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Frontiers in Endocrinology 2023This study aimed to investigate the diagnostic value of luteinizing hormone (LH) basal values and sex hormone-binding globulin (SHBG) for rapidly progressive central...
OBJECTIVE
This study aimed to investigate the diagnostic value of luteinizing hormone (LH) basal values and sex hormone-binding globulin (SHBG) for rapidly progressive central precocious puberty (RP-CPP).
METHODS
A total of 121 girls presenting with secondary sexual characteristics were selected from the Department of Pediatric Endocrinology, Lianyungang Clinical Medical College of Nanjing Medical University, from May 2021 to June 2023. The children were followed up for 6 months and were divided into three groups: RP-CPP group (n=40), slowly progressive central precocious puberty (SP-CPP) group (n=40), and premature thelarche (PT) group (n=41). The differences in LH basal values and SHBG among girls in the three groups were compared. ROC curves were drawn to analyze the value of LH basal values and SHBG in identifying RP-CPP.
RESULTS
Significant differences were observed in age, height, predicted adult height (PAH), weight, body mass index (BMI), bone age (BA), BA-chronological age (CA), LH basal, LH peak, FSH basal, LH peak/FSH peak, estradiol (E2), testosterone, and SHBG levels between the RP-CPP group and the SP-CPP and PT groups (P < 0.05). The LH basal value in the RP-CPP group was higher than that in the SP-CPP group and the PT group, while SHBG levels were lower than in the latter two groups, and these differences were statistically significant (P < 0.05). When the LH basal value was ≥0.58 IU/L and SHBG was ≤58.79 nmol/L, the sensitivity for diagnosing RP-CPP was 77.5% and 67.5%, and the specificity was 66.7% and 74.1%.
CONCLUSION
Detection of basal LH and SHBG levels allows for early diagnosis of the progression of central precocious puberty.
Topics: Child; Female; Humans; Early Diagnosis; Follicle Stimulating Hormone; Luteinizing Hormone; Puberty, Precocious; Sex Hormone-Binding Globulin
PubMed: 38317710
DOI: 10.3389/fendo.2023.1273170 -
Srpski Arhiv Za Celokupno Lekarstvo 2006Precocious puberty in girls is generally defined as appearance of secondary sexual characteristics before eight years of age. Menarche before the ninth birthday may...
INTRODUCTION
Precocious puberty in girls is generally defined as appearance of secondary sexual characteristics before eight years of age. Menarche before the ninth birthday may serve as an additional criterion. Precocious puberty is divided in central precocious puberty and pseudoprecocious puberty. Central precocious puberty (GnRH dependent) occurs because of premature activation of hypothalamic-pituitary-gonadal axis and activity of gonadotrophins. Pseudoprecocious puberty (GnRH independent) is caused by activity of sexual steroids that are not the result of gonadotrophin activity.
OBJECTIVE
Objective of our study was to examine the etiology, clinical and laboratory manifestations of isosexual pseudoprecocious puberty in girls.
METHOD
In the period between 1995 and 2004, clinical and laboratory sings of 34 girls with precocious puberty were studied at the Endocrine Department of the Institute of Mother and Child Health Care of Serbia. Initial evaluations included height measurement, staging of puberty, bone age assessment and pelvic ultrasound. Important diagnostic sonographic parameters of precocious puberty were the volumes of ovaries and uterus as well as ovarian structure. The initial hormonal evaluation included measuring of plasma oestradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH). The luteinizing hormone releasing hormone (LHRH) stimulation test was used to evaluate LH and FSH responsiveness (60 microg/m2 LHRH-Relefact LHRH, Ferring). Blood samples were collected at 0, 20 and 60 minutes. Basal and GnRH stimulated LH and FSH were determined by immunoradiometric assay. Estradiol concentration was measured using the fluoroimmunometric assay.
