-
European Review For Medical and... Oct 2023Although there is a relationship between earlier onset of puberty and increased adiposity tissue. Publications in the literature on adiposis in patients with central...
OBJECTIVE
Although there is a relationship between earlier onset of puberty and increased adiposity tissue. Publications in the literature on adiposis in patients with central precocious puberty (CPP) and visceral fat thickness (VFT) have conflicting results. So, in this study, we aimed to evaluate the relationship between sexual maturation and obesity in the development of early puberty and to examine their relationship with pelvic sonographic parameters.
PATIENTS AND METHODS
A total of 126 girls [patients - premature thelarche (PT) and CPP - and controls] were included in this study. Anthropometric and ultrasonographic evaluations were made by the same pediatric endocrinologist and pediatric radiologist, respectively. Pubertal stages were made according to the Tanner stages. Height, weight, and body mass index were measured as anthropometric measurements, and visceral, subcutaneous, and transabdominal fat thicknesses were measured in sonographic evaluation.
RESULTS
The study population was divided into three groups: 44 healthy subjects to Group 1, 23 patients with PT to Group 2, and 59 patients with CPP to Group 3. When we evaluated the anthropometric and ultrasonographic parameters according to pubertal status, significant differences, especially between Group 1 and Group 3, were observed in all data. In the multiple logistic regression analysis, the endometrial thickness (OR = 7.521, p < 0.001) and VFT (OR = 1.530, p < 0.001) were found to be independent predictors of precocious puberty.
CONCLUSIONS
It has been found that VFT and endometrial thickness measurements, which are evaluated quickly and accurately by USG, are important predictors of prepubertal precociousness.
Topics: Child; Female; Humans; Puberty, Precocious; Intra-Abdominal Fat; Puberty; Anthropometry; Obesity
PubMed: 37843336
DOI: 10.26355/eurrev_202310_33950 -
BMC Pediatrics Apr 2023To investigate the differential diagnosis of girls aged 6 to 8 years with idiopathic premature thelarche (IPT) and central precocious puberty (CPP) during the COVID-19...
BACKGROUND
To investigate the differential diagnosis of girls aged 6 to 8 years with idiopathic premature thelarche (IPT) and central precocious puberty (CPP) during the COVID-19 pandemic. We explored predicted adult height (PAH) discrepancy to guide appropriate diagnosis and treatment.
METHODS
From January 2020 to December 2021, Chinese girls aged 6 to 8 years with precocious puberty were recruited. They were divided into IPT and CPP groups. Clinical characteristics, including height, weight, body mass index (BMI), basal luteinizing hormone (LH), oestradiol, uterine length and volume, follicle numbers (d > 4 mm) and bone age (BA) were recorded. We analysed differential diagnosis and PAH discrepancy in both groups. Binary logistic regression analysis was used to explore risk factors for CPP, and receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of related indexes.
RESULTS
Sixty patients, including 40 girls with IPT and 20 girls with CPP, were recruited. The prevalence of overweight and obesity in the entire cohort was 25% (15/60) and was significantly higher in IPT than CPP, 32.5% (13/40) vs. 10% (2/20), respectively (P=0.045). There were significant differences in LH, uterine volume, follicle numbers and BA (P<0.05). The impaired PAH of IPT and CPP was 0.01 ± 1.19 SD and 0.62 ± 0.94 SD with significant differences (P=0.047). Logistic regression analysis showed that LH and follicle numbers were independent risk factors for CPP. The ROC curve showed that the area under the curve (AUC) of LH and follicle numbers were 0.823 and 0.697. The sensitivity and specificity of LH with a cut off of 0.285 IU/L were 78.9% and 77.8%. The sensitivity and specificity of follicle numbers with a cut off of 3.5 were 89.5% and 52.8%.
CONCLUSION
The prevalence of overweight and obesity in 6- to 8-year-old girls with precocious puberty was high. Auxological data should not be used in the differential diagnosis of IPT and CPP. Basal LH above 0.285 IU/L and follicle numbers greater than 4 were important features suggestive of CPP. PAH was impaired in individuals with CPP, but it was not impaired in individuals with IPT.
