Objective:To review the scientific research results of early puberty in children in the past decade,and to explore the current status,hot spots and frontiers of research in the field of early puberty in children.Metho...Objective:To review the scientific research results of early puberty in children in the past decade,and to explore the current status,hot spots and frontiers of research in the field of early puberty in children.Methods:From January 1,2014 to April 30,2024,literature on early puberty in children was retrieved from CNKI database and Web of Science(WOS)core collection.CiteSpace6.3.R1 software was used for bibliometric analysis of authors,institutions and key words,and related visual maps were drawn.Results:A total of 1548 English literatures and 1113 Chinese literatures were included.The number of published papers in both Chinese and English showed an increasing trend.The authors of the high production in Chinese were Ye Jin and Yang Li,and the high production institutions were the pediatrics department of Hubei University of Chinese Medicine and Shuguang Hospital Affiliated to Shanghai University of Chinese Medicine.The authors are Latronico,Ana Claudia,and Universidade de Sao Paulo.Hot topics in Chinese and English studies include bone age,hormones,genetic inheritance,the correlation between precocious puberty and obesity and short stature.Conclusion:There is an increasing trend of research in the field of early puberty in children.The research on physical identification of children with precocious puberty and the dynamic detection of precocious puberty,height and obesity by Internet is worthy of continuous attention by domestic scholars.展开更多
Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice...Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice enter puberty only 4–5 days earlier than normal mice),the related research is limited.Methods:Therefore,the MKRN3-modified rabbit was developed using CRISPR(clus-tered regularly interspaced short palindromic repeats)gene editing technology.The genotype identification and phenotype evaluation of MKRN3-modified rabbits were carried out.Results:The first estrus of MKRN3-modified female rabbits was observed~27 days earlier than that of wild-type female rabbits,with a typical CPP phenotype.This study found increased gonadotropin releasing hormone(GnRH)and decreased gonadotropin inhibiting hormone(GnIH)in the hypothalamus of the CPP rabbit model with MKRN3 gene mutation.Although this study failed to fully clarify the pathogenesis of CPP caused by MKRN3 mutation,it found some differentially expressed genes and potential pathways through transcriptome sequencing.Conclusions:This study established a novel CPP model:paternal MKRN3 gene-modified rabbit.It is hoped that the establishment of this model will help researchers better understand,treat,and prevent CPP in the future.展开更多
In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the trea...In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.展开更多
BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in girls.Makorin ring finger protein 3(MKRN3),a maternal...BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in girls.Makorin ring finger protein 3(MKRN3),a maternal imprinted gene with a highly conserved sequence,is the most common genetic etiology associated with CPP.Approximately 50 different mutations in MKRN3 have been found in CPP.CASE SUMMARY This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years.The left hand bone age of both patients revealed advanced age(9 years).Pelvic B ultrasound indicated enlargement of the ovaries.Luteinizing hormone(LH)releasing hormone testing confirmed CPP.Wholeexome sequencing detected the c.841C>T mutation in MKRN3,leading to a single base substitution,in the twins.This mutation was inherited from the father and paternal grandmother.After 3 mo of treatment with a gonadotropin-releasing hormone analog,levels of LH,follicle-stimulating hormone,and estradiol in the proband’s sister returned to normal levels.CONCLUSION Here,we report a rare mutation(c.841C>T)in MKRN3 in identical twin sisters with CPP.展开更多
Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive...Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children’s Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40–140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1–6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.展开更多
Objective:To observe the clinical efficacy of different dosage forms of lepraline acetate(LA)in the treatment of girls with central precocious puberty(CPP).Methods:72 CPP girls treated in the Department of Pediatrics ...Objective:To observe the clinical efficacy of different dosage forms of lepraline acetate(LA)in the treatment of girls with central precocious puberty(CPP).Methods:72 CPP girls treated in the Department of Pediatrics of Huai'an First People's Hospital from February 2021 to August 2022 were included as subjects and divided into two groups:3-month LA group(n=34)and 1-month LA group(n=38).Both group girls were treated for 6 months.Serum hormone levels,body mass index(BMI),bone age/chronological age(BA/CA)and pelvic color ultrasound were detected at 0 and 6 months after treatment,and the changes of various indexes were compared before and after treatment.Results:1)There were no significant differences in baseline data between the two groups before treatment(P>0.05).2)After 6 months of treatment,BA/CA decreased,growth rate slowed down,and predicted adult height increased in both groups(P<0.05),but there were no significant differences between groups(P>0.05).3)After 6 months of treatment,there waere no significant differences in luteinizing hormone(LH)inhibition ratio between the 3 month and 1 month dosage groups(P>0.05).After treatment,the peak value of serum LH and FSH,estradiol level,uterine volume,bilateral ovarian volume,maximum follicle diameter and the number of follicles 4mm were significantly decreased in the two groups,but there were no significant differences between the two groups(P>0.05).4)There were no significant differences in the levels of thyroid hormone,fasting blood glucose and triglyceride between the two groups before and after treatment(P>0.05).Total cholesterol levels were increased after treatment(P<0.05),but there was no significant difference between groups(P>0.05).5)No serious adverse reactions occurred during the treatment of the two dosage forms of LA,but the 3-month dosage form of LA reduced the treatment cost and improved the treatment compliance.Conclusion:The short-term efficacy of 3-month LA in the treatment of CPP in girls is similar to that of 1-month LA.The 3-month dosage form LA is a safe,effective,and economical method for the treatment of CPP in girls.展开更多
