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Journal of Pediatric Endocrinology &... May 2017The aim of this study was to determine the serum levels of kisspeptin and ghrelin (GAH), as well as the relationship of these two peptides with each other in premature...
BACKGROUND
The aim of this study was to determine the serum levels of kisspeptin and ghrelin (GAH), as well as the relationship of these two peptides with each other in premature thelarche (PT) and premature adrenarche (PA) cases and to investigate the possibility of using these peptides as markers in the differentiation of puberty disorders.
METHODS
A PT group aged 1-8 years (n = 40), a PA group aged 1-9 years (n = 23, female/male = 20/3) and control groups consistent with each of the previous groups in terms of age and gender were created for the study. Kisspeptin and ghrelin levels were measured with ELISA methods from blood samples drawn while fasting in the morning.
RESULTS
When the PT group was compared with the controls, the plasma kisspeptin levels of the cases were significantly higher than the control group (165.47 ± 15.45 pmol/L, 96.82 ± 12.33 pmol/L, p = 0.005, respectively). Kisspeptin levels in the PA group did not show a difference with the control group (121.36 ± 17.99 pmol/L, 95.52 ± 11.54 pmol/L, p = 0.249, respectively). No significant difference could be found when GAH levels in the PT and PA groups were compared with controls. No significant correlation was found between kisspeptin and GAH levels in the PT and PA groups.
CONCLUSIONS
Our results indicate that kisspeptin plays an important role in the PT, but GAH is not associated with puberty disorders.
Topics: Adrenarche; Biomarkers; Case-Control Studies; Child; Child, Preschool; Female; Ghrelin; Humans; Infant; Kisspeptins; Male; Puberty, Precocious; Sexual Maturation
PubMed: 28422705
DOI: 10.1515/jpem-2016-0127 -
Frontiers in Endocrinology 2022Sexual development is a complex mechanism activated by the hypothalamic-pituitary-gonadal axis. Over the last one hundred years there has been a decline in the age at... (Review)
Review
Implicating factors in the increase in cases of central precocious puberty (CPP) during the COVID-19 pandemic: Experience of a tertiary centre of pediatric endocrinology and review of the literature.
Sexual development is a complex mechanism activated by the hypothalamic-pituitary-gonadal axis. Over the last one hundred years there has been a decline in the age at puberty onset in industrialised countries. Some Italian studies showed an increase in diagnoses of Central Precocious Puberty (CPP) during the COVID-19 pandemic. It is thus supposed that in this period there was an increased impact of factors that can influence pubertal development. Our retrospective monocentric study aimed to confirm the existence of this phenomenon and analysed possible related factors. We retrospectively evaluated clinical, laboratory, radiological and ultrasound (US) data of 154 girls referred to our Tertiary Centre of Paediatric Endocrinology from January 2019 to April 2021 for different forms of Precocious Puberty. We subdivided the cases into subgroups according to the final diagnosis: CPP, Early Puberty (EP), isolated thelarche and isolated pubarche. The observation period was subdivided into: Period 1, before lockdown (1 January 2019 - 8 March 2020) and Period 2, lockdown and the following months (9 March 2020 - 30 April 2021). Period 2 was further divided into "restrictive lockdown period" (Period 2.1) (March 2020 - 14 June 2020, in which the schools were closed) and "less restrictive lockdown period" (Period 2.2) (15 June 2020 - 30 April 2021). We analysed data regarding the use of electronic devices before and during lockdown in a group of girls with CPP diagnosed in Period 2 and we compared the data with that of a control group. Our data show an increase in the number of new diagnoses of CPP during lockdown and in the following months, compared with the previous period. We also detected a higher use of PCs and smartphones in girls with CPP diagnosed in Period 2, compared with the control group. The percentage of the presence of endometrial rhyme detected during the pelvic ultrasound was higher in girls with CPP in Period 2, compared with the previous period. Based on our data we assume there was an environmental effect on pubertal timing that calls our attention to factors such as food, use of electronic devices and stress. We will need further studies to better understand this data.