Topics: Female; Adult; Humans; Child; Puberty, Precocious; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Pilot Projects; Overweight; Diagnosis, Differential; Pandemics; COVID-19; Luteinizing Hormone; Obesity; COVID-19 Testing
PubMed: 37081435
DOI: 10.1186/s12887-023-04009-x -
Turk Pediatri Arsivi 2020To determine the clinical, anthropometric, and laboratory parameters that could be used for differentiating central precocious puberty from premature thelarche in girls...
AIM
To determine the clinical, anthropometric, and laboratory parameters that could be used for differentiating central precocious puberty from premature thelarche in girls who had breast development between the ages of 3 and 8 years.
MATERIAL AND METHODS
The study included 344 girls (196 girls with idiopathic central precocious puberty, 148 girls with premature thelarche) who underwent gonadotropin- releasing hormone stimulation tests for breast development. Age at diagnosis, bone age, anthropometric measurements, basal/stimulated hormone levels were recorded. Univariate regression analysis was performed to determine the parameters that could be used for differentiating precocious puberty from premature thelarche. Significant parameters in univariate analyses were grouped according to the thresholds determined using receiver operating characteristic curves and reevaluated through multivariate analysis.
RESULTS
The bone age, height-standard deviation score, body mass index-standard deviation score, and growth velocity-standard deviation score at diagnosis were found to be higher; pubertal stages were found to be more advanced; uterus and ovary volumes were found to be larger; and the basal/peak luteinizing hormone, follicle-stimulating hormone, luteinizing hormone/follicle-stimulating hormone levels were found to be higher in the subjects with precocious puberty. There was no difference between estradiol levels between the two groups. The best thresholds to differentiate the two groups were found as 0.65 IU/L (78% sensitivity, 100% specificity), 1.9 IU/L (100% sensitivity, 72% specificity), 0.25 (67% sensitivity, 100% specificity) and 1.1 (69% sensitivity, 71% specificity), respectively, for basal luteinizing hormone, follicle-stimulating hormone, luteinizing hormone/follicle-stimulating hormone ratio, and the growth velocity-standard deviation score.
CONCLUSION
In girls presenting with early breast development, a basal luteinizing hormone level of ≥0.65 IU/L and a luteinizing hormone/follicle-stimulating hormone ratio of ≥0.25 are sensitive ways to demonstrate activation of the hypothalamo-pituitary-gonadal axis. Among these, the variable that gives the best sensitivity and specificity is the measurement of basal luteinizing hormone levels (≥0.65 IU/L), which can be used as a screening test in the diagnosis of central precocious puberty.
PubMed: 32684758
DOI: 10.14744/TurkPediatriArs.2019.03708 -
Endocrine Connections Sep 2021To evaluate the characteristics and significance of serum kisspeptin and makorin ring finger protein 3 (MKRN3) levels for the diagnosis of central precocious puberty...
OBJECTIVE
To evaluate the characteristics and significance of serum kisspeptin and makorin ring finger protein 3 (MKRN3) levels for the diagnosis of central precocious puberty (CPP) in girls.
METHOD
Thirty four individuals with CPP, 17 individuals with premature thelarche (PT), and 28 age-matched prepubertal girls as normal control (NC) were recruited in this case-control study. Physical measurements included BMI and tests for breast, bone, and sexual characteristics. Biochemical measurements included serum LH, FSH, estradiol, insulin-like growth factor-1, MKRN3, and kisspeptin. Blood samples were taken from individuals with CPP and PT before the gonadotrophin-releasing hormone stimulation test and at 30, 60, 90, and 120 min after injection with triptorelin.
RESULTS
Serum kisspeptin levels were higher in the CPP group when compared to the NC group (P = 0.020), while serum MKRN3 levels were lower in the two groups (P = 0.028). There were no significant differences between the CPP and PT groups as well as the PT and NC groups (all, P > 0.05). The cut-off value of serum kisspeptin differentiating patients with CPP from those without CPP was 0.40 nmol/L, with 82.4% sensitivity and 57.1% specificity, while the cut-off value of serum MKRN3 was 0.33 pmol/L, with 79.4% sensitivity and 53.6% specificity. The area under the curves (AUCs) of both kisspeptin and MKRN3 for differentiating those girls with CPP from PT were less than 0.5.
