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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 -
Indian Journal of Endocrinology and... 2023In this study, it was aimed to examine the clinical and laboratory findings that can be used to predict central precocious puberty (CPP) in cases whose breast...
AIM
In this study, it was aimed to examine the clinical and laboratory findings that can be used to predict central precocious puberty (CPP) in cases whose breast development started before the age of 8.
MATERIALS AND METHODS
The chronological age, anthropometric measurements, bone age (BA), hormone test results and pelvic ultrasonography findings of the cases were recorded. Those with a peak luteinizing hormone (LH) level of ≥5 IU/L in the gonadotropin-releasing hormone (GnRH) stimulation test were classified as CPP and those with a peak LH level of <5 IU/L were classified as prepubertal cases. A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic accuracy of laboratory variables.
FINDINGS
A total of 297 female cases were included in the study. The age at the time of admission, height-standard deviation score (SDS), BA, the long axis of the uterus and the volumes of the right and left ovaries of the cases diagnosed with CPP were found to be significantly higher than those of the prepubertal group. The cut-off value providing the best sensitivity (99%) and specificity (99%) for the peak LH was found to be 4.55; the cut-off value providing the best sensitivity (94%) and specificity (85%) for the peak LH/follicle-stimulating hormone (FSH) ratio was found to be 0.32 and the cut-off value providing the best sensitivity (47%) and specificity (93%) for the basal LH was found to be 0.13.
CONCLUSION
We believe that in female cases with early breast development, a peak LH level of ≥4.55 may possibly indicate CPP and a basal LH level of <0.13 can significantly rule out CPP.
PubMed: 37583412
DOI: 10.4103/ijem.ijem_245_22 -
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 -
Pakistan Journal of Medical Sciences 2024To explore the changes of serum-related indexes at different time points, so as to identify the critical time of converting from simple premature thelarche (PT) to...
OBJECTIVE
To explore the changes of serum-related indexes at different time points, so as to identify the critical time of converting from simple premature thelarche (PT) to idiopathic central precocious puberty (ICPP).
METHODS
This is a retrospective study. The subjects of the study were 50 girls with PT who were admitted to the Children's Hospital of Hebei Province from January 2019 to September 2020. The enrolled 50 children were divided into the conversion group(n=12) and the non-conversion group(n=38) according to whether PT was converted into ICPP during follow-up. Furthermore, the levels of serum-related indexes and uterine and ovarian volumes were compared after the diagnosis of PT.
RESULTS
The IGF-1 and IGFBP-3 levels of children in the conversion group began to change significantly from six months after the diagnosis, with statistically significant differences when compared with the levels of children at the initial diagnosis, three months and those of the non-conversion group at the same time points (0.05). The levels of vitamin-D, DHEA and leptin began to change significantly at nine months after the diagnosis (0.05). Besides, uterine and ovarian volumes in the conversion group began to increase significantly six months after the diagnosis, with statistically significant differences when compared with those in the non-conversion group (0.05).
CONCLUSION
Findings in our study suggest that regular monitoring of vitamin-D, IGF-1, IGFBP-3, DHEA and leptin levels, and uterine and ovarian volumes can predict the conversion from PT to ICPP at an early stage.
PubMed: 38356806
DOI: 10.12669/pjms.40.3.7447 -
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 Endocrinology 2020The aim of this study was to evaluate the levels of kisspeptin and AMH in children with PT or CPP or controls to provide a reference for diagnosis and prognosis.
AIM
The aim of this study was to evaluate the levels of kisspeptin and AMH in children with PT or CPP or controls to provide a reference for diagnosis and prognosis.
METHODS
38 Chinese children with central precocious puberty (CPP), 38 Chinese children with premature thelarche (PT), and 75 controls were recruited.
RESULTS
In CPP girls, AMH levels decreased significantly compared to control girls at T2 stage. Compared with the PT and control groups, AMH is the lowest in girls in the CPP group at T3 stage. Kisspeptin decreased significantly in girls in the PT group and increased significantly in girls in the control group from T2 stage to T3 stage. At T3 stage, kisspeptin was significantly higher in girls in the CPP and control groups than in the PT group. In the control group, kisspeptin was significantly higher in boys than in girls at T2 stage. AMH and height were negatively correlated in the girls group.
CONCLUSIONS
Kisspeptin and AMH have a unique significance in the auxiliary diagnosis, the differential diagnosis, the treatment, and prognosis of sexual puberty disorder.
PubMed: 33293954
DOI: 10.1155/2020/3126309 -
Journal of Ovarian Research Nov 2023Existing studies have investigated the relationship between the levels of serum inhibin B (INHB), anti-müllerian hormone (AMH) and precocious puberty in girls, but the... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS
Existing studies have investigated the relationship between the levels of serum inhibin B (INHB), anti-müllerian hormone (AMH) and precocious puberty in girls, but the results are inconsistent.
OBJECTIVE
The aim of this meta-analysis was to assess whether the INHB and AMH levels changed in girls with precocious puberty relative to healthy controls.
METHODS
PubMed, Embase, Cochrane Library and Web of Science were searched through June 2022. We included observational clinical studies reporting the serum levels INHB and AMH in girls with precocious puberty. Conference articles and observational study abstracts were included if they contained enough information regarding study design and outcome data. Case series and reports were excluded. An overall standard mean difference (SMD) between precocious puberty and healthy controls was estimated using a DerSimonian-Laird random-effects model.
RESULTS
A total of 11 studies featuring 552 girls with precocious puberty and 405 healthy girls were selected for analysis. The meta-analysis showed that the INHB level of precocious puberty [including central precocious puberty (CPP) and premature the larche (PT)] were significantly increased. While there was no significant association between precocious puberty [including CPP, PT, premature pubarche (PP) and premature adrenarche (PA)] and the level of serum AMH.
