Constitution of children with idiopathic central precocious puberty and rapidly progressive early development / 国际中医中药杂志

Objective:Exploratory study on the relationship between TCM syndrome types, TCM constitution and clinical symptoms of idiopathic central precocious puberty children and rapidly progressive early development children in Shanghai, so as to provide a basis for early intervention and syndrome differentiation and treatment.Methods:A cross-sectional study and retrospectively enrolled. Through questionnaire survey, the basic information, clinical symptoms and TCM constitution of children diagnosed with idiopathic central precocious puberty and rapidly progressive early development were collected from the Pediatric Endocrinology Clinic of Affiliated Shuguang Hospital of Shanghai University of Traditional Chinese Medicine from July to August 2022, and the correlation between the distribution, differentiation and clinical symptoms of TCM constitution in children with idiopathic central precocious puberty and children with rapidly progressive precocious puberty in Shanghai were explored through data analysis.Results:① Fast progressive early development children with higher BMI and age than idiopathic central precocious puberty were statistically significant ( P<0.05), and no significant difference in the sex composition ratio between the two groups. ② Among children with idiopathic central precocious puberty and children with rapid progressive early development, the proportion of liver depression fire syndrome was the highest, 59.15% (42/71) and 46.51% (60/129) respectively, and the proportion of Qi depression was the highest, 35.21% (25/71) and 36.43% (47/129) respectively. However, there was no significant difference in the TCM syndrome types and physical distribution of the two groups. ③ The TCM syndrome types of 200 precocious children weres correlated with physical distribution, among which Yin deficiency fire flourishing syndrome was significantly associated with Yin deficiency, liver stagnation fire syndrome was significantly correlated with qi depression, and phlegm dampness obstruction syndrome was significantly correlated with phlegm dampness and Yang deficiency ( P<0.01). ④ A total of 200 children with precocious puberty were more female than male, male BMI was higher than female, and the BMI of children with precocious puberty was higher than other syndrome types, and the differences were statistically significant ( P<0.01). Liver stasis fire syndrome was the highest proportion between boys and girls, but there was no obvious difference in TCM syndrome types between different genders. The highest proportion of breast pain in clinical symptoms was 22.19% (69/311). Conclusion:Children with idiopathic central precocious puberty and rapidly progressive early development children have differences in age and BMI, with no obvious difference in gender composition, TCM syndrome type and physical distribution, but there is a correlation between TCM syndrome type and physical constitution of precocious puberty children.

Study on the Distribution Characteristics of Traditional Chinese Medicine Syndrome Types in Girls with Idiopathic Central Precocious Puberty from Hainan Province / 广州中医药大学学报

Objective To investigate the distribution characteristics of traditional Chinese medicine(TCM)syndromes in girls with idiopathic central precocious puberty(ICPP)from Hainan province.Methods A total of 216 cases of ICPP girls admitted to Hainan Women and Children's Medical Centre from January 2019 to December 2021 were retrospectively collected.The frequency statistics and grading of TCM syndromes in the included ICPP girls were carried out,and the distribution characteristics of TCM syndromes were discussed on the basis of the analysis of the three TCM syndrome types of yin deficiency and fire exuberance syndrome,qi and blood insufficiency syndrome and incoordination between heart and kidney syndrome.Results(1)The age of ICPP onset in 216 girls were between 4 and 10 years old,with an average onset age of(7.15±1.06)years.The highest incidence rate of ICPP was found in the girls aged over 7 years old while less than 8 years old,which was 49.54%.(2)Of the three TCM syndrome types,yin deficiency and fire exuberance syndrome accounted for the highest proportion(147 cases,68.06%),followed by the qi and blood insufficiency syndrome(41 cases,18.98%)and the incoordination between heart and kidney syndrome(28 cases,12.96%).(3)The common 16 TCM symptoms(frequency＞25.0%)in descending order of frequency were aversion to heat and night sweating,feverish sensation in soles and palms,breast distension and pain,irritability,thready and rapid pulse,dry stools,dry throat and mouth,hot flushes,excessive intake of fat and sweet food,red tongue with less fur,depression,mental weakness,flushed cheeks,insomnia and dreaminess,red tongue with yellow fur,and bitterness and dryness in the mouth.(4)The distribution of the age in ICPP girls with various syndromes was as follows:yin deficiency and fire exuberance syndrome and qi and blood insufficiency syndrome were more common in the ICPP girls aged over 7 years old while less than 8 years old(accounting for 58.50%and 51.22%),and incoordination between heart and kidney syndrome was more common in ICPP girls aged over 8 years old while less than 9 years old(accounting for 89.29%).Conclusion Yin deficiency and fire exuberance syndrome is the common TCM syndrome that accounts for the highest proportion in ICPP girls from Hainan province.The study of the distribution of TCM syndromes in girls with precocious puberty will be helpful for the observation of the early clinical symptoms of precocious puberty and early diagnosis of the disease,and can provide clues and evidence for the clinical diagnosis and medication for girls with ICPP.

