Progressive Central Precocious Puberty Research Articles

Osteocalcin: may be a useful biomarker for early identification of rapidly progressive central precocious puberty in girls.

To assess serum osteocalcin (OC) as a potential biomarker for the early detection of rapidly progressive central precocious puberty (RP-CPP) in girls. Serum OC levels were quantified using enzyme-linked immunosorbent assays (ELISAs). In the retrospective analysis, receiver operating characteristic (ROC) curve analysis was employed to evaluate the ability of OC to identify RP-CPP. A prospective study and screening tests were utilized to assess the potential of OC for use in the early prediction of RP-CPP. Variable selection in the multivariate analysis was conducted using the Bayesian Information Criterion (BIC) and binary logistic regression was employed to construct the diagnostic prediction model. Girls with RP-CPP had significantly higher serum OC levels compared to girls with non-rapidly progressive central precocious puberty (NRP-CPP) (149.04±40.50 vs. 89.10±31.83 ng/mL, P < 0.001). The optimal OC cut-off point for differentiating RP-CPP from NRP-CPP was 107.05 ng/mL, the area under the ROC curve (AUC) was 0.90 (95%CI: 0.851-0.949; P < 0.001), with a sensitivity of 91.1% and specificity of 70.7%. The results of the prospective study indicated that changes in OC precede alterations in estradiol (E2) and bone age (BA). A diagnostic prediction model that includes duration of breast development, BA, OC, high-density lipoprotein cholesterol (HDL-C), and uterine length achieved an AUC of 0.961, with a sensitivity of 94.1% and specificity of 91.5% for the detection of RP-CPP. If OC is excluded from the model, the AUC decreases to 0.894, with sensitivity and specificity declining to 80.5% and 83.1%, respectively. Serum OC levels may serve as a promising biomarker for the early differentiation between RP-CPP and NRP-CPP in girls. The diagnostic prediction model that incorporates duration of breast development, BA, OC, HDL-C, and uterine length effectively identifies girls with RP-CPP.

7063 Serum Alkaline Phosphatase Level as a Marker for Progressive Central Precocious Puberty

Abstract Disclosure: V.M. Figueredo: None. T. Seeherunvong: None. Background: Precocious puberty is typically associated with a speed up in growth, risk of premature growth plate closure and reduced adult height. Serum alkaline phosphatase (ALP) is a biochemical indicator of bone turnover and studies have shown greater serum ALP levels in pubertal individuals compared to prepubertal controls. We examined serum ALP levels among children with various form of early puberty. We investigated whether serum ALP levels were significantly different between children with premature thelarche or premature adrenarche compared to those with central precocious puberty (CPP). Methods: We conducted a retrospective chart review of patients with early pubertal development attending a pediatric endocrinology clinic between 2017 and 2023. Information on height, weight, serum ALP levels and bone age was obtained. Patients were considered to have CPP based on the results on a GnRH test. Patients with diagnosis of premature adrenarche or premature thelarche were included as controls. This study was approved by Institutional Review Board (IRB). Analysis of data was performed using IBM SPSS Statistics version 29.0.1.0 (171). Results: Among 72 patients included in the study, 22 patients had progressive CPP whereas 50 patients had premature adrenarche or premature thelarche. The prevalence of abnormally elevated serum ALP levels was greater among patients with CPP (22.7%) than among patients with premature adrenarche or premature thelarche (6%). Using logistic binomial regression analysis, serum ALP levels were significantly elevated (p=0.042) in subjects with progressive CPP compared to patients with premature adrenarche or premature thelarche. Both groups had similar BMI values. BMI z-scores and advanced bone age were positively correlated. BMI (p=0.08) and advanced bone age were not significantly different (p=0.12) in the group with CPP compared with the group comprising patients with either premature adrenarche or premature thelarche. Conclusion: These findings suggest that serum ALP levels are helpful as a tool to help distinguish CPP from premature adrenarche or premature thelarche in the evaluation of patients with initial early pubertal development. Presentation: 6/1/2024

Osteocalcin: A potential marker to identify and monitor girls with rapidly progressive central precocious puberty.

