Premature Thelarche Group Research Articles

Serum nesfatin-1 and leptin levels in non-obese girls with premature thelarche.

We aimed to investigate serum nesfatin-1 level in girls with premature thelarche (PT) and its relationship with anthropometric parameters and leptin, which are involved in the initiation of pubertal process. Non-obese girls who presented with the complaint of early (2-8 years) and isolated breast development were included in the study. The control group consisted of age-matched healthy prepubertal girls. Auxological measurements were performed in all subjects. Gonadotropin-releasing hormone (GnRH) stimulation test and bone age assessment were conducted in subjects with early breast development. Girls with a bone age/chronologic age ratio <1.2 and a peak luteinizing hormone (LH) response to GnRH stimulation <5 mIU/L were included in the PT group. The study included 22 non-obese girls with PT and 24 healthy prepubertal controls. Body mass index (BMI), BMI-standard deviation score (SDS) and height SDS were similar between the groups (p > 0.05). Serum leptin and nesfatin-1 levels were found significantly higher in the PT group compared to controls (p < 0.05). No correlation was detected between nesfatin-1 and basal LH, basal follicle stimulating hormone (FSH), stimulated peak LH, peak FSH, leptin levels and anthropometric parameters in the PT group (p > 0.05). Results of the present study showed that serum nesfatin-1 and leptin levels are significantly higher in girls with PT than in prepubertal controls. This finding suggests that similar to leptin, nesfatin-1 may also have a central or peripheral role in the initiation of pubertal process and may be related to PT pathogenesis.

Significance of serum neurokinin B and kisspeptin levels in the differential diagnosis of premature thelarche and idiopathic central precocious puberty

The aim of the present study was to investigate the diagnostic role of serum neurokinin B level and its relationship with kisspeptin and leptin, which are known to be involved in the initiation of pubertal process. Girls who presented with breast development (<8 years) were included in the study. All patients underwent bone age assessment. Basal levels of serum follicle stimulating hormone and luteinizing hormone were measured and gonadotropin releasing hormone stimulation test was performed. Patients with a bone age/chronological age ratio >1 and a peak luteinizing hormone response in gonadotropin releasing hormone stimulation test >5mIU/L were included in the central precocious puberty group, while patients who did not meet these criteria were included in the premature thelarche group. Patients with organic pathologies were excluded. Healthy prepubertal girls with similar age were included as the control group. Leptin, kisspeptin and neurokinin B levels were measured by ELISA method. The study included 20 girls with idiopathic central precocious puberty 22 girls with premature thelarche and 24 prepubertal controls. While serum kisspeptin, leptin and neurokinin B levels were significantly higher in central precocious puberty and premature thelarche groups compared to controls, no significant difference was found between central precocious puberty and premature thelarche groups. Increased serum levels of leptin, kisspeptin and neurokinin B in patients with premature thelarche and central precocious puberty suggest that they take part during the initiation of pubertal process, however, these markers are not able to differentiate patients with central precocious puberty from premature thelarche.

AMH levels at central precocious puberty and premature thelarche: is it a parameter?

The possible difference of antimüllerian hormone (AMH) levels at central precocious puberty (CPP) and premature thelarche (PT) has not been properly evaluated. By evaluating AMH levels in girls with diagnosed CPP and PT, we aim to show the change of AMH levels at the pubertal onset. Sixty-five girls who have breast development before the age of 8 years and 25 healthy girls were enrolled in the study. The subjects were divided into two groups as CPP and PT, according to results of GnRH test. AMH levels were determined in the two groups. The mean AMH levels of the CPP group were significantly lower than those in the PT group (13.57±9.85 pmol/L and 58.42±12.78 pmol/L, respectively, p=0.022). These results suggest that the AMH levels decrease in the duration of the hypothalamus-pituitary-ovarian axis activation. We thought that AMH might/may be a marker for distinguishing between CPP and PT.

Serum bisphenol A concentration and premature thelarche in female infants aged 4-month to 2-year.