Topics: Child; Female; Humans; Communicable Disease Control; COVID-19; Pandemics; Puberty, Precocious; Retrospective Studies
PubMed: 36531478
DOI: 10.3389/fendo.2022.1032914 -
Pediatric Endocrinology, Diabetes, and... 2021Knowledge of uterine and ovarian growth patterns during early age and puberty helps in investigating disorders of pubertal development i.e. precocious puberty, premature... (Observational Study)
Observational Study
INTRODUCTION
Knowledge of uterine and ovarian growth patterns during early age and puberty helps in investigating disorders of pubertal development i.e. precocious puberty, premature thelarche, or pubarche. There is a paucity of data for uterine and ovarian parameters. Aim of the study: The aim of this study is to present normative data for Uterine length, Mean ovarian volume (MOV), and fundo cervical ratio (FCR) from 5 to 16 years in healthy girls from north India and to correlate these parameters with age, weight, height, and pubertal Tanner staging.
MATERIAL AND METHODS
A cross-sectional observational study was performed on 130 healthy girls age 5 to 16 years. Age, anthropometric parameters were measured and the pubertal stage was categorized using Tanner staging. All subjects underwent pelvic ultrasonography for the measurement of uterine and ovarian parameters.
RESULTS
Normative data of uterine length, MOV, and FCR were presented as mean, SD, median, and 95% confidence interval as per age and Tanner stage. A progressive increase in uterine length, MOV & FCR was observed with increasing age, weight, height, and Tanner stage (p < 0.001). A sudden significant increment in uterine length and MOV was observed between the age of 11-12 and 12-13 years (p < 0.001). Uterine length of < 4 cm, MOV < 2 cm3 and FCR < 1 were specific to identify pre-pubertal girls.
CONCLUSIONS
Normative data of uterine and ovarian parameters generated in our study by ultrasonography would be useful for screening girls with abnormalities of pubertal development.
Topics: Adolescent; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; India; Ovary; Puberty, Precocious; Ultrasonography; Uterus
PubMed: 33599435
DOI: 10.5114/pedm.2020.103112 -
Journal of the Endocrine Society Jul 2017Premature adrenarche (PA) has been associated with increased metabolic risk.
CONTEXT
Premature adrenarche (PA) has been associated with increased metabolic risk.
OBJECTIVE
To describe the risk of precocious thelarche (PT; <8 years), pubarche (PP; girls <8 years, boys <9 years), and gonadarche (PG; <9 years) in children with high dehydroepiandrosterone sulphate (DHEAS [HD]) vs those with normal DHEAS (ND).
SETTING AND INTERVENTION
Longitudinal Chilean cohort (n = 1052, 49.9% girls). Annual clinical examination including secondary sex characteristics by Tanner staging. Logistic regression models were adjusted by age and BMI.
MAIN OUTCOME
Assess the relationship between DHEAS and premature thelarche, gonadarche, and pubarche in both sexes.
RESULTS
At age of DHEAS determination, overweight/obesity was present in 44.3% of boys and 42.9% of girls. Incidences of any precocious event were observed in 17.2% of boys and in 25.4% of girls, presented as 8.7% of PG and 8.5% of PP in boys and as 21.3% of PT and 4.1% of PP in girls. In crude and adjusted models in boys, HD did not increase the risk of earlier pubertal events. Conversely, girls with HD had a 2.6 times greater risk of early thelarche and a three times greater risk of early pubarche compared with girls with ND concentrations.
CONCLUSION
In Chilean adolescents, precocious events of pubertal development were in line with the worldwide secular trend of earlier sexual maturation. HD was only associated with PT and PP in girls. Continuous follow-up of this cohort is a unique opportunity to prospectively address and analyze the interrelationships among HD, early growth, and adiposity as determinants of gonadarche, pubertal rate/sequence progression, and ovarian function.
