Gonadotropin-Dependent Precocious Puberty: Single-Center Experience From Western India

Objective: To describe the characteristics of gonadotropin-dependent precocious puberty (GDPP) in Indian children. Methods: Clinical profiles of GDPP (n=78, 61 females) and premature thelarche (n=12) from a single center in Western India were retrospectively studied. Results: Pubertal onset was earlier in boys than girls (29 vs 75 months, respectively; P=0.008). The basal luteinizing hormone (LH) was ?0.3 mIU/mL, except 18% of GDPP girls. At 60 minutes after GnRHa-stimulation, all patients (except one girl) had LH ?5 mIU/mL. The GnRHa-stimulated LH/FSH ratio was ?0.34 at 60 minutes in girls with GDPP unlike premature thelarche. Only one girl had an allergic reaction to long-acting GnRH agonist. Among GnRH agonist-treated girls (n=24), the predicted final adult height was -1.67±1.5 SDS, whereas the attained final height was -0.25±1.48 SDS. Conclusion: We establish the safety and efficacy of long acting GnRH agonist therapy in Indian children with GDPP. The 60-minute stimulated serum LH/FSH of ?0.34 differentiated GDPP from premature thelarche.

Detection of glucolipid metabolism and sex hormones among female children with precocious puberty / 预防医学

Objective@#To investigate glucolipid metabolism and sex hormone levels among female children with precocious puberty, so as to provide insights into the illustration of pathogenesis of precocious puberty. @*Methods@#A total of 110 female children with precocious puberty treated in Huzhou Maternity & Child Health Care Hospital during the period from May 2019 through May 2021 were enrolled and assigned into the idiopathic central precocious puberty (ICPP) group and the premature thelarche alone (PT) group according to the results of gonadotropin-releasing hormone stimulation tests. The follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), testosterone (T), prolactin (PRL), fasting insulin (FINS), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB) andlipoprotein-a [Lp (a)] levels were detected and compared in children between the ICPP and PT groups.@*Results@#There were 70 cases in the ICCP group, with a mean age of (7.62±1.13) years and a mean body mass index (BMI) of (16.30±2.21) kg/m2 and 40 cases in the PT group, with a mean age of (7.42±1.04) years and a mean BMI of (16.70±2.10) kg/m2 (both P>0.05). The FSH [(3.58±0.80) vs. (2.22±0.75) IU/L], LH [(1.40±0.28) vs. (0.25±0.12) IU/L], P [(0.29±0.12) vs. (0.18±0.08) ng/mL], E2 [(23.28±4.23) vs. (15.54±2.75) pg/mL] and PRL [(8.56±1.93) vs. (6.54±1.50) ng/mL], FINS [(13.24±2.54) vs. (11.10±2.49) U/L], TG [(1.36±0.17) vs. (1.21±0.27) mmol/L], LDL-C [(3.10±0.44) vs. (2.81±0.60) mmol/L], ApoB [(0.78±0.19) vs. (0.71±0.14) g/L] and Lp (a) levels [(252.45±52.10) vs. (202.60±41.28) mg/L] were significantly higher in the ICPP group than in the PT group (all P<0.05).@*Conclusion@#The levels of sex hormones and glucolipid metabolism parameters are significantly higher among female children with ICPP than among those with PT.

Basal serum luteinizing hormone value as the screening biomarker in female central precocious puberty

