of amino-terminal pro-C-type natriuretic peptide ( NT-proCNP), insulin-like growth factor 1 (IGF-1) and procollagen type 1 amino-terminal propeptide (P1NP) were measured. Height velocity ( HV) , height SD score for bone age ( HtSDSBA ) , PAH and the serum indexes mentioned above were com-pared at the beginning and the end of the treatment.RESULTS: After 6 months of the treatment, HV, ΔHtSDSBA andΔPAH of the girls treated with GnRHa +GH were statistically higher than those of the girls given GnRHa alone ( P <0.01).Serum concentrations of NTproCNP, P1NP and IGF-1 were not significantly different between the beginning and the end of the 6-month combined treatment.The girls treated with GnRHa alone showed a significant decrease in both serum NTproCNP and P1NP levels (P<0.05) and no significant change of serum IGF-1 level after 6 months of the treatment. CONCLUSION:In the CPP or EFP girls who are in mid-and late puberty and at great bone ages, the combined treatment with GnRHa and GH may accelerate linear growth and improve predicted adult height.This effect of GH is not attributed to the change of serum IGF-1 level, and may be related in part to the acceleration of CNP-mediated long bone growth.

Final height outcome of boys with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogue / 中华内分泌代谢杂志

Objective To observe the final adult height of 20 boys with idiopathic central precocious puberty (ICPP) treated with slow-releasing gonadotropin-releasing hormone analogue(GnRHa).Methods Twenty boys with ICPP were treated with GnRHa for( 20.0 ± 6.1 ) months.At the beginning of therapy,mean chronological age and bone age was( 11.4 ± 1.0 ) years and ( 13.0 ± 0.4 ) years,respectively,GnRHa was discontinued when the boys reached the chronological age and bone age of( 13.2 ± 1.1 ) years and ( 13.7 ± 0.6 ) years,respectively.After the end of treatment,all the boys had been followed up for( 3.3 ± 1.5 ) years and had achieved adult height.Comparisons were made among their predicted adult height ( PAH ),final adult height ( FAH ),and target height ( THt ).The long-term outcome of final adult height in boys with ICPP was investigated after GnRHa treatment.Results All the boys reached target height range.Final height was similar to the target height [ ( 169.8 ± 5.8 vs 167.8 ± 4.6 ) cm,P＞0.05 ].The height gain,defined as the difference between predicted adult height at the start of treatment using the height SDS for bone age and actual adult height was( 3.62 ± 3.57 ) cm with the residual growth capacity of ( 11.82 ±3.99)cm,PAH significantly improved after GnRHa treatment compared with before treatment [ ( 169.0 ± 5.0 vs166.2 ± 4.2 ) cm,P＜0.01 ].There were no differences among PAH,FAH,and THt.Conclusion GnRHa treatment improves final height within the range of target height in boys with central precocious puberty.

Efficacy of a Single Luteinizing Hormone Measurement after GnRH Agonist Administration for Therapeutic Monitoring of Girls with Central Precocious Puberty

PURPOSE: The effectiveness of gonadotropin releasing hormone (GnRH) agonist therapy in central precocious puberty (CPP) depends on the suppression of luteinizing hormone (LH) secretion. The purpose of this study was to determine the utility of a single luteinizing hormone measurement after GnRH agonist injection for the therapeutic monitoring of CPP. METHODS: The study included 148 females with CPP who had been treated with GnRH agonist. During the therapy, suppression of their pubertal development was assessed based on their height standard deviation score (SDS), bone age, and pubertal stage. Every six months, their serum LH and follicular stimulating hormone (FSH) levels were measured using immunoradiometric assays. Their estradiol levels were also assayed using radioimmunoassay two hours following GnRH agonist administration. RESULTS: The means of the onset age, bone age, and chronological age were 7.2 +/- 0.93, 10.1 +/- 1.1, and 8.2 +/- 0.94 years, respectively. Eight patients had pathologic intracranial lesions including harmatoma, hydrocephalus, meningitis, astrocytoma, and Rathke's cleft cyst. The basal and peak LH levels were 1.56 +/- 1.1 and 18.2 +/- 12.1 IU/L, respectively. In 39 females with CPP, pubertal development was not sufficiently suppressed even after one year of therapy. The receiver operating characteristic (ROC) curve showed a cutoff value of LH for pubertal suppression of less than 2.5 IU/L. The area under the curve (AUC) was 0.674. CONCLUSION: The cutoff value of 2.5 IU/L for a LH measurement, taken two hours following subcutaneous GnRH agonist injection, is adequate for therapeutic monitoring of females with CPP. This method is both convenient and cost effective.

Changes in the Predicted Adult Height after Gonadotropin-Releasing Hormone Agonist Treatment in Girls with Idiopathic True Precocious Puberty

PURPOSE: We evaluated the effects of the timing of treatment initiation with gonadotropin-releasing hormone agonist (GnRHa) on the change in predicted adult height (PAH) in girls with idiopathic true precocious puberty (TPP). METHODS: Data for this retrospective study were collected on 104 girls with TPP who were treated with GnRHa for 36 months, between January 2002 and March 2012. RESULTS: The PAH SDS differed before and after treatment in all patients (-1.91 +/- 1.47 vs. -1.37 +/- 1.17 after 1 year of treatment, -1.96 +/- 1.58 vs. -0.48 +/- 1.11 after 3 years of treatment) as well as in Group 1 (-2.15 +/- 1.54 vs. -1.51 +/- 1.20 after 1 year of treatment, -2.09 +/- 1.59 vs. -0.55 +/- 1.19 after 3 years of treatment) and Group 2 (-1.57 +/- 1.34 vs. -1.17 +/- 1.12 after 1 year of treatment, -1.50 +/- 1.55 vs. -0.21 +/- 0.74 after 3 years of treatment). This result could be due to improvement in bone age advancement during the treatment. The difference between mid-parental height SDS and PAH SDS was decreased after GnRHa treatment. However, the means of PAH SDS did not surpass the mid-parental height SDS. CONCLUSION: GnRHa treatment can preserve growth potential by slowing bone age progression, resulting in short adult height, but it cannot alter the genetic growth potential.

