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Purpose: Three-month gonadotropin-releasing hormone agonists (GnRHas) are expected to achieve better compliance in patients with central precocious puberty (CPP) compared to the monthly formulation. However, 1-month depot remains the dominant choice for conventional treatment worldwide. Our study aimed to investigate the long-term efficacy of a 3-month GnRHa for CPP treatment. Methods: In this retrospective study, 69 Korean girls with CPP were prescribed either triptorelin pamoate (TP) 3-month depot (n=29) or triptorelin acetate (TA) 1-month depot (n=40) and were followed for 1 year after the end of treatment. Auxological, radiological, and biochemical data were collected every 6 months. Results: Baseline characteristics were similar between the 2 groups. In the TP 3-month depot group, 27 of 29 patients (93.1%) exhibited suppressed luteinizing hormone level (below 2.5 IU/L) after 6 months of treatment, and this suppression level was reserved until the final injection. The degree of bone age advancement in the TP 3-month depot group decreased from 1.8±0.4 years at the start of treatment to 0.6±0.5 years at 1-year posttreatment. The gain in predicted adult height (PAH) 1 year after the end of treatment was similar between the TP 3-month and TA 1-month depot groups (5.2±3.1 and 5.3±2.4 cm, respectively; P=0.875). Conclusion: A 3-month depot of triptorelin effectively inhibited gonadal and sex hormones, suppressed bone maturation, and increased PAH. For patient convenience, we suggest a 3-month GnRHa regimen as a promising CPP treatment option. [ABSTRACT FROM AUTHOR]

Precocious puberty is diagnosed when pubertal characteristics appear before the age of 8 years in females. The most common form is gonadotropin-dependent, called axial. The primary method of treatment is administration of gonadotrophin-releasing hormone analogues (GnRHa). The aim of the study was to verify hypothesis that GnRHa therapy in the childhood may be of additive risk factor for polycystic ovary syndrome (PCOS) in adulthood. Material and Methods: The study group consists of 24 women (median age 22 88 years, median BMI 23.5) treated with GnRHa for central precocious puberty in childhood. The control group includes 40 women (median age 23 years, median BMI 25.6) diagnosed with isolated premature thelarche and not using GnRHa in the childhood. Anthropometric measurements, ultrasound examination of minor pelvis and hormonal profile were performed. PCOS diagnosis was based on Rotterdam criteria. Results: The study confirmed a higher prevalence of PCOS in the study group (50%) than in the control group (10%); p=0.0006. Significant, linear correlation between free testosterone levels and ovarian size was found in the study group (R=0.45 p= 0.03). Conclusions: GnRHa therapy during childhood may have a potential influence on incidence of PCOS in the adulthood. Therefore, in this group of patients longterm follow-up focused on screening for PCOS would seem beneficial. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to explore the impact of gonadotropin-releasing hormone agonists (GnRHa) on final adult height (FAH) in girls with early and fast puberty. Methods: A retrospective study was conducted by reviewing data from the medical records of the Pediatric Endocrinology Clinics between January 1, 2010, and December 31, 2020, at MacKay Children's Hospital. The treatment group included 109 patients who received 3.75 mg monthly for at least 1 year, whereas the control group consisted of 95 girls who received no treatment. Results: The treatment group was significantly older at the time of inclusion (chronological age (CA1), treatment vs. control, 8.7 vs. 8.4 years, p < 0.001), had a more advanced bone age (BA) (BA1, 11.5 vs. 10.8 years, p < 0.001), BA1-CA1 (2.7 vs. 2.2 years, p < 0.001), and shorter predicted adult height (PAH1) (153.3 vs. 157.1 cm, p = 0.005) that was significantly lower than their target height (Tht) (PAH1-Tht, -3.9 vs. -1.3 cm, p = 0.039). The FAHs of the GnRHa and the control group were similar (157.0 vs. 156.7 cm, p = 0.357) and were not significantly different from their Tht (FAH vs. Tht in the GnRHa group, 157.0 vs. 157.0 cm; control group, 156.7 vs. 157.0 cm). In the subgroup analysis, FAH was significantly higher after GnRHa treatment in those with PAH1 less than 153 cm and Tht (154.0 vs. 152.0 cm, p = 0.041), and those whose CA1 was between 8 and 9 years (158.0 vs. 155.4 cm, p = 0.004). We defined satisfactory FAH outcome as FAH- PAH1>5 cm and significant factors were GnRHa therapy, PAH1 shorter than their Tht, age younger than 9 years, and faster growth velocity during the first year. Discussion: GnRHa is effective in restoring the Tht in some early and fast pubertal girls, especially in those with poorly PAH (PAH lower than 153 cm and shorter than their target height). A younger age at initiation of treatment and a faster growth velocity during treatment are associated with a better height gain. [ABSTRACT FROM AUTHOR]

The Committee of Central Precocious Puberty of Korean Pediatrics and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidencebased 2022 clinical practice guidelines for central precocious puberty in Korean children and adolescents. These guidelines provide the grade of recommendations, which includes both the strength of recommendations and the level of evidence. In the absence of sufficient evidence, recommendations are based on expert opinion. These guidelines have been revised and supplement the previous guidelines "Clinical Guidelines for Precocious Puberty 2011," and are drawn from a comprehensive review of the latest domestic and international research and the grade of recommendation appropriate to the domestic situation. This review summarizes the newly revised guidelines into 8 key questions and 27 recommendations and consists of 4 sections: screening, diagnosis, treatment, and long-term outcome of central precocious puberty. [ABSTRACT FROM AUTHOR]