Van Wyk-Grumbach syndrome (VWGS) is characterized by juvenile hypothyroidism, delayed bone age, isosexual precocious puberty and massive ovarian cysts. We report such a case in a 7-year-old girl who presented with a b...Van Wyk-Grumbach syndrome (VWGS) is characterized by juvenile hypothyroidism, delayed bone age, isosexual precocious puberty and massive ovarian cysts. We report such a case in a 7-year-old girl who presented with a bilateral pelvic pain, abdominal distension and signs of hypothyroidism. Physical examination showed a breast development and lack of pubic and axillary hair. There was no clitoromegaly. Pelvic ultrasonography and CT scan showed enlarged bilateral multiloculared multicystics ovarian masses. The pituitary MRI was recommended before an elevated prolactin, revealed a large sellar and suprasellar mass. The patient was started on thyroid replacement using L-Thyroxine. Clinically, the patient’s fatigue, pelvic pain, and abdominal distension are resolved. During the follow-up, her thyroid functions and serum prolactin normalized within 8 months. Ultrasonography revealed regression of ovarian cysts in 2 months measuring, with normal sized ovaries in 14 months.展开更多
Autoimmune polyglandular syndrome type 1 (APS-1) is one of the rare inherited disorder that affects both sexes alike. Although in specific autoimmune dysfunction associated with this syndrome found to be more common i...Autoimmune polyglandular syndrome type 1 (APS-1) is one of the rare inherited disorder that affects both sexes alike. Although in specific autoimmune dysfunction associated with this syndrome found to be more common in females than males. It has specific criteria usually presented at a specific age. The object of this clinical case report is to highlight this unusual presentation of such condition which is the presence of APS-1 with precocious puberty and alopecia Universalis without any associated symptoms of APS-1 and the gene variations that never had been found before. And up to our knowledge, this is the 1st case in our population and worldwide that has such combination and this is unusual clinical presentation. Autoimmune polyglandular syndrome type 1 (APS-1) is one of the rare inherited disorder that affects both sexes alike. Although in specific autoimmune dysfunction associated with this syndrome found to be more common in females than males. It has specific criteria usually presented at a specific age. The object of this clinical case report is to highlight this unusual presentation of such condition which is the presence of APS-1 with precocious puberty and alopecia Universalis without any associated symptoms of APS-1 and the gene variations that never had been found before. And up to our knowledge, this is the 1st case in our population and worldwide that has such combination and this is unusual clinical presentation.展开更多
Objectives: To investigate the potential role of GABAB Receptors (GABABRs) involved in the effect of Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM) treatment on precocious puberty. Methods: Female Spr...Objectives: To investigate the potential role of GABAB Receptors (GABABRs) involved in the effect of Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM) treatment on precocious puberty. Methods: Female Sprague-Dawley rats were randomly divided into four groups: normal (N), central precocious puberty (CPP) model (M), CPP fed with normal saline (S) and CPP fed with Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM). Rats of postnatal day 5 were given a single subcutaneous injection of 240 μg danazol to establish CPP model rats. Rats of S and TCM groups were continuously administered with saline or nourishing “Yin”-removing “Fire” Chinese herb mixture since postnatal day 15. The expression of GABABRs was detected by means of real-time PCR and immunohistochemistry. Results: The expression of hypothalamic GnRH mRNA in M was significantly increased on the day of pre-puberty when compared with that of N (P < 0.01). On the day of onset-puberty, LH levels were higher in M than those in N (P < 0.01), while the serum E2 and LH levels of TCM decreased when compared with those of M (P <sub>B1</sub> receptor (GABABR1) immunoreactive cells in the arcuate nucleus (ARN) was decreased in M when compared with that of N (P < 0.05) and increased in TCM compared with that of M (P < 0.05);simultaneously, the expression of GABABR1 mRNA in hypothalamus was significantly decreased in M when compared with that of N (P < 0.01) and increased in TCM compared with that of M (P < 0.01). On the day of onset-puberty, the number of GABABR1 immunoreactive cells in medial septum (MS) was decreased in M compared with that in N (P < 0.05) and increased in TCM comparing with that of M (P < 0.05);meanwhile, the mRNA expression of GABABR1 in hypothalamus was decreased in M compared with that in N (P <sub>B2</sub> receptor (GABABR2) immunoreactive cells in the ARN, MS and diagnonal band of broca (DBB) were decreased in M when compared with those of N (P < 0.05) and increased in TCM compared with those of M (P < 0.05) on the day of onset-puberty. At the same time, the mRNA expression of GABABR2 was significantly decreased in M compared with that of N (P < 0.01). Conclusions: These results indicated that the GABABRs might involve in the curative effect of Nourishing “Yin”-Removing “Fire” Chinese herbal mixture on CPP rats.展开更多
Objective:This study aimed to evaluate the therapeutic effects of leuprolide acetate extended-release microspheres for injection in children with pediatric precocious puberty.Methods:A total of 110 cases of pediatric ...Objective:This study aimed to evaluate the therapeutic effects of leuprolide acetate extended-release microspheres for injection in children with pediatric precocious puberty.Methods:A total of 110 cases of pediatric precocious puberty admitted between January 2019 and December 2021 were selected and randomized into two groups using a random number table,with 55 cases in the control group and 55 cases in the experimental group.The control group received conventional treatment,while the experimental group was treated with leuprolide acetate extended-release microspheres for injection.The therapeutic effects were observed,and changes in sex hormone levels,ovarian volume,growth indices,and the incidence of adverse reactions were statistically compared between the groups.Results:The experimental group demonstrated superior outcomes in terms of sex hormone levels,ovarian volume,and growth indices compared to the control group.Additionally,the incidence of adverse reactions in the experimental group was significantly lower(P<0.05).Conclusion:The application of leuprolide acetate extended-release microspheres for the treatment of pediatric precocious puberty is associated with improved therapeutic effects and higher safety.展开更多