Research progress in the relationship between vitamin D deficiency and central precocious puberty in children / 中国儿童保健杂志

Central precocious puberty (CPP) is an endocrine disease of children due to the early onset of hypothalamic-pituitary-gonadal axis function. This leads to increased secretion of gonadotropin release impulse, causing the development of internal and external genitalia and the presentation of secondary sex characteristics. Studies have found that the onset of CPP in children may be related to vitamin D deficiency. Vitamin D, affected by sunlight duration, acts on neurons and neurotransmitters in the hypothalamic-pituitary-gonadal axis, promotes obesity and affects the expression level of insulin-like growth factor-1, which are four factors involved in the occurrence and development of CPP. The overall effect of vitamin D combined with gonadotropin-releasing hormone analogues on CPP is significant. This article reviews the correlation between vitamin D deficiency and CPP, as well as the possible mechanism of action, in order to provide some theoretical basis for researchers.

Correlation analysis between serum vitamin D level and central precocious puberty in girls / 中国现代医生

Objective To investigate the correlation between serum vitamin D level and central precocious puberty(CPP)in girls.Methods A total of 103 girls(case group)with central precocious puberty from Ningbo Woman and Children's Hospital and 53 healthy girls(control group)from health check-ups in Ningbo Women and Children's Hospital were collected as subjects.The serum levels of 25-hydroxyvitamin D3[25(OH)D3]in the two groups were detected by chemiluminescence method.The weight and height of girls in the case group were measured.The serum levels of follicle-stimulating hormone(FSH)and its peak value,luteinizing hormone(LH)and its peak value,estradiol(E2),prolactin(PRL),human chorionic gonadotropin(HCG)and thyroid function were measured by radioimmunoassay.The peak value of LH/FSH was calculated.B ultrasound examination of uterine adnexa was completed to calculate uterine volume and bilateral ovarian volume.According to the results of serum 25-(OH)D3,girls in the case group were divided into normal vitamin D group and vitamin D deficiency group,and the differences of hormone levels,uterine and ovarian development between the two groups were compared.Results The serum level of 25-(OH)D3 in case group was lower than that in control group,and the vitamin D deficiency rate in case group was higher than that in control group,with statistical significance(P<0.05).The age of breast nodules in vitamin D deficiency group was lower than that in vitamin D normal group(P<0.05).There were no significant differences in body weight,height,body mass index(BMI),uterine volume and left ovarian volume between vitamin D normal group and vitamin D deficiency group(P>0.05),and the right ovarian volume in vitamin D deficiency group was significantly higher than that in vitamin D normal group(P<0.05).There were no significant differences in serum levels of FSH,LH,PRL,HCG,peak value of FSH and thyroid function between normal and deficient groups(P>0.05).The levels of E2,LH and LH/FSH in vitamin D deficiency group were significantly higher than those in vitamin D normal group(P<0.05);25-(OH)D3 was negatively correlated with LH/FSH peak(r=-0.197,P<0.05),but was not significantly correlated with thyroid function,FSH,LH,PRL,E2,HCG,FSH and LH peak(P>0.05).Conclusion Vitamin D deficiency is associated with central precocious puberty in girls.Vitamin D deficiency may lead to early onset of precocious puberty.Vitamin D deficiency may affect the hypothalamic-pituitary-gonadal axis function,resulting in changes in reproductive hormone indexes and consequent increase in ovarian volume in girls.