RESULTS
Thirty-four girls aged 6 months to 9 years (mean age 4.5 years) with precocious puberty were studied during the period of 9 years. Eleven girls presented with breast development, six with vaginal bleeding and seventeen with signs of puberty. On the basis of clinical signs, bone age, estradiol levels and LHRH test, premature thelarche was diagnosed in eleven patients (32.4%), premature menarche in six (17.6%) and central precocious puberty in ten girls (29.4%). Seven girls (20.6%) presented with pseudoprecocious puberty. Pelvic ultrasound examination revealed unilateral ovarian cysts in six patients and granulosa cell tumor in one. Elevated estrogen serum levels and failure of gonadotropin responses after gonadotropin releasing hormone were the classical findings in patients with isosexual pseudoprecocious puberty during the acute period of disease. In four patients, the cyst decreased spontaneously after several months, while in two patients, the cyst was removed by laparotomy. Surgical treatment was performed in a patient with granulosa cell tumor.
CONCLUSION
Our work demonstrates that autonomous functional ovarian follicle cyst is the most often cause of isosexual pseudoprecocious puberty. Short period of observation is suggested because the cyst can resolve spontaneously. On the other hand, juvenile granulosa cell tumor, as highly malignant tumor, should be removed as soon as diagnosis is established.
Topics: Child; Child, Preschool; Estradiol; Female; Follicle Stimulating Hormone; Granulosa Cell Tumor; Humans; Infant; Luteinizing Hormone; Ovarian Cysts; Ovarian Neoplasms; Puberty, Precocious
PubMed: 17009609
DOI: 10.2298/sarh0608305m -
Korean Journal of Pediatrics Aug 2015It is difficult to differentiate between central precocious puberty (CPP) and premature thelarche (PT) in girls. The aim of this study was to investigate the diagnostic...
PURPOSE
It is difficult to differentiate between central precocious puberty (CPP) and premature thelarche (PT) in girls. The aim of this study was to investigate the diagnostic usefulness of pelvic ultrasonography to distinguish between CPP and PT in girls with early breast development.
METHODS
This study included girls with early breast development who visited the clinic between January 2012 and December 2013. Clinical, laboratory, and pelvic ultrasonographic data were evaluated. CPP and PT were confirmed using the gonadotropin-releasing hormone stimulation test.
RESULTS
A total of 248 girls aged 7-8 years were included, among whom 186 (75.0%) had CPP and 62 (25.0%) had PT. The uterine length, transverse diameter, fundus, volume, and cross-sectional area were significantly larger in the CPP group (uterine length, 2.45±0.50 cm vs. 2.63±0.49 cm, P=0.015; uterine volume, 0.95±0.62 cm(3) vs. 1.35±0.76 cm(3), P<0.001). However, there were no differences in the fundus/cervix ratio and ovarian measurements. In receiver operating characteristic analysis, a uterine volume of at least 1.07 cm(3) was the most predictive parameter for CPP with an area under the curve of 0.670 (95% confidence interval, 0.593-0.747).
CONCLUSION
Uterine measurements by pelvic ultrasonography in girls with early pubertal development were significantly larger in the CPP group. However, the diagnostic value of ultrasonographic parameters was not high because of a considerable overlap of values between the two groups. Therefore, pelvic ultrasonography in combination with clinical and laboratory tests may be useful to distinguish between CPP and PT in girls.