Efficacy of a Single Luteinizing Hormone Measurement after GnRH Agonist Administration for Therapeutic Monitoring of Girls with Central Precocious Puberty

PURPOSE: The effectiveness of gonadotropin releasing hormone (GnRH) agonist therapy in central precocious puberty (CPP) depends on the suppression of luteinizing hormone (LH) secretion. The purpose of this study was to determine the utility of a single luteinizing hormone measurement after GnRH agonist injection for the therapeutic monitoring of CPP. METHODS: The study included 148 females with CPP who had been treated with GnRH agonist. During the therapy, suppression of their pubertal development was assessed based on their height standard deviation score (SDS), bone age, and pubertal stage. Every six months, their serum LH and follicular stimulating hormone (FSH) levels were measured using immunoradiometric assays. Their estradiol levels were also assayed using radioimmunoassay two hours following GnRH agonist administration. RESULTS: The means of the onset age, bone age, and chronological age were 7.2 +/- 0.93, 10.1 +/- 1.1, and 8.2 +/- 0.94 years, respectively. Eight patients had pathologic intracranial lesions including harmatoma, hydrocephalus, meningitis, astrocytoma, and Rathke's cleft cyst. The basal and peak LH levels were 1.56 +/- 1.1 and 18.2 +/- 12.1 IU/L, respectively. In 39 females with CPP, pubertal development was not sufficiently suppressed even after one year of therapy. The receiver operating characteristic (ROC) curve showed a cutoff value of LH for pubertal suppression of less than 2.5 IU/L. The area under the curve (AUC) was 0.674. CONCLUSION: The cutoff value of 2.5 IU/L for a LH measurement, taken two hours following subcutaneous GnRH agonist injection, is adequate for therapeutic monitoring of females with CPP. This method is both convenient and cost effective.

Growth Status and Body Composition in Children with Central Precocious Puberty and Early Puberty

PURPOSE: The aim of this study was to analyze the growth status and body composition in children with central precocious puberty (CPP ) and early puberty (EP). METHODS: One hundred and five girls (mean age, 7.7 +/- 0.8 years) with early thelarche were included, and a gonadotropin-releasing hormone (GnRH) stimulation test was performed. We divided the subjects into two groups based on peak leuteinizing hormone (LH) levels; peak LH level > or = 5 mIU/L was diagnosed as CPP (n = 49), and peak LH level < 5 mIU/L was diagnosed as EP (n = 56). Patients' height, weight, and body composition were measured, and their body mass index (BMI) and Z-score were calculated. Fat mass (FF), fat-free mass (FFM), fat mass index (FMI), fat-free mass index (FFMI), and percent of body fat (PBF) were compared. RESULTS: Height, weight, and height Z-score were not significantly different between the CPP and EP groups. Weight Z-score (P = 0.045), BMI (P = 0.015), BMI Z-score (P = 0.006), PBF (P = 0.018), FM (P = 0.047), and FMI (P = 0.017) in the EP group were significantly greater than in the CPP group. CONCLUSION: In EP girls, increased BMI was attributed to increased FMI. Body-composition analysis might be a useful tool in monitoring life style modification during pubertal growth.

Changes in the Predicted Adult Height after Gonadotropin-Releasing Hormone Agonist Treatment in Girls with Idiopathic True Precocious Puberty

PURPOSE: We evaluated the effects of the timing of treatment initiation with gonadotropin-releasing hormone agonist (GnRHa) on the change in predicted adult height (PAH) in girls with idiopathic true precocious puberty (TPP). METHODS: Data for this retrospective study were collected on 104 girls with TPP who were treated with GnRHa for 36 months, between January 2002 and March 2012. RESULTS: The PAH SDS differed before and after treatment in all patients (-1.91 +/- 1.47 vs. -1.37 +/- 1.17 after 1 year of treatment, -1.96 +/- 1.58 vs. -0.48 +/- 1.11 after 3 years of treatment) as well as in Group 1 (-2.15 +/- 1.54 vs. -1.51 +/- 1.20 after 1 year of treatment, -2.09 +/- 1.59 vs. -0.55 +/- 1.19 after 3 years of treatment) and Group 2 (-1.57 +/- 1.34 vs. -1.17 +/- 1.12 after 1 year of treatment, -1.50 +/- 1.55 vs. -0.21 +/- 0.74 after 3 years of treatment). This result could be due to improvement in bone age advancement during the treatment. The difference between mid-parental height SDS and PAH SDS was decreased after GnRHa treatment. However, the means of PAH SDS did not surpass the mid-parental height SDS. CONCLUSION: GnRHa treatment can preserve growth potential by slowing bone age progression, resulting in short adult height, but it cannot alter the genetic growth potential.