Legius syndrome combined with central precocious puberty: a case report and literature review / 中华神经科杂志

Objective:To investigate the clinical phenotype and genotypic characteristics of Legius syndrome.Methods:The clinical data of a child with precocious puberty and scattered café-au-lait macules admitted to Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University in July 2021 were retrospectively analyzed. Trio-whole exome sequencing (trio-WES) was used for genetic analysis to confirm the molecular diagnosis of the family. The relevant literature was reviewed to summarize the clinical characteristics of the disease.Results:The proband was a 10-year and 9-month-old girl, presenting with more than 5 café-au-lait macules with diameter>5 mm on the face and trunk, freckles in the axillary, without Lisch tubercles of iris and tumor signs of neurofibromatosis type 1, diagnosed as central precocious puberty at the age of 8. trio-WES results of the family revealed a spontaneous heterozygous nonsense mutation c.751(exon7) C>T in SPRED1 gene, causing a nonsense mutation in the amino acid sequence p.Arg251Ter (p. Ter251 *). Literature review showed a total of 88 pathogenic mutations were reported in SPRED1 gene, including frameshift mutations (41/88), nonsense mutations (31/88), splice mutations (7/88), missense mutations (6/88), and others (3/88), and no mutational hotspots were found. Clinical phenotype was as follows:>5 café-au-lait macules accounted for 92.8% (168/181), armpit and inguinal freckles 43.5% (73/168), macrocephaly 21.4% (31/145), learning disability 18.0% (30/166), psychomotor retardation 13.8% (22/159), lipoma (adult) 13.7% (21/153), Noonan facial sign 12.1% (21/173), and tumor phenotype of neurofibromatosis type 1 was not reported. Conclusions:The central precocious puberty phenotype of Legius syndrome was not reported in China. The clinical phenotype of Legius syndrome was mild, with a large variation, but without neurofibromatosis type 1 tumor phenotype. Genetic testing can be beneficial for early diagnosis of Legius syndrome.

Value of basal luteinizing hormone level combined with uterine volume measurement in the early diagnosis of central precocious puberty in girls with different Tanner stages / 中国当代儿科杂志

OBJECTIVES@#To study the value of basal luteinizing hormone (LH) level combined with uterine volume measurement in the early diagnosis of central precocious puberty (CPP) in girls with different Tanner stages.@*METHODS@#A retrospective analysis was performed on the girls who presented with breast development before the age of 8 years and attended the Third Affiliated Hospital of Zhengzhou University from January 2017 to September 2022. According to the results of gonadotropin-releasing hormone (GnRH) agonist test, the girls with peak LH ≥5.0 IU/L and peak LH/follicle stimulating hormone ≥0.6 were enrolled as the positive group, and the other girls were enrolled as the negative group. The two groups were compared in terms of the basal LH level and uterine volume. The receiver operating characteristic (ROC) curve was used to analyze their value in the early diagnosis of CPP.@*RESULTS@#For the girls with Tanner B2 and B3 stages, the positive group had significantly higher basal LH level and uterine volume than the negative group (P<0.05). The basal LH level had an optimal cut-off value of 0.325 IU/L and 0.505 IU/L respectively in the diagnosis of Tanner stage B2/B3 CPP, while uterine volume had an optimal cut-off value of 1.639 mL and 2.158 mL respectively. Basal LH level combined with uterine volume measurement had a significantly larger area under the ROC curve than uterine volume measurement alone (P<0.001), but with no significant difference compared with that of basal LH level measurement alone (P>0.05).@*CONCLUSIONS@#Basal LH level combined with uterine volume measurement is valuable in the early diagnosis of CPP in girls with different Tanner stages, which provides a basis and guiding significance for clinical diagnosis of CPP.