CONCLUSIONS
Serum levels of kisspeptin and MKRN3 may play an auxiliary role in predicting CPP. However, the two measurements were not able to differentiate girls with CPP from PT and prepubertal control. This study emphasizes the need to search for markers to simplify the accurate diagnosis of CPP in girls.
PubMed: 34414898
DOI: 10.1530/EC-21-0182 -
Frontiers in Endocrinology 2022To investigate the associations between physical and pubertal development based on the breast development outcomes in girls.
OBJECTIVE
To investigate the associations between physical and pubertal development based on the breast development outcomes in girls.
METHODS
This was a retrospective study. A total of 452 girls aged 6~8 years were included. Based on their breast development outcomes, the patients were divided into an idiopathic central precocious puberty (ICPP) group and a premature thelarche (PT) group. Anthropometry included measurements of height, weight, and BMI. ICPP was diagnosed when five diagnostic criteria from the current guidelines were met.
RESULTS
The girls with breast development at initial evaluation had a median age of 6.9 years. In total, 31.4% of patients were diagnosed with ICPP, and ICPP was rare in girls <7 years old (19%). Patients who presented with recurrence of breast development in the PT group accounted for 38.4%. At initial evaluation, the height, weight, BMI and bone age (BA) of the girls in the PT group corresponded to those of a normally developing girl at ages 7.8 years, 8.2 years, 8.6 years and 7.6 years, respectively. The girls in the ICPP group had a mean age of 7.3 years, and their mean height, weight, and BMI were 129.6 cm, 28.4 kg, and 17.0 kg/m, which corresponded to the mean of a normally developing girl at ages 8.5 years, 9.1 years, and 10.5 years, respectively; these patients had BA of 9.2 years. Additionally, based on receiver operating characteristic (ROC) curve analysis, when the basal luteinizing hormone (LH) level was 0.32 IU/L and BMI reached 16.4 kg/m, CPP was diagnosed in patients meeting all five diagnostic criteria for CPP, and the specificity and sensitivity were 71.9% and 88.2%, respectively.
CONCLUSIONS
Girls with breast development before 8 years old had a high proportion of recurrence of breast development. The physical development of these girls at the time of breast development preceded that of normally developing girls by 1-2 years. BMI is an independent risk factor for early pubertal development, and is a simple and clear predictor of ICPP. In addition to the five classic diagnostic criteria, CPP is diagnosed when physical development corresponds to the mean for a 10.5 years old girl.
Topics: Female; Humans; Child; Body Mass Index; Luteinizing Hormone; Retrospective Studies; Puberty, Precocious; Body Height
PubMed: 36339403
DOI: 10.3389/fendo.2022.991908 -
Italian Journal of Pediatrics Dec 2019Premature thelarche (PT) is a benevolent ailment affecting young girls. Multiple factors are reported to correlate with this condition, but the mechanisms responsible... (Comparative Study)
Comparative Study
BACKGROUND
Premature thelarche (PT) is a benevolent ailment affecting young girls. Multiple factors are reported to correlate with this condition, but the mechanisms responsible for the onset of PT have not yet been fully investigated. This study aimed to evaluate the relationship of nutrient intake, insulin resistance and lipid profile with PT.
METHODS
Two hundred sixty-three girls with PT, and 222 healthy girls of similar age were enrolled into this study. Their demographics, Tanner stage of breast development, nutrient intake, insulin resistance and lipid profiles were compared.
RESULTS
Daily protein and fat intakes, insulin resistance parameters including serum insulin-like growth factor 1, fasting glucose to insulin ratio, quantitative insulin check index and homeostasis model of assessment of insulin resistance, as well as serum levels of triacylglycerol, total cholesterol and low-density lipoprotein, were all significantly altered in PT patients. Daily intake of energy and carbohydrate, and serum level of high-density lipoprotein protein were statistically indistinguishable between PT patients and healthy controls.
CONCLUSION
Chinese girls with PT are potentially insulin resistant, which warrants more clinical attention and further investigation to address the underlying etiology.