PURPOSE: Precocious puberty refers to the development of secondary sex characteristics before ages 8 and 9 years in girls and boys, respectively. Central precocious puberty (CPP) is caused by premature activation of the hypothalamus-pituitary-gonadal (HPG) axis and causes thelarche in girls before the age of 8. A gonadotropin-releasing hormone (GnRH) stimulation test is the standard diagnostic modality for diagnosing CPP. However, the test cannot always be used for screening because it is expensive and time-consuming. This study aimed to find alternative reliable screening parameters to identify HPG axis activation in girls <8 years old (CPP) and for girls 8–9 years old (early puberty, EP). METHODS: From January 2013 to June 2015, medical records from 196 girls younger than 9 years old with onset of breast development were reviewed, including 126 girls who had a bone age (BA) 1 year above their chronological age. All patients underwent a GnRH stimulation test, and 117 underwent pelvic sonography. The girls were divided into 4 groups based on age and whether the GnRH stimulation test showed evidence of central puberty. Subanalyses were also conducted within each group based on peak luteinizing hormone (LH) level quartiles. RESULTS: Basal serum LH level was the most sensitive marker for screening CPP and EP. The cutoff values were 0.245 IU/L for CPP under 8 years old (P=0.049, area under the curve [AUC]=0.764, 88% sensitivity, 48% specificity) and 0.275 IU/L for EP between 8–9 years old (P=0.005, AUC=0.813, 79% sensitivity, 77% specificity). Peak LH level decreased as BMI z-score among subgroups increased when there was no difference in BA; however, higher BA eliminated this effect. CONCLUSION: Basal serum LH level is a useful screening parameter for diagnosing CPP and EP in girls. Peak LH levels were lower with increasing BMI z-score, although older BA eliminated this effect.

THE PUBERTY PROFILE OF FEMALE ADOLESCENTS IN CHERAS, MALAYSIA

@#Objectives: The objectives of our study were to determine the mean age of onset of thelarche and menarche, to determine the ages of each stage of puberty and to investigate if there are any ethnic differences in these ages amongst female adolescents in Kuala Lumpur, Malaysia. Methods: This was a cross-sectional study involving three secondary schools in Cheras, Kuala Lumpur. A total of 730 students were recruited via stratified random sampling. Self-administered survey forms on menstruation and puberty were used. Results: Out of 730 recruited respondents, 385 (52.74%) completed the survey and informed consents were obtained from their parents/legal guardians. Our respondents’ ages ranged between 13 to 17 years old with the median (IQR) age of 14.00(2.00) years. With regards to ethnicity, 329 (85.50%) were Malay, 46 (11.90%) were Chinese, 9 (2.30%) were Indian and 1(0.30%) was a Bajau. The mean age for breast development (thelarche) and menarche were 11.72 ±1.10 and 11.97±1.11 years respectively. The majority, 363 (94.30%), out of 385 respondents had attained menarche. There appeared to be a later onset of puberty amongst Malays comparatively. Conclusion: The mean ages of pubertal onset and menarche amongst female adolescents in the Cheras area are similar to those reported worldwide.

Clinical and Laboratory Findings and Ultrasound Assessment in the Differential Diagnosis of Central Precocious Puberty and Premature Thelarche / 医学研究杂志

Objective The differential diagnosis of female precocious puberty (PP) and premature breast development (PT) was made by ultrasound and related hormone levels,so as to provide the basis for clinical diagnosis.Methods In this study,from 2015 to 2016 due to early breast enlargement (age ＜ 8 years) to our hospital pediatric patients with children,according to the diagnostic criteria were divided into PP group and PT group.Ultrasonography was performed on all patients and graded according to the criteria.At the same time,the levels of clinical and hormones were compared between the two groups.ROC analysis was used to identify the significant differences.Results In this study,a total of 60 cases of female children,including PP and PT children were 30 cases.Ultrasonic breast grading was positively correlated with age,BA,BD,LH level,FSH level and E2 level,but there was no correlation between BA/CA.There was no statistical difference between the breast ultrasound and the breast diameter (P ＜ 0.05).The levels of LH and FSH,basal LH/ FSH,LF and FSH peak and LH/FSH peak in the PP group were significantly higher than those in the PT group (P ＜ 0.05).The ROC analysis found 100％ sensitivity and 85％ specificity for LH/FSH peak ＞0.25 for diagnosis of PP,with a 72％ sensitivity and a specificity of 65％ for basal LH ＞ 0.1 mIU/ml.The SHBG level was the only one that did not overlap [PP:80.6 (62.3-95.4) vs PT:114.5 (107.6-121.5)].There was no significant difference in kisspeptin,leptin and neurokinin B between the two groups (P ＞ 0.05).Conclusion Breast ultrasound by grading and measurement of breast buds can be effective in evaluating the development of female precocious puberty breast development,but can not identify PP and PT.The study found that SHBG concentration and peak ratio of LH/FSH can effectively identify PP and PT,but kisspeptin,neurokinin B and leptin is not enough to identify PP and PT.

Age of Onset of Puberty in Apparently Healthy School Girls from Northern India.