To evaluate the suitability of serum osteocalcin (OC) as a marker to distinguish between rapidly and non-rapidly progressive central precocious puberty (RP-CPP and NRP-CPP), as well as its potential to assess growth rates following treatment with gonadotropin-releasing hormone agonist (GnRHa). Serum levels of OC were measured using enzyme-linked immunosorbent assays in girls diagnosed with either RP-CPP or NRP-CPP as well as in normal control subjects. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value for OC. Multivariate linear regression analysis was used to analyse the main influencing factors associated with OC. Serum OC levels were higher in the CPP girls when compared to normal controls (110.76 ± 43.69 vs 55.97 ± 20.96 ng/mL, P < 0.001). The level in the RP-CPP group was higher than the NRP-CPP group (153.28 ± 33.89 vs 88.33 ± 29.26 ng/mL, P < 0.001). The cut-off value of OC levels for distinguishing between RP-CPP and NRP-CPP was 107.05 ng/mL, the sensitivity was 94.7% and the specificity was 77.8%, which was superior to using the basal luteinising hormone (B-LH) levels, and the area under ROC curve (AUC) were 0.933 versus 0.695, respectively. Following 1-2 years of treatment with GnRHa for girls with CPP, both OC levels and the growth rates decreased to pre-pubertal values. B-LH levels, bone age and body weight were also significant factors, which affected OC levels. Serum OC levels may be a useful marker for distinguishing RP-CPP from NRP-CPP. In addition, it was also found to be a useful predictor for growth rate during GnRHa treatment.

The value of luteinizing hormone basal values and sex hormone-binding globulin for early diagnosis of rapidly progressive central precocious puberty.

This study aimed to investigate the diagnostic value of luteinizing hormone (LH) basal values and sex hormone-binding globulin (SHBG) for rapidly progressive central precocious puberty (RP-CPP). A total of 121 girls presenting with secondary sexual characteristics were selected from the Department of Pediatric Endocrinology, Lianyungang Clinical Medical College of Nanjing Medical University, from May 2021 to June 2023. The children were followed up for 6 months and were divided into three groups: RP-CPP group (n=40), slowly progressive central precocious puberty (SP-CPP) group (n=40), and premature thelarche (PT) group (n=41). The differences in LH basal values and SHBG among girls in the three groups were compared. ROC curves were drawn to analyze the value of LH basal values and SHBG in identifying RP-CPP. Significant differences were observed in age, height, predicted adult height (PAH), weight, body mass index (BMI), bone age (BA), BA-chronological age (CA), LH basal, LH peak, FSH basal, LH peak/FSH peak, estradiol (E2), testosterone, and SHBG levels between the RP-CPP group and the SP-CPP and PT groups (P < 0.05). The LH basal value in the RP-CPP group was higher than that in the SP-CPP group and the PT group, while SHBG levels were lower than in the latter two groups, and these differences were statistically significant (P < 0.05). When the LH basal value was ≥0.58 IU/L and SHBG was ≤58.79 nmol/L, the sensitivity for diagnosing RP-CPP was 77.5% and 67.5%, and the specificity was 66.7% and 74.1%. Detection of basal LH and SHBG levels allows for early diagnosis of the progression of central precocious puberty.

Analysis of serum insulin-like growth factor-1, fibroblast growth factor 23, and Klotho levels in girls with rapidly progressive central precocious puberty

To study the levels of serum insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF23), and Klotho, and to study their relationship with girls with rapidly progressive central precocious puberty (RP-CPP). This is a cross-sectional study on the progression rate of central precocious puberty in girls, who complained of breast development before the age of 8 years and were followed between June 2021 and June 2022. At the same time, 28 healthy girls less than 8 years old who had not started puberty were recruited as the control group. The physical examination and laboratory evaluation of each group was completed. Only patients with CPP received pelvic ultrasound examination and bone age test. Bone age index (BAI), basal LH levels (BLH), basal LH levels/basal FSH levels (BFSH), peak LH (PLH)/peak FSH (PFSH), IGF-1, Klotho, FGF23, and ovarian volume in the RP-CPP group were higher than those in slowly progressive CPP (SP-CPP) group. In the RP-CPP group, IGF-1 was correlated with Klotho, FGF23, and BLH; Klotho was correlated with FGF23 and BLH; FGF23 was correlated with BLH.Conclusion: The BLH, FGF23, Klotho, and IGF-1 have a certain correlation with RP-CPP, which may play an important role in the speed of girls’ sexual development.What is Known:• The association between IGF-1 and RP-CPP.What is New:• We found the association between FGF23, Klotho and RP-CPP.