PubMed: 29264531
DOI: 10.1210/js.2017-00120 -
Frontiers in Endocrinology 2017We describe the etiology, MRI findings, and growth patterns in girls who had presented with signs of precocious puberty (PP), i.e., premature breast development or early...
INTRODUCTION
We describe the etiology, MRI findings, and growth patterns in girls who had presented with signs of precocious puberty (PP), i.e., premature breast development or early menarche. Special attention was paid to the diagnostic findings in 6- to 8-year-olds.
MATERIALS AND METHODS
We reviewed the medical records of 149 girls (aged 0.7-10.3 years) who had been evaluated for PP in the Helsinki University Hospital between 2001 and 2014.
RESULTS
In 6- to 8-year-old girls, PP was most frequently caused by idiopathic gonadotropin-releasing hormone (GnRH)-dependent PP (60%) and premature thelarche (PT; 39%). The former subgroup grew faster (8.7 ± 2.0 cm/year, = 58) than the girls with PT (7.0 ± 1.1 cm/year, = 32) ( < 0.001), and the best discrimination for GnRH-dependent PP was achieved with a growth velocity cut-off value of 7.0 cm/year (sensitivity 92% and specificity 58%) [area under the curve 0.82, 95% confidence interval (CI) 0.73-0.91, < 0.001]. Among asymptomatic and previously healthy 6- to 8-year-old girls with GnRH-dependent PP, one (1.7%, 95% CI 0.3-9.7%) had a pathological brain MRI finding requiring surgical intervention (craniopharyngioma). In girls younger than 3 years, the most frequent cause of breast development was PT, and, in 3- to 6-year-olds, GnRH-dependent PP.
CONCLUSION
In 6- to 8-year-old girls, analysis of growth velocity is helpful in differentiating between PT and GnRH-dependent PP. Although the frequency of clinically relevant intracranial findings in previously healthy, asymptomatic 6- to 8-year-old girls was low, they can present without any signs or symptoms, which favors routine MRI imaging also in this age group.
PubMed: 28878739
DOI: 10.3389/fendo.2017.00213 -
The Journal of Clinical Endocrinology... Jan 2021The exact mechanisms that trigger the onset of puberty are not well known. Adipomyokines are postulated to stimulate the central neural network. In the present study, we...
AIM
The exact mechanisms that trigger the onset of puberty are not well known. Adipomyokines are postulated to stimulate the central neural network. In the present study, we investigated irisin levels in girls with central precocious puberty (CPP), slowly progressing precocious puberty (SPPP), or premature thelarche (PT); we also studied prepubertal girls and to determine if this adipomyokine could be used as a marker in this context.
METHODS
A total of 94 girls including 33 with CPP, 31 with precocious puberty (PP) variants (SPPP or PT), and 30 healthy controls were enrolled to the study. The mean irisin levels were compared between groups. The bivariate correlations of irisin levels with clinical and laboratory parameters were assessed. Multivariate linear regression analysis was performed to determine independent predictive factors of irisin levels.
RESULTS
Irisin levels were higher in the CPP group compared with the other groups (CPP group: 723.25 ± 62.35 ng/mL; PP variants group: 529.60 ± 39.66 ng/mL; and control group: 325.03 ± 27.53 ng/mL) (P < 0.001). Irisin levels were positively correlated with body mass index standard deviation scores (BMI-SDS), height-SDS, weight-SDS, bone age, uterus long axis, ovary size, baseline FSH and LH, and peak LH levels. Multivariate linear regression analysis revealed that irisin levels had the strongest correlation with peak LH. The other independent predictive factor of irisin levels was BMI-SDS.
CONCLUSIONS
The mean irisin levels were higher in patients with CPP compared with other groups. The results of this study imply that increased irisin levels may be used as a marker of CPP provided that these findings are confirmed in larger prospective studies.
