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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 -
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 -
Acta Bio-medica : Atenei Parmensis Dec 2023The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to...
BACKGROUND
The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to comprehensively analyze and summarize research articles to elucidate the potential link between precocious or early pubertal onset (CPP) and crucial health factors.
METHODS
We conducted a systematic review of studies published from -January 2000 to March 2023, sourced from databases of Medline, PubMed, Google Scholar and Web of Science. We assessed the relationship between CPP and final adult height (FHt), bone health, reproductive function, body mass index, metabolic and cardiovascular abnormalities, and increased cancer risk.
RESULTS
Upon reviewing and analyzing selected studies, the following key findings emerged: (a) treating CPP in girls before age 6-7 and in boys before age 9 improves FHt; (b) bone mineral density (BMD) decreases during GnRHa treatment but normalizes afterward, with no lasting effects on peak bone mass during puberty; (c) GnRH treatment does not negatively affect menstrual cycles; however, untreated CPP increases the risk of premature or early-onset menopause; (d) the incidence of PCOS/hyperandrogenemia may be slightly elevated in women with a history of CPP, but overall reproductive function remains largely unaffected; (e) earlier thelarche and menarche may enhance susceptibility to breast carcinogenesis; (f) CPP contributes to an increased risk of obesity and type 2 diabetes in both genders; (g) early menarche may slightly increase the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk of depression and anxiety disorders.
CONCLUSION
Monitoring and early diagnosis of these conditions are of paramount importance for successful management.
Topics: Female; Humans; Male; Child; Diabetes Mellitus, Type 2; Gonadotropin-Releasing Hormone; Puberty, Precocious; Obesity; Puberty
PubMed: 38054666
DOI: 10.23750/abm.v94i6.15316 -
Journal of the Formosan Medical... Nov 2011In May 2011, the illegal use of the phthalate plasticizer di(2-ethylhexyl) phthalate in clouding agents for use in foods and beverages was reported in Taiwan. This food... (Review)
Review
In May 2011, the illegal use of the phthalate plasticizer di(2-ethylhexyl) phthalate in clouding agents for use in foods and beverages was reported in Taiwan. This food scandal has caused shock and panic among the majority of Taiwanese people and has attracted international attention. Phthalate exposure is assessed by ambient monitoring or human biomonitoring. Ambient monitoring relies on measuring chemicals in environmental media, foodstuff and consumer products. Human biomonitoring determines body burden by measuring the chemicals, their metabolites or specific reaction products in human specimens. In mammalian development, the fetus is set to develop into a female. Because the female phenotype is the default, impairment of testosterone production or action before the late phase may lead to feminizing characteristics. Phthalates disrupt the development of androgen-dependent structures by inhibiting fetal testicular testosterone biosynthesis. The spectrum of effects obtained following perinatal exposure of male rats to phthalates has remarkable similarities with the human testicular dysgenesis syndrome. Epidemiological studies have suggested associations between phthalate exposure and shorter gestational age, shorter anogenital distance, shorter penis, incomplete testicular descent, sex hormone alteration, precocious puberty, pubertal gynecomastia, premature thelarche, rhinitis, eczema, asthma, low birth weight, attention deficit hyperactivity disorder, low intelligence quotient, thyroid hormone alteration, and hypospadias in infants and children. Furthermore, many studies have suggested associations between phthalate exposure and increased sperm DNA damage, decreased proportion of sperm with normal morphology, decreased sperm concentration, decreased sperm morphology, sex hormone alteration, decreased pulmonary function, endometriosis, uterine leiomyomas, breast cancer, obesity, hyperprolactinemia, and thyroid hormone alteration in adults. Finally, the number of phthalate-related scientific publications from Taiwan has increased greatly over the past 5 years, which may reflect the health effects from the illegal addition of phthalate plasticizer to clouding agent in foodstuff over the past two decades.