COVID-19 pandemic phases and female precocious puberty: The experience of the past 4 years (2019 through 2022) in an Italian tertiary center.

Since the outbreak of COVID-19 pandemic, several centers of pediatric endocrinology worldwide have observed a significant increase in the number of girls presenting with precocious or early puberty. We aimed to compare the incidence rates of female precocious puberty before and during the different phases of COVID-19 pandemic. We have retrospectively analyzed all the consultations recorded in the outpatient clinic database of the Endocrinology Unit of Bambino Gesù Children's Hospital, Rome, Italy, from the lockdown start in March 2020 up to September 2020, in comparison with the consultations recorded in the same months of 2019, 2021 and 2022. Age, height, weight, body mass index, Tanner's pubertal stage and bone age at presentation, birth weight, ethnicity, family history of central precocious puberty (CPP), maternal age at menarche, history of adoption were retrieved from clinical records. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) both at baseline and after gonadotropin-releasing hormone (GnRH) stimulation, and basal estradiol levels were collected. In 2019, 78 girls with suspected precocious puberty were referred for endocrinological consultation, compared to 202 girls in 2020, 158 girls in 2021 and 112 girls in 2022.A significant increase in the proportion of girls diagnosed with rapidly progressive CPP was observed in 2020, compared to 2019 (86/202 vs. 18/78, p<0.01). In the following periods of 2021 and 2022, a gradual decrease in the number of cases of progressive CPP was evident, so much that the number of cases was not significantly different from that observed in 2019 (56/158 in 2021 and 35/112 in 2022, p=0.054 and p=0.216 respectively, compared to 2019). Our research suggests that drastic lifestyle changes, such as those imposed by COVID-19 lockdown, and the consequent stress may affect the regulation of pubertal timing. The remarkable increase in CPP cases observed during the 2020 first pandemic wave seems to be reduced in 2021 and 2022, concurrently with the progressive resumption of daily activities. These data seem to support the hypothesis of a direct relationship between profound life-style changes related to the pandemic and the rise in precocious puberty cases.

Adult height of children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Congenital adrenal hyperplasia attributable to 21-hydroxylase deficiency (21-OHD) is a disorder of adrenal steroidogenesis. Achievement of optimal growth by such patients is challenging. We evaluated the adult height of Taiwanese children with 21-OHD and the effect of a gonadotropin-releasing hormone analogue (GnRHa) in patients with central precocious puberty (CPP) complicating 21-OHD. Among 116 patients with 21-OHD in Taiwan, 90 who had attained adult height were subjected to an analysis of height outcomes. Nine with progressive CPP were treated with GnRHa and the effects of this therapy on adult height were further analyzed. In the pre-screening era, the percentage of boys with 21-OHD was lower than expected. Although neonatal screening can prevent mortality caused by adrenal crisis, some cases may be missed. The pooled mean adult height of the 78 patients treated with conventional therapy were -1.1 SD and -0.5 SD adjusting for the genetic potential. The disease features affecting height outcomes are the genetic height potential and in boys the simple virilizing type. Nine patients with CPP were treated with GnRHa in addition to conventional therapy; the mean adult height increased from the predicted -4.1 SD to -1.0 SD after 6.0±2.5 years of treatment. Patients with 21-OHD had poorer mean adult height. A high caregiver's index of suspicion is required for the early diagnosis of patients with 21-OHD missed on neonatal screening. Adjuvant therapy with GnRHa can improve the adult height of patients with CPP complicating 21-OHD.

Rapid progressive central precocious puberty: diagnostic and predictive value of basal sex hormone levels and pelvic ultrasound.