Objective: To determine the age of pubertal onset and menarche in school-going girls, and to assess the impact of obesity on pubertal timing. Design: Cross-sectional Setting: Seven schools across Delhi, India. Participants: 2010 school girls, aged 6-17 years Methods: Anthropometric measurement and pubertal staging was performed for all subjects. Menarche was recorded by ‘status quo’ method. Body mass index was used to define overweight/obesity. Serum gonadotropins and serum estradiol were measured in every sixth participant. Main outcome measure: Age at thelarche and menarche—analyzed for entire cohort and stratified based on body mass index. Results: Median (95% CI) ages of thelarche, pubarche and menarche were 10.8 (10.7-10.9) y, 11.0. y (10.8-11.2) y and 12.4 y (12.2-12.5) y. Overweight/obese girls showed six months earlier onset of thelarche and menarche than those with normal BMI (P<0.05). Serum gonadotropins did not vary significantly in overweight/obese subjects. Conclusion: The study provides the normative data for pubertal growth in Indian girls. Pubertal onset occurs earlier in overweight and obese girls.

Telarquia precoz en la niñez: causas y estudio / Premature thelarche in childhood: causes and study

Se define Telarquía Precoz como la aparición del botón mamario antes de los ocho años en ausencia de otros signos de pubertad. En los primeros años de vida puede ser secundaria al fenómeno de la minipubertad, mientras que en la etapa escolar podría ocurrir debido a la interacción entre disruptores endocrinológicos y la obesidad. Una parte importante se mantiene estacionaria o revierte, mientras que un pequeño porcentaje puede evolucionar hacia la pubertad precoz. Se debe realizar una anamnesis y examen físico adecuado buscando otros signos puberales, una buena curva de crecimiento y puede complementarse con imágenes y con un seguimiento para intentar determinar aquellas pacientes que evolucionarán hacia la pubertad precoz.

Premature thelarche is defined as the breast bud appearance before eight years, without other signs of puberty development. During the first years of life it can be secondary to the minipuberty phenomenon, while during school period it's usually secondary to the interaction between endocrine disruptors and obesity. Although most of cases remain stable or regresses, a small percentage can evolve to precocious puberty. An appropriate clinical history and physical exam looking for other signs of precocious puberty must be held, complemented with the correspondent follow up and images studies, in order to diagnose patients that will evolve to precocious puberty.

Relationship of endocrine disruptors (bisphenol A and diethyl phthalate) with premature thelarche in infant girls / 第二军医大学学报

Objective To study the relationship of endocrine disruptors (EDCs) with premature thelarche in the 0-3 years old baby girls. Methods A total of 60 infant girls diagnosed with premature thelarche were selected as the case group in Children’s Hospital Affiliated to Chongqing Medical University between August 2013 and June 2014, and another 60 healthy girls were included into a control group. Their parents were asked to finish questionnaires and each participants underwent B ultrasonic examination. The serum samples were obtained from both groups by professional doctors to examine the levels of estradiol, follicle stimulation hormone, luteinizing hormone, bisphenol A and diethyl phthalate. Results There were no significant differences in the age, FSH or LH levels between the case group and the control group (P=0.745, 0.721 and 0.195, respectively); the level of E2 in the case group was significantly higher than that in the control group (P=0.017); bisphenol A and diethyl phthalate levels in the case group were significantly higher than those in the control group ([272.9±101.3] μg/L vs [21.8±18.4] μg/L, P=0.000; [0.8±0.3] mg/L vs [0.3±0.1] mg/L,P=0.000). There was a positive correlation between the bisphenol A and diethyl phthalate in the case group (r=0.061, P=0.002), but not in the control group(r=0.302,P=0.102). There was no significant correlation between the sex hormone and the two EDCs (bisphenol A or diethyl phthalate) (P>0.05). Conclusion Premature thelarche in the infant girls between 0 and 3 years old is associated with serum estrogen level, bisphenol A and ethyl phthalate levels, and there is no relationship between genetic factors and environmental factors.