OBJECTIVE:To establish a quantification model of Traditional Chinese Medicine(TCM)syndromes by sampling patients undergoing idiopathic precocious puberty(IPP)and early puberty.METHODS:A questionnaire for classifying a...OBJECTIVE:To establish a quantification model of Traditional Chinese Medicine(TCM)syndromes by sampling patients undergoing idiopathic precocious puberty(IPP)and early puberty.METHODS:A questionnaire for classifying and quantifying TCM syndromes was designed and administered.All the results were analyzed;the relationship between 3 types of syndrome and 47symptoms were summated.Meanwhile,the frequency distribution of each symptom or sign was aggregated.Fuzzy mathematics was used to develop a quantification model ofTCM syndromes.RESULTS:We found that precocious puberty had 3types of syndrome,including hyperactivity of fire due to Yin deficiency(Syndrome I),depressed liver Qi transforming into fire(Syndrome II),and end retention of damp heat(Syndrome III).In the IPP group,Syndrome I was the most common principal syndrome(100%).Forty-six patients(43.81%)werediagnosed with Syndrome I accompanied by Syndrome II and 11(10.48%)were diagnosed with Syndrome I accompanied by Syndrome III.In the early puberty group,Syndrome I was also the main syndrome(98.39%).The degrees of most symptoms were mild to moderate.Reddened tongue was the most common tongue manifestation(62.86%prevalence)in the IPP group.The most common pulse manifestations were slippery pulse,thread pulse,and taut pulse.The Asymptotic Normalization Coefficient(ANC)method was used to quantify the TCM syndromes in 167 cases.Diagnostic accuracy rate reached 91%,comparable to expert diagnosis.CONCLUSION:We find that there are 3 types of syndrome in the IPP group and in the early puberty group.Syndrome I(hyperactivity of fire due to Yin deficiency)is the main syndrome in the two groups.ANC may be an appropriate for quantification model ofTCM syndromes.展开更多
In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central preco...In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty （ICPP）, 46 girls with ICPP were treated with GnRHa. Triptorelin （Decapeptyl, 3.75 mg） was administered subcutaneously （SC） at 6-weeks intervals or intramuscularly （IM） at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage, bone age, uterine volume and ovarian size, serum levels of luteinizing hormone （LH）, follicle stimulating hormone （FSH） and estradiol （E2）, were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics. Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment. The height velocity was decreased significandy from 6.3±1.4 cm/year to 5.8：1：1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBAgdeltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively. The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in di- ameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients, which disappeared after 6- 12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was concluded that both IM and SC triptorelin administrations were clinically effective. They induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6-weeks intervals at a dosage of 3.75 mg be a safe and acceptable regimen for ICPP.展开更多
Background The diagnosis of central precocious puberty(CPP)relies on a gonadotropin releasing hormone stimulation test to assess the activation of the hypothalamic-pituitary-gonadal axis;this is costly and painful.Bil...Background The diagnosis of central precocious puberty(CPP)relies on a gonadotropin releasing hormone stimulation test to assess the activation of the hypothalamic-pituitary-gonadal axis;this is costly and painful.Bile acids(BAs)have emerged as pivotal signaling molecules in the reproductive system.This study aimed to identify circulating BA profile signatures and explored if they may serve as biomarkers for CPP diagnosis in girls.Methods We enrolled 431 girls,including 241 in the training cohort and 190 in the validation cohort.Participants were divided into four groups based on their body mass index Z-score and whether they were diagnosed with CPP.Ultra-performance liquid chromatography coupled with tandem mass spectrometry was performed to quantify 38 serum BAs.Results There were 18 individual BAs that were statistically different between CPP and non-CPP counterparts.The majority of these BAs(14/18)correlated significantly with sex-related hormones(P<0.05).In girls with normal weight(NW),a logistic regression model combining chenodeoxycholic acid,tauro α-muricholic acid,and 6-ketolithocholic acid achieved an area under the receiver operating characteristic curve(AUC)of 0.885.For girls who were overweight/obese(OB),hyocholic acid and taurohyocholic acid enhanced the diagnostic efficiency of basal luteinizing and follicle stimulating hormones to an AUC value 0.914.In validation cohort,75.34%NW girls and 84.09%OB girls were accurately classified.Conclusions Serum BA profiles of CPP girls showed significant changes that were associated with serum sex-related hormone levels.BA profiles could be potential biomarkers in CPP diagnosis and screening.展开更多
Background：In central precocious puberty （CPP）,the pulse secretion and release ofgonadotropin-releasing hormone （GnRH） are increased due to early activation of the hypothalamic-pituitary-gonadal axis,resulting in...Background：In central precocious puberty （CPP）,the pulse secretion and release ofgonadotropin-releasing hormone （GnRH） are increased due to early activation of the hypothalamic-pituitary-gonadal axis,resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics.The CPP without organic disease is known as idiopathic CPP （ICPP）.The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin （GnRH analog） in girls with ICPP.Methods：A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups.One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate,79 girls in the control group were treated with imported leuprorelin acetate.They all were treated and observed for 6 months.After 6-month treatment,the percentage of children with peak luteinizing hormone （LH） ≤3.3 U/L,the percentage of children with peak LH/peak follicle stimulating