To estimate the association between serum bisphenol A and premature thelarche in female infants aged 4-mo to 2-y. A total of 251 female infants (aged 4 mo to 2 y) with premature thelarche and 33 healthy age-matched control subjects were analyzed. All participants underwent physical examination and serum bisphenol A was measured by ultra-performance liquid chromatography tandem mass spectrometry. Serum bisphenol A concentration in the premature thelarche group (3.48 ng/ml, 95%CI: 0.09-140.26) was significantly higher than that in the control group (1.70 ng/ml, 95%CI: 0.06-51.78) (p = 0.039). There was no correlation between age and serum bisphenol A (BPA) level. Univariate logistic regression analysis showed that serum BPA concentration positively associated with premature thelarche, and the effect of BPA fell down as the age grew. This hospital-based study implied that there is an association between serum BPA concentrations and premature thelarche. Additionally, serum BPA levels were markedly higher in infants aged 4-mo to 2-y-old, raising a concern for public health authorities.

Significance of Kisspeptin levels in diagnosis and therapeutic evaluation of idiopathic central precocious puberty in girls

Objective To explore the significance and value of Kisspeptin in the diagnosis and therapeutic evaluation for idiopathic central precocious puberty(ICPP) in girls. Methods Twenty-four girls with ICPP and 21 girls with premature thelarche(PT) who were hospitalized in the Children's Hospital of Jiangxi Province from Jun.2012 to Jan.2013 were selected as ICPP group and PT group, and 25 healthy girls were selected as healthy control group.The coagulation vein blood in ICPP girls before treatment and after 6 months treatment and PT girls and healthy girls were collected, and enzyme linked immunosorbent assay was used to detect the plasma Kisspeptin level, and t test was used to analyze the differences among the 4 groups. Results The Kisspeptin level of girls with ICPP[(1.80±0.13) μg/L] was apparently higher than that of PT groups [(1.41±0.10) μg/L] and healthy control group[(1.39±0.13) μg/L], and the differences were statistically significant(t=10.974, 14.787, all P=0.000). However, the difference of Kisspeptin between PT group and healthy control group was not statistically significant(t=10.970, P=0.095). In addition, the Kisspeptin level of ICPP girls who undewent 6-month treatment [(1.49±0.15) μg/L ]was significantly lower than that before treatment, and the difference was statistically significant(t=10.80, P<0.05); but, compared with PT group and healthy control group, there was no significant difference(t=6.32, P=0.060; t=7.44, P=0.214). Conclusions Kisspeptin level is related with pubertal development, and it can be used as an important evidence in ICPP diagnosis and an important parameter in ICPP therapeutic evaluation. Key words: Kisspeptin; Idiopathic central precocious puberty; Premature thelarche

Elevated Leptin Levels in Nonobese Girls With Premature Thelarche

Background and AimIt has been reported that leptin receptors have been also shown in mammary epithelial cells, and it has been suggested that leptin is involved in the control of...

Value of pelvic sonography in the diagnosis of various forms of precocious puberty in girls

To evaluate the role of pelvic sonography (US) in the diagnosis and differentiation of various forms of precocious puberty in girls, and to explore reliable cutoff points of pelvic US measurements for differentiating between these conditions. Uterine length, uterine cross-sectional area, uterine volume, fundocervical ratio, and ovarian volumes of 143 healthy girls were compared with those of 125 girls with different forms of sexual precocity. Ovaries were morphologically classified as homogenous, paucicystic, multicystic, macrocystic, and isolated cystic. Almost all US measurements of girls with central precocious puberty in the 0- to 8-year age group were significantly increased compared with controls and girls with premature thelarche and adrenarche (p < 0.05, except for ovarian volumes in premature thelarche group), whereas no statistically significant difference was found in the 8- to 10-year group (p > 0.05). Ovarian morphology distributions did not differ significantly between patient subgroups, but all had more mature forms compared with controls. Due to the wide overlap between the measurements, no reliable cutoff points could be determined by charting receiver operating characteristics curves. Pelvic US can improve the diagnosis of central precocious puberty in girls of 0-8 years of age but provides no reliable type differentiation alone. It provides no valuable information for this diagnosis in girls of 8-10 years of age.