Hormonas exógenas en carne de pollo, creencias populares y evidencias científicas con relación a la crianza de aves de corral / Exogenous hormones in chicken, popular beliefs and scientific evidence regarding poultry breeding

Existe la creencia popular de que el pollo habitualmente consumido contiene hormonas u otras sustancias para acelerar su crecimiento. Llamativamente este concepto con frecuencia es sostenido y validado por médicos y especialistas de la Nutrición. Objetivos: analizar la información científica disponible para evaluar si existen evidencias que avalen la creencia de la utilización de hormonas en los pollos de consumo habitual, con el objeto de acelerar su crecimiento. Materiales y métodos: se realizó una exhaustiva búsqueda bibliográfica que incluyó el origen de esta creencia, la evolución genética del pollo actual, los métodos de crianza, la legislación nacional e internacional y los controles que realizan las autoridades sanitarias para la evaluación de la carne aviar. Asimismo, se efectuó una revisión para conocer si existe evidencia científica sobre los efectos fisiopatológicos que algunos profesionales de la salud atribuyen al consumo de pollo, como ser mayor incidencia de ginecomastia, pubertad precoz en ni- ños, telarca precoz en niñas, aumento de incidencia de cáncer de mama, así como recidivas y/o metástasis del mismo. Resultados: en la búsqueda realizada no se ha hallado bibliografía a nivel nacional o internacional que avale la aplicación de hormonas a los pollos. La legislación nacional vigente lo prohíbe taxativamente. No se han encontrado en los controles realizados por el Servicio Nacional de Sanidad Animal y Calidad Agroalimentaria (SENASA) en la República Argentina, existencia de hormonas exógenas en pollos en los últimos 10 años. Además no se ha encontrado evidencia científica de que el consumo de carne de pollo y/o sus derivados provoque o aumente el riesgo de pubertad precoz en niños y telarca precoz en niñas, ginecomastia en hombres y cáncer de mama en mujeres...

There is the popular belief that hormones or other substances are usually administered to chicken to enhance its growth. Remarkably, this concept is frequently supported and validated by physicians and nutrition specialists. Objectives: to analyze the scientific information available and evaluate if there is supporting evidence to prove that hormones are administered to chicken to enhance growth. Material and methods: a comprehensive bibliographic research was performed including the origin of the myth, the current genetic evolution of chicken, breeding methods, national and international legislation and health controls on the evaluation of poultry meat. Moreover, a review was conducted to know if there is scientific evidence regarding the physiopathology effects that some healthcare professionals attribute to chicken consumption, such as higher incidence of gynecomastia, precocious puberty in boys, precocious thelarche in girls, increased incidence of breast cancer, as well as recurrence and/or metastasis. Results: there is no national and international literature supporting hormone administration to chickens and it is prohibited by the effective national laws. Controls and monitoring performed by the Argentine Food Safety and Quality Service (SENASA) found no exogenous hormones in poultry meat in the Argentine Republic over the last 10 years. No literature was found supporting the belief that poultry meat consumption causes or increases precocious puberty in boys and premature thelarche in girls, gynecomastia in men and breast cancer in women. Conclusions: poultry for consumption has never received hormones of any type; therefore, it is a popular misconception with no scientific support.

Significance of Kisspeptin levels in diagnosis and therapeutic evaluation of idiopathic central precocious puberty in girls / 中华实用儿科临床杂志

Objective To explore the significance and value of Kisspeptin in the diagnosis and therapeutic evaluation for idiopathic central precocious puberty(ICPP) in girls.Methods Twenty-four girls with ICPP and 21 girls with premature thelarche(PT) who were hospitalized in the Children's Hospital of Jiangxi Province from Jun.2012 to Jan.2013 were selected as ICPP group and PT group,and 25 healthy girls were selected as healthy control group.The coagulation vein blood in ICPP girls before treatment and after 6 months treatment and PT girls and healthy girls were collected,and enzyme linked immunosorbent assay was used to detect the plasma Kisspeptin level,and t test was used to analyze the differences among the 4 groups.Results The Kisspeptin level of girls with ICPP [(1.80 ± 0.13) μg/L]was apparently higher than that of PT groups [(1.41 ± 0.10) μg/L] and healthy control group[(1.39 ± 0.13) μg/L],and the differences were statistically significant (t =10.974,14.787,all P =0.000).However,the difference of Kisspeptin between PT group and healthy control group was not statistically significant(t =10.970,P =0.095).In addition,the Kisspeptin level of ICPP girls who undewent 6-month treatment [(1.49 ± 0.15) μg/L] was significantly lower than that before treatment,and the difference was statistically significant (t =10.80,P ＜ 0.05) ;but,compared with PT group and healthy control group,there was no significant difference (t =6.32,P =0.060 ; t =7.44,P =0.214).Conclusions Kisspeptin level is related with pubertal development,and it can be used as an important evidence in ICPP diagnosis and an important parameter in ICPP therapeutic evaluation.

