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.

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.

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.

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.

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.

Longitudinal follow-up to near final height of auxological changes in girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analog and grouped by pretreatment body mass index level

PURPOSE: Reported changes in body mass index (BMI) in central precocious puberty (CPP) during and after gonadotropin-releasing hormone analog (GnRHa) treatment are inconsistent. We, therefore, investigated auxological parameters in GnRHa-treated girls with idiopathic CPP (ICPP) until attainment of near final height (NFH). METHODS: From the medical records of 59 ICPP girls who attained NFH after GnRHa therapy, auxological changes were compared between overweight (BMI≥85th percentile) and normal-weight (BMI < 85th percentile) groups. BMIs were changed into standard deviation scores (BMISDSs) for subject chronologic age (BMISDS-CA) and bone age (BMISDS-BA). RESULTS: The incidence of overweight including obesity was high at the start of therapy (35.6%). The predicted adult height (PAH) at start of therapy was significantly shorter than the midparental height (MPH), whereas PAH at end of therapy approached MPH, and NFH was greater than MPH. Height velocity (HV) in the overweight group was higher during GnRHa therapy than that in the normal-weight group, but those in the two groups were not different after therapy until NFH. Both BMISDS-CA and BMISDS-BA increased significantly during therapy, but both BMISDSs decreased significantly after therapy until NFH. At NFH, neither BMISDS was different from that at baseline. In the normal-weight group, both BMISDSs increased during therapy and were maintained until NFH. In the overweight group, neither BMISDS changed during therapy, but there was a decrease after therapy until NFH. CONCLUSIONS: The different patterns of BMISDS change during and after GnRHa therapy until NFH between the 2 groups were related to the different HV during GnRHa therapy.

Therapeutic Effect of Triptorelin Acetate Combined with Psychological Intervention in the Treatment of Id-iopathic Central Precocious Puberty / 中国药师

Objective: To study the therapeutic effect of triptorelin acetate combined with psychological intervention on the chil-dren with idiopathic central precocious puberty. Methods: Totally 40 cases of central precocious puberty were randomly divided into the observation group and the control group with 20 ones in each. The control group was injected with triptorelin acetate, once every 28 d; the observation group was given psychological intervention on the basis of the control group, once every 28 d. The emotional stabili-ty, depressive psychology, treatment compliance, height, body weight, growth rate, bone age ( BA) and adult height ( PAH) of the two groups before and after one-year treatment were observed and compared. Results: After the one-year treatment, the scores of emo-tional stability and depressive psychological HAMD in the observation group were significantly lower than those in the control group (P<0. 05), and the medication compliance was significantly higher in the observation group than that in the control group (P<0. 05). The growth rate and adult height of the children in the observation group were significantly higher than those in the control group (P<0. 05). Conclusion: Triptorelin acetate combined with psychological intervention in the treatment of children with idiopathic central precocious puberty can relieve depression, stabilize mood and improve medication compliance, and also effectively improve the growth rate and adult prediction height of the children.

Association of ring-finger protein 3 (MKRN3) gene rs2239669 polymorphism with central precocious puberty susceptibility / 临床儿科杂志

Objectives To explore the association between the single nucleotide polymorphism (SNP) rs2239669 in makorin ring-finger protein 3 (MKRN3) gene and the susceptibility to central precocious puberty (CPP). Methods A case-control study including 246 children with CPP and 269 healthy children was performed.The genotype and MKRN3 expression levels of patients were analyzed by PCR-HRM and RT-PCR,respectively. Results SNP rs2239669 genotype (TT,TC,CC) and allele frequencies (T and C) were different between cases and controls,with higher CC genotype in CPP patients. Under recessive model (CC/TT+TC),CC genotype was higher in CPP group and associated with higher risk of CPP (95%CI:1.062-2.143,P=0.021). MKRN3 expression levels were different among patients with different genotypes,of which TT genotype had the highest level followed by TC and CC (0.376±0.094, 0.330±0.068, 0.250±0.072, P=0.041). Conclusions MKRN3 SNP rs2239669 was associated with increased risk of CPP, and patients with TT genotype had higher MKRN3 levels.

Research progress of height improvement in central precocious puberty / 国际儿科学杂志

Central precocious puberty (CPP) is a disease that results from the premature activation of hypothalamic-pituitary-gonadal axis(before 8 years in girls and 9 years in boys).The CPP children show abnormally early appearance of secondary sexual characteristics.Genetic factors,ethnicity,environmenal factors have been involved in the pathogenesis of CPP.Gonadotropin-releasing hormone analogues(GnRHa) are the most common drugs for CPP.The factors of GnRHa treatment on height improvement include the age of puberty onset and the age of treatment initiation.The CPP girls diagnosed and treated before the age of 6 have the best effect,so CPP children need early treatment.Adequate treatment duration is an important factor to ensure height improvement,at least 2 years.The CPP children that are younger according to the bone age have more favorable outcomes of height improvement.By delaying epiphyseal closure,aromatase inhibitors can improve the height of CPP boys.KISS1 、KISS1R 、MKRN3 and other genes are related to CPP,early identification of CPP genes can play a guiding role in early intervention.For the CPP girls treated with GnRHa,when the growth rate is less than 4cm/year,recombinant human growth hormone can effectively improve adult height.Appropriate aerobic exercise can also improve height.This article reviews the factors and strategies of height improvement in central precocious puberty.