Topics: Age Factors; Blood Glucose; Case-Control Studies; Child; China; Energy Intake; Female; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Nutrients; Puberty, Precocious; Reference Values; Risk Assessment; Statistics, Nonparametric
PubMed: 31856872
DOI: 10.1186/s13052-019-0758-z -
JAMA Network Open Sep 2020A growing body of literature suggests that exposure to early-life adversity (ELA) is associated with accelerated biological aging, offering 1 mechanism through which ELA...
IMPORTANCE
A growing body of literature suggests that exposure to early-life adversity (ELA) is associated with accelerated biological aging, offering 1 mechanism through which ELA may be associated with an increased risk for age-related disease. These investigations, however, have been predominantly cross-sectional and focused on adults and females.
OBJECTIVE
To evaluate associations of threat-related (ie, physical abuse) and deprivation-related (ie, emotional neglect) ELA exposure with cellular and reproductive strategy metrics of biological aging among boys and girls with specific genetic backgrounds around the period of pubertal onset.
DESIGN, SETTING, AND PARTICIPANTS
In this cohort study, 997 boys and girls in grade 1 to grade 3 from 3 large elementary schools were recruited from Bengbu, Anhui Province, China, and were followed up from March 21, 2016 (baseline; wave 1), for 4 consecutive years, through March 25, 2019.
MAIN OUTCOMES AND MEASURES
The outcome was accelerated biological aging in both cellular and reproductive strategy metrics: telomere attrition and age at thelarche (for girls) and testicular maturation (for boys). Multi-informant assessment of exposure to threat-related and deprivation-related ELA was done at baseline (wave 1) and 1-year follow-up (wave 2). The polygenic risk score (PRS) was computed based on 17 single-nucleotide variations for early pubertal timing.
RESULTS
Of the 997 participants (579 girls [58.1%]; mean [SD] age at baseline, 8.0 [0.8] years), 550 (55.2%) reported exposure to threat-related ELA and 443 (44.4%) reported exposure to deprivation-related ELA. Threat-related ELA was associated with onset of thelarche 2.6 months earlier and deprivation-related ELA with onset of thelarche 3.3 months earlier in exposed girls than in unexposed peers; these associations were observed only among girls with a low PRS. Among boys, a similar pattern was found. Threat-related ELA was associated with testicular volume of 4 mL or more 1.4 months earlier and deprivation-related ELA was associated with testicular volume of 4 mL or more 2.3 months earlier than in unexposed peers but only among those with a low PRS. Boys and girls with greater exposure to threats showed a significantly higher percentage of telomere length change during 1-year follow-up, but only among those with low PRS (boys: β = 1.50; 95% CI, 0.80-2.21; P < .001; girls: β = 2.40; 95% CI, 1.78-3.05; P < .001) and moderate PRS (boys: β = 1.09; 95% CI, 0.43-1.75; P = .001; and girls: β = 1.27; 95% CI, 0.77-1.77; P < .001). No associations of deprivation-related ELA with percentage of telomere length change were found.
CONCLUSIONS AND RELEVANCE
This study suggests that the accelerating association of ELA with biological aging might occur at an earlier age and in a genetic background-dependent and dimension-specific manner.
Topics: Adverse Childhood Experiences; Aging; Aging, Premature; Causality; Child; Child Abuse; Child Development; China; Female; Gene-Environment Interaction; Humans; Male; Puberty; Risk Assessment; Sex Factors; Sexual Maturation; Telomere Homeostasis
PubMed: 32955573
DOI: 10.1001/jamanetworkopen.2020.13588 -
Clinical and Experimental Pediatrics Jun 2024Kisspeptin and delta-like 1 homolog (DLK1) are neuropeptides that reportedly play an important role in pubertal timing by activating and inhibiting the...
BACKGROUND
Kisspeptin and delta-like 1 homolog (DLK1) are neuropeptides that reportedly play an important role in pubertal timing by activating and inhibiting the hypothalamic-pituitary-gonadal axis, respectively. Consequently, serum kisspeptin and DLK1 levels may be novel biomarkers for differentiating between central precocious puberty (CPP) and premature thelarche (PT) in girls and used to monitor CPP treatment.