Aim: In this study, it was aimed to examine the clinical and laboratory findings that can be used to predict central precocious puberty (CPP) in cases whose breast development started before the age of 8. Materials and Methods: The chronological age, anthropometric measurements, bone age (BA), hormone test results and pelvic ultrasonography findings of the cases were recorded. Those with a peak luteinizing hormone (LH) level of =5 IU/L in the gonadotropin-releasing hormone (GnRH) stimulation test were classified as CPP and those with a peak LH level of <5 IU/L were classified as prepubertal cases. A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic accuracy of laboratory variables. Findings: A total of 297 female cases were included in the study. The age at the time of admission, height-standard deviation score (SDS), BA, the long axis of the uterus and the volumes of the right and left ovaries of the cases diagnosed with CPP were found to be significantly higher than those of the prepubertal group. The cut-off value providing the best sensitivity (99%) and specificity (99%) for the peak LH was found to be 4.55; the cut-off value providing the best sensitivity (94%) and specificity (85%) for the peak LH/follicle-stimulating hormone (FSH) ratio was found to be 0.32 and the cut-off value providing the best sensitivity (47%) and specificity (93%) for the basal LH was found to be 0.13. Conclusion: We believe that in female cases with early breast development, a peak LH level of =4.55 may possibly indicate CPP and a basal LH level of <0.13 can significantly rule out CPP. [ABSTRACT FROM AUTHOR]

The etiology of central precocious puberty (CPP) is multiple and heterogeneous, including congenital and acquired causes that can be associated with structural or functional brain alterations. All causes of CPP culminate in the premature pulsatile secretion of hypothalamic GnRH and, consequently, in the premature reactivation of hypothalamic-pituitary-gonadal axis. The activation of excitatory factors or suppression of inhibitory factors during childhood represent the 2 major mechanisms of CPP, revealing a delicate balance of these opposing neuronal pathways. Hypothalamic hamartoma (HH) is the most well-known congenital cause of CPP with central nervous system abnormalities. Several mechanisms by which hamartoma causes CPP have been proposed, including an anatomical connection to the anterior hypothalamus, autonomous neuroendocrine activity in GnRH neurons, trophic factors secreted by HH, and mechanical pressure applied to the hypothalamus. The importance of genetic and/or epigenetic factors in the underlying mechanisms of CPP has grown significantly in the last decade, as demonstrated by the evidence of genetic abnormalities in hypothalamic structural lesions (eg, hamartomas, gliomas), syndromic disorders associated with CPP (Temple, Prader-Willi, Silver-Russell, and Rett syndromes), and isolated CPP from monogenic defects (MKRN3 and DLK1 loss-of-function mutations). Genetic and epigenetic discoveries involving the etiology of CPP have had influence on the diagnosis and familial counseling providing bases for potential prevention of premature sexual development and new treatment targets in the future. Global preventive actions inducing healthy lifestyle habits and less exposure to endocrine-disrupting chemicals during the lifespan are desirable because they are potentially associated with CPP. [ABSTRACT FROM AUTHOR]

The aim was to develop a model to predict the adult height (AH) of idiopathic central precocious puberty (ICPP) girls who underwent gonadotropin-releasing hormone analog (GnRHa) treatment. Data analysis included 258 girls with ICPP. Among them, 101 girls who reached final AH (FAH) with GnRHa treatment were analyzed to verify three previous prediction models and develop a unique model based on multiple linear regression. The control group consisted of 41 untreated ICPP girls. Moreover, 116 girls treated with GnRHa who almost attained FAH were included for external validation. Based on our cohorts, all of the three previously published models underestimated the FAH with an R of 0.667, 0.793, and 0.664. The AH prediction model was built as follows: Calculated AH (cm) = 1.89630 * Height SDS + 2.29927 * Height SDS for bone age + 0.40776 * Target height + 100.16684 (R2 = 0.66 and adjusted R2 = 0.65). Internal validation showed a mean root mean squared error (RMSE) of 2.16 cm and a mean absolute error (MAE) of 1.64 cm. External validation showed that a significant error (> 1 SD) appeared only in 7 of 116 girls (6.0%). The model is displayed on the website: http://cpppredict.shinyapps.io/dynnomapp. Conclusion: A model for predicting the AH of girls with ICPP was developed incorporating the variables of height SDS, height SDS for bone age, and target height. The internal and external validation ensures an appropriate degree of discrimination and calibration of the prediction model. What is Known: • Uncertainty prevails as how to predict the adult height of patients with central precocious puberty following gonadotropin-releasing hormone analog treatment. • Previous models for predicting adult height of girls with idiopathic central precocious puberty have not been proven translational to the Chinese population. What is New: • This study develops a new model for predicting the adult height of idiopathic central precocious puberty girls who underwent gonadotropin-releasing hormone analog treatment. • The internal and external validation assures a good degree of discrimination and calibration of the prediction model in this study. [ABSTRACT FROM AUTHOR]

