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Hormone Research in Paediatrics 2021The aim of this study is to determine the cutoff values of gonadotropin response to gonadotropin-releasing hormone analogs (GnRHas) corresponding to the activation of...
Assessment of Gonadotropin Concentrations Stimulated by Gonadotropin-Releasing Hormone Analog by Electrochemiluminescence in Girls with Precocious Puberty and Premature Thelarche.
OBJECTIVE
The aim of this study is to determine the cutoff values of gonadotropin response to gonadotropin-releasing hormone analogs (GnRHas) corresponding to the activation of the hypothalamic-pituitary-gonadal axis that could differentiate central precocious puberty (CPP) from premature thelarche (PT) and using the electrochemiluminescence assay method.
METHODS
A total of 49 girls underwent the stimulation test with an intramuscular injection of 3.75 mg leuprolide acetate. Based on the clinical and laboratory characteristics, they were divided into two groups: CPP (n = 22) and PT (n = 27). Baseline estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were collected before GnRHa administration and LH and FSH at 60 and 120 min, respectively, after GnRHa administration.
RESULTS
The girls with CPP presented an increased height Z-score, advanced bone age, and higher baseline LH, FSH, estradiol, and LH/FSH ratio in relation to PT (p < 0.001). Stimulated LH differed significantly between the two groups, and the LH cutoff values were ≥4.29 IU/L (p < 0.001) and ≥3.95 IU/L at 60 and 120 min, respectively (p < 0.001). The LH peak was found at 60 min after stimulation.
CONCLUSIONS
The GnRHa test is effective in distinguishing CPP from PT, and a single sampling, at 60 min, with LH concentrations above 4.29 may be the parameter of choice with the advantage of greater convenience and practicality.
Topics: Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Luteinizing Hormone; Puberty, Precocious
PubMed: 34933304
DOI: 10.1159/000521593 -
The Journal of Clinical Endocrinology... Aug 2022Congenital generalized lipodystrophy, type 1 (CGL1), due to biallelic pathogenic variants in AGPAT2, is characterized by the near total loss of body fat from the face,...
CONTEXT
Congenital generalized lipodystrophy, type 1 (CGL1), due to biallelic pathogenic variants in AGPAT2, is characterized by the near total loss of body fat from the face, trunk, and extremities. Patients develop premature diabetes, hypertriglyceridemia, hepatic steatosis, and polycystic ovary syndrome. However, sparing of the facial fat and precocious pubertal development has not been previously reported in CGL1.
CASE DESCRIPTION
We report a 21-year-old woman of European descent with CGL1 who had sparing of the facial fat and premature thelarche at birth with premature pubarche and menstrual bleeding at age 3 years. Her serum 17-OH progesterone level rose to 1000 ng/dL (30.26 nmol/L) after cosyntropin stimulation test, suggestive of nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency. Hydrocortisone replacement therapy from age 3.5 to 10 years resulted in cessation of menstruation and growth of pubic hair, and a reduction of breast size. Sanger and whole-exome sequencing revealed compound heterozygous variants c.493-1G>C; p.(Leu165_Gln196del), and c.del366_588+534; p.(Leu123Cysfs*55) in AGPAT2 plus c.806G>C; p.(Ser269Thr) and c.844G>T; p.(Val282Leu) in CYP21A2. She developed diabetes at age 13 requiring high-dose insulin and had 7 episodes of acute pancreatitis due to extreme hypertriglyceridemia in the next 5 years. Metreleptin therapy was initiated at age 18 and after 3 years, she had remission of diabetes and hypertriglyceridemia; however, menstrual irregularity and severe hirsutism did not improve.
CONCLUSION
Concomitant NCAH in this CGL1 patient was associated with precocious pubertal development and sparing of facial fat. Metreleptin therapy drastically improved her hyperglycemia and hyperlipidemia but not menstrual irregularity and hirsutism.