Objectives Data on the predictive values of parameters included in the diagnostic work-up for precocious puberty (PP) remain limited. We detected the diagnostic value of basal sex hormone levels, pelvic ultrasound parameters and bone age assessment for activation of the hypothalamic-pituitary-gonadal axis in girls with PP, in order to help in the decision to perform GnRH testing. Patients and methods We retrospectively considered 177 girls with PP. According to puberty evolution, the girls were divided into two groups: rapid progressive central precocious puberty (RP-CPP) and non/slowly progressive/transient forms (SP-PP). In all patients we considered Tanner stage, basal luteinizing hormone (LH) and estradiol (E2) values, bone age, and pelvis examination. We assessed the diagnostic value of each variable and identified the number of pathological parameters that best identify patients with RP-CPP. Results Basal LH≥0.2IU/L, E2 level ≥ 50pmol/L, uterine longitudinal diameter ≥3.5cm, transverse uterine diameter ≥1.5cm, endometrial echo and ovarian volume ≥2cm3 were significantly associated with RP-CPP (p≤0.01). The ability to diagnose RP-CPP was enhanced with increasing number of pathological hormonal and instrumental parameters (p<0.001). With more than three parameters detected, sensitivity and specificity reached 58% (95%CI 48-67) and 85% (95%CI 74-92), respectively, with a PPV=86% (95%CI 76-93) and PPN=54% (95%CI 43-54); the area under the ROC curve was 0.71 (95%CI 0.65-0.78). Conclusion Despite the availability of different tests, diagnosing RP-CPP remains difficult. A diagnosis model including at least three hormonal and/or ultrasound parameters may serve as a useful preliminary step in selecting patients who require GnRH testing for early detection of RC-PP.

SUN-LB18 Serum 25-Hydroxyvitamin D Is Not Associated With the Type of Central Precocious Puberty in Girls

[Objective] To evaluate the clinical value of serum 25-hydroxyvitamin D (25OHD) in girls with different types of central precocious puberty (CPP), in order to provide basis for the clinical diagnosis and treatment. [Methods] 340 CPP girls diagnosed in our hospital from January 2016 to January 2018 were enrolled and retrospectively studied. According to the progression of Tanner stage ≥1 during 6 months, bone age(BA) levels were higher than chronological age of more than 1 year. 226 patients were included in the rapidly progressive CPP group (RP-CPP), while 114 patients were included in the slowly progressive CPP group (SP-CPP) as a control. We analyzed the correlation between serum 25OHD levels and the different puberty characteristics (BA, disease course, body mass index (BMI), bone mineral density (BMD), serum LH peak to FSH peak ratio (LHP/FSHP), insulin-like growth factor 1(IGF1)) of two groups. According to sunshine duration, the sampling season was divided into two groups (December to May, June to November), then we compare the correlation between different serum 25OHD levels and season of sampling as well as the different puberty characteristics respectively. [Results] (1) The mean serum 25OHD levels of CPP girls were 15.89±6.87ng/ml. The 25OHD levels of 68 (20.0%), 95 (27.9%) and 167 (49.1%) patients were <10, 10-15 and 16-29 ng/mL, respectively. Only 10 (2.9%) patients had normal 25OHD (>30 ng/mL). (2) No significant difference in serum 25OHD levels between RP-CPP group and SP-CPP group (F =0.809, p=0.369) was found. There is no correlation of BMD and disease course between the two groups (p>0.1). Bone age, BMI, LHP/FSHP and IGF1 levels in RP-CPP group were higher than SP-CPP group (P<0.05). Logistic regression analysis showed that BMI, LHP/FSHP and IGF1 were the independent risk factors for CPP (OR 2.690, 1.005, 3.288, respectively). (3) There were significant differences among different serum 25OHD levels as for season, disease course and IGF1 (p<0.05). The correlation with the season was the highest (r=0.402, p<0.001). [Conclusions] (1) Vitamin D levels are generally insufficient in CPP girls and are not related to different types of CPP. (2) The higher BMI, IGF1, LHP/FSHP levels are, the easier CPP girls will transfer to RP-CPP, but not associated with vitamin D levels. (3) CPP girls suffer from vitamin D deficiency in seasons of winter and spring easilier.

Clinical Trial of Rapid Progressive Central Precocious Puberty With Integrative Chinese and Western Medicine

Clinical Trial of Rapid Progressive Central Precocious Puberty With Integrative Chinese and Western Medicine

Arterial Spin Labeling and Central Precocious Puberty.

