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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 -
Indian Pediatrics Jun 2023To describe the characteristics of gonadotropin-dependent precocious puberty (GDPP) in Indian children.
OBJECTIVE
To describe the characteristics of gonadotropin-dependent precocious puberty (GDPP) in Indian children.
METHODS
Clinical profiles of GDPP (n=78, 61 females) and premature thelarche (n=12) from a single center in Western India were retrospectively studied.
RESULTS
Pubertal onset was earlier in boys than girls (29 vs 75 months, respec-tively; P=0.008). The basal luteinizing hormone (LH) was ≥0.3 mIU/mL, except 18% of GDPP girls. At 60 minutes after GnRHa-stimulation, all patients (except one girl) had LH ≥5 mIU/mL. The GnRHa-stimulated LH/FSH ratio was ≥0.34 at 60 minutes in girls with GDPP unlike premature thelarche. Only one girl had an allergic reaction to long-acting GnRH agonist. Among GnRH agonist-treated girls (n=24), the predicted final adult height was -1.67±1.5 SDS, whereas the attained final height was -0.25±1.48 SDS.
CONCLUSION
We establish the safety and efficacy of long acting GnRH agonist therapy in Indian children with GDPP. The 60-minute stimulated serum LH/FSH of ≥0.34 differentiated GDPP from premature thelarche.
Topics: Child; Female; Male; Adult; Humans; Puberty, Precocious; Gonadotropin-Releasing Hormone; Follicle Stimulating Hormone; Retrospective Studies; Luteinizing Hormone; Puberty
PubMed: 37211886
DOI: No ID Found -
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 -
AJR. American Journal of Roentgenology Mar 2015OBJECTIVE. We analyzed the correlation between breast development and ultrasound-measured breast bud diameter. We also evaluated different breast ultrasound findings in... (Comparative Study)
Comparative Study
OBJECTIVE. We analyzed the correlation between breast development and ultrasound-measured breast bud diameter. We also evaluated different breast ultrasound findings in pediatric subjects with precocious puberty and premature thelarche while comparing bone age and hormone levels. MATERIALS AND METHODS. We performed a retrospective study with a sample of 90 girls (mean age, 7.8 years) who underwent breast ultrasound for evaluation of early breast development between March 2011 and February 2013. We evaluated breast ultrasound grade, bud diameter, and clinical characteristics including bone age and hormone levels. Among the 90 girls, 69 were up to 8 years old (mean age, 7.3 years). We divided them into healthy, precocious puberty, and premature thelarche groups and evaluated the clinicoradiologic findings for each group. RESULTS. Breast ultrasound grade was correlated with age, bone age, bud diameter, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2). Bud diameter was correlated with age, bone age, LH, FSH, and E2. However, the difference between bone age and chronological age was not correlated with ultrasound grade or bud diameter. Among 69 girls up to 8 years old, including 11 healthy girls (15.9%), 26 girls with precocious puberty (37.7%) (mean [SD] age, 7.3 years), and 32 girls with premature thelarche (46.4%) (mean age, 7.2 years), there were no significant differences in other variables except values for bone age (p = 0.001) and difference between bone age and chronological age (p < 0.001). CONCLUSION. Breast ultrasound might be useful for evaluating sexual development with respect to bud diameter or ultrasound grade. However, its ability to distinguish precocious puberty from premature thelarche is limited.
Topics: Age Determination by Skeleton; Breast; Child; Child, Preschool; Diagnosis, Differential; Estradiol; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Puberty, Precocious; Retrospective Studies; Ultrasonography, Mammary
PubMed: 25714294
DOI: 10.2214/AJR.14.12565 -
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 -
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 -
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 -
Biomolecules Feb 2024Endocrine-disrupting chemicals (EDCs) may impact the development of prostate cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in...
Endocrine-disrupting chemicals (EDCs) may impact the development of prostate cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 which are involved in the production of androgens or estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women. Essential oils or their metabolites, like lavender oil and tea tree oil, have been reported to act as potential EDCs and contribute towards sex steroid imbalance in cases of prepubertal gynecomastia in boys and premature thelarche in girls due to the exposure to lavender-based fragrances. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1. Computational docking was performed to predict the binding of essential oils with CYP17A1 and CYP19A1. Functional assays were performed using the radiolabeled substrates or Liquid Chromatography-High-Resolution Mass Spectrometry and cell viability assays were carried out in LNCaP cells. Many of the tested compounds bind close to the active site of CYP17A1, and (+)-Cedrol had the best binding with CYP17A1 and CYP19A1. Eucalyptol, Dihydro-β-Ionone, and (-)-α-pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these essential oils in various beauty and hygiene products is common, but only limited knowledge about their potential detrimental side effects exists. Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output and ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for novel compounds against hyperandrogenic disorders such as PCa and PCOS.
Topics: Male; Humans; Female; Androgens; Gonadal Steroid Hormones; Oils, Volatile; Steroids; Polycystic Ovary Syndrome; Cytochrome P-450 Enzyme System
PubMed: 38397440
DOI: 10.3390/biom14020203