Telarca precoz / Precocious thelarche

Introducción: telarca precoz está definida por la presencia de desarrollo mamario antes de los ocho años de edad, en ausencia de otros signos clínicos de maduración sexual. Material y métodos: se estudiaron a las niñas menores de ocho años de edad, atendidas en el consultorio de endocrinología pediátrica del Hospital Santa Cruz, durante cinco años, que acudieron a consulta por presentar telarca precoz. Resultados: se atendieron 119 niñas; el 70% de ellas era menor de dos años; la mayoría (86% del total) presentaba talla adecuada para la edad; se diagnosticó sobrepeso en el 33% de las pacientes (n=39) y obesidad en el 10% de los casos (n=12); la edad ósea se encontró acorde a la edad cronológica en 108 niñas (91% del total), siendo la ecografía ginecológica normal al igual que los niveles plasmáticos de LH y FSH (rango prepuberal), prolactina, estradiol y TSH, en 116 pacientes (97% de los casos). Se diagnosticó pubertad precoz en tres niñas y 116 pacientes (97%) presentaron telarca precoz. Conclusión: la telarca precoz no siempre es una condición autolimitada; es importante controlar periódicamente a las niñas afectadas.

Introduction: the precocious thelarche is defined by the presence of breast development before eight years of age, in the absence of other clinical signs of sexual maturation. Methods: we studied girls under eight years old, attended at the pediatric endocrinology clinic of the Hospital Santa Cruz, during five years, who went to the doctor because of thelarche. Results: we attended 119 girls, 70% of them were younger had two years, most (86% of total) had age appropriate stature, overweight was diagnosed in 33% of patients (n=39) and obesity in 10% of the cases (n=12), bone age was found according to chronological age in 108 girls (91% of total), with normal gynecological ultrasound as plasma levels of LH and FSH (prepubertal range), prolactin, estradiol and TSH in 116 patients (97% of cases). Precocious puberty was diagnosed in three girls; 116 patients (97% of the total) had precocious thelarche. Conclusions: the precocious thelarche is not always a self-limited condition, so it is important to periodically check the girls affected.

Diagnosis and constitutional and laboratory features of Korean girls referred for precocious puberty / 소아과

PURPOSE: Precocious puberty is defined as breast development before the age of 8 years in girls. The present study aimed to reveal the diagnosis of Korean girls referred for precocious puberty and to compare the constitutional and endocrinological features among diagnosis groups. METHODS: The present study used a retrospective chart review of 988 Korean girls who had visited a pediatric endocrinology clinic from 2006 to 2010 for the evaluation of precocious puberty. Study groups comprised fast puberty, true precocious puberty (PP), pseudo PP, premature thelarche, and control. We determined the height standard deviation score (HSDS), weight standard deviation score (WSDS), and body mass index standard deviation score (BMISDS) of each group using the published 2007 Korean growth charts. Hormone tests were performed at our outpatient clinic. RESULTS: The PP groups comprised fast puberty (67%), premature thelarche (17%), true PP (15%), and pseudo PP (1%). Advanced bone age and levels of estradiol, basal luteinizing hormone (LH), and peak LH after gonadotropin-releasing hormone stimulation testing were significantly high in the fast puberty and true PP groups compared with the control group. HSDS, WSDS, and BMISDS were significantly higher in the true PP group than in the control group (P<0.05). CONCLUSION: The frequent causes of PP were found to be fast puberty, true PP, and premature thelarche. Furthermore, BMISDS were significantly elevated in the true PP group. Therefore, we emphasize the need for regular follow-up of girls who are heavier or taller than others in the same age group.

