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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 -
Clinical Endocrinology Jun 2023There is controversial results about serum kisspeptin, neurokinin-B (NKB), anti-Müllerian hormone (AMH) and inhibin B (INHB) levels in girls with central precocious...
Serum kisspeptin, neurokinin B and inhibin B levels can be used as alternative parameters to distinguish idiopathic CPP from premature thelarche in the early stages of puberty.
OBJECTIVE
There is controversial results about serum kisspeptin, neurokinin-B (NKB), anti-Müllerian hormone (AMH) and inhibin B (INHB) levels in girls with central precocious puberty (CPP). Aim of this study is to evaluate serum levels of these four peptides in patients presented with early pubertal signs, and to evaluate their diagnostic validity in the diagnosis of CPP.
DESIGN
Cross-sectional study.
PATIENTS
Study included 99 girls (51 CPP, 48 premature thelarche [PT]) whose breast development started before 8 years and 42 age-matched healthy prepubertal girls. Clinical findings, antropometric measurements, laboratory and radiological findings were recorded. Gonadotropin-releasing hormone (GnRH) stimulation test was performed in all cases with early breast development.
MEASUREMENTS
Kisspeptin, NKB, INHB and AMH levels were measured in fasting serum samples using enzyme-linked immunosorbent assay method.
RESULTS
There was no statistically significant difference between mean ages of girls with CPP (7.1 ± 1.2 years), PT (7.2 ± 1.3 years) and prepubertal controls (7.0 ± 1.0 years). Serum kisspeptin, NKB and INHB levels were higher in CPP group compared to PT and control groups, while serum AMH level was lower in CPP group. Serum kisspeptin, NKB, and INHB were all positively correlated with bone age (BA) advancement, and peak luteinizing hormone in GnRH test. Multiple stepwise regression analysis revealed that the most important factors used to differentiate CPP from PT were advanced BA, serum kisspeptin, NKB and INHB levels (AUC: 0.819, p < .001).
CONCLUSIONS
We, first showed in the same patients' group that serum kisspeptin, NKB and INHB were higher in patients with CPP and can be used as alternative parameters to distinguish CPP from PT.
Topics: Female; Humans; Child, Preschool; Child; Kisspeptins; Puberty, Precocious; Neurokinin B; Cross-Sectional Studies; Puberty; Anti-Mullerian Hormone; Gonadotropin-Releasing Hormone; Follicle Stimulating Hormone
PubMed: 36879296
DOI: 10.1111/cen.14906 -
Clinical Pediatric Endocrinology : Case... 2022We aimed to determine the prevalence of early puberty in girls with premature pubarche and analyze the time interval between their pubarche and succeeding thelarche....
We aimed to determine the prevalence of early puberty in girls with premature pubarche and analyze the time interval between their pubarche and succeeding thelarche. This study included 60 female children with premature pubarche. We retrospectively collected clinical, laboratory, and radiological findings from all participants. We investigated the time interval between pubarche and thelarche in cases wherein premature pubarche was followed by thelarche. The mean age at onset of pubarche was 6.93 ± 0.79 yr old. Among the participants, 16.7% were preterm, 20% were small for gestational age (SGA), and 55% were overweight or obese. The mean time interval between pubarche and thelarche was 11.20 ± 7.41 mo. The mean serum DHEA-S level was higher in the preterm group (p = 0.016), and DHEA-S levels were generally higher in the SGA group (p = 0.004). This study documented the presence of being overweight or obese and having more advanced growth than their genetic potential in half of the patients who had premature pubarche. In addition to these identified risk factors, obesity-independent DHEA-S levels were observed to be higher in patients who had early puberty with the first six months of their follow-up considered to be the most critical time in predicting early puberty.
PubMed: 35002065
DOI: 10.1297/cpe.2021-0042 -
The Journal of Clinical Endocrinology... Jan 2024Nonprogressive premature thelarche (PT) is a self-limiting variant of early puberty, while idiopathic central precocious puberty (ICPP) is a disorder that causes...
CONTEXT
Nonprogressive premature thelarche (PT) is a self-limiting variant of early puberty, while idiopathic central precocious puberty (ICPP) is a disorder that causes progressive development of secondary sexual characteristics and often requires treatment. The diagnostic differentiation between these conditions is important but can be challenging since they often both initially present clinically with isolated breast development.