To evaluate anon-invasive method to assess the progressivity of idiopathic central precocious puberty (CPP) by quantifying perfusion of the pituitary stalk with arterial spin labeling (ASL) and using the gonadotropin-releasing hormone (GnRH) test as areference test to define progressive CPP. In asingle center retrospective study, 52consecutive patients, observed between October 2015 and April 2017 and referred with early signs of puberty, were evaluated using the GnRH test and cerebral magnetic resonance imaging (MRI). Patients with peripheral or non-idiopathic puberty were excluded. The distribution of perfusion values between patients with progressive and non-progressive CPP was compared using anonparametric Mann-Whitney U‑test. In this study 35 patients were included and 29 had progressive CPP. These patients displayed significantly higher cerebral blood flow (CBF) values than the 6patients with non-progressive CPP (p = 0.006). The median CBF for patients with non-progressive and progressive CPP was 45.25 ml/min/100 g (interquartile range 36.9-54) vs. 65 ml/min/100 g (interquartile range 55.5-74.5), respectively. To determine if the CPP was progressive, the best CBF threshold was 55.5 ml/min/100 g with asensitivity of 76%, aspecificity of 83% and an accuracy of 77%. There were strong significant correlations between CBF and LH peak (r = 0.67, p < 0.001) and between CBF and LH/FSH peaks ratio [r = 0.71, p < 0.001] during the GnRH test. Arterial spin labelling (ASL) offers anovel tool to assess the progressivity of idiopathic CPP.

A multi-center clinical study of early predictors and follow-up parameters for girls with rapidly progressive central precocious puberty

Objective To study the early diagnostic predictors and key follow-up parameters for girls with rapidly progressive central precocious puberty(RP-CPP). Methods A total of 260 girls with CPP participated in a prospective, nonrandomized, multi-center, nested case control study. After follow-up six months without any therapy, 114 girls were divided into RP-CPP(n=70)and slowly progressive CPP(SP-CPP)(n=44)groups. Results The basal serum LH and insulin-like growth factor Ⅰstandard deviation score(IGF-ⅠSDS)were the important risk factors of RP-CPP(OR 4.04, 1.578), especially the former. The receiver operating characteristic(ROC)curve revealed that the areas under the ROC curve of basal LH and IGF-ⅠSDS were 0.83 and 0.807, respectively. The levels of basal LH and IGF-ⅠSDS were at 0.52 mIU/ml and 0.35 respectively for the accuracy diagnosis of RP-CPP with the maximum Youden indexs. After follow-up for six months, the change levels of height, breast stages, bone age/chronological age ratio, serum LH, uterine and ovarian volume in RP-CPP group were significantly higher than those in SP-CPP group(all P<0.05). Conclusions The level of basal serum LH and IGF-ⅠSDS may be used as the risk predictors for early diagnosis for girls with RP-CPP. The change levels of basal LH, progress rates of gonad and sex character, height, and impaired growth potential seem to be the key follow-up parameters for CPP progress. (Chin J Endocrinol Metab, 2017, 33: 312-316) Key words: Central precocious puberty; Predictors; Follow-up parameters

Serum Anti-Müllerian Hormone and Inhibin B as Potential Markers for Progressive Central Precocious Puberty in Girls

Study ObjectiveTo investigate the potential of serum anti-Müllerian hormone (AMH) and inhibin B (INHB) levels as markers for pubertal progression rate in girls with central precocious puberty (CPP). Design, Setting, Participants, Interventions, and Main Outcome MeasuresA total of 148 girls were enrolled, including 65 girls with premature thelarche and 83 girls with CPP, grouped on the basis of the results of gonadotropin-releasing hormone stimulation tests. Girls with CPP underwent a 6-month follow-up, and were further divided into 2 subgroups: the progressive CPP (P-CPP) group (n = 55) and the slowly P-CPP (SP-CPP) group (n = 28). Serum AMH and INHB levels were assessed in all enrolled girls. Using receiver operating characteristic curves, we analyzed the diagnostic performance of AMH and INHB to differentiate the 2 forms of CPP. ResultsOur data showed that AMH and INHB offer the potential to act as markers that distinguish SP-CPP from P-CPP. Compared with the SP-CPP group, girls with P-CPP showed lower AMH levels and higher INHB levels. On the basis of the receiver operating characteristics analysis, the area under the curve was 0.92 for the combination of AMH and INHB, with 80% sensitivity and 89.3% specificity. ConclusionOur results suggest that serum AMH and INHB levels provide a promising method in differentiating SP-CPP from P-CPP.

Central precocious puberty: revisiting the diagnosis and therapeutic management.