The prevalence and risk factors of premature thelarche and pubarche in 4‐ to 8‐year‐old girls

To assess the prevalence of premature thelarche (PT) and pubarche in healthy 4- to 8-year-old girls and to investigate factors associated with early pubertal development. Eight hundred and twenty girls were examined by two paediatric endocrinologists to determine Tanner staging. The effects of body mass index, gestational age, intrauterine growth status, age at the first tooth eruption, socio-economical status, maternal age of menarche and consumption of certain food items on early pubertal development were analysed through parametric and nonparametric tests. The prevalence of PT and of premature pubarche was 8.9% and 4.3%, respectively. We found a strong association between the prevalence of PT and the body mass index standard deviation scores (BMI SDS). There were more girls with BMI SDS values above 1 in the PT group (56.1%) than among the remaining subjects (22.9%). Premature thelarche was not significantly associated with intrauterine growth, premature birth, socioeconomic status, age of first tooth eruption or maternal age of menarche. Similarly, the amount of milk, eggs, chicken or fish consumed was not associated with PT. None of the investigated factors were associated with premature pubarche. Occurrence of PT is strongly associated with BMI SDS. Studies investigating secular trends in pubertal development must consider a secular change in body mass index.

Plasma kisspeptin levels in normal female pubertal stages and in girls with idiopathic central precocious puberty

Objective To investigate the pattern of plasma kisspeptin levels in normal female during various pubertal Tanner stages and the girls with idiopathic central precocious puberty(ICPP) or with premature thelarche(PT), and to evaluate the significance of detecting plasma kisspeptin levels as a new criterion for early differentiation between ICPP and PT.Methods Each study group of normal pubertal females with Tanner stage Ⅰ to Ⅴ comprised 16 to 19 individuals.The levels of plasma kisspeptin were also detected in girls with ICPP(n= 10)or PT(n = 12).The plasma kisspeptin levels were detected by enzyme-linked immunosorbent assay (ELISA).Results The level of kisspeptin was significantly higher in ICPP group than in that of PT group [(1.73±0.23 vs1.43±0.29) ng/ml, P＜0.05].Among the normal pubertal females, the level of kisspeptin decreased gradually from Tanner stage Ⅱ to Tanner stage Ⅴ, being highest in Tanner stage Ⅱ [(1.73±0.22) ag/ml] ,lower in stage Ⅳ and Ⅴ than in stage Ⅰ and Ⅲ (P＜0.01).Conclusions Plasma kisspeptin level was the highest during Tanner stage Ⅱ in normal female pubertal development.It is significant to detect plasma kisspeptin level for the differential diagnosis of ICPP and PT. Key words: Kisspeptin; Idiopathic central precocious puberty; Premature thelarche; Tanner stages; Female

Subcutaneous Gonadotropin-Releasing Hormone Agonist (Triptorelin) Test for Diagnosing Precocious Puberty

Background: A test involving 100 μg of intravenous gonadotropin-releasing hormone (GnRH) is a gold standard for confirming the diagnosis of central precocious puberty (CPP). However, intravenous GnRH for testing is commercially limited. Objective: To develop subcutaneous GnRH agonist (GnRH-A) testing and define a peak luteinizing hormone (LH) cutoff value in diagnosing CPP. Methods: A retrospective study of 101 girls with sexual precocity was undertaken. All girls underwent 100 μg subcutaneous GnRH-A (triptorelin) testing. Blood samples before and 30, 60, 90 and 120 min after GnRH-A injection were analyzed for LH and follicle-stimulating hormone levels. Criteria for diagnosing CPP include accelerated height, advanced bone age and pubertal-sized uterus and ovaries. Results: Fifty-five girls were documented as having CPP. The remaining 46 girls were diagnosed with premature thelarche (PT). Peak LH concentration in the CPP group was significantly greater than that of the PT group with a median (range) of 10.0 IU/l (2.93–65.39) and 3.04 IU/l (0.19–8.82), respectively. Peak LH was achieved within 60 min following GnRH-A injection. Peak LH of 6 IU/l provided the most appropriate cutoff level in diagnosing CPP with a sensitivity of 89.1% and a specificity of 91.3%. Conclusion: Subcutaneous GnRH-A can be used as an alternative to confirm the diagnosis of CPP.