Serum 25-hydroxyvitamin D levels and the risk of idiopathic central precocious puberty in girls

Abstract Introduction Prior studies have found inconsistent results regarding the relationship between vitamin D status and Idiopathic Central Precocious Puberty (ICPP). Objective To assess the role of serum 25-hydroxyvitamin D (25 [OH]D) levels in ICPP development. Method The authors retrospectively collected data from 221 girls with ICPP and 144 healthy girls between January 2017 and December 2019. The participants' serum 25(OH)D levels were measured using an automatic chemiluminescence method, and the association between serum 25(OH)D levels and the risk of ICPP was assessed using multivariate logistic regression analysis. Odds Ratios (OR) with 95% Confidence Intervals (95% CI) were calculated as effect estimates. Results Serum 25(OH)D levels in the ICPP group were significantly lower than those in healthy controls (p < 0.001). Multivariate analysis indicated that girls with insufficient vitamin D levels (OR = 0.201; 95% CI 0.094-0.428; p < 0.001) and sufficient vitamin D levels (OR = 0.141; 95% CI 0.053-0.375; p < 0.001) both had a lower risk of ICPP than girls with vitamin D deficiency. Moreover, the authors found that the height (p = 0.014), weight (p = 0.014), breast stage (p = 0.010), mother's height (p < 0.001), and luteinizing hormone/follicle-stimulating hormone ratio (p = 0.010) in girls with ICPP could be associated with levels of vitamin D. Conclusion This study found that a low serum 25(OH)D level is an independent risk factor for ICPP, and several characteristics of girls with ICPP could be affected by their vitamin D status.

Effects of Jiuwei Chushi Decoction on sex hormone and Kisspeptin protein expression of Central Precocious Puberty rats / 国际中医中药杂志

Objective:To observe the effect of Jiuwei Chushi Decoction on sex hormone level of serum and Kisspeptin protein expression in hypothalamus of Central Precocious Puberty (CPP) rats model.Methods:After sixty female rat were breeded from SD rats, they are randomly divided into six groups, which are normal control group, model group, Gonadorelin group, and high, medium and low dose group of Jiuwei Chushi Decoction, 10 in each group. In addition to the normal control group, the other groups were subcutaneously injected with N-methyl-DL-aspartic acid to establish CPP model. Gonadorelin group was subcutaneously injected with Gonadorelin 100 μg/(kg·d), and high, medium and low dose group of Jiuwei Chushi Decoction were intragastrated with Jiuwei Chushi Decoction extract at 5.75, 2.87 and 1.43 ml/(kg·d) respectively. The levels of Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH),Estradiol (E 2) were detected by ELISA, and the protein expressions of Gonadotropin-releasing Hormone (GnRH) and Kisspeptin in hypothalamus were detected by Western Blot. Results:Compared with the model group, the levels of LH and E 2 of the low, medium and high dose group of Jiuwei Chushi Decoction were significantly decreased ( P<0.05), while the FSH level was significantly increased ( P<0.05). The relative protein expression of GnRH (0.657±0.110, 0.536±0.152 vs. 0.912±0.219) and Kisspeptin (0.508±0.035,0.347±0.073 vs. 0.659±0.030) in the medium and high dose group of Jiuwei Chushi Decoction was lower than that of model group. Conclusion:Jiuwei Chushi Decoction could affect hypothalamic Kisspeptin protein expression, inhibite hypothalamic GnRH expression, and decrease LH and E 2 levels in the serum of CPP rats.

Research progress of the efficacy and safety of 3-month depot Leuprorelin in the treatment of central precocious puberty / 中华实用儿科临床杂志

Central precocious puberty (CPP) is a common pediatric endocrine disease caused by premature activation of the hypothalamic-pituitary-gonadal axis, featured by rapid development of internal and external reproductive organs and secondary sexual characteristics in girls before age 8 and boys before age 9.The gonadotropin-releasing hormone analogue (GnRHa) is the first choice for the treatment of CPP.Currently, 3.75 mg/ month sustained -release short-acting dosage form (1M depot formulations) is the most commonly used in China.The development of long-acting dosage form will reduce injection times and clinic visits.At present, the 3-month long-acting dosage form (11.25 mg 3M depot formulations) of Leprorelin microsphere has been approved in China.However, clinical practice experience of 3-month Leuprorelin acetate depot formulations is lacking in China.Therefore, in this paper, existing clinical evidence for this dosage form was reviewed to provide evidence-based medicine support for its clinical application.