Clinical and laboratory diagnosis and treatment of central precocious puberty (CPP) remain challenging due to lack of standardization. The aim of this revision was to address the diagnostic and therapeutic features of CPP in Brazil based on relevant international literature and availability of the existing therapies in the country. The diagnosis of CPP is based mainly on clinical and biochemical parameters, and a period of follow-up is desirable to define the "progressive" form of sexual precocity. This occurs due to the broad spectrum of pubertal development, including isolated premature thelarche, constitutional growth and puberty acceleration, progressive and nonprogressive CPP, and early puberty. Measurement of basal and stimulated LH levels remains challenging, considering that the levels are not always in the pubertal range at baseline, short-acting GnRH is not readily available in Brazil, and the cutoff values differ according to the laboratory assay. When CPP is suspected but basal LH values are at prepubertal range, a stimulation test with short-acting or long-acting monthly GnRH is a diagnostic option. In Brazil, the treatment of choice for progressive CPP and early puberty is a long-acting GnRH analog (GnRHa) administered once a month or every 3 months. In Brazil, formulations of GnRHa (leuprorelin and triptorelin) are available and commonly administered, including 1-month depot leuprorelin 3.75 mg and 7.5 mg, 1-month depot triptorelin 3.75 mg, and 3-month depot leuprorelin 11.25 mg. Monthly or 3-month depot GnRHa are effective and safe to treat CPP. Arch Endocrinol Metab. 2016;60(2):163-72.

Growth Outcome during GnRH Agonist Treatments for Slowly Progressive Central Precocious Puberty

Background: Gonadotropin-releasing hormone agonists (GnRHa) represent the gold-standard treatment for central precocious puberty (CPP). In CPP children, GnRHa treatment slows bone age progression and preserves adult height (Ht) by suppressing sexual steroid secretion. In some patients, however, GnRHa induce an inappropriate growth deceleration impairing Ht outcome. Furthermore, slowly progressive CPP (spCPP) forms were reported which do not need GnRHa treatment. Methods: We evaluated the growth outcome of 26 spCPP girls treated with triptorelin (TR) and 21 with leuprorelin acetate (LA) for 36.5 ± 0.7 months. Results: GnRHa treatment induced a progressive growth deceleration in both spCPP groups. No difference in bone maturation was detected (p > 0.05; TR vs. LA group), however compared to LA, TR treatment resulted in significantly higher Ht after 24 months (p < 0.05; LA vs. TR group). Although target height (TH) standard deviation score (SDS) and predicted adult height (PAH)-SDS at diagnosis were similar in both spCPP groups (p > 0.05; LA vs. TR group), final height (FH-SDS) was lower in LA-treated subjects (p < 0.05; LA vs. TR group). In both spCPP groups, FH-SDS was significantly lower than TH-SDS (p < 0.001) but not lower than PAH-SDS at diagnosis (p > 0.05). Ht-SDS correlated with 17β-estradiol (E₂) blood levels in both spCPP groups (p < 0.0001) throughout GnRHa treatment, and E₂ values were higher in the TR- than in the LA-treated patients during the 12 months after GnRHa administration (p < 0.05; LA vs. TR group). GnRHa-induced E₂ secretion and Ht-SDS at GnRHa withdrawal correlated positively with FH (p < 0.01 and p < 0.001, respectively). Conclusions: The effectiveness of GnRHa treatment in improving FH in spCPP girls was doubtful.

Utility of breast ultrasonography in the diagnostic work‐up of precocious puberty and proposal of a prognostic index for identifying girls with rapidly progressive central precocious puberty

To determine the utility of breast ultrasono- graphy in the diagnostic work-up of precocious puberty and to create a prognostic index for early differentiation between non/slowly progressive or transient forms of precocious puberty and rapidly progressive central precocious puberty. We recruited consecutively 60 girls with precocious pubertal development. In all the girls we evaluated Tanner stage, basal and gonadotropin-releasing hormone (GnRH)-stimulated follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, estradiol (E2) levels, and bone age, and performed pelvis and breast ultrasound examinations. Logistic regression models were fitted to identify possible diagnostic factors for rapidly progressive central precocious puberty and non/slowly progressive or transient forms. Ultrasound breast volume>or=0.85 cm3 was associated with rapidly progressive central precocious puberty (P=0.01). Uterine volume>or=5 cm3, LH peak>or=7 IU/L, presence of an endometrial echo, E2 levels>or=50 pmol/L and bone age>2 SD above expected were significantly associated with rapidly progressive central precocious puberty. A multivariate model including uterine volume, E2 level, bone age, presence of an endometrial echo and ultrasound breast volume revealed a strong ability to classify rapidly progressive forms. From this multivariate analysis a prognostic index for rapidly progressive central precocious puberty was defined. Ultrasound imaging allows better definition of the breast and the maturation stage than does use of Tanner's stages. Ultrasound breast volume>or=0.85 cm3 is an independent predicting factor of rapidly progressive central precocious puberty. A prognostic index that was created from a multivariate model including uterine volume, E2 level, presence of an endometrial echo, bone age and ultrasonographically determined breast volume, may help in the early differentiation between rapidly progressive central precocious puberty and non/slowly progressive or transient forms.