Topics: Age Determination by Skeleton; Biomarkers; Body Mass Index; Case-Control Studies; Child; Female; Fibronectins; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Puberty, Precocious; Turkey
PubMed: 33034623
DOI: 10.1210/clinem/dgaa720 -
Hormone Research in Paediatrics 2019The aim of this work was to investigate the prevalence of premature thelarche (PT) in 18-month-old girls, and the incidence of clinically evaluated PT for girls aged... (Clinical Trial)
Clinical Trial
Prevalence of Premature Thelarche at 18 Months of Age: A Population- and Hospital-Based Study of Prevalence and Incidence in Girls Born at Northern Älvsborg County Hospital in Sweden.
OBJECTIVE
The aim of this work was to investigate the prevalence of premature thelarche (PT) in 18-month-old girls, and the incidence of clinically evaluated PT for girls aged 18-36 months.
METHODS
In the prevalence substudy, a prospective population-based cohort of 3,140 girls born at Northern Älvsborg county hospital (NÄL) in Trollhättan, Sweden, was followed for 2 years. Girls with breast development at the 18-month health check were referred to one pediatric center in NÄL for evaluation. All girls with PT were included and followed for clinical outcome and 17β-estradiol. The prospective incidence substudy covered 8 years in a 10-year period and included all girls aged 18-36 months born at NÄL who were clinically evaluated for PT.
RESULTS
The prevalence of PT at 18 months in our cohort was 1.6/1,000. The 5 girls with PT no longer showed symptoms at the follow-up 3-6 months later. The incidence was 1.1/1,000 for girls aged 18-36 months and 1.0/1,000 for girls aged 18-30 months who were clinically evaluated for their PT.
CONCLUSION
This is the first prospective population-based study of PT and it shows a prevalence of PT at age 18 months of 1.6/1,000. The incidence of clinically evaluated PT was 1.1/1,000. Our result is in line with other studies reporting the incidence of PT from medical records (0.4-40/1,000). The outcome of PT in our study, as in the other studies, is that the great majority of girls show only benign symptoms.
Topics: Breast; Child; Child, Preschool; Estradiol; Female; Follow-Up Studies; Hospitals, County; Humans; Incidence; Infant; Prevalence; Prospective Studies; Puberty, Precocious; Retrospective Studies; Sweden
PubMed: 31167216
DOI: 10.1159/000500356 -
Endocrine Connections Feb 2021The objective of this study was to analyze whether some auxological characteristics or a single basal gonadotropin measurement will be sufficient to distinguish the...
OBJECTIVE
The objective of this study was to analyze whether some auxological characteristics or a single basal gonadotropin measurement will be sufficient to distinguish the prepubertal from pubertal status.
METHODS
Auxologycal characteristics were recorded and serum LH and FSH were measured by immunochemiluminescence assays before and after GnRH stimulation test in a sample of 241 Caucasian girls with breast budding between 6- and 8-years old. Peak LH levels higher than 5 IU/L were considered a pubertal response. Area under the curve, cut-off points, sensitivity, and specificity for auxologycal variables and basal gonadotropins levels were determined by receiver operating curves.
RESULTS
There were no significant differences in age at onset, weight, height, BMI and height velocity between both groups. Bone age was significantly higher in pubertal girls (P < 0.05), although with limited discriminatory capacity. The sensitivity and specificity for the basal LH levels were 89 and 82%, respectively, for a cut off point of 0.1 IU/L. All girls in the pubertal group had a basal LH higher than 1.0 IU/L (positive predictive value of 100%). There was a wide overlap of basal FSH and LH/FSH ratio between prepubertal and pubertal girls.
CONCLUSIONS
Auxologycal characteristics should not be used only in the differential diagnosis between prepubertal from pubertal status in 6- to 8-year-old girls. We found a high specificity of a single basal LH sample and it would be useful for establishing the diagnosis of puberty in this age group, reducing the need for GnRH stimulation testing.