hormone （FSH） ratio 〈0.6,the improvements of secondary sexual characteristics,gonadal development and sex hormone levels,the change of growth rate of bone age （BA） and growth velocity,and drug adverse effects between two groups were compared.Results：After the treatment,the percentage of children with a suppressed LH response to GnRH,defined as a peak LH ≤3.3 U/L,at 6 months in test and control groups were 96.80% and 96.20%,respectively,and the percentage of children with peak LH/FSH ratio ≤0.6 at 6 months in test and control groups were 93.60% and 93.70%,respectively.The sizes of breast,uterus and ovary of children and the levels of estradiol （E2） were significantly reduced,and the growth rate of BA was also reduced.All the differences between pre-and post-treatment in each group were statistically significant （P 〈 0.05）,but the differences of the parameters between two groups were not significant （P 〉 0.05）.Conclusions：Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP.Its effectiveness and safety are comparable with imported leuprorelin.展开更多
The relationship between vitamin D deficiency and idiopathic central precocious puberty （ICPP） has been recently documented. In this study, 280 girls diagnosed with ICPP and 188 normal puberty control girls of simil...The relationship between vitamin D deficiency and idiopathic central precocious puberty （ICPP） has been recently documented. In this study, 280 girls diagnosed with ICPP and 188 normal puberty control girls of similar ages were enrolled and retrospectively studied. The ICPP group had significantly lower serum 25- hydroxyvitamin D （25[OH]D） levels than the control group. Furthermore, a nonlinear relationship was found between serum 25[OH]D and ICPP, and a cut-offpoint for serum 25[OH]D was found at 31.8 ng/ml for ICPP with and without adjusting the different confounding factors. Girls with serum 25[OH]D 〉~ 31.8 ng/ml had a lower odds ratio （unadjusted： OR 0.36, 95% CI 0.15 to 0.83, P 〈 0.05; height and weight adjusted： OR 0.44, 95~0 CI 0.18 to 1.08, P = 0.072; BMI adjusted： OR 0.36, 95% CI 0.16 to 0.84, P 〈 0.05）. The ICPP subjects with 25[OH]D deficiency had a higher body mass index （BMI） than the subjects from the two other subgroups. Correlation analysis showed that vitamin D level is correlated with BMI and some metabolic parameters in the ICPP group. Our study suggested that vitamin D status may be associated with ICPP risk and may have a threshold effect on ICPP.展开更多
Childhood obesity and obesity-related metabolic complications are induced by a high-fat postnatal diet. The lack of a suitable animal model, however, remains a considerable challenge in obesity studies. In the current...Childhood obesity and obesity-related metabolic complications are induced by a high-fat postnatal diet. The lack of a suitable animal model, however, remains a considerable challenge in obesity studies. In the current study, we provided high-fat diet （HFD） to dams during lactation and to pups after weaning. We also developed a novel model of C57BL/6J mouse pups with HFD-induced postnatal obesity. Results showed that feeding with HFD induces fat deposition and obesity in pups. Furthermore, HFD more potently increased the body weight （BW） of male than female pups. HFD-fed female pups were obese, underwent precocious puberty, and showed increased kisspeptin expression in the hypothalamus. However, parental obesity and precocious puberty exerted no synergistic effects on the HFD-induced postnatal weight gain and puberty onset of the pups. Interestingly, some HFD-fed litters with normal BW also exhibited precocious puberty. This finding suggested that diet composition but not BW triggers puberty onset. Our model suggests good construction validity of obesity and precocious puberty. Furthermore, our model can also be used to explore the mutual interactions between diet-induced postnatal childhood obesity and puberty.展开更多
Objective: To find effective therapeutic approach for treating true idiopathic precocious puberty suitable to our national condition and different from gonadotrophin releasing hormone analogue. Methods: One hundred an...Objective: To find effective therapeutic approach for treating true idiopathic precocious puberty suitable to our national condition and different from gonadotrophin releasing hormone analogue. Methods: One hundred and six girls with idiopathic precocious puberty were divided into 3 groups. The 51 girls in the TCMWM group were treated with Chinese herbal medicine combined with megestrol acetate (MA), 35 girls in the MA group treated with megestrol acetate alone, and 20 girls were taken as control group and given no treatment at all. Luteinizing hormone releasing hormone (LHRH) stimulating test were performed before and after treatment, and the size of the uterus and ovary, linear growth rate, X-ray bone age measurement and final height prediction were also observed simultaneously. Results: After treated with TCM-WM for 2.7 years in average,the luteinizing hormone (LH) peak value of LHRH stimulating test was reduced from 48. 5 ± 5. 2 IU/L to 12.2 ± 1. 3 IU/L, size of uterus and ovary decreased, secondary sexual characteristics regressed, the bone age difference/chronological age difference value (ΔBA/ΔCA) reduced from 1. 35 ± 0. 09 to 0. 65 ± 0. 05 and predictive final height increased from 153. 3 ± 0. 5 cm to 158. 5 ± 0. 6 cm. Conclusion: TCM-WM therapy could not only modulate the function of hypothalamic-pituitary-ovarian axis and the development of internal genitalia, but also could decelerate skeletal growth, delay skeletal maturation, and thereby prevent premature epiphyseal fusion and increase the final height of patients.展开更多
There is increasing evidence that patients with gonad dysplasia,as characterized by absent or incomplete puberty,can also exhibit central precocious puberty(CPP).Herein,we review the reported cases that manifest with ...There is increasing evidence that patients with gonad dysplasia,as characterized by absent or incomplete puberty,can also exhibit central precocious puberty(CPP).Herein,we review the reported cases that manifest with both gonad dysplasia and CPP.Further,we examine the hypothesis that these patients exhibit a normal hypothalamic-pituitarygonadal axis,hypogonadism,and the presence of residual gonadal function,and that the onset of disease is related to early initiation of the hypothalamic-pituitary-gonadal axis.Thus,we suggest that CPP is a prelude of some partial hypogonadism.展开更多
BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explor...BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.展开更多
