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.

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.

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.

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.

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.

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