Topics: Acute Disease; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Child; Child, Preschool; Female; Hirsutism; Humans; Hyperinsulinism; Hyperlipidemias; Hypertriglyceridemia; Infant, Newborn; Lipodystrophy, Congenital Generalized; Menstruation Disturbances; Pancreatitis; Puberty, Precocious; Steroid 21-Hydroxylase; Young Adult
PubMed: 35857714
DOI: 10.1210/clinem/dgac406 -
Indications of younger age at menarche in Greek adolescents but with no relation to body mass index.Hormones (Athens, Greece) Apr 2024This study aimed to present recent trends in the pubertal timing of a Greek female sample.
PURPOSE
This study aimed to present recent trends in the pubertal timing of a Greek female sample.
METHODS
Data were collected retrospectively from medical records of healthy females aged 6-18 years who attended a tertiary Adolescent Friendly Health Center over a 5-year period (2016-2020) and included gestational age, birth anthropometrics, and age of thelarche and/or pubarche and/or menarche, along with corresponding anthropometric, hormonal, and biochemical measurements.
RESULTS
Data from 298 girls' medical records were included in the analysis. Median age at menarche, thelarche, and pubarche was 12, 9, and 9 years, respectively. The mean interval between pubertal onset and menarche was 1.99 years. The mean body mass index (BMI) at menarche and thelarche was 20.99 kg/m and 18.90 kg/m, respectively. The mean weight at menarche was 49.6 kg, whereas the mean height difference between thelarche and menarche was 19.17 cm. Among participants, 6.3% had premature menarche, while 24.0% had premature thelarche. Birth weight was moderately correlated with BMI at thelarche/pubarche (r=0.334, p = 0.005). Birth weight and BMI at thelarche/pubarche were not predictive of premature menarche or premature thelarche. Median (interquartile range, IQR) levels at menarche vs. thelarche were significantly higher for insulin-like growth factor-1 [358.00 (140.50) vs. 176.00 (55.00) ng/ml], follicle stimulation hormone [5.65 (3.14) vs. 3.10 (4.23) mIU/ml], testosterone [25.50 (31.00) vs. 13.00 (21.00) ng/dl], dehydroepiandrosterone sulfate [117.00 (112.50) vs. 46.40 (51.90) µg/dl], and insulin [17.40 (15.05) vs. 8.47 (4.97) µIU/ml].
CONCLUSION
The timing of pubertal stages in the Greek female sample studied followed the recent international downward trends. Younger age at menarche was not related to BMI.
PubMed: 38647964
DOI: 10.1007/s42000-024-00557-8 -
International Journal of Pediatric... 2016Premature thelarche (PT) seems to be increasing and it is difficult to differentiate its early stages from precocious puberty (PP). Clinical and biochemical parameters...
Increasing incidence of premature thelarche in the Central Region of Denmark - Challenges in differentiating girls less than 7 years of age with premature thelarche from girls with precocious puberty in real-life practice.
BACKGROUND
Premature thelarche (PT) seems to be increasing and it is difficult to differentiate its early stages from precocious puberty (PP). Clinical and biochemical parameters are warranted to differentiate the two diagnoses.
METHODS
One hundred ninety-one girls aged 0.5-7 years were included. Diagnoses were validated and the girls were categorized to the groups PP (n = 27) and PT (n = 164). Anthropometry, Tanner stages, ethnicity, bone age, and biochemistry, were recorded. Conventional variables for diagnosing PP were compared between the groups at time of referral to identify parameters predictive for the diagnosis.
RESULTS
The referral rate of PT increased from 1998-2013. Girls with PT and PP differed with regards to age at referral, body mass index standard deviation scores (BMISDS), ethnicity, bone age advancement, basal luteinizing hormone (LH), gonadotropin releasing hormone (GnRH) stimulated LH and follicle stimulating hormone (FSH), basal and stimulated LH/FSH ratio, and sex-hormone binding globulin (SHBG). Apart from SHBG there was considerable overlap of the variables between the PT and the PP groups.