基金Shaanxi Provincial People’s Hospital Science and Technology Talent Support Program(Project No.:2023LJ-02)。
文摘Objective:To review the scientific research results of early puberty in children in the past decade,and to explore the current status,hot spots and frontiers of research in the field of early puberty in children.Methods:From January 1,2014 to April 30,2024,literature on early puberty in children was retrieved from CNKI database and Web of Science(WOS)core collection.CiteSpace6.3.R1 software was used for bibliometric analysis of authors,institutions and key words,and related visual maps were drawn.Results:A total of 1548 English literatures and 1113 Chinese literatures were included.The number of published papers in both Chinese and English showed an increasing trend.The authors of the high production in Chinese were Ye Jin and Yang Li,and the high production institutions were the pediatrics department of Hubei University of Chinese Medicine and Shuguang Hospital Affiliated to Shanghai University of Chinese Medicine.The authors are Latronico,Ana Claudia,and Universidade de Sao Paulo.Hot topics in Chinese and English studies include bone age,hormones,genetic inheritance,the correlation between precocious puberty and obesity and short stature.Conclusion:There is an increasing trend of research in the field of early puberty in children.The research on physical identification of children with precocious puberty and the dynamic detection of precocious puberty,height and obesity by Internet is worthy of continuous attention by domestic scholars.
基金National Natural Science Foundation of China,Grant/Award Number:82101937Guangdong Medical Science and Technology Research Fund Project,China,Grant/Award Number:B2024069Guangzhou Science and Technology Plan Project,China,Grant/Award Number:2024A04J4923 and SL2023A04J02229。
文摘Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice enter puberty only 4–5 days earlier than normal mice),the related research is limited.Methods:Therefore,the MKRN3-modified rabbit was developed using CRISPR(clus-tered regularly interspaced short palindromic repeats)gene editing technology.The genotype identification and phenotype evaluation of MKRN3-modified rabbits were carried out.Results:The first estrus of MKRN3-modified female rabbits was observed~27 days earlier than that of wild-type female rabbits,with a typical CPP phenotype.This study found increased gonadotropin releasing hormone(GnRH)and decreased gonadotropin inhibiting hormone(GnIH)in the hypothalamus of the CPP rabbit model with MKRN3 gene mutation.Although this study failed to fully clarify the pathogenesis of CPP caused by MKRN3 mutation,it found some differentially expressed genes and potential pathways through transcriptome sequencing.Conclusions:This study established a novel CPP model:paternal MKRN3 gene-modified rabbit.It is hoped that the establishment of this model will help researchers better understand,treat,and prevent CPP in the future.
文摘In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.
基金by the key Research and Development Program of Zhejiang Province(No.2020C03121).
文摘BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in girls.Makorin ring finger protein 3(MKRN3),a maternal imprinted gene with a highly conserved sequence,is the most common genetic etiology associated with CPP.Approximately 50 different mutations in MKRN3 have been found in CPP.CASE SUMMARY This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years.The left hand bone age of both patients revealed advanced age(9 years).Pelvic B ultrasound indicated enlargement of the ovaries.Luteinizing hormone(LH)releasing hormone testing confirmed CPP.Wholeexome sequencing detected the c.841C>T mutation in MKRN3,leading to a single base substitution,in the twins.This mutation was inherited from the father and paternal grandmother.After 3 mo of treatment with a gonadotropin-releasing hormone analog,levels of LH,follicle-stimulating hormone,and estradiol in the proband’s sister returned to normal levels.CONCLUSION Here,we report a rare mutation(c.841C>T)in MKRN3 in identical twin sisters with CPP.
文摘Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children’s Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40–140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1–6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.
基金Jiangsu Province Maternal and Child Health Care Project (No.FYX202213)。
文摘Objective:To observe the clinical efficacy of different dosage forms of lepraline acetate(LA)in the treatment of girls with central precocious puberty(CPP).Methods:72 CPP girls treated in the Department of Pediatrics of Huai'an First People's Hospital from February 2021 to August 2022 were included as subjects and divided into two groups:3-month LA group(n=34)and 1-month LA group(n=38).Both group girls were treated for 6 months.Serum hormone levels,body mass index(BMI),bone age/chronological age(BA/CA)and pelvic color ultrasound were detected at 0 and 6 months after treatment,and the changes of various indexes were compared before and after treatment.Results:1)There were no significant differences in baseline data between the two groups before treatment(P>0.05).2)After 6 months of treatment,BA/CA decreased,growth rate slowed down,and predicted adult height increased in both groups(P<0.05),but there were no significant differences between groups(P>0.05).3)After 6 months of treatment,there waere no significant differences in luteinizing hormone(LH)inhibition ratio between the 3 month and 1 month dosage groups(P>0.05).After treatment,the peak value of serum LH and FSH,estradiol level,uterine volume,bilateral ovarian volume,maximum follicle diameter and the number of follicles 4mm were significantly decreased in the two groups,but there were no significant differences between the two groups(P>0.05).4)There were no significant differences in the levels of thyroid hormone,fasting blood glucose and triglyceride between the two groups before and after treatment(P>0.05).Total cholesterol levels were increased after treatment(P<0.05),but there was no significant difference between groups(P>0.05).5)No serious adverse reactions occurred during the treatment of the two dosage forms of LA,but the 3-month dosage form of LA reduced the treatment cost and improved the treatment compliance.Conclusion:The short-term efficacy of 3-month LA in the treatment of CPP in girls is similar to that of 1-month LA.The 3-month dosage form LA is a safe,effective,and economical method for the treatment of CPP in girls.