Gonadotropin-releasing Hormone Stimulation Test for Precocious Puberty / 대한진단검사의학회지

BACKGROUND: Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard to identify central precocious puberty (CPP). This test requires multiple blood samples at different time points to measure gonadotropin levels, and is therefore expensive, time-consuming, and uncomfortable for patients. We aimed to simplify the GnRH stimulation test to require fewer blood samples. METHODS: A study of 166 girls with precocious puberty was undertaken. Blood samples were obtained at 0, 15, 30, 45, 60, 90, and 120 min after GnRH administration, and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. For each parameter, the sensitivities and specificities were estimated and ROC curves were constructed. RESULTS: One hundred and twenty-eight patients (77.1%) were diagnosed for CPP. Peak LH levels were achieved 30 min after GnRH stimulation in patients with CPP. Further, 98.4% of the 45-min samples were diagnostic for CPP, and the cumulative frequency of LH values of > or =5 IU/L was 100% at 45 min. Using this cut-off value for LH, the ROC curve for LH at 45 min showed the highest sensitivity (98.4%) and specificity (100%) in the diagnosis of CPP. CONCLUSIONS: Values of LH measured from a single blood sample obtained at 45 min in the GnRH stimulation test may be adequate for the diagnosis of CPP. Two samples, taken at 30 and 45 min after stimulation, were able to accurately diagnose CPP in 100% of the patients in this study.

Plasma kisspeptin levels in normal female pubertal stages and in girls with idiopathic central precocious puberty / 中华内分泌代谢杂志

Objective To investigate the pattern of plasma kisspeptin levels in normal female during various pubertal Tanner stages and the girls with idiopathic central precocious puberty(ICPP) or with premature thelarche(PT), and to evaluate the significance of detecting plasma kisspeptin levels as a new criterion for early differentiation between ICPP and PT.Methods Each study group of normal pubertal females with Tanner stage Ⅰ to Ⅴ comprised 16 to 19 individuals.The levels of plasma kisspeptin were also detected in girls with ICPP(n= 10)or PT(n = 12).The plasma kisspeptin levels were detected by enzyme-linked immunosorbent assay (ELISA).Results The level of kisspeptin was significantly higher in ICPP group than in that of PT group [(1.73±0.23 vs1.43±0.29) ng/ml, P＜0.05].Among the normal pubertal females, the level of kisspeptin decreased gradually from Tanner stage Ⅱ to Tanner stage Ⅴ, being highest in Tanner stage Ⅱ [(1.73±0.22) ag/ml] ,lower in stage Ⅳ and Ⅴ than in stage Ⅰ and Ⅲ (P＜0.01).Conclusions Plasma kisspeptin level was the highest during Tanner stage Ⅱ in normal female pubertal development.It is significant to detect plasma kisspeptin level for the differential diagnosis of ICPP and PT.

The Auxological and Hormonal Differences in Girls with Atypical Thelarche and Central Precocious Puberty / 대한소아내분비학회지

PURPOSE:We compared anthropomorphic measures and hormone levels in girls with atypical thelarche (AT) and central precocious puberty (CPP) and tried to find out factors discriminating AT from CPP. METHODS:We analyzed clinical and laboratory data of 62 girls with precocious breast development from May 2004 to May 2008 at Kangnam St. Marys Hospital. Immunoradiometeric assay (IRMA) was used to estimate gonadotropins and growth related hormones. CPP was diagnosed if peak luteinizing hormone (LH) level was >6.9 IU/L after gonadotropin hormone releasing hormone (GnRH) stimulation test. A multiple logistic regression analysis and the area under the receiver operating characteristics curve (AUC) were used to analyse the prediction capacity of variable factors to diagnose CPP. RESULT:The basal LH levels (P=0.001), IGF-I levels (P=0.049) and the peak LH levels (P<0.001) in GnRH-stimulation test in girls with CPP were higher than those with AT. Girls with AT had a lower degree of breast maturation than girls with CPP (P=0.001). A multivariate logistic regression model including the basal LH levels and IGF-I levels revealed a strong relation of the basal LH levels to CPP [OR:2.7, 95% confidence interval (CI): 1.1-6.7, P=0.035]. The AUC for basal LH levels showed prediction capacity of basal LH levels to diagnose CPP [AUC: 0.70, 95% CI: 0.57-0.81, P=0.009]. The statistically ideal cut-off value of basal LH levels to discriminate CPP from AT was 2.66 IU/L (sensitivity 40%, specificity 98%) and the clinically meaningful cut-off value was 1.86 IU/L (sensitivity 70%, specificity 62%). CONCLUSION:These results suggest that the basal LH level using IRMA could be a useful parameter discriminating AT from CPP. Further study with larger number of subjects will be needed.