OBJECTIVE
To describe relevant clinical variables in a large cohort of girls referred for early puberty, and to evaluate clinical and biochemical parameters to distinguish between girls with ICPP and PT.
METHODS
This retrospective study included 1361 girls referred with signs of early puberty to a single, tertiary center from 2009 to 2019. We evaluated clinical presentation, medical history, growth velocity, bone age, hormonal serum concentrations, and gonadotropin-releasing hormone (GnRH) test results.
RESULTS
Central precocious puberty was diagnosed in 11% (ICPP: n = 143, organic CPP: n = 11) girls, whereas 8% (n = 91 girls) presented with PT. Receiver operating characteristic (ROC) analysis showed several biochemical and anthropometric markers as potential parameters to differentiate between ICPP and PT; however, none were individually adequate. Principal component analysis (PCA)-derived clinical and hormone profiles could predict girls with ICPP from girls with PT with a specificity of 90% and sensitivity of 84%, outperforming any single marker.
CONCLUSION
Differentiation of girls with ICPP and PT can be supported by individual clinical and biochemical parameters. However, dimension reduction of clinical and hormonal profiles by PCA improved the diagnostic value, which in the future may support the diagnostic process as a supplement to the GnRH test in evaluation of pubertal disorders.
Topics: Female; Humans; Puberty, Precocious; Retrospective Studies; Principal Component Analysis; ROC Curve; Gonadotropin-Releasing Hormone
PubMed: 37698163
DOI: 10.1210/clinem/dgad535 -
Journal of Clinical Research in... Sep 2019Antimüllerian hormone (AMH) concentrations in mini puberty are higher than those reported for the prepubertal period. In this study we investigated AMH concentrations...
OBJECTIVE
Antimüllerian hormone (AMH) concentrations in mini puberty are higher than those reported for the prepubertal period. In this study we investigated AMH concentrations in infants with premature thelarche (PT). A healthy control group was used for comparison.
METHODS
Forty five female infants with PT, aged between one and three years and a control group consisting of 37 healthy girls in the same age range were included in the study. Bone age, pelvic ultrasonography, and concentrations of luteinizing hormone, follicle-stimulating hormone (FSH), estradiol and AMH of the patient group were evaluated. Only serum AMH concentration of the control group was evaluated.
RESULTS
Median (range) serum AMH concentrations in the subjects were 1.66 ng/mL (11.85 pmol/L) [0.15-6.32 ng/mL (1.07-45.12 pmol/L)] and were significantly lower (p=0.025) than for the control group; 1.96 ng/mL (13.99 pmol/L) [0.60-8.49 ng/mL (4.28-60.64 pmol/L)]. AMH and FSH were negatively correlated (r=-0.360, p=0.015) in infants with PT. There was no correlation between AMH and uterine size, uterine volume, endometrial thickness, fundocervical ratio, ovarian size or volume, follicle size and follicle number.
CONCLUSION
This is the first study that investigates AMH concentrations in infants with PT. The low AMH levels in these infants and the negative correlation between AMH and FSH suggests that AMH may play a role in suppressing pubertal findings during infancy and that decreased AMH may cause PT in infancy.
Topics: Anti-Mullerian Hormone; Biomarkers; Case-Control Studies; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Prognosis; Prospective Studies; Puberty, Precocious
PubMed: 30859797
DOI: 10.4274/jcrpe.galenos.2019.2018.0293 -
Factors affecting bone maturation in Chinese girls aged 4-8 years with isolated premature thelarche.BMC Pediatrics Jul 2020In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, some IPT girls confirmed by gonadotropin-releasing...
BACKGROUND
In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, some IPT girls confirmed by gonadotropin-releasing hormone (GnRH) stimulation test could show another trend. We analysed BA and possible potentiating factors in a selected group of girls aged 4-8 years with IPT.
METHODS
IPT girls confirmed by GnRH stimulation test aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital were included in this retrospective study. They were divided into two groups with advanced BA of 2 years as the cut-off. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS for comparisons of advanced BA.