CONCLUSIONS
First, the incidence of PT appears to increase. Second, SHBG was the variable which best discriminated PT from PP. Third, stimulated LH in 1-3 years old girls with PT is similar to stimulated LH in 5-7 years old girls with PP. Age, BMISDS, ethnicity, bone age, stimulated gonadotropins and LH/FSH and SHBG are all useful variables for differentiating PP from PT. However normative data for stimulated LH and FSH in the age group 0.5-7 years are warranted.
PubMed: 26909102
DOI: 10.1186/s13633-016-0022-x -
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 -
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 -
Journal of Pediatric Endocrinology &... Nov 2021There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic-pituitary-gonadal axis. However, the effect of gonadotropin-releasing hormone...
OBJECTIVES
There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic-pituitary-gonadal axis. However, the effect of gonadotropin-releasing hormone (GnRH) stimulation on AMH levels is not clearly known. In the study, we aimed to evaluate the effect of GnRH stimulation on AMH levels in central precocious puberty (CPP) and isolated premature thelarche (PT) groups.
METHODS
Sixty-three girls with breast development before the age of 8 were enrolled in the study. GnRH test was performed on all subjects. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels were taken at basal, 40th, and 90th minute of GnRH test. Subjects were grouped as CPP and PT group.
RESULTS
After GnRH stimulation, AMH levels increased significantly at the 40th minute and the stimulating effect of GnRH on AMH continued till the 90th minute (p: 0.0001). There was a positive correlation between basal and 90th-minute AMH levels (r: 479, p: 0.0001). The highest FSH, LH, and AMH times were significantly different after the GnRH stimulation (p: 0.001, p: 0.001, and p: 0.007). Although the CPP group had a lower basal AMH level than the PT group's basal AMH level; AMH response to GnRH stimulation was not different (p>0.05).
CONCLUSIONS
In our study, which examined the effect of GnRH stimulation on AMH levels in early pubertal development disorders for the first time, GnRH stimulated AMH secretion rapidly, correlated with basal AMH. Basal AMH levels were lower in patients with CPP than in those with PT; however, the effect of GnRH stimulation on AMH levels was similar in both groups.
Topics: Anti-Mullerian Hormone; Child; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Puberty, Precocious
PubMed: 34344062
DOI: 10.1515/jpem-2021-0343 -
Hormone Research in Paediatrics 2016Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants and have shown endocrine disruption properties in experimental studies. The aim of this study... (Clinical Trial)
Clinical Trial
BACKGROUND/AIMS
Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants and have shown endocrine disruption properties in experimental studies. The aim of this study was to investigate the association between the exposure to PBDEs and alterations of puberty in girls referred for idiopathic central precocious puberty (ICPP) and premature thelarche (PT).
METHODS
A case-control study was conducted in 124 girls: 37 girls with ICPP (mean age 7.4 ± 0.9 years), 56 with PT (mean age 5.7 ± 2.1 years) and 31 controls (mean age 5.4 ± 1.9 years). PBDE serum concentrations, hormone levels and anthropometry were assessed. PBDE concentrations were corrected for total serum lipid content. Individual exposure to PBDEs was evaluated through ad hoc questionnaires.
RESULTS
PBDE serum concentrations corrected for total lipid content were significantly higher in girls with PT (mean 1.49 ± 0.63 log ng/g) than in controls (mean 1.23 ± 0.54 log ng/g; p < 0.05). PT girls showed higher levels of PBDE than ICPP girls (1.49 ± 0.63 vs. 1.37 ± 0.49 log ng/g), though this was not significant. An analysis of the questionnaires revealed no significant differences in exposure between the three groups.
CONCLUSION
Our findings suggest that higher concentrations of serum PBDEs are associated with PT in girls.
Topics: Breast; Child; Child, Preschool; Cross-Sectional Studies; Female; Halogenated Diphenyl Ethers; Humans; Puberty, Precocious
PubMed: 27035145
DOI: 10.1159/000444586