PubMed: 26388894
DOI: 10.3345/kjp.2015.58.8.294 -
Medicine Mar 2018Rapid and noninvasive diagnosis on and differentiation between normal, central precocious puberty (CPP), and isolated precocious puberty (IPP) is imperative before a... (Observational Study)
Observational Study
Rapid and noninvasive diagnosis on and differentiation between normal, central precocious puberty (CPP), and isolated precocious puberty (IPP) is imperative before a decision can be made with gonadotropin-releasing hormone (GnRH) agonist treatment. Our study aims to evaluate such a role by pelvic ultrasound.We consecutively enrolled 84 cases of IPP (59 with premature thelarche/ pubarche and 25 with premature menarche), 47 CPP, and 177 age-matched normal controls. The IPP and CPP were diagnosed by clinical examination and GnRH-stimulation test and confirmed by over 2 years' follow-up. All subjects underwent pelvic ultrasound examination for length, width, thickness, volume of uterine/cervix/ovaries, fundal/cervical thickness ratio, endometrial thickness, and averaged maximal diameter of largest follicles. Statistical comparisons of these sonographic parameters between disease groups were made according to age intervals.It was found that between CPP and normal girls, 10 and 12 ultrasound parameters differed significantly in the >6 to 8 and >8 to 10 years age interval, respectively. Cervical thickness and endometrial thickness was the best discriminating parameter in the 2 intervals by receiver operating characteristic (ROC) curve analysis, and the cutoff, sensitivity and specificity associated with was 0.73 cm, 93.30%, 85.70%, and 0.26 cm, 76.92%, 100%, respectively. Between CPP and IPP, 2 and 5 parameters differed significantly in the >6 to 8 and >8 to 10 years age interval. Cervical length was the best discriminating parameter in both age intervals. The cutoff, sensitivity, and specificity associated were 1.49 cm, 93.33%, 55.17%, and 1.88 cm, 100%, 71.43%, respectively; Finally between normal and IPP girls, 4, 7, and 5 parameters differed significantly in the 0 to 6, >6 to 8, and >8 to 10 years intervals, respectively. Ovarian thickness, ovarian width, and cervix thickness was the best parameter for the 3 age interval respectively, and the cutoff, sensitivity and specificity associated were 0.98 cm, 76.46%, 84.85%, 1.39 cm, 85.71%,73.81%, and 0.75 cm, 90.48%, 64.21%, respectively.Our results indicate that pelvic ultrasonography could serve as a complementary tool for differentiation between normal girls and girls with different forms of sexual precocity in China. The best discriminating parameter changes according to precocity forms and age intervals.
Topics: Case-Control Studies; Child; China; Female; Genitalia, Female; Gonadotropin-Releasing Hormone; Humans; Pelvis; Puberty, Precocious; ROC Curve; Ultrasonography
PubMed: 29517679
DOI: 10.1097/MD.0000000000010092 -
BMC Pediatrics Jul 2022We report five patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), four of whom presented with precocious puberty and one with growth hormone deficiency...
BACKGROUND
We report five patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), four of whom presented with precocious puberty and one with growth hormone deficiency (GHD. Our five children add to the growing endocrine data base of MRKHS.
CASE PRESENTATION
We retrospectively reviewed clinical data of 5 MRKHS patients from 2017 to 2020. The clinical features, hormonal profiles, radiological imaging and genetic analyses were collated. The age range of the 5 patients at diagnosis was 6.7-9.1 years. Four presented with premature thelarche, and one presented with short stature. External genitalia were normal in all patients. Gonadotropin-releasing hormone stimulation tests for the 5 patients revealed peak luteinizing hormone and follicular stimulating hormone levels of 3.57, 6.24, 11.5, 4.44 and 4.97 IU/L and 9.41, 16.7, 13.8, 14.2 and 10.3 mIU/mL, respectively. Growth hormone stimulation for one patient with short stature was consistent with GHD with a peak level of GH was 7.30 ng/mL. Imaging disclosed advanced bone age in four patients and no skeletal abnormalities in any of the patients. Ultrasonography of the abdomen revealed bilateral polycystic kidneys in one patient. Pelvic magnetic resonance imaging confirmed no uterus in five patients. All of the patients had a normal karyotype (46, XX). In one patient, whole-exome sequencing detected a deletion of 17q12(chr17:36,046,434-36,105,050, hg19) encompassing the HNF1B gene.
CONCLUSIONS
We report the unusual co-occurrence of precocious puberty and GHD in patients with MRKHS, highlighting that abnormal puberty and growth development may represent initial unexplained manifestations. Whether the deletion of 17q 22 begat GHD is unclear.
Topics: 46, XX Disorders of Sex Development; Child; Child, Preschool; Congenital Abnormalities; Female; Growth Hormone; Humans; Mullerian Ducts; Puberty, Precocious; Retrospective Studies; Vagina
PubMed: 35836205
DOI: 10.1186/s12887-022-03474-0 -
BMC Pediatrics Jul 2008It is sometimes difficult to distinguish between premature thelarche and precocious puberty in girls who develop breasts before the age of 8 years. We evaluated the...