RESULTS
Overall, 423 subjects were included and classified into the advanced BA group (48.7%, n = 206) and control group (51.3%, n = 217). The advanced BA group had significantly higher BMI SDS, serum DHEAS SDS, IGF-1 SDS, androstenedione and fasting insulin and significantly lower sex hormone binding globulin (all p < 0.001). Serum IGF-1 SDS (OR = 1.926, p<0.001), BMI SDS (OR = 1.427, p = 0.001) and DHEAS SDS (OR = 1.131, p = 0.005) were independent risk factors for significantly advanced BA. In the multiple linear regression model, serum IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 19.3% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n = 237), overweight (19.15%, n = 81) and obesity (24.82%, n = 105). The proportion of advanced BA in obesity group was significantly higher than those of normal weight and overweight groups (χ = 18.088, p<0.001). In the subgroup with normal weight, higher serum IGF-1 SDS (p = 0.009) and DHEAS SDS (p = 0.003) affected BA advancement independent of BMI SDS.
CONCLUSIONS
Girls with IPT confirmed by GnRH stimulation test aged 4-8 years might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.
Topics: Body Mass Index; Child; Child, Preschool; China; Female; Humans; Obesity; Puberty, Precocious; Retrospective Studies
PubMed: 32727432
DOI: 10.1186/s12887-020-02256-w -
Endocrine Mar 2022Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). However, intravenous GnRH is not always...
PURPOSE
Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). However, intravenous GnRH is not always readily available. The aim of the present study was to evaluate the diagnostic accuracy of triptorelin-stimulated luteinizing hormone (LH) concentrations in the diagnosis of CPP among girls presenting with premature thelarche compared to the gold standard GnRH test.
METHODS
A prospective, case-control (CPP vs isolated premature thelarche), clinical study evaluating the diagnostic accuracy of triptorelin-stimulated LH concentrations in 60 girls with premature thelarche was performed. All girls underwent stimulation with subcutaneous triptorelin injection and intravenous GnRH in a randomized order. During the stimulation test with triptorelin, LH and FSH were measured at time 0, 30, 60, 90, 120, and 180 min after the injection. Estradiol was sampled 24 h after the injection. During the GnRH test, LH and FSH were measured at time 0, 30, 45, and 60 min. Girls with peak GnRH-stimulated LH concentrations ≥5.0 IU/L were classified as having CPP. Area under the curve (AUC) for triptorelin-stimulated LH concentrations was assessed using the receiver operating characteristic (ROC) analysis.
RESULTS
Triptorelin-stimulated LH concentrations were significantly higher in girls who had CPP according to the GnRH test (53.3%). LH peaked at 180 min after the triptorelin injection. The highest diagnostic accuracy for CPP (AUC = 0.973, sensitivity 96.9%, specificity 89.3%) at 180 min was at a LH concentration ≥3.4 IU/L. The 24 h estradiol concentration did not improve the predictive model.
CONCLUSIONS
Measuring LH concentrations 180 min after triptorelin injection with a cut-off value of ≥3.4 IU/L demonstrated a high diagnostic accuracy compared to the GnRH test. Thus, stimulation with triptorelin can be used as a reliable alternative for diagnosing CPP in girls with premature thelarche.
Topics: Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Prospective Studies; Puberty, Precocious; Triptorelin Pamoate
PubMed: 34826116
DOI: 10.1007/s12020-021-02947-z -
International Journal of Environmental... Mar 2023This case-control study aims to evaluate the oxidant-antioxidant balance in girls having central precocious puberty (CPP) and premature thelarche (PT). Thirty-four girls...
This case-control study aims to evaluate the oxidant-antioxidant balance in girls having central precocious puberty (CPP) and premature thelarche (PT). Thirty-four girls having CPP, 24 girls having PT, and 49 healthy growing girls between 7 and 9 years of age admitted to child health supervision were enrolled. Total antioxidant and oxidant capacity, myeloperoxidase, catalase, superoxide dismutase, total thiol, native thiol, and disulfide levels were analyzed in serum samples. Low total oxidant status (<12.0) was found to be highest in the CPP group, lowest in the control group, and the PT group was in between them. After controlling bone age and z score for body mass index, generalized linear models revealed lower oxidative stress index values in the CPP and the PT groups than the control group. Other studied parameters did not differ among groups. Precocious puberty in girls is associated with some changes in the oxidant-antioxidant status.
Topics: Child; Female; Humans; Puberty, Precocious; Luteinizing Hormone; Follicle Stimulating Hormone; Antioxidants; Case-Control Studies; Oxidants
PubMed: 35000523
DOI: 10.1080/09603123.2022.2025767 -
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 -
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