It is important to understand what variables influence change in predicted adult height (PAH) throughout GnRHa treatment for central precocious puberty (CPP) to individualize treatment decisions and optimize care. Changes in PAH, chronological age (CA), bone age (BA), BA/CA, and height velocity (HV) were evaluated in girls with CPP throughout treatment with leuprolide acetate (n=77). A second analysis focused on changes in the 3 years preceding the first observed BA of ≥12 years. Relationships were characterized using plot inspection and linear mixed-effects analyses. Association between treatment duration and last assessed PAH was examined using multiple linear regression models. BA/CA and HV showed a nonlinear change during treatment, with the largest changes and improvement in PAH observed in the first 6–18 months. Rate of BA advancement tended to decrease more slowly in girls initiating treatment at a younger BA. On-treatment change in PAH was predicted by concurrent BA/CA change, HV, and BA, as well as CA at treatment initiation. Last assessed PAH was positively associated with longer treatment durations (primary/exploratory models cut-offs of ≥33/≥55 months). These findings support individualized monitoring during GnRHa treatment. Initial response should be interpreted with caution until 6–18 months after treatment initiation and failure should not be assumed based on continued bone maturation in girls starting therapy at a younger age. Treatment cessation should not be automatically based on a diminishing change in PAH or HV, as ongoing treatment may result in continued increase or maintenance of PAH. [ABSTRACT FROM AUTHOR]

Background: Triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist, is available in 1-, 3-, and 6-month formulations to treat central precocious puberty (CPP). The triptorelin pamoate 22.5-mg 6-month formulation recently approved for CPP offers greater convenience to children by reducing the injection frequency. However, worldwide research on using the 6-month formulation to treat CPP is scarce. This study aimed to determine the impact of the 6-month formulation on predicted adult height (PAH), changes in gonadotropin levels, and related variables. Methods: We included 42 patients (33 girls and nine boys) with idiopathic CPP treated with a 6-month triptorelin (6-mo TP) formulation for over 12 months. Auxological parameters, including chronological age, bone age, height (cm and standard deviation score [SDS]), weight (kg and SDS), target height (TH), and Tanner stage, were evaluated at baseline, and after 6, 12, and 18 months of treatment. Hormonal parameters, including serum luteinizing hormone (LH), folliclestimulating hormone (FSH), and estradiol for girls or testosterone for boys, were analyzed concurrently. Results: The mean age at treatment initiation was 8.6 ± 0.83 (8.3 ± 0.62 for girls, 9.6 ± 0.68 for boys). The peak LH level following intravenous GnRH stimulation at diagnosis was 15.47 ± 9.94 IU/L. No progression of the modified Tanner stage was observed during treatment. Compared to baseline, LH, FSH, estradiol, and testosterone were significantly reduced. In particular, the basal LH levels were well suppressed to less than l.0 IU/L, and the LH/FSH ratio was less than 0.66. The bone age/chronological age ratio remained stable with a decreasing trend (1.15 at the start of treatment, 1.13 at 12 months, 1.11 at 18 months). PAH SDS increased during treatment (0.77 ± 0.79 at baseline, 0.87 ± 0.84 at the start of treatment, 1.01 ± 0.93 at six months, and 0.91 ± 0.79 at 12 months). No adverse effects were observed during treatment. Conclusion: The 6-mo TP suppressed the pituitary-gonadal axis stably and improved the PAH during treatment. Considering its convenience and effectiveness, a significant shift to long-acting formulations can be expected. [ABSTRACT FROM AUTHOR]

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Objective: The onset of puberty in children is occurring at an increasingly earlier ages. During the coronavirus 2019 pandemic, children experienced epidemic-related changes such as stress, sedentary lifestyle, and weight gain. Materials and Methods: Auxological, clinical, endocrinological, and radiological data in the files of 57 patients who were given gonadotropin-releasing hormone analog therapy with the diagnosis of central precocious puberty between April 1 and July 1, 2019 (group 1) and April 1 and July 1, 2020 (group 2) were analyzed retrospectively. Results: A total of 27 patients (26 girls, 1 boy) in group 1 and 30 patients (28 girls, 2 boys) in group 2 were diagnosed with central precocious puberty. Mean ages at diagnosis for groups 1 and 2 were 28.54 ± 0.94 and 7.92 ± 0.96 years, respectively (P = .018). Mean bone age at diagnosis for group 1 was 9.78 ± 1.48 (6.8-12), and for group 2 it was 8.78 ± 1.11 (6.5-12) years (P = .013). The mean age of starting treatment in groups 1 and 2 was 8.94 ± 0.17 (6.8-9.8) and 8.07 ± 0.02 (5.8-10) years, respectively (P = .002). Average birth weights for groups 1 and 2 were 950 ± 1100 (2300-3400) and 3180 ± 717 (870-3820) g, respectively (P = .012). Treatment was started when breast stage was T3 in 57.69% of group 1 and T2 in 75% of group 2, and a statistical difference was found between them (P = .006) and uterine length was higher in group 2 (P = .144). Conclusion: During the coronavirus 2019 pandemic, patients who start central precocious puberty therapy were of younger age. In our single-center experience, coronavirus 2019 was not seen to have a significant impact on central precocious puberty. [ABSTRACT FROM AUTHOR]