文摘Van Wyk-Grumbach syndrome (VWGS) is characterized by juvenile hypothyroidism, delayed bone age, isosexual precocious puberty and massive ovarian cysts. We report such a case in a 7-year-old girl who presented with a bilateral pelvic pain, abdominal distension and signs of hypothyroidism. Physical examination showed a breast development and lack of pubic and axillary hair. There was no clitoromegaly. Pelvic ultrasonography and CT scan showed enlarged bilateral multiloculared multicystics ovarian masses. The pituitary MRI was recommended before an elevated prolactin, revealed a large sellar and suprasellar mass. The patient was started on thyroid replacement using L-Thyroxine. Clinically, the patient’s fatigue, pelvic pain, and abdominal distension are resolved. During the follow-up, her thyroid functions and serum prolactin normalized within 8 months. Ultrasonography revealed regression of ovarian cysts in 2 months measuring, with normal sized ovaries in 14 months.
文摘Autoimmune polyglandular syndrome type 1 (APS-1) is one of the rare inherited disorder that affects both sexes alike. Although in specific autoimmune dysfunction associated with this syndrome found to be more common in females than males. It has specific criteria usually presented at a specific age. The object of this clinical case report is to highlight this unusual presentation of such condition which is the presence of APS-1 with precocious puberty and alopecia Universalis without any associated symptoms of APS-1 and the gene variations that never had been found before. And up to our knowledge, this is the 1st case in our population and worldwide that has such combination and this is unusual clinical presentation. Autoimmune polyglandular syndrome type 1 (APS-1) is one of the rare inherited disorder that affects both sexes alike. Although in specific autoimmune dysfunction associated with this syndrome found to be more common in females than males. It has specific criteria usually presented at a specific age. The object of this clinical case report is to highlight this unusual presentation of such condition which is the presence of APS-1 with precocious puberty and alopecia Universalis without any associated symptoms of APS-1 and the gene variations that never had been found before. And up to our knowledge, this is the 1st case in our population and worldwide that has such combination and this is unusual clinical presentation.
文摘Objectives: To investigate the potential role of GABAB Receptors (GABABRs) involved in the effect of Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM) treatment on precocious puberty. Methods: Female Sprague-Dawley rats were randomly divided into four groups: normal (N), central precocious puberty (CPP) model (M), CPP fed with normal saline (S) and CPP fed with Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM). Rats of postnatal day 5 were given a single subcutaneous injection of 240 μg danazol to establish CPP model rats. Rats of S and TCM groups were continuously administered with saline or nourishing “Yin”-removing “Fire” Chinese herb mixture since postnatal day 15. The expression of GABABRs was detected by means of real-time PCR and immunohistochemistry. Results: The expression of hypothalamic GnRH mRNA in M was significantly increased on the day of pre-puberty when compared with that of N (P < 0.01). On the day of onset-puberty, LH levels were higher in M than those in N (P < 0.01), while the serum E2 and LH levels of TCM decreased when compared with those of M (P <sub>B1</sub> receptor (GABABR1) immunoreactive cells in the arcuate nucleus (ARN) was decreased in M when compared with that of N (P < 0.05) and increased in TCM compared with that of M (P < 0.05);simultaneously, the expression of GABABR1 mRNA in hypothalamus was significantly decreased in M when compared with that of N (P < 0.01) and increased in TCM compared with that of M (P < 0.01). On the day of onset-puberty, the number of GABABR1 immunoreactive cells in medial septum (MS) was decreased in M compared with that in N (P < 0.05) and increased in TCM comparing with that of M (P < 0.05);meanwhile, the mRNA expression of GABABR1 in hypothalamus was decreased in M compared with that in N (P <sub>B2</sub> receptor (GABABR2) immunoreactive cells in the ARN, MS and diagnonal band of broca (DBB) were decreased in M when compared with those of N (P < 0.05) and increased in TCM compared with those of M (P < 0.05) on the day of onset-puberty. At the same time, the mRNA expression of GABABR2 was significantly decreased in M compared with that of N (P < 0.01). Conclusions: These results indicated that the GABABRs might involve in the curative effect of Nourishing “Yin”-Removing “Fire” Chinese herbal mixture on CPP rats.