Phthalate Exposure in Girls During Early Puberty

The aim of this study was to determine the levels of phthalate ester metabolites in girls in early puberty, and the associated environmental factors for phthalate exposure. A case-control study was conducted in which we recruited girls in early puberty, including 30 girls with premature thelarche (PT) and 26 with central precocious puberty (CPP), and 33 normal controls. The mean urine levels of monomethyl phthalate (MMP) were significantly higher in the PT group (96.5 +/- 134.0 ng/ml) than in the control group (26.4 +/- 30.0 ng/ml; p = 0.005). The levels of monobutyl phthalate (MBuP) correlated with the intake of seafood, drink and the use of plastic cups. The levels of mono-(2-ethylhexyl) phthalate (MEHP) correlated with the intake of seafood and meat and exposure plastic handi-wrap. Significantly higher MMP in the PT girls revealed that phthalate may be one of the environmental causes of early puberty in Taiwanese girls.

Relationship of plasma ghrelin and adenohypophyseal hormone levels in female precocious puberty

To investigate the relationship of plasma ghrelin and adenohypophyseal hormone levels in female precocious puberty. A total of 84 patients aged from 6 to 9 years were enrolled in this study. They were divided into idiopathic central precocious puberty (ICPP) and premature thelarche(PT)groups according to their secondary sexual characteristics, bone age, volumes of uterus and ovary, and results of GnRH test. Plasma ghrelin levels were measured by radioimmunoassay. ACTH, TSH, PRL, GH, LH and FSH were measured by chemoluminescence technique. Ghrelin levels in ICPP group were Log (2.42+/-0.26) ng/L, which were significantly lower than those in PT group and controls [Log (2.62+/-0.21) ng/L and Log (2.58+/-0.44) ng/L, respectively, P<0.05]. However there was no significant difference between PT group and controls(P>0.05). Ghrelin levels of ICPP girls with Tanner III were Log (2.31+/-0.24) ng/L, significantly lower than those of ICPP girls with Tanner II [Log (2.53+/-0.24) ng/L, P<0.05]. By bivariate correlation analysis, ghrelin levels in precocious puberty girls were negatively correlated with ACTH, PRL and LH15, LH30 and LH60 in GnRH test(r=-0.248, -0.235, -0.445, 0.405, 0.398, respectively, P<0.05). No significant correlation was found between ghrelin and GH, LH0(-2), FSH0(-2), and FSH15, FSH30 and FSH60 in GnRH test. ICPP girls have lower plasma ghrelin levels, which are decreased with the development of Tanner stage. The plasma ghrelin levels are negatively correlated with ACTH, PRL and LH.

Ultrasonographic and clinical parameters for early differentiation between precocious puberty and premature thelarche

To determine if uterine and ovarian measurements can significantly distinguish between precocious puberty (PP) and premature thelarche (PT) and whether ultrasound has any advantage over the gonadotropin-releasing hormone (GnRH) stimulation test. Prospective. One hundred and three girls referred consecutively for evaluation of breast budding before age 8 years underwent physical examination, GnRH stimulation test, bone age assessment, and transabdominal pelvic ultrasound. The diagnosis of PP or PT was based on clinical judgment. The clinical, laboratory, and ultrasound data of the PP and PT groups were compared. Eighty-one girls were diagnosed with PP and 22 with PT. Significant differences in most of the uterine and ovarian measurements were found between the groups. On logistic regression analysis, bone age standard deviation score, uterine transverse diameter, and uterine volume were the most significant variables predicting PP. Comparison of 30 girls with PP and 21 with PT in whom peak luteinizing hormone was <5 mIU/ml on the GnRH stimulation test, using analysis of variance, yielded significant differences in uterine width (P<0.001), fundus diameter (P <0.04), uterine volume (P= 0.006), and ovarian circumference (P <0.02). Increased uterine and ovarian measurements may be an early and sensitive sign of PP. Pelvic ultrasound, a noninvasive, inexpensive, and reliable tool, may give the clinician a complementary indication to the GnRH test in distinguishing isolated PT from early-stage PP in girls with early breast budding.