Pubertal onset is known to result from reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, which is controlled by complex interactions of genetic and nongenetic factors. Most cases of precocious puberty (PP) are diagnosed as central PP (CPP), defined as premature activation of the HPG axis. The cause of CPP in most girls is not identifiable and, thus, referred to as idiopathic CPP (ICPP), whereas boys are more likely to have an organic lesion in the brain. ICPP has a genetic background, as supported by studies showing that maternal age at menarche is associated with pubertal timing in their offspring. A gain of expression in the kisspeptin gene (KISS1), gain-offunction mutation in the kisspeptin receptor gene (KISS1R), loss-of-function mutation in makorin ring finger protein 3 (MKRN3), and loss-of-function mutations in the delta-like homolog 1 gene (DLK1) have been associated with ICPP. Other genes, such as gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), lin-28 homolog B (LIN28B), neuropeptide Y (NPYR), tachykinin 3 (TAC3), and tachykinin receptor 3 (TACR3), have been implicated in the progression of ICPP, although their relationships require elucidation. Environmental and socioeconomic factors may also be correlated with ICPP. In the progression of CPP, epigenetic factors such as DNA methylation, histone posttranslational modifications, and noncoding ribonucleic acids may mediate the relationship between genetic and environmental factors. CPP is correlated with short- and long-term adverse health outcomes, which forms the rationale for research focusing on understanding its genetic and nongenetic factors. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Current Pediatrics / Guncel Pediatri is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Longer-acting gonadotropin-releasing hormone analogs (GnRHa) have been widely used for central precocious puberty (CPP) treatment. However, the follow-up of patients after this treatment are still scarce. Our aim was to describe anthropometric, metabolic, and reproductive follow-up of CPP patients after treatment with leuprorelin acetate 3-month depot (11.25 mg). Twenty-two female patients with idiopathic CPP were treated with leuprorelin acetate 3-month depot (11.25 mg). Their medical records were retrospectively evaluated regarding clinical, hormonal, and imaging aspects before, during, and after GnRHa treatment until adult height (AH). At the diagnosis of CPP, the mean chronological age (CA) was 8.2 ± 1.13 year, and mean bone age (BA) was 10.4 ± 1.4 year. Mean height SDS at the start and the end of GnRHa treatment was 1.6 ± 0.8 and 1.3 ± 0.9, respectively. The mean duration of GnRHa treatment was 2.8 ± 0.8 year. Mean predicted adult heights (PAH) at the start and the end of GnRH treatment was 153.2 ± 8.6 and 164.4 ± 7.3 cm, respectively (p<0.05). The mean AH was 163.2 ± 6.2 cm (mean SDS: 0.1 ± 1). All patients were within their target height (TH) range. There was a decrease in the percentage of overweight and obesity from the diagnosis until AH (39–19% p>0.05). At the AH, the insulin resistance and high LDL levels were identified in 3/17 patients (17.6%) and 2/21 patients (9.5%), respectively. The mean CA of menarche was 12.2 ± 0.5 years. At the AH, PCOS was diagnosed in one patient (4.8%). Long-term anthropometric, metabolic, and reproductive follow-up of patients with CPP treated with longer-acting GnRHa revealed effectivity, safety, and favorable outcomes. [ABSTRACT FROM AUTHOR]

The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. It is classified as central precocious puberty when premature maturation of the hypothalamic-pituitary-gonadal axis occurs, and as peripheral precocious puberty when there is excessive secretion of sex hormones, independent of gonadotropin secretion. Precocious sexual maturation is more common in girls, generally central precocious puberty of idiopathic origin. In boys, it tends to be linked to central nervous system abnormalities. Clinical evaluation should include a detailed history and physical examination, including anthropometric measurements, calculation of growth velocity, and evaluation of secondary sexual characteristics. The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. Hormonal assessment and imaging are required for diagnosis and identification of the etiology. Genetic testing should be considered if there is a family history of precocious puberty or other clinical features suggestive of a genetic syndrome. Long-acting gonadotropin-releasing hormone analogs are the standard of care for central precocious puberty management, while peripheral precocious puberty management depends on the etiology. Conclusion: The aim of this review is to address the epidemiology, etiology, clinical assessment, and management of precocious sexual maturation. What is Known: • The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. • Long-acting gonadotropin-releasing hormone agonist (GnRHa) is the standard of care for CPP management, and adequate hormone suppression results in the stabilization of pubertal progression, a decline in growth velocity, and a decrease in bone age advancement. What is New: • Most cases of precocious sexual maturation are gonadotropin-dependent and currently assumed to be idiopathic, but mutations in genes involved in pubertal development have been identified, such as MKRN3 and DLK1. • A different preparation of long-acting GnRHa is now available: 6-month subcutaneous injection. [ABSTRACT FROM AUTHOR]