文摘Objective:This study aimed to evaluate the therapeutic effects of leuprolide acetate extended-release microspheres for injection in children with pediatric precocious puberty.Methods:A total of 110 cases of pediatric precocious puberty admitted between January 2019 and December 2021 were selected and randomized into two groups using a random number table,with 55 cases in the control group and 55 cases in the experimental group.The control group received conventional treatment,while the experimental group was treated with leuprolide acetate extended-release microspheres for injection.The therapeutic effects were observed,and changes in sex hormone levels,ovarian volume,growth indices,and the incidence of adverse reactions were statistically compared between the groups.Results:The experimental group demonstrated superior outcomes in terms of sex hormone levels,ovarian volume,and growth indices compared to the control group.Additionally,the incidence of adverse reactions in the experimental group was significantly lower(P<0.05).Conclusion:The application of leuprolide acetate extended-release microspheres for the treatment of pediatric precocious puberty is associated with improved therapeutic effects and higher safety.
基金Supported by the National Natural Science Foundation of China(No.81072841)the Shanghai Science and Technology Research Grant Program(No.09dZ1971600)State Key Clinical Department of TCM pediatrics
文摘OBJECTIVE:To establish a quantification model of Traditional Chinese Medicine(TCM)syndromes by sampling patients undergoing idiopathic precocious puberty(IPP)and early puberty.METHODS:A questionnaire for classifying and quantifying TCM syndromes was designed and administered.All the results were analyzed;the relationship between 3 types of syndrome and 47symptoms were summated.Meanwhile,the frequency distribution of each symptom or sign was aggregated.Fuzzy mathematics was used to develop a quantification model ofTCM syndromes.RESULTS:We found that precocious puberty had 3types of syndrome,including hyperactivity of fire due to Yin deficiency(Syndrome I),depressed liver Qi transforming into fire(Syndrome II),and end retention of damp heat(Syndrome III).In the IPP group,Syndrome I was the most common principal syndrome(100%).Forty-six patients(43.81%)werediagnosed with Syndrome I accompanied by Syndrome II and 11(10.48%)were diagnosed with Syndrome I accompanied by Syndrome III.In the early puberty group,Syndrome I was also the main syndrome(98.39%).The degrees of most symptoms were mild to moderate.Reddened tongue was the most common tongue manifestation(62.86%prevalence)in the IPP group.The most common pulse manifestations were slippery pulse,thread pulse,and taut pulse.The Asymptotic Normalization Coefficient(ANC)method was used to quantify the TCM syndromes in 167 cases.Diagnostic accuracy rate reached 91%,comparable to expert diagnosis.CONCLUSION:We find that there are 3 types of syndrome in the IPP group and in the early puberty group.Syndrome I(hyperactivity of fire due to Yin deficiency)is the main syndrome in the two groups.ANC may be an appropriate for quantification model ofTCM syndromes.
文摘In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty （ICPP）, 46 girls with ICPP were treated with GnRHa. Triptorelin （Decapeptyl, 3.75 mg） was administered subcutaneously （SC） at 6-weeks intervals or intramuscularly （IM） at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage, bone age, uterine volume and ovarian size, serum levels of luteinizing hormone （LH）, follicle stimulating hormone （FSH） and estradiol （E2）, were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics. Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment. The height velocity was decreased significandy from 6.3±1.4 cm/year to 5.8：1：1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBAgdeltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively. The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in di- ameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients, which disappeared after 6- 12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was concluded that both IM and SC triptorelin administrations were clinically effective. They induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6-weeks intervals at a dosage of 3.75 mg be a safe and acceptable regimen for ICPP.
基金supported by the Key Research and Development Program of Zhejiang(No.2023C03047)the National Key Research and Development Program of China(No.2021YFC2701900)the National Natural Science Foundation of China(Nos.82170583 and 82370863).
文摘Background The diagnosis of central precocious puberty(CPP)relies on a gonadotropin releasing hormone stimulation test to assess the activation of the hypothalamic-pituitary-gonadal axis;this is costly and painful.Bile acids(BAs)have emerged as pivotal signaling molecules in the reproductive system.This study aimed to identify circulating BA profile signatures and explored if they may serve as biomarkers for CPP diagnosis in girls.Methods We enrolled 431 girls,including 241 in the training cohort and 190 in the validation cohort.Participants were divided into four groups based on their body mass index Z-score and whether they were diagnosed with CPP.Ultra-performance liquid chromatography coupled with tandem mass spectrometry was performed to quantify 38 serum BAs.Results There were 18 individual BAs that were statistically different between CPP and non-CPP counterparts.The majority of these BAs(14/18)correlated significantly with sex-related hormones(P<0.05).In girls with normal weight(NW),a logistic regression model combining chenodeoxycholic acid,tauro α-muricholic acid,and 6-ketolithocholic acid achieved an area under the receiver operating characteristic curve(AUC)of 0.885.For girls who were overweight/obese(OB),hyocholic acid and taurohyocholic acid enhanced the diagnostic efficiency of basal luteinizing and follicle stimulating hormones to an AUC value 0.914.In validation cohort,75.34%NW girls and 84.09%OB girls were accurately classified.Conclusions Serum BA profiles of CPP girls showed significant changes that were associated with serum sex-related hormone levels.BA profiles could be potential biomarkers in CPP diagnosis and screening.