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 Efficacy of Modified Huqianwan Combined with Auricular Acupressure with Seeds on Central Precocious Puberty due to Yin Deficiency and Fire Hyperactivity / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Huqianwan combined with auricular acupressure with seeds on girls with central precocious puberty （CPP） due to Yin deficiency and fire hyperactivity. Method:A total of 150 cases were randomly divided into three groups （A group，B group， and C group），with 50 cases in each group. The cases received modified Huqianwan，Zhibo Dihuangwan，and modified Huqianwan combined with auricular acupressure with seeds， respectively， for 12 weeks. The traditional Chinese medicine （TCM） symptoms，bone age difference/chronological age difference （ΔBA/ΔCA）， predicted adult height （PAH），ovarian volume，uterine volume，breast nodule index，serum sex hormones ［follicle-stimulating hormone （FSH），luteinizing hormone （LH），and estradiol （E₂）］，and serum kisspeptin-1 （KISS-1）/G protein-coupled receptor 54 （GPR54）/hypothalamic gonadotropin-releasing hormone （GnRH） signaling pathway of the three groups were observed before and after treatment. The clinical efficacy and safety of the three groups were evaluated. Result:The total effective rate was 97.9% in the C group， which was higher than 81.3% in the A group （<italic>χ</italic>²=4.516，<italic>P</italic><0.05） and 71.4% in the B group （<italic>χ</italic>²=5.162，<italic>P</italic><0.05）. Compared with the results in the A group after treatment，TCM syndrome，ΔBA/ΔCA，E₂，LH，KISS-1，GPR54，and GnRH decreased（<italic>P</italic><0.05），and ovarian volume，uterine volume，and breast nodule index were reduced （<italic>P</italic><0.05），but PAH increased in the C group （<italic>P</italic><0.05）. Compared with the B group after treatment，the C group showed decreased TCM syndrome，ΔBA/ΔCA， FSH，E₂，LH，KISS-1，GPR54，and GnRH （<italic>P</italic><0.05），reduced ovarian volume，uterine volume，and breast nodule index （<italic>P</italic><0.05），and increased PAH（<italic>P</italic><0.05）. During the study，there was one case of anorexia in the A group，and no obvious adverse reactions were found in the B group and the C group. Conclusion:Modified Huqianwan combined with auricular acupressure with seeds can significantly increase the PAH of girls with CPP due to Yin deficiency and fire hyperactivity and improve the serum sex hormones and the KISS-1/GPR54/GnRH signaling pathway.

Effect of gonadotropin-releasing hormone analogue treatment in improving final adult height of children with central precocious puberty or early and fast puberty: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To systematically evaluate the effect of gonadotropin-releasing hormone analogue (GnRHa) treatment on the final adult height of children over 6 years of age with central precocious puberty (CPP) or early and fast puberty (EFP).@*METHODS@#PubMed, MEDLINE, Embase, Cochrane Library, CNKI, and Wanfang Data were searched for related articles on GnRHa treatment for children with CPP or EFP. Stata 12.0 software was used to perform a Meta analysis of related data.@*RESULTS@#A total of 10 studies were included, and the total sample size was 720 children, with 475 children in the GnRHa treatment group and 245 children in the control group. The Meta analysis showed that compared with the control group, the GnRHa treatment group had significantly better final adult height (@*CONCLUSIONS@#GnRHa treatment is safe and effective in improving the final adult height of children over 6 years of age with CPP or EFP.

Central nervous system imaging in girls with central precocious puberty: when is necessary?