Hypothalamic hamartoma (HH) is a rare, congenital, and benign lesion of the tuber cinereum, typically presenting with central precocious puberty (CPP), gelastic seizure, and developmental delay. This study aimed to investigate CPP in HH patients and compare clinical features between before and after gonadotropin-releasing hormone (GnRH) agonist treatment. A total of 30 HH patients under 18 years of age who visited Severance Children's Hospital between January 2005 and May 2020 were retrospectively reviewed. Fourteen patients were male (46.7%) and sixteen (53.3%) were female, with a mean age at diagnosis was4.2 ± 2.9 years. During follow-up, 24 patients (80.0%) were diagnosed with CPP, 15 patients (50.0%) had gelastic seizure, and 13 patients (43.3%) had developmental delay. The gelastic seizure was significantly associated with sessile type HH rather than pedunculated type HH (85.7% vs. 18.8%, p = 0.001). After GnRH agonist treatment, discrepancies between bone age and chronological age decreased (3.3 ± 1.3 years to 2.0 ± 1.7 years, p = 0.002). Additionally, height standard deviation score for bone age was increased, and predicted adult height increased significantly in females, while males showed an increasing trend. Clinical symptoms of HH were closely associated with the location of HH, and GnRH agonist treatment was safe and effective in the management of CPP caused by HH. [ABSTRACT FROM AUTHOR]

Objective: Data about GnRHa on adult height in girls with central precocious puberty (CPP) have shown variable results, ranging from improvement of growth prognosis to lack of any benefit. This study was designed to delineate the criteria to decide which girls with idiopathic CPP (iCPP) will have a height benefit from GnRHa treatment. Design: Retrospective Patients: 102 girls with iCPP who had reached final height (FH) were included. Measurements: Auxological, hormonal and radiological findings at treatment onset, and FHs were extracted from records. Results: Most important factor affecting height gain was chronological age (CA) at treatment onset. All the girls treated ≤6.4 years of age achieved a height gain of ≥1SDS, while none of the girls treated ≥8.3 years of age made the target. 75.6% of patients who started GnRHa between the ages of 6.4 and 8.3 years had a height gain of ≥1SDS. Most important factors affecting height gain in those treated 6.4‐8.3 years were advanced bone age (BA), basal estradiol (E2) and pubertal stage (r2: 0.906; P <.001). All individuals with BA advancement of ≥2.6 years or E2 of ≥32.6 pg/ml or pubertal stage of ≥3 had significant height gain, and none of the cases with BA advancement of <2 years or E2 of <21.5 pg/ml or pubertal stage of <2 had a height gain of ≥1SDS. Conclusions: Treatment with GnRHa is unquestionably beneficial to improve FH in girls with iCPP when initiated ≤6.4 years of age. GnRHa treatment after 8.3 years of age may not improve FH. Girls between the ages of 6.4 and 8.3 years at presentation can have a better height gain if BA (≥2.6 years over CA) and pubertal findings (pubertal stage ≥3 or E2 ≥32.6 pg/ml) are well‐advanced. [ABSTRACT FROM AUTHOR]

Objective: Premature thelarche (PT) is defined as isolated breast development in girls before eight years of age. Gonadotropin-releasing hormone (GnRH) stimulation test is sometimes used to distinguish between PT and central precocious puberty (CPP), although the interpretation of the test at early ages is challenging. The objective of this study was to determine the follicle stimulating hormone (FSH) and luteinizing hormone (LH) responses to GnRH stimulation in girls with PT below 3 years of age. Methods: A standardized GnRH stimulation test, bone age and pelvic ultrasound were evaluated and those without pubertal progression after a minimum of one-year follow up were included in the study. Results: On GnRH stimulation test, the median (range) baseline LH was 0.29 (0.10-0.74) IU/L, baseline FSH was 4.96 (3.18-7.05) mIU/mL, and the peak median LH was 5.75 (3.31-8.58) IU/L with the peak mean±standard deviation FSH was 40.38±20.37 mIU/mL. Among the patients, 33.3% (n=10) had baseline LH >0.3 IU/L, 67% (n=20) had peak LH >5 IU/l and 16.6% (n=5) >10 IU/L. The mean peak LH/FSH ratio was 0.17±0.09 and was =0.43 in all participants. Conclusion: Although consensus statements usually define baseline LH >0.3-0.5 IU/L, peak LH >5 IU/L, and LH/FSH ratios >0.66- 1.0 as diagnostic cut-offs for CPP, in children below 3 years of age, the baseline and peak LH values may be similar to pubertal values, possibly due to mini-puberty. A dominant FSH response on GnRH stimulation test is more valuable than the peak LH response in the diagnosis of PT. [ABSTRACT FROM AUTHOR]