PubMed: 33416514
DOI: 10.1530/EC-20-0651 -
BMC Pediatrics Sep 2020To date, the gonadotropin-releasing hormone (GnRH) stimulation test is still the gold standard for precocious puberty (PP) diagnosis. However, it has many disadvantages,...
BACKGROUND
To date, the gonadotropin-releasing hormone (GnRH) stimulation test is still the gold standard for precocious puberty (PP) diagnosis. However, it has many disadvantages, including low sensitivity, high cost, and invasive operation. This study aims to evaluate whether magnetic resonance imaging (MRI)-derived variables, including pituitary volume (PV), could be used as diagnostic factors for PP in girls, providing a non-invasive diagnostic approach for PP.
METHODS
A total of 288 young female patients who presented to the Clinic of Pediatric Endocrinology for evaluation of PP from January 2015 to December 2017 were enrolled. The sample included 90 girls diagnosed with premature thelarche (PT), 133 girls determined as idiopathic central precocious puberty (ICPP), 35 early pubertal girls, and 30 normal girls. All patients received pituitary MRI examinations.
RESULTS
The largest PV and pituitary height were shown in the ICPP and pubertal groups, followed by the PT group. The receiver operating characteristic (ROC) curve analysis showed that PV is a predictive marker for ICPP, with a sensitivity of 54.10% and a specificity of 72.20% at the cutoff value of 196.01 mm. By univariate analysis, PV was positively associated with peak luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), age, bone age, and body mass index (BMI) (all P < 0.05). However, bone age and peak LH were the only significant predictors of PV as demonstrated by the stepwise multivariate regression analysis (Model: PV = 9.431 * bone age + 1.230 * peak LH + 92.625 [P = 0.000, R = 0.159]).
CONCLUSIONS
The PV in the ICPP group was significantly higher than in PT and control groups, but there was no reliable cutoff value to distinguish ICPP from PT. Pituitary MRI should be combined with clinical and laboratory tests to improve the diagnostic value of PV for PP.
Topics: Body Mass Index; Child; Female; Follicle Stimulating Hormone; Humans; Infant; Luteinizing Hormone; Puberty, Precocious; ROC Curve
PubMed: 32891123
DOI: 10.1186/s12887-020-02283-7 -
International Journal of Environmental... Apr 2022Humans are exposed to residues of organophosphate and neonicotinoid pesticides, commonly used in agriculture. Children are particularly vulnerable and, among possible...
Humans are exposed to residues of organophosphate and neonicotinoid pesticides, commonly used in agriculture. Children are particularly vulnerable and, among possible adverse outcomes, the increased incidence of premature mammary gland development (thelarche) has raised concern. We evaluated the toxicological effects of chlorpyrifos (CPF), imidacloprid (IMI) and glyphosate (GLY) at exposure concentrations occurring in children on the tumorigenic MCF-7 and non-tumorigenic MCF-12A breast cell lines, as representative of the target organ model, assessing cytotoxicity, apoptosis, necrosis, intracellular reactive oxygen species (ROS) and ATP levels, 17β-estradiol secretion and gene expression of nuclear receptors involved in mammary gland development. The pesticides decreased cell vitality in MCF-7 and cell proliferation in MCF-12A cells. ATP levels were decreased in MCF-7 cells by pesticides and apoptosis was increased in MCF-12A cells only by GLY (2.3 nM). ROS production was decreased by pesticides in both cell lines, except IMI (1.6 nM) in MCF-7 cells. Endocrine disrupting activity was highlighted by induction of 17β-estradiol secretion and modulation of the gene expression of estrogen alpha and beta, progesterone, androgen, and aryl hydrocarbon receptors in both cell lines. The use of MCF-7 and MCF-12A cells highlighted dissimilar modes of action of each pesticide at low human relevant concentrations.
Topics: Adenosine Triphosphate; Breast Neoplasms; Child; Estradiol; Female; Humans; MCF-7 Cells; Pesticides; Reactive Oxygen Species
PubMed: 35457321
DOI: 10.3390/ijerph19084453