ABSTRACT Objectives The determinants of an increased risk of an organic pathology underlying central precocious puberty (CPP) in girls remain contentious. The present study aimed to determine the clinical and hormonal findings that can be used to differentiate organic and idiopathic CPP in girls as a screening method so that only those considered likely to have organic CPP undergo cranial magnetic resonance imaging (MRI). Subjects and methods The medical records of 286 girls that received GnRH agonist (GnRHa) therapy for CPP were retrospectively evaluated. Chronological and bone age, height, pubertal stage, and basal/stimulated gonadotropin and estradiol (E2) levels, as well as cranial MRI findings at the time CPP was diagnosed were recorded. Clinical and hormonal parameters that can be used to differentiate between girls with organic and idiopathic CPP were identified using ROC curves. Results Organic CPP was noted in 6.3% of the participants. Puberty started before age 6 years in 88.9% of the girls with organic CPP. Mean E2 and peak luteinizing hormone (LH) levels were higher in the girls with organic CPP than in those with idiopathic CPP that were matched for pubertal stage, as follows: early stage puberty (Tanner 2 and 3): E2: 62.4 ± 19.8 pg/mL vs. 29.1 ± 9.5 pg/mL; peak LH: 16.8 ± 3.2 IU/L vs. 12.2 ± 3.7 IU/L; advanced stage puberty (Tanner 4): mean E2: 87.6 ± 3.4 pg/mL vs. 64.6 ± 21.2 pg/mL; peak LH: 20.8 ± 0.4 IU/L vs. 16.6 ± 5.8 IU/L (P < 0.001 for all). Thresholds for differentiating organic and idiopathic CPP in girls with early-stage puberty were 38.1 pg/mL for E2 (100% sensitivity and 80.4% specificity) and 13.6 IU/L for peak LH (100% sensitivity and 66.4% specificity). Conclusion Pubertal symptoms and signs generally begin before age 6 years and hormone levels are much higher than expected for pubertal stage in girls with organic CPP. Based on the present findings, cranial MRI is recommended for girls aged < 6 years, as the risk of diagnosing an organic pathology is highest in this age group. Hormone levels higher than expected for pubertal stage might be another indication for cranial MRI, regardless of patient age. Cranial MRI should be performed in girls with early-stage puberty, and an E2 level > 38 pg/mL and/or a peak LH level > 13.6 IU/L.

Long-term effects of GnRHa on central precocious puberty or early and fast puberty children / 中华内分泌代谢杂志

Objective@#To investigate the long-term effects of GnRHa treatment on final height gain, gonadal function, and body mass index(BMI) in children with central precocious puberty(CPP) or early and fast puberty(EFP), and to explore the influencing factors of height gain and early predictors.@*Methods@#Fifty patients with CPP and 44 patients with EFP who were treated with GnRHa for more than 2 years were enrolled(80 females and 14 males). Body height, bone age, BMI, gonads hormone, uterus and ovarian volumes(female), testicular volume(male), and other parameters before and after treatment were measured.@*Results@#(1)For girls: GnRHa plus GH treatment gained more final height compared with GnRHa treatment [(10.69±5.73) cm vs (7.42±5.76) cm, P<0.05]. Height lost >5cm at the initial treatment benefited much more for the final height compared with height lost<5cm [(10.65±3.32) cm vs (6.51±3.40) cm, P<0.01]. The proportion of overweight/obesity decreased when reaching the final height compared with the initial treatment and stopping the treatment. Serum LH level, uterine and ovarian volume were significantly decreased after stopping treatment compared with before treatment, and increased half a year to 1 year after stopping treatment.100% of girls had menarche and 95% reached the regular cycle 3 years after stopping treatment.(2)For boys: GnRHa plus GH treatment and GnRHa treatment gained height by(8.78±5.2) and(7.99±4.82) cm, respectively. Serum LH level and testicular volume were significantly decreased after stopping treatment as compared with those before treatment, and increased for half a year to 1 year after stopping treatment.@*Conclusion@#GnRHa treatment can significantly improve the final height for girls with CPP and EFP. The patients with more height lost could gain more height, which can be used as a predictor of height gain.