Copyright of Türk Pediatri Arşivi is the property of Aves Yayincilik Ltd. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Gonadotropin-releasing hormone agonist (GnRHa) is a safe and effective therapy used to treat central precocious puberty (CPP). Although most studies have reported no significant difference in body mass index (BMI) in girls during and after GnRHa therapy, few studies have investigated changes in BMI in boys with CPP. This study evaluated the effects of GnRHa therapy on BMI in boys with CPP. Methods: This study included 75 boys with CPP at Ajou University Hospital between January 1, 2007 and December 31, 2016, who treated with leuprorelin acetate or triptorelin acetate every 4 weeks for at least 2 years. The subjects were divided into 3 groups according to BMI: normal weight, overweight, and obese. We analyzed the BMI standard deviation score (SDS) in each group before therapy and after 1 year and 2 years of therapy. Results: Of the 75 boys, 37 were in the normal weight group, 21 were in the overweight group, and 17 were in the obese group. Magnetic resonance imaging that was performed before treatment showed abnormal findings in 9 boys. The mean BMI SDS for all participants at initiation was 1.0±0.8, and that in the normal weight, overweight, and obese groups was 0.3±0.4, 1.3±0.1, and 1.9±0.3, respectively. There were no significant differences in BMI SDS in any group after 1 or 2 years of treatment. Conclusion: The BMI SDS in boys with CPP did not significantly change over 2 years of GnRHa therapy. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to evaluate FSH, LH responses obtained during LHRH-ST according to two different cut-off values, to determine the diagnostic response times, and to find the optimal blood collection times that could reduce the economic and time burden of LHRH-ST. Materials and Methods: Patients who underwent LHRH-ST in our clinic with the preliminary diagnosis of precocious puberty (PP) between 01/08/2016 and 31/12/2017 were retrospectively enrolled to the study. In this study 207 girls with PP were included and some of them (102 according to C1 and 139 according to C2) had central PP (CPP). Test response and response times were evaluated according to both cut-off values of stimulated peak LH pubertal responses as 5 mIU/ml (the 1st cut-off = C1) and 3.3 mIU/ml (the 2nd cut-off = C2). Results: Totally, 207 girls with a mean age of 7.5 ± 1.22 (3.4-9.5) years were included in the study. With LHRH-ST; 49.2% (n = 102), 67% (n = 139) of the cases were in pubertal period according to C1, C2, respectively. According to C1; pubertal LH was present in 94.1% (n = 96) of 102 patients who reached pubertal LH value in 45th minutes. The highest pubertal response was obtained in the 45th minute. According to C2, of 139 patients who reached pubertal LH; pubertal LH was determined in 98.5% (n = 137) in the 45th minute. Pubertal LH levels were determined according to both cut-off values in all 27 patients with baseline LH ≥0.31 mIU/ml. Conclusion: It was determined that measuring LH at 45th minutes during LHRH-ST was sufficient in 94.1% of the cases according to C1 and 97.1% of the cases according to C2. It was concluded that the 30th, 45th, and 60th minute samples were enough to assess pubertal LH response in 100%of the cases. If the basal LH is found to be ≥0.31 mIU/ml in girls with puberty findings, we recommend that the diagnosis of precocious puberty would be made without performing LHRH-ST. [ABSTRACT FROM AUTHOR]

Introduction: Loss-of-function mutation of MKRN3 represents the most frequent genetic cause of familial central precocious puberty (CPP). The outcomes of gonadotropin-releasing hormone analog (GnRHa) treatment in CPP patients with MKRN3 defects are unknown. Objective: To describe the clinical and hormonal features of patients with CPP with or without MKRN3 mutations after GnRHa treatment. Anthropometric, metabolic and reproductive parameters were evaluated. Patients and Methods: Twenty-nine female patients with CPP due to loss-of-function mutations in the MKRN3 and 43 female patients with idiopathic CPP were included. Their medical records were retrospectively evaluated for clinical, laboratory, and imaging study, before, during, and after GnRHa treatment. All patients with idiopathic CPP and 11 patients with CPP due to MKRN3 defects reached final height (FH). Results: At the diagnosis, there were no significant differences between clinical and laboratory features of patients with CPP with or without MKRN3 mutations. A high prevalence of overweight and obesity was observed in patients with CPP with or without MKRN3 mutations (47.3 and 50%, respectively), followed by a significant reduction after GnRHa treatment. No significant differences in the values of mean FH and target height were found between the 2 CPP groups after GnRHa treatment. Menarche occurred at the expected age in patients with or without CPP due to MKRN3 mutations (11.5 ± 1.3 and 12 ± 0.6 years, respectively). The prevalence of polycystic ovarian syndrome was 9.1% in patients with CPP due to MKRN3 mutations and 5.9% in those with idiopathic CPP. Conclusion: Anthropometric, metabolic, and reproductive outcomes after GnRHa treatment were comparable in CPP patients, with or without MKRN3 mutations, suggesting the absence of deleterious effects of MKRN3 defects in young female adults' life. [ABSTRACT FROM AUTHOR]

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 ≥ 50 pmol/L, uterine longitudinal diameter ≥ 3.5 cm, transverse uterine diameter ≥ 1.5 cm, endometrial echo and ovarian volume ≥ 2 cm3 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. [ABSTRACT FROM AUTHOR]