CONCLUSION
Scientific evidence suggested that the INHB level, but not the AMH level, altered in girls with precocious puberty compared with healthy controls. Through our results we think that INHB level might be a marker for the auxiliary diagnosis of precocious puberty (especially CPP and PT). Therefore, it is important to evaluate and thoroughly investigate the clinical indicators (e.g., INHB) in order to ensure early diagnosis and medical intervention, and the risk of physical, psychological and social disorders in immature girls with precocious puberty is minimized.
Topics: Female; Humans; Anti-Mullerian Hormone; Follicle Stimulating Hormone; Inhibins; Observational Studies as Topic; Puberty, Precocious
PubMed: 37996919
DOI: 10.1186/s13048-023-01302-2 -
Acta Bio-medica : Atenei Parmensis Nov 2021Sexual precocity refers to the appearance of physical and hormonal signs of pubertal development at an earlier age. It may be considered as the expression of secondary...
Sexual precocity refers to the appearance of physical and hormonal signs of pubertal development at an earlier age. It may be considered as the expression of secondary sexual characteristics prior to the pubertal age In central precocious puberty (CPP), which is gonadotropin-dependent, early maturation of the entire hypothalamic-pituitary-gonadal (HPG) axis occurs, with the full spectrum of physical and hormonal changes of puberty. True precocious puberty in girls must also be distinguished from premature thelarche (PT), usually with breast development before the age of 3 years, and premature pubarche (PA), with the isolated development of pubic hair. These conditions are not usually associated with accelerated growth rate or advancement in bone age. Clinical, laboratory and instrumental evaluations are necessary for the diagnosis. Pelvic ultrasound could serve as a complementary tool for the diagnosis, treatment and follow-up of CPP. The interpretation of clinical, laboratory and strumental data must be performed by an expert pediatric endocrinologist to maximize the diagnostic value in females with pubertal disorders.
Topics: Child; Child, Preschool; Female; Humans; Puberty; Puberty, Precocious; Ultrasonography
PubMed: 34738554
DOI: 10.23750/abm.v92i5.12295 -
Annals of Pediatric Endocrinology &... Jun 2023Intravenous gonadotropin-releasing hormone (IV GnRH) testing is the gold standard for confirming a central precocious puberty (CPP) diagnosis. However, this test is not...
The utilization of basal luteinizing hormone in combination with the basal luteinizing hormone and follicle-stimulating hormone ratio as a diagnostic tool for central precocious puberty in girls.
PURPOSE
Intravenous gonadotropin-releasing hormone (IV GnRH) testing is the gold standard for confirming a central precocious puberty (CPP) diagnosis. However, this test is not widely available commercially. Therefore, our study aim was to establish cutoff values for basal gonadotropin level and gonadotrophin responses to a 100-μg subcutaneous IV GnRH test that can distinguish between CPP and premature thelarche (PT) to discover a simple method to detect CPP.
METHODS
Girls between the ages of 6 and 8 years who attended the pediatric endocrinology outpatient clinic at our tertiary hospital between 2019 and 2022 were included in this study. They were evaluated for breast development, and a subcutaneous 100-μg GnRH test was administered by measuring the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in blood samples at baseline and then 30, 60, 90, and 120 minutes after injection. CPP is characterized by increased height velocity, advanced bone age, and progression of breast development. The cutoff value for diagnosis of CPP was determined using a receiver operating characteristic (ROC) analysis.
RESULTS
In 86 Thai girls (56 with CPP and 30 with PT), the ROC analysis showed 71.4% and 100% sensitivity and specificity, respectively, for basal LH (cutoff ≥ 0.2 IU/L) plus the basal LH/FSH ratio (cutoff ≥ 0.1). The optimal cutoff values for peak LH (cutoff ≥ 7 IU/L) demonstrated a sensitivity of 94.6% and a specificity of 100%, whereas the LH value at 30 and 60 minutes after injection (cutoff ≥ 6 IU/L) demonstrated sensitivities of 92.9% and 94.6% and a specificity of 100%, respectively.
CONCLUSION
Combining the basal LH (cutoff: 0.2 IU/L) and the basal LH/FSH ratio (cutoff: 0.1) can easily and cost-effectively diagnose CPP in a girl in breast Tanner stage II.
PubMed: 37401058
DOI: 10.6065/apem.2346072.036 -
International Journal of Molecular... May 2020Several pesticides are recognized as endocrine-disrupting chemicals (EDCs) since they can interfere with the dysregulation of sexual, thyroid and neuro-endocrine...
Several pesticides are recognized as endocrine-disrupting chemicals (EDCs) since they can interfere with the dysregulation of sexual, thyroid and neuro-endocrine hormones. Children are particularly vulnerable to the adverse effects of EDCs due to their developmental stage, peculiar lifestyle and dietary habits. In this context, the exposure to pesticides represents an important risk factor associated with early development. This study deals with the possible association between exposure to pesticides and idiopathic premature thelarche in girls from areas of intensive agriculture practice in the Centre of Italy. An integrated approach was set up, including: (i) a case-control study on girls with idiopathic premature thelarche; (ii) the evaluation of multiple pesticides exposure in girls; (iii) the evaluation of multiple pesticides in food; (iv) the dietary intake of pesticide residues; (v) the assessment of toxicological effects of widely used pesticides by in vitro model. Data integration will provide an estimate of the predictive risk of potential effects on girls' health, linked to dietary intake.
Topics: Child; Dietary Exposure; Endocrine Disruptors; Female; Humans; Pesticides; Puberty, Precocious
PubMed: 32384657
DOI: 10.3390/ijms21093282