Leptin changes in Taiwanese girls with central precocious puberty before and during the GnRH agonist treatment.

To examine the relationship between leptin serum levels and pubertal development in girls with progressive central precocious puberty. We longitudinally investigated the leptin levels of 37 girls with central precocious puberty before and during treatment with the gonadotropin-releasing hormone agonist depot (leuprorelin acetate). Leptin and other hormone levels were determined by radioimmunoassay. Girls with central precocious puberty before treatment showed no significant difference in leptin levels as compared to the puberty stage at diagnosis of disease. In addition, the changes in leptin concentrations of girls with central precocious puberty during treatment were not statistically significant. In the Spearman correlation analysis of leptin levels with body mass index, bone age, chronological age, clinical pubertal signs along with luteinizing, follicle-stimulating, and estradiol hormone levels, we found that body mass index, weight, and chronological age were significantly correlated with leptin levels (p < 0.05) at both 3 and 6 months of leuprorelin treatment. Leptin levels increased with body mass index; however, this trend did not reach statistical significance at all follow-up time points. These data demonstrated that treatment with depot gonadotropin-releasing hormone agonist does not influence leptin concentrations. Serum leptin levels in patients with central precocious puberty are associated with body weight and body mass index.

Precocious puberty and statural growth.

Precocious puberty results mostly from the precocious activation of the gonadotropic axis. Although the age limits have recently been discussed, most physicians consider that onset of pubertal development before the age of 8 years in a girl or 9 years in a boy warrants at least a clinical and bone age evaluation by a paediatric endocrinologist. The major concern in precocious puberty is the underlying condition, and central nervous system or gonadal neoplasm have to be formally excluded as a first step in the diagnosis. A secondary concern is height, since precocious puberty leads to accelerated growth, accelerated bone maturation and ultimately reduced stature. Precocious puberty is heterogeneous and strict criteria should be used to define it, both in terms of age and in terms of potential for progression. Depot forms of GnRH agonists are now the standard treatment for progressive central precocious puberty and aim at alleviating the clinical symptoms of early pubertal development, their psychological consequences and the effects on growth. Here, we review the consequences of both central and gonadotropin-independent precocious puberty on adult stature and the information available on outcomes using the therapeutic regimens currently available. In girls with progressive precocious puberty, all published evidence indicates a gain of adult height over height predicted before treatment or over untreated historical controls. However, the apparent height gain (derived from the comparison of predicted and actual heights) is very variable, in large part due to the inaccuracy of height prediction methods. In girls with onset of puberty at the lower half of the normal age (8-10 years) distribution, trials using GnRH agonists have given negative results (no benefit of treatment). In boys, precocious puberty is rare and fewer results are available but point in the same direction. The most appropriate time for interrupting the treatment is still controversial. In conclusion, GnRH agonists restore adult height in children when it is compromised by precocious puberty.

Management and outcome of central precocious puberty

Management and outcome of central precocious puberty

CENTRAL PRECOCIOUS PUBERTY: An Overview of Diagnosis, Treatment, and Outcome

Central precocious puberty (CPP) is physiologically normal puberty beginning early. It is the consequence of early increased regulation of gonadotropin releasing hormone (GnRH) stimulation of pituitary gonadotropin release causing pubertal changes and accelerated growth. GnRH stimulation testing is the definitive diagnostic test--pubertal gonadotropin responses being indicative of CPP. Among patients with progressive CPP, GnRH analogue therapy is effective by decreased regulation of gonadotropin secretion. Pubertal progression is stopped, and accelerated growth rate and compromised adult height are precluded or alleviated. Outcome data have not identified unusual sequelae.