Pioneering studies on monogenic central precocious puberty

ABSTRACT Pubertal timing in humans is determined by complex interactions including hormonal, metabolic, environmental, ethnic, and genetic factors. Central precocious puberty (CPP) is defined as the premature reactivation of the hypothalamic-pituitary-gonadal axis, starting before the ages of 8 and 9 years in girls and boys, respectively; familial CPP is defined by the occurrence of CPP in two or more family members. Pioneering studies have evidenced the participation of genetic factors in pubertal timing, mainly identifying genetic causes of CPP in sporadic and familial cases. In this context, rare activating mutations were identified in genes of the kisspeptin excitatory pathway (KISS1R and KISS1 mutations). More recently, loss-of-function mutations in two imprinted genes (MKRN3 and DLK1) have been identified as important causes of familial CPP, describing novel players in the modulation of the hypothalamic-pituitary-gonadal axis in physiological and pathological conditions. MKRN3 mutations are the most common cause of familial CPP, and patients with MKRN3 mutations present clinical features indistinguishable from idiopathic CPP. Meanwhile, adult patients with DLK1 mutations present high frequency of metabolic alterations (overweight/obesity, early onset type 2 diabetes and hyperlipidemia), indicating that DLK1 may be a novel link between reproduction and metabolism. Arch Endocrinol Metab. 2019;63(4):438-44

Movement Disorder Early in the Presentation of Two Children with Subacute Sclerosing Pan-Encephalitis

Subacute sclerosing panencephalitis(SSPE) is a progressive degenerative disease caused by measles infection with overall poor prognosis in spite multiple modalities of treatment. The course of the disease is characterized by progressive neurological decline in the form of behavioral and personality changes followed by a stage of characteristic periodic myoclonic spasms followed by a stage of quadriplegia movement disorder, vegetative state and frequently early death. Here we report two cases with atypical presentation of early rather than late movement disorder during illness and the unusual association of central precocious puberty preceding the course of illness in one of the cases

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.

Herlyn-Werner-Wunderlich Syndrome with Central Precocious Puberty: A Case Report

Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital anomaly of the genitourinary tract comprising uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Patients with HWW syndrome usually present symptoms such as dysmenorrhea, abdominal pain, pelvic mass, and purulent vaginal discharge. If not treated at an appropriate time, complications such as infertility, endometriosis, pyosalpinx, and subsequent pelvic adhesions may occur. Here, we report a case of HWW syndrome in a 7-year-old-girl who was also diagnosed as having central precocious puberty. She was brought to the pediatric department with chief complaints of lump in her breast and vaginal discharge. When she was around 2 months old, she was confirmed to have a single kidney on ultrasonography. We checked her past medical history and diagnosed her as having HWW syndrome based on the results of imaging studies, including abdominal ultrasonography and pelvic magnetic resonance imaging. She underwent treatment with gonadotropin-releasing hormone analogue for 2 years. During 24 months of follow-up, she showed no serious problems or complications. If renal anomalies are identified immediately after birth or in infancy, further screening tests should be conducted prior to menstruation for determining congenital abnormalities of the reproductive tract and vice versa.

Comparative study of GnRHa stimulation test and GnRH stimulation test / 国际儿科学杂志

Objective To compare the results of GnRHa stimulation test and GnRH stimulation test in girls with Idiopathic central precocious puberty.Methods The girls aged 6-10 who were diagnosed with early breast development (＜ 8 years old) from January 2016 to June 2018 were randomly divided into GnRHa stimulation test group and GnRH stimulation test group according to clinical manifestations,auxiliary examinations and follow-up.The difference in the results of the stimulation test between the two groups was compared.Results A total of 108 girls were enrolled in this study,and 40 (37％) of the GnRHa stimulation tests were performed.Among them,25 (63％) patients with idiopathic central precocious puberty had the confirmed diagnosis,and the GnRH stimulation test was performed.Of the 68 (63％) patients,30 (44％) had idiopathic central precocious puberty.The peaks of LH in the GnRHa challenge test group and the GnRH challenge test groupwere 11.33 (6.81,15.79) and 7.89 (5.35,14.21),and the FSH peaks were 15.68 (10.18,20.06) and 17.26 (13.34,21.42),showing no significant differences (U =1078.50,P =0.07;U =1617.50,P=0.10).Thepeak values of LH/FSH were0.86 (0.37,1.17)and0.52 (0.31,0.83),respectively,and there was a statistical difference (U =953.00,P =0.01).GnRH challenge test showed the ICPP sensitivity of 90.91％ (81.10％-100.72％),specificity of 94.29％ (86.60％-101.98％),total coincidence rate of 92.65％ (86.44 ％-98.85％),Yoden index of 0.85 (0.72％-0.98％).Sensitivity of the GnRHa challenge test showed the ICPP diagnosis rate of 95.24％ (86.13％-104.35％),specificity of 73.68％ (53.88％-93.48％),total coincidence rate of 85.00％ (73.93％-96.07％),Yoden index of 0.69 (0.47-0.91).Conclusion For the diagnosis of idiopathic central precocious puberty in girls,the GnRHa challenge test is more sensitive than the GnRH challenge test,and the specificity and the Yoden index are both low.Therefore,routine use of GnRHa stimulation test as the replacement of GnRH stimulation test is not recommended.