Objective: Doses of gonadotropin releasing hormone (GnRH) analogues used to treat idiopathic central precocious puberty (iCPP) vary among clinicians. Study aims were to evaluate the efficacy of a monthly 3.75 mg dose of leuprolide acetate (LA) to suppress the hypothalamo-pituitary-gonadal (HPG) axis in girls with iCPP and to determine factors that may have an impact on the supressing dose. Methods: Study subjects were 220 girls receiving LA for iCPP. LA was started at a dose of 3.75 mg/28 days. Suppression was assessed using the GnRH test at the third month. To assess clinical suppression signs and symptoms of puberty were also evaluated. The dose of LA was increased to 7.5 mg/28 days in those who had a peak luteinising hormone (LH) ≥2 IU/L and in whom adequate clinical suppression of puberty was absent. Receiver operating characteristic curves were used to determine thresholds for clinical and hormonal factors affecting the suppressing dose of LA. Logistic regression analyses were used to investigate thresholds which might differentiate between those requiring high dose for suppression and those in whom lower dose LA was adequate. Results: Peak stimulated LH <2 IU/L was achieved in 88.6% with a dose of LA of 3.75 mg (0.11±0.03 mg/kg). Significant variables for differentiating the two doses were body weight (Wt) of 36.2 kg and/or body mass index (BMI)-standard deviation scores (SDS) of 1.64 (p<0.001). Multiple logistic regressions showed that Wt and BMI-SDS values above thresholds indicated requirement of LA at a dose of 7.5 mg/28 days (p<0.001). Conclusion: Monthly injections of 3.75 mg LA is an effective treatment in the majority of girls with iCPP. However, a higher initial dose may be preferred in patients with a Wt ≥36 kg or BMI-SDS ≥1.6 for effective suppression of the HPG axis. [ABSTRACT FROM AUTHOR]

Introduction: Studies evaluating effects of gonadotropin-releasing hormone agonist (GnRHa) on weight and body-mass-index (BMI) in girls with idiopathic central precocious puberty (iCPP) include short-term effects. The aim of this study is to investigate changes in BMI during and 2 years after completion of GnRHa to determine the factors that may impact BMI in girls with iCPP. Methods: Medical files of 138 girls who completed GnRHa were evaluated. All patients had weight and height measurements at the beginning and end of treatment, and 111 patients had anthropometric measurements 2 years after the completion of treatment. Results: In the beginning, 82 (59.4%) had normal weight (NW), 42 (30.4%) were overweight (OW), and 14 (10.2%) were obese (OB). Analysis of BMI-standard deviation score (SDS) in the whole group showed an overall increase during GnRHa treatment (0.92 ± 0.74 vs. 1.20 ± 0.51, p < 0.001). Changes in BMI-SDS (ΔBMI-SDS) during GnRHa differed between NW and OW/OB (0.45 ± 0.31 vs. 0.03 ± 0.20, p < 0.001). BMI-SDSs of both groups returned to baseline scores (or initial levels) 2 years after the completion of treatment. Two factors affecting ΔBMI-SDS in multiple linear regression analyses were baseline BMI and Δheight-SDS, both correlated negatively with ΔBMI-SDS. Conclusions: The present study is one of the studies evaluating BMI change over a long period of time in girls with CPP. Although BMI-SDS increased during GnRHa in NW girls, it was reversible in follow-up after treatment. However, BMI-SDS did not change during and in follow-up in OW/OB girls. Conserving BMI-SDS in OW/OB girls may be related to the fact that weight management programs were recommended for these patients. Dietary recommendations should be provided for children with NW who undergo GnRHa, as is the case for OW patients. [ABSTRACT FROM AUTHOR]

Background: The standard treatment of central precocious puberty (CPP) is gonadotropin-releasing hormone analogues (GnRHa). It is a concern that children treated with GnRHa are at risk of developing obesity which could impair the treatment outcomes. This study aimed to investigate the effect of GnRHa on body mass index (BMI) standard deviation score (SDS), and the influence of BMI status on treatment outcomes in children with idiopathic CPP (iCPP). Methods: A retrospective cohort study in children with iCPP who completed GnRHa treatment and had attained near final adult height (NFAH) was conducted. Children with a history of disease or drug ingestion which could affect their BMI were excluded. BMI, BMI SDS, height (Ht), Ht SDS, predicted adult height (PAH), and NFAH were compared at baseline, 1 and 2 years during treatment, and at NFAH according to the baseline BMI status; normal weight and overweight/obesity. Results: Fifty-eight children with iCPP treated with GnRHa were enrolled. The BMI SDS was significantly increased at 1 and 2 years during treatment in the overweight/obese group and at 1 year during treatment in the normal-weight group. However, at NFAH (2 years after treatment discontinuation), the BMI SDS was not statistically different from baseline in both groups. Ht gain, change in Ht SDS and BMI SDS were not statistically different from the baseline in both groups. Conclusions: GnRHa results in a transient increase in BMI SDS during treatment and returned to baseline after treatment cessation. The benefit of GnRHa treatment on final Ht improvement is similar between overweight/obese and normal-weight patients. [ABSTRACT FROM AUTHOR]

Background: The use of gonadotropin-releasing hormone agonists (GnRHa) for pubertal suppression has been associated with increased body mass index (BMI) in female subjects with central precocious puberty (CPP), although results have been so far conflicting. This study examined the effects of GnRHa therapy in both genders and in subjects treated for CPP, early puberty or short stature. Methods: This was a longitudinal retrospective study of subjects followed at outpatient pediatric endocrinology clinics of an academic medical center from 2005 to 2014 receiving GnRHa therapy. Results: At 12 months, subjects on depot GnRHa had a statistically significant increase in BMI standard deviation score (SDS) from baseline (0.13 ± 0.35, p < 0.02). Subjects with short stature (0.17 ± 0.34, p < 0.02) but not early or precocious puberty, and subjects with normal baseline BMI (0.18 ± 0.38, p < 0.02) had significant increases in BMI SDS; no significance was noted at 24 months. Male subjects did not have a significant increase in BMI SDS, whereas female subjects did (0.11 ± 0.36, p < 0.01). Conclusions: Subjects with short stature, normal BMI at baseline and female sex had significant increases in BMI SDS at 12 months. This is the first study to show an increase in BMI SDS in children treated with GnRHa for short stature, and is one of the few studies to assess BMI changes in males. [ABSTRACT FROM AUTHOR]