文摘Background：In central precocious puberty （CPP）,the pulse secretion and release ofgonadotropin-releasing hormone （GnRH） are increased due to early activation of the hypothalamic-pituitary-gonadal axis,resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics.The CPP without organic disease is known as idiopathic CPP （ICPP）.The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin （GnRH analog） in girls with ICPP.Methods：A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups.One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate,79 girls in the control group were treated with imported leuprorelin acetate.They all were treated and observed for 6 months.After 6-month treatment,the percentage of children with peak luteinizing hormone （LH） ≤3.3 U/L,the percentage of children with peak LH/peak follicle stimulating hormone （FSH） ratio 〈0.6,the improvements of secondary sexual characteristics,gonadal development and sex hormone levels,the change of growth rate of bone age （BA） and growth velocity,and drug adverse effects between two groups were compared.Results：After the treatment,the percentage of children with a suppressed LH response to GnRH,defined as a peak LH ≤3.3 U/L,at 6 months in test and control groups were 96.80% and 96.20%,respectively,and the percentage of children with peak LH/FSH ratio ≤0.6 at 6 months in test and control groups were 93.60% and 93.70%,respectively.The sizes of breast,uterus and ovary of children and the levels of estradiol （E2） were significantly reduced,and the growth rate of BA was also reduced.All the differences between pre-and post-treatment in each group were statistically significant （P 〈 0.05）,but the differences of the parameters between two groups were not significant （P 〉 0.05）.Conclusions：Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP.Its effectiveness and safety are comparable with imported leuprorelin.
文摘The relationship between vitamin D deficiency and idiopathic central precocious puberty （ICPP） has been recently documented. In this study, 280 girls diagnosed with ICPP and 188 normal puberty control girls of similar ages were enrolled and retrospectively studied. The ICPP group had significantly lower serum 25- hydroxyvitamin D （25[OH]D） levels than the control group. Furthermore, a nonlinear relationship was found between serum 25[OH]D and ICPP, and a cut-offpoint for serum 25[OH]D was found at 31.8 ng/ml for ICPP with and without adjusting the different confounding factors. Girls with serum 25[OH]D 〉~ 31.8 ng/ml had a lower odds ratio （unadjusted： OR 0.36, 95% CI 0.15 to 0.83, P 〈 0.05; height and weight adjusted： OR 0.44, 95~0 CI 0.18 to 1.08, P = 0.072; BMI adjusted： OR 0.36, 95% CI 0.16 to 0.84, P 〈 0.05）. The ICPP subjects with 25[OH]D deficiency had a higher body mass index （BMI） than the subjects from the two other subgroups. Correlation analysis showed that vitamin D level is correlated with BMI and some metabolic parameters in the ICPP group. Our study suggested that vitamin D status may be associated with ICPP risk and may have a threshold effect on ICPP.
文摘Childhood obesity and obesity-related metabolic complications are induced by a high-fat postnatal diet. The lack of a suitable animal model, however, remains a considerable challenge in obesity studies. In the current study, we provided high-fat diet （HFD） to dams during lactation and to pups after weaning. We also developed a novel model of C57BL/6J mouse pups with HFD-induced postnatal obesity. Results showed that feeding with HFD induces fat deposition and obesity in pups. Furthermore, HFD more potently increased the body weight （BW） of male than female pups. HFD-fed female pups were obese, underwent precocious puberty, and showed increased kisspeptin expression in the hypothalamus. However, parental obesity and precocious puberty exerted no synergistic effects on the HFD-induced postnatal weight gain and puberty onset of the pups. Interestingly, some HFD-fed litters with normal BW also exhibited precocious puberty. This finding suggested that diet composition but not BW triggers puberty onset. Our model suggests good construction validity of obesity and precocious puberty. Furthermore, our model can also be used to explore the mutual interactions between diet-induced postnatal childhood obesity and puberty.
文摘Objective: To find effective therapeutic approach for treating true idiopathic precocious puberty suitable to our national condition and different from gonadotrophin releasing hormone analogue. Methods: One hundred and six girls with idiopathic precocious puberty were divided into 3 groups. The 51 girls in the TCMWM group were treated with Chinese herbal medicine combined with megestrol acetate (MA), 35 girls in the MA group treated with megestrol acetate alone, and 20 girls were taken as control group and given no treatment at all. Luteinizing hormone releasing hormone (LHRH) stimulating test were performed before and after treatment, and the size of the uterus and ovary, linear growth rate, X-ray bone age measurement and final height prediction were also observed simultaneously. Results: After treated with TCM-WM for 2.7 years in average,the luteinizing hormone (LH) peak value of LHRH stimulating test was reduced from 48. 5 ± 5. 2 IU/L to 12.2 ± 1. 3 IU/L, size of uterus and ovary decreased, secondary sexual characteristics regressed, the bone age difference/chronological age difference value (ΔBA/ΔCA) reduced from 1. 35 ± 0. 09 to 0. 65 ± 0. 05 and predictive final height increased from 153. 3 ± 0. 5 cm to 158. 5 ± 0. 6 cm. Conclusion: TCM-WM therapy could not only modulate the function of hypothalamic-pituitary-ovarian axis and the development of internal genitalia, but also could decelerate skeletal growth, delay skeletal maturation, and thereby prevent premature epiphyseal fusion and increase the final height of patients.
文摘There is increasing evidence that patients with gonad dysplasia,as characterized by absent or incomplete puberty,can also exhibit central precocious puberty(CPP).Herein,we review the reported cases that manifest with both gonad dysplasia and CPP.Further,we examine the hypothesis that these patients exhibit a normal hypothalamic-pituitarygonadal axis,hypogonadism,and the presence of residual gonadal function,and that the onset of disease is related to early initiation of the hypothalamic-pituitary-gonadal axis.Thus,we suggest that CPP is a prelude of some partial hypogonadism.
文摘BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.