Relationship between serum dehydroepiandrosterone levels and female precocious puberty

To investigate the relationship of serum dehydroepiandrosterone (DHEA) levels and female precocious puberty. The serum levels of DHEA and dehydroepiandrosterone sulfate (DHEAS) were measured by ELISA in 60 idiopathic central precocious puberty (ICPP) girls, 62 premature thelarche (PT) girls and 31 age-matched health prepuberty girls. Bone age,volume of uterus and ovary, DHEA and DHEAS were re-measured in 3, 12 months after treatment with Diphereline in ICPP girls. (1) The Log(DHEA) and Log(DHEAS) were (0.81 +/-0.36)microg/L and (2.31 +/-0.31)microg/L in ICPP group, (0.72 +/-0.30)microg/L and (2.31 +/-0.28)mg/L in PT group, and (0.32 +/-0.26)microg/L and (2.16+/-0.27)microg/L in controls (P <0.05). However, no significant differences were found between ICPP and PT group (P >0.05). Moreover, the serum levels of DHEA and DHEAS in precocious puberty girls with Tanner III stage were significant higher than those with Tanner II stage (P <0.05). (2) With bivariate correlation analysis, Log(DHEA) was positively correlated with height, bone age, volume of uterus and ovary (r=0.429, 0.339, 0.217, 0.282; all P<0.05), while no significant correlation with Log(LH peak), Log(FSH peak) and BMI (r=0.135, -0.165, 0.059). Log(DHEAS) was positively correlated with height,bone age and volume of ovary (r=0.319, 0.210, 0.181; P <0.05), while no correlated with Log(LH peak), Log(FSH peak), volume of uterus and BMI (r=0.012, -0.173, 0.146 and 0.081 respectively). (3) Serum Log (DHEA) and Log(DHEAS) of 32 ICPP were decreased from (0.83 +/-0.35) microg/L and (2.27 +/-0.30)microg/L to (0.68 +/-0.44)microg/L and (2.11 +/-0.43)microg/L (P<0.05) 3 months after treatment. The serum Log(DHEA) and Log(DHEAS) in 12 months after treatment were (0.78 +/-0.30)microg/L and (2.40+/-0.34)microg/L, which was not significantly different with that before treatment (P>0.05). However, the volume of uterus and ovary, bone age/age in 12 months after treatment were significantly different with those before treatment (2.82 +/-1.52 compared with 1.09 +/-0.50 ml, 3.15 +/-1.13 compared with 1.18 +/-0.42 ml, 1.43 +/-0.23 compared with 1.25 +/-0.12, all P<0.05). (1) The serum levels of DHEA and DHEAS are increased in precocious puberty girls with the development of Tanner stage. (2) Serum levels of DHEA and DHEAS are declined transiently when the hypothalamic-pituitary-gonadal axis is inhibited. (3) Serum DHEA is associated with the acceleration of growth and bone age in precocious puberty girls.

Simplified gonadorelin stimulation test in diagnosis of precocious puberty

To assess the diagnostic value of the simplified gonadorelin stimulation test for precocious puberty. Two hundred and ninety-two girls with signs of advanced breast development received the gonadorelin stimulation test. According to the result of gonadorelin stimulation test, the girls were divided into 3 groups: 151 with central precocious puberty (CPP),119 with premature thelarche (PT) and 22 with peripheral precocious puberty (PPP). LH or FSH levels at 15 min, 30 min, 60 min in PPP group were not significantly different (P>0.05). Those were significantly different in PT group (P<0.01). The highest levels of LH were at 30 min and the highest levels of FSH were at 60 min. LH or FSH levels at 15 min, 30 min, 60 min in CPP group were significantly different (P<0.01) with the highest levels at 30 min. The ratio of basal LH and FSH >0.2 had a diagnostic sensitivity of 48.3 % and specificity of 69.7%. Taking the LH/FSH ratio >0.9 at 15 min, 30 min, 60 min as cut-off value, the diagnostic sensitivity was 80.1%, 68.9% and 38.4%, and the specificity was 90.8%, 96.6% and 69.7%, respectively. The LH/FSH ratio>0.9 at 15 min after gonadorelin stimulation test can be used as a cut-off value to differentiate CPP from PT and blood sample at 60 min were not necessary.