Update on the etiology, diagnosis and therapeutic management of sexual precocity: [review]

Precocious puberty is defined as the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Gonadotropin-dependent precocious puberty (GDPP) results from the premature activation of the hypothalamic-pituitary-gonadal axis and mimics the physiological pubertal development, although at an inadequate chronological age. Hormonal evaluation, mainly through basal and GnRH-stimulated LH levels shows activation of the gonadotropic axis. Gonadotropin-independent precocious puberty (GIPP) is the result of the secretion of sex steroids, independently from the activation of the gonadotropic axis. Several genetic causes, including constitutive activating mutations in the human LH-receptor gene and activating mutations in the Gs protein a-subunit gene are described as the etiology of testotoxicosis and McCune-Albright syndrome, respectively. The differential diagnosis between GDPP and GIPP has direct implications on the therapeutic option. Long-acting gonadotropin-releasing hormone (GnRH) analogs are the treatment of choice in GDPP. The treatment monitoring is carried out by clinical examination, hormonal evaluation measurements and image studies. For treatment of GIPP, drugs that act by blocking the action of sex steroids on their specific receptors (cyproterone, tamoxifen) or through their synthesis (ketoconazole, medroxyprogesterone, aromatase inhibitors) are used. In addition, variants of the normal pubertal development include isolated forms of precocious thelarche, precocious pubarche and precocious menarche. Here, we provide an update on the etiology, diagnosis and management of sexual precocity.

A puberdade precoce é definida como o desenvolvimento dos caracteres sexuais secundários antes dos 8 anos nas meninas e dos 9 anos nos meninos. A puberdade precoce dependente de gonadotrofinas (PPDG) resulta da ativação prematura do eixo hipotálamo-hipófise-gonadal e mimetiza o desenvolvimento puberal fisiológico, embora em idade cronológica inadequada. A avaliação hormonal, principalmente os valores de LH basal e após estímulo com GnRH exógeno confirmam a ativação do eixo gonadotrófico. A puberdade precoce independente de gonadotrofinas (PPIG) é o resultado da secreção de esteróides sexuais independentemente da ativação do eixo gonadotrófico. Diversas causas genéticas, incluindo mutações ativadoras constitutivas no gene do receptor do LH humano e mutações ativadoras no gene da subunidade a da proteína G representam as etiologias da testotoxicose e da síndrome de McCune Albright, respectivamente. O diagnóstico diferencial entre PPDG e PPIG tem implicação direta na opção terapêutica. Análogos de GnRH de ação prolongada é o tratamento de escolha da PPDG. A monitorização do tratamento da PPDG é realizada pelo exame clínico, avaliação hormonal e exames de imagem. Para o tratamento da PPIG, são usadas drogas que bloqueiam a ação dos esteróides sexuais nos seus receptores específicos (ciproterona, tamoxifeno) ou bloqueiam a sua síntese (cetoconazol, medroxiprogesterona e inibidores da aromatase). Variantes do desenvolvimento puberal normal incluem as formas isoladas de telarca, pubarca e menarca precoces. Nesta revisão, atualizamos a etiologia, o diagnóstico e tratamento da precocidade sexual.

Premature thelarche: clinical and laboratorial assessment by immunochemiluminescent assay

In order to establish cut-off limits and to distinguish isolated premature thelarche (IPT) from precocious puberty (PP), we evaluated data from 79 girls with premature thelarche, comparing basal and stimulated LH and FSH serum concentrations with those from 91 healthy girls. A GnRH stimulation test was performed in 10 normal girls and in 42 with premature thelarche. Comparison among groups was performed by Kruskal-Wallis and Dunn’s tests. LH values were significantly greater in girls with IPT than in control groups. Basal gonadotropin concentrations were higher in patients with PP than in controls, but not different from patients with IPT. Peak LH levels after GnRH stimulation distinguished those two groups, with a cut-off value of 4.0 IU/L, but still with minimal overlap. In conclusion, a girl with premature thelarche and LH peak value above 4.5 IU/L has, indeed, PP, but values between 3.5 and 4.5 IU/L point to careful follow-up.