BACKGROUND
It is sometimes difficult to distinguish between premature thelarche and precocious puberty in girls who develop breasts before the age of 8 years. We evaluated the frequencies of the signs associated with breast development and the factors influencing the presentation of girls with idiopathic central precocious puberty (CPP).
METHODS
353 girls monitored 0.9 +/- 0.7 year after the onset of CPP.
RESULTS
The age at CPP was < 3 years in 2%, 3-7 years in 38% and 7-8 years in 60% of cases. Pubic hair was present in 67%, growth rate greater than 2 SDS in 46% and bone age advance greater than 2 years in 33% of cases. Breast development was clinically isolated in 70 (20%) cases. However, only 31 of these (8.8% of the population) had a prepubertal length uterus and gonadotropin responses to gonadotropin releasing hormone and plasma estradiol. The clinical picture of CPP became complete during the year following the initial evaluation.25% of cases were obese. The increase in weight during the previous year (3.7 +/- 1.4 kg) and body mass index were positively correlated with the statural growth and bone age advance (P < 0.0001). There was no relationship between the clinical-biological presentation and the age at puberty, the interval between the onset of puberty and evaluation, or the presence of familial CPP.
CONCLUSION
The variation in presentation of girls with CPP does not depend on their age, interval between the onset and evaluation, or familial factors. This suggests that there are degrees of hypothalamic-pituitary-ovarian activation that are not explained by these factors.
Topics: Age Determination by Skeleton; Age of Onset; Body Height; Body Mass Index; Body Weight; Breast; Child; Child, Preschool; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Puberty, Precocious; Retrospective Studies; Uterus
PubMed: 18601733
DOI: 10.1186/1471-2431-8-27 -
Frontiers in Endocrinology 2024Precocious puberty is diagnosed when pubertal characteristics appear before the age of 8 years in females. The most common form is gonadotropin-dependent, called axial....
UNLABELLED
Precocious puberty is diagnosed when pubertal characteristics appear before the age of 8 years in females. The most common form is gonadotropin-dependent, called axial. The primary method of treatment is administration of gonadotrophin-releasing hormone analogues (GnRHa). The aim of the study was to verify hypothesis that GnRHa therapy in the childhood may be of additive risk factor for polycystic ovary syndrome (PCOS) in adulthood.
MATERIAL AND METHODS
The study group consists of 24 women (median age 22 88 years, median BMI 23.5) treated with GnRHa for central precocious puberty in childhood. The control group includes 40 women (median age 23 years, median BMI 25.6) diagnosed with isolated premature thelarche and not using GnRHa in the childhood. Anthropometric measurements, ultrasound examination of minor pelvis and hormonal profile were performed. PCOS diagnosis was based on Rotterdam criteria.
RESULTS
The study confirmed a higher prevalence of PCOS in the study group (50%) than in the control group (10%); p=0.0006. Significant, linear correlation between free testosterone levels and ovarian size was found in the study group (R=0.45 p= 0.03).
CONCLUSIONS
GnRHa therapy during childhood may have a potential influence on incidence of PCOS in the adulthood. Therefore, in this group of patients long-term follow-up focused on screening for PCOS would seem beneficial.
Topics: Female; Humans; Young Adult; Adult; Child; Gonadotropin-Releasing Hormone; Puberty, Precocious; Polycystic Ovary Syndrome; Prevalence
PubMed: 38327564
DOI: 10.3389/fendo.2024.1314752 -
Annals of Pediatric Endocrinology &... Sep 2019Precocious puberty refers to the development of secondary sex characteristics before ages 8 and 9 years in girls and boys, respectively. Central precocious puberty (CPP)...
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.
PubMed: 31607109
DOI: 10.6065/apem.2019.24.3.164 -
Environmental Science and Pollution... Sep 2018Phthalates and bisphenol A (BPA), plasticizers used in several products of daily life, are considered as endocrine disrupters, therefore children exposure is...