Topics: Animals; Beverages; Body Burden; Diethylhexyl Phthalate; Environmental Monitoring; Female; Fetus; Food Safety; Humans; Male; Models, Animal; Plasticizers; Spermatozoa
PubMed: 22118310
DOI: 10.1016/j.jfma.2011.09.002 -
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 -
Frontiers in Pediatrics 2019Puberty is a sensitive period of life characterized by the appearance of secondary sex characteristics which leads to a complete sexual maturation. It physiologically... (Review)
Review
Puberty is a sensitive period of life characterized by the appearance of secondary sex characteristics which leads to a complete sexual maturation. It physiologically starts between the age of 8 and 13 years in girls and 9 and 14 years in boys. In the last two decades, several studies have showed that start of puberty has moved up to younger ages by 12-18 months, and some of the hypotheses trying to explain this change include the role of nutritional status and obesity and the influence of extrinsic factors such as exposure to endocrine-disrupting chemicals (EDCs), as well. The hypothalamic-hypophysis-gonadal axis develops during embryogenesis, and except for a period of activation immediately after birth, remains suppressed until the onset of pubertal development. At the beginning of puberty, the pulse generator is reactivated, probably due to progressive stimulatory influences on GnRH neurons from glial signals and neurotrasmitters. Kisspeptin and its receptor play a fundamental role in this phase. Premature Pubarche/Adrenarche, Premature Thelarche, and Premature Menarche are incomplete forms of precocious pubertal development that have their origin in endocrine mechanisms that only recently have started to be understood. It is important to distinguish these forms from the complete ones in order to reassure patients and parents about the non-evolution of pubertal progression and avoid non-useful treatments with analogous LHRH.
PubMed: 31139600
DOI: 10.3389/fped.2019.00147 -
The British Journal of Dermatology Dec 2015Multiple congenital melanocytic naevi (CMN) is a rare mosaic RASopathy, caused by postzygotic activating mutations in NRAS. Growth and hormonal disturbances are...
BACKGROUND
Multiple congenital melanocytic naevi (CMN) is a rare mosaic RASopathy, caused by postzygotic activating mutations in NRAS. Growth and hormonal disturbances are described in germline RASopathies, but growth and hormone status have not previously been investigated in individuals with CMN.
OBJECTIVES
To explore premature thelarche, undescended testes, and a clinically abnormal fat distribution with CMN through prospective endocrinological assessment of a cohort of subjects with CMN, and a retrospective review of longitudinal growth of a larger group of patients with CMN from outpatient clinics (which included all subjects in the endocrinological assessment group).
PATIENTS AND METHODS
Longitudinal growth in a cohort of 202 patients with single or multiple CMN was compared with the U.K. National Child Measurement Programme 2010. Forty-seven children had hormonal profiling including measurement of circulating luteinizing hormone, follicle-stimulating hormone, thyroid stimulating hormone, adrenocorticotrophic hormone, growth hormone, prolactin, pro-opiomelanocortin, estradiol, testosterone, cortisol, thyroxine, insulin-like growth factor-1 and leptin; 10 had oral glucose tolerance testing 25 had dual-energy X-ray absorptiometry scans for body composition.
RESULTS
Body mass index increased markedly with age (coefficient 0·119, SE 0·016 standard deviation scores per year), at twice the rate of the U.K. population, due to increased adiposity. Three per cent of girls had premature thelarche variant and 6% of boys had persistent undescended testes. Both fat and muscle mass were reduced in areas underlying large naevi, resulting in limb asymmetry and abnormal truncal fat distribution. Anterior pituitary hormone profiling revealed subtle and variable abnormalities. Oral glucose tolerance tests revealed moderate-severe insulin insensitivity in five of 10, and impaired glucose tolerance in one.
CONCLUSIONS
Interpersonal variation may reflect the mosaic nature of this disease and patients should be considered individually. Postnatal weight gain is potentially related to the underlying genetic defect; however, environmental reasons cannot be excluded. Naevus-related reduction of fat and muscle mass suggests local hormonal or metabolic effects on development or growth of adjacent tissues, or mosaic involvement of these tissues at the genetic level. Premature thelarche and undescended testes should be looked for, and investigated, as for any child.
Topics: Absorptiometry, Photon; Adolescent; Case-Control Studies; Child; Child, Preschool; Cryptorchidism; Female; Glucose Tolerance Test; Growth Disorders; Hormones; Humans; Infant; Male; Nevus, Pigmented; Prospective Studies; Puberty; Puberty, Precocious
PubMed: 26286459
DOI: 10.1111/bjd.14091