Com o objetivo de estabelecer o valor de corte e distinguir telarca precoce isolada (TPI) de puberdade precoce (PP), avaliamos 79 meninas com telarca precoce, comparando as dosagens basais e pós-estímulo de LH e FSH com grupo-controle. O teste de estímulo com GnRH foi realizado em 10 meninas normais e em 42 com telarca precoce. Os testes de Kruskal-Wallis and Dunn foram usados na comparação dos grupos. Os níveis de LH foram significativamente mais elevados no grupo com TPI, quando comparados com controles. As gonadotrofinas basais foram mais elevadas naquelas com PP que nos controles, mas não diferiram do grupo com TPI. O pico de LH após GnRH distinguiu estes dois grupos, com valor de corte de 4,0 UI/L, apesar de pequena sobreposição. Concluímos que uma menina com telarca precoce e LH pós-estímulo acima de 4,5 UI/L apresenta PP, mas valores entre 3,5 e 4,5 UI/L requerem seguimento cuidadoso.

Clinical and Endocrinologic Characteristics of Children Referred for Precocious Puberty / 대한소아내분비학회지

PURPOSE: Precocious puberty is defined as the onset of secondary sexual characteristics before 8 year of age in girls and 9 year in boys. The purpose of this study is to analyze the spectrum of diagnoses made in a consecutive group of children referred for signs of precocious puberty and evaluate the clinical and endocrinologic characteristics of patients with precocious puberty. METHODS: The charts of all 948 children referred for evaluation of signs of precocious puberty between January 2003 and June 2007 in several referral centers were reviewed. Clinical features including age of onset, presenting symptoms, yearly growth rate, bone age advancement, weight, height, and body mass index were analysed and endocrine investigations included basal and gonadotropin releasing hormone (GnRH)-stimulated levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) as well as sex hormones. RESULTS: Of the 948 children referred for signs of precocious puberty, 915 (96.5%) were female and 33 (3.5%) were male. The final diagnoses made were early puberty (39%), premature thelarche (31%), true precocious puberty (27%) and precocious pseudopuberty (1%). The increases in yearly growth rate and bone age advancement were significant in true precious puberty group (P<0.05). The height and weight standard deviation score were significantly increased in true precious puberty and premature thelarche group compared to the average level according to gender and age (P<0.05). Endocrinologic studies showed that the level of basal LH, basal estradiol and GnRH-stimulated peak LH, peak FSH, peak LH/basal LH, peak FSH/basal FSH, peak LH/peak FSH ratio was all significantly higher in true precicous puberty group and early puberty group when compared to premature thelarche group (P<0.05). Neurogenic true precocious puberty among true precocious puberty was more common in boys (3 out of 7, 42.8%) than in girls (27 out of 253, 10.7%). Endocrinologic studies did not show any difference between idiopathic precocious puberty and neurogenic precocious puberty. CONCLUSION: The result of this study showed the proportion of true precocious puberty among the children referred for early pubertal signs was rather high. Collectively assessing all available data including detailed history, growth records, physical findings, laboratory studies and radiological imaging is important in the evaluation of a child with concerns of early pubertal maturation. Foregoing extensive studies regarding incidence and causes of true precocious puberty should be needed.

Clinical and Laboratorial Assessment for Identifying Isolated Premature Thelarche and Central Precocious Puberty / 实用儿科临床杂志

3-8 years old group(group C2) with 50 cases] were detected.A gonadotropin releasing hormone analogue(GnRHa) stimulation test was performed in 140 girls with IPT.The 140 girls were divided into 3 groups:IPT group,CPP group,and peripheral precocious puberty group(PPP group).Kruskal-Wallis and Mann-Whitneg tests were performed on the data between every groups.Results For basal LH levels,there were significant diffe-rences between IPT1 group and group C1,among IPT2 group,CPP group and group C2(Pa0.05).For peak LH/FSH ratios,there was significant difference between IPT2 group and CPP group(P