Phthalates and bisphenol A (BPA), plasticizers used in several products of daily life, are considered as endocrine disrupters, therefore children exposure is particularly relevant. The LIFE PERSUADED project aims to define the following: (a) the evaluation of internal levels of DEHP's metabolites and BPA in Italian children and their mothers, (b) the association of the exposure with puberty development and obesity diseases, and (c) the effects of exposure in juvenile in vivo model. The cross-sectional study has involved 2160 mother-child pairs, including males and females, children and adolescents, from urban and rural areas of North, Center, and South Italy. A structured questionnaire and a food diary are designed to evaluate the association between lifestyle variables potentially related to DEHP/BPA exposure and internal levels, through univariate and multivariate analyses. Two pilot case-control studies are carried out on idiopathic premature thelarche and precocious puberty (30 girls each group, aged 2-7 years) and idiopathic obesity (30 boys and 30 girls, aged 6-10 years), matched to healthy controls. BPA and DEHP's metabolites are analyzed in urine samples from all recruited subjects. Clinical and toxicological biomarkers are evaluated in serum of case-control subjects. Moreover, the toxicity study is carried out in a juvenile rodent model exposed to mixtures of BPA and DEHP at dose levels recorded in children population. The scientific results of LIFE PERSUADED will contribute to risk assessment of BPA and DEHP.
Topics: Adolescent; Adult; Animals; Benzhydryl Compounds; Child; Child, Preschool; Endocrine Disruptors; Environmental Exposure; Environmental Monitoring; Environmental Pollutants; Epidemiologic Studies; Female; Humans; Italy; Life Style; Male; Mothers; Pediatric Obesity; Phenols; Phthalic Acids; Puberty, Precocious; Rats; Surveys and Questionnaires
PubMed: 29974441
DOI: 10.1007/s11356-018-2660-4 -
Clinical Epigenetics May 2024Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal...
BACKGROUND
Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal expressed genes and a silencing the paternally expressed genes in the 14q32 imprinted domain. Classical TS14 phenotypic features include pre- and postnatal short stature, small hands and feet, muscular hypotonia, motor delay, feeding difficulties, weight gain, premature puberty along and precocious puberty.
METHODS
An exon array comparative genomic hybridization was performed on a patient affected by psychomotor and language delay, muscular hypotonia, relative macrocephaly, and small hand and feet at two years old. At 6 years of age, the proband presented with precocious thelarche. Genes dosage and methylation within the 14q32 region were analyzed by MS-MLPA. Bisulfite PCR and pyrosequencing were employed to quantification methylation at the four known imprinted differentially methylated regions (DMR) within the 14q32 domain: DLK1 DMR, IG-DMR, MEG3 DMR and MEG8 DMR.
RESULTS
The patient had inherited a 69 Kb deletion, encompassing the entire DLK1 gene, on the paternal allele. Relative hypermethylation of the two maternally methylated intervals, DLK1 and MEG8 DMRs, was observed along with normal methylation level at IG-DMR and MEG3 DMR, resulting in a phenotype consistent with TS14. Additional family members with the deletion showed modest methylation changes at both the DLK1 and MEG8 DMRs consistent with parental transmission.
CONCLUSION
We describe a girl with clinical presentation suggestive of Temple syndrome resulting from a small paternal 14q32 deletion that led to DLK1 whole-gene deletion, as well as hypermethylation of the maternally methylated DLK1-DMR.
Topics: Humans; Calcium-Binding Proteins; DNA Methylation; Chromosomes, Human, Pair 14; Intercellular Signaling Peptides and Proteins; Genomic Imprinting; Membrane Proteins; Child; Male; Comparative Genomic Hybridization; Female; Chromosome Deletion; Child, Preschool; Phenotype; Abnormalities, Multiple; Imprinting Disorders; Muscle Hypotonia; Facies
PubMed: 38715103
DOI: 10.1186/s13148-024-01652-8