Advanced bone age as an indicator facilitates the diagnosis of precocious puberty / Idade óssea avançada como um indicador de facilitação do diagnóstico de puberdade precoce

Abstract Objective: Diagnosis of central precocious puberty has always been challenging in clinical practice. As an important method in the diagnosis of central precocious puberty, luteinizing hormone-releasing hormone stimulation test is complex and time-consuming. In many cases, clinical traits are inconsistent with luteinizing hormone-releasing hormone stimulation test results, therefore not reliable for diagnosis. In this study, the authors intended to find an indicator that predicts the results of the luteinizing hormone-releasing hormone stimulation test among subjects with early pubertal signs. Methods: Cases of 382 girls with early breast development before 8 years old and luteinizing hormone-releasing hormone stimulation test before 9 years old were included and underwent follow-up tests. Patients with peak luteinizing hormone level ≥5 IU/L were considered positive in the luteinizing hormone-releasing hormone stimulation test. Anthropometric data, body mass index, bone age evaluation, blood hormones levels of luteinizing hormone, estradiol, follicle-stimulating hormone, and uterine and ovarian volumes were analyzed. Results: Subjects with positive results in the initial test demonstrated early bone maturation, accelerated growth, and elevated basal blood luteinizing hormone, estradiol, and follicle-stimulating hormone levels, when compared with subjects with negative results in the initial test. Subjects with positive results in the follow-up test presented a more advanced bone age and more accelerated linear growth, when compared with subjects with negative results in the follow-up test. Conclusions: According to the statistical analysis, advanced bone age is the most effective predictor of the result of luteinizing hormone-releasing hormone stimulation test.

Resumo Objetivo: O diagnóstico da puberdade precoce central sempre foi complicado na prática clínica. Como um importante método no diagnóstico de puberdade precoce central, o teste de estimulação do hormônio liberador do hormônio luteinizante é complexo e demorado. Em muitos casos, as características clínicas são incompatíveis com os resultados do teste de estimulação do hormônio liberador do hormônio luteinizante e, assim, não são confiáveis para o diagnóstico. Neste estudo, visamos constatar um indicador que previsse os resultados do teste de estimulação do hormônio liberador do hormônio luteinizante entre indivíduos com sinais puberais precoces. Métodos: Foram incluídos casos de 382 meninas com desenvolvimento precoce das mamas antes dos 8 anos de idade e teste de estimulação do hormônio liberador do hormônio luteinizanteantes dos 9 anos e elas foram submetidas a testes de acompanhamento. Os resultados das pacientes com nível máximo de hormônio luteinizante ≥ 5 IU/L foram consideradas positivos no teste de estimulação do hormônio liberador do hormônio luteinizante. Foi feita uma análise dos dados antropométricos, do índice de massa corporal, da avaliação da idade óssea, dos níveis sanguíneos de hormônio luteinizante, volumes uterinos e ovarianos de estradiol (E2) e do hormônio folículo-estimulante. Resultados: Os indivíduos com resultado positive no teste inicial demonstraram maturação precoce do osso, crescimento acelerado e níveis sanguíneos elevados de hormônio luteinizante, estradiol e hormônio folículo-estimulante, em comparação aos indivíduos com resultados negativos no teste inicial. Os indivíduos com resultados positivos no teste de acompanhamento apresentaram um maior avanço na idade óssea e crescimento linear mais acelerado, em comparação aos indivíduos com resultados negativos no teste de acompanhamento. Conclusões: De acordo com a análise estatística, a idade óssea avançada é o indicador mais efetivo do resultado do teste de estimulação do hormônio liberador do hormônio luteinizante.