PURPOSE
To compare baseline serum kisspeptin and DLK1 levels in girls with CPP at diagnosis and after treatment to age-matched girls with PT.
METHODS
This prospective longitudinal study included girls with precocious puberty and girls with PT who experienced breast development before 8 years of age and peak luteinizing hormone levels of ≥6 versus <6 IU/L after a gonadotropin-releasing hormone (GnRH) stimulation test. Serum kisspeptin and DLK1 levels were determined in both groups at baseline and after 6 months of GnRH analog treatment in the CPP group and analyzed by enzyme-linked immunosorbent assay.
RESULTS
The study divided a total of 48 girls into CPP (n=24; mean age, 7.7±0.7 years) and PT (n=24; mean age, 7.4±0.8 years) groups. The baseline median serum kisspeptin levels were 50.5 pg/mL (range, 38.2-77 pg/mL) and 49.5 pg/mL (range, 39.7-67.6 pg/mL), respectively (P=0.89), while the baseline median serum DLK1 levels were 6.5 ng/mL (range, 5.9-7.5 ng/mL) and 6 ng/mL (4.4-14.4 ng/mL), respectively (P=0.68). After 6 months of GnRH analog treatment in the CPP group, the median serum kisspeptin level was lower (46.4 ng/mL; range, 37.1-60 ng/mL) than that at baseline (P=0.002), while the median serum DLK1 level was higher (7 ng/mL; range, 6.7-8.9) than that at baseline (P=0.002).
CONCLUSION
Our findings suggest that baseline serum kisspeptin and DLK1 levels are not reliable biomarkers for differentiating between CPP and PT. However, significant changes in serum kisspeptin and DLK1 levels may be used to monitor CPP treatment.
PubMed: 38772409
DOI: 10.3345/cep.2023.01361 -
Asian Biomedicine : Research, Reviews... Feb 2021The criterion standard gonadotropin-releasing hormone (GnRH) stimulation tests to diagnose central precocious puberty (CPP) are time-consuming, inconvenient, and...
BACKGROUND
The criterion standard gonadotropin-releasing hormone (GnRH) stimulation tests to diagnose central precocious puberty (CPP) are time-consuming, inconvenient, and expensive.
OBJECTIVES
To determine predictive cut-off values codetermined by ultrasonographic parameters and basal gonadotropin levels in girls with premature sexual development and compare them results of criterion standard tests in a study of diagnostic accuracy.
METHODS
Retrospective review of hormonal investigations and ultrasonographic uterine and ovarian parameters in a consecutive sample of girls at a single center, tertiary care hospital in Bangkok, Thailand.
RESULTS
We separated data from 68 girls (age range 2-12 years) into 2 groups based on their response to a GnRH analogue agonist stimulation test. A "prepubertal response" group included girls with premature thelarche and thelarche variants (n = 18, 6.37 ± 1.77 years) and a "pubertal response" group, including girls with CPP (n = 50, 8.46 ± 1.46 years); excluding patients with pathological causes (n = 0). The basal level of luteinizing hormone (LH) had the largest area under receiver operating characteristic curves (AUC) of 0.84; 95% confidence interval [CI] 0.74-0.93) compared with basal levels of follicle stimulating hormone (AUC 0.77; 95% CI 0.64-0.90) or estradiol (0.70; 95% CI 0.56-0.85). An optimal cut-off of 0.25 IU/L LH was related to a pubertal response to GnRH analogue agonist stimulation tests with 75.0% sensitivity, 88.9% specificity, 94.7% positive predictive value (PPV), and 57.1% negative predictive value. Uterine and ovarian cut-off volumes of 3.5 cm and 1.5 cm were related to a pubertal response with 88.6% and 76.2% PPV, respectively. A uterine width cut-off of 1.7 cm combined with a basal LH cut-off of 0.25 IU/L increased specificity and PPV to 100%.
CONCLUSION
Combining uterine and ovarian ultrasonographic parameters with basal gonadotropin levels, especially uterine width and basal LH level, appears useful for diagnosis of CPP.
PubMed: 37551300
DOI: 10.2478/abm-2021-0004 -
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