Objective: Longitudinal data regarding random luteinizing hormone (LH) concentrations in patients with idiopathic central precocious puberty (ICPP) during treatment are limited. Therefore, we sought to evaluate random LH and estradiol concentrations during monthly leuprolide injection and their associations with pubertal progression and final adult height (FAH) in girls with ICPP. Methods: Medical records of 27 girls with ICPP who had attained FAH were reviewed. Patients' height, weight, Tanner stage, growth rate (GR), bone age, random LH measured by both immunoradiometric and immunochemiluminescent methods, follicular-stimulating hormone (FSH) and estradiol levels were monitored until FAH. Results: Treatment was started at a mean (±standard deviation) age of 8.1±0.6 years with mean duration of 3.9±0.2 years. At six months of follow-up, random LH (p=0.048), FSH (p<0.001) and estradiol (p=0.023) concentrations were decreased compared with baseline. Thereafter, random LHs were well suppressed. GRs gradually decreased to prepubertal norm by month 12. Seventeen patients (63%) exhibited pubertal LH concentrations at least once during treatment visits. Furthermore, 43 of a total 116 (37%) LH measurements were found elevated. However, those patients with elevated random LH did not show signs of pubertal progression. After treatment, mean FAH was greater than predicted adult height (p<0.0001) and target height (p=0.03). At no time points of treatment did random LH, FSH and estradiol correlate with GRs or FAH. Conclusion: Elevated random LH is commonly found in ICPP girls during monthly leuprolide treatment. However, these elevations were not associated with clinical progression of puberty or decreased FAH, suggesting that it is not a reliable method for CPP monitoring. [ABSTRACT FROM AUTHOR]

Aim: Gonadotropin-releasing hormone agonists (GnRHa) are widely used in the treatment of central precocious puberty (CPP). There is concern that GnRHa treatment, whose positive effects on the adult height are known, may cause weight gain and body mass index (BMI) increase. The aim of this study was to assess the effect of the GnRHa treatment on BMI and height in female patients with CPP. Materials and Methods: Ninety-two patients diagnosed with idiopathic CPP and 22 patients diagnosed with organic CPP, who received GnRHa treatment were included in the study. Data taken on the treatment start date, 6th month, 1st and 2nd year for height, weight, BMI and bone age were obtained retrospectively from the file records. Results: BMI standard deviation score (SDS) increased during the treatment period in all the patients. In the second year of GnRHa treatment, BMI SDS was higher in the organic CPP, compared to the idiopathic CPP (0.66±0.84 and 1.35±0.72, p=0.007). In both groups, at the beginning of GnRHa treatment, the BMI SDS increase was higher in those patients with normal weight compared to those who were overweight/obese. In both groups, the prevalence of obesity was higher than the reference population at the beginning of treatment. An increase was determined in the height SDS and predicted adult height in both groups according to bone age. Conclusion: In patients with CPP, the prevalence of obesity was higher in the first application compared to the reference population. In CPP, BMI SDS increased with GnRHa treatment. The weight of the patients at the beginning of the treatment affected the weight and BMI change with GnRHa treatment. Those patients with organic CPP were more prone to weight gain and BMI increase. [ABSTRACT FROM AUTHOR]

Background: Puberty is associated with a physiological decline in insulin sensitivity (IS). Overweight (OW) and obesity (OB) are common among girls with central precocious puberty (CPP). CPP is considered a risk factor for metabolic diseases. The aim of this study was to assess surrogate measures of IS, body mass index (BMI) and other metabolic parameters in CPP girls at diagnosis and during treatment with gonadotropin-releasing hormone analogues (GnRHa). Methods: We present a prospective longitudinal study of CPP girls. The standard oral glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR), whole-body IS index (ISI) and fasting lipid profiles were evaluated at diagnosis, and at 6 and 12 months of treatment. Results: Nineteen CPP girls were included; 17 were evaluable. At baseline, seven patients had normal weight (NW), five were OW and five were OB. During GnRHa treatment no significant changes were observed in BMI, HOMA-IR or ISI when considering the whole group. Whereas, when we analyzed patients according to BMI status, in NW patients, BMI increased significantly with no changes in HOMA-IR or ISI along treatment. In the OW/OB group, no significant differences were observed in BMI, HOMA-IR or ISI. Conclusions: Girls with CPP showed a high frequency of OW/OB and a high prevalence of IR. GnRHa did not affect BMI, IS or the lipid profile when considering the whole cohort of patients. However, there was an increase in BMI in NW girls but not in OW/OB patients. [ABSTRACT FROM AUTHOR]

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Copyright of Gynecological Endocrinology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Triptorelin depot is largely used to treat central precocious puberty (CPP) in children. Areas covered: This review updates triptorelin depot treatment of CPP, focusing on trials that compared 3.75 mg/28 day treated and untreated children till the adult height (AH). Efficacy of the new 11.25 mg/90 days or 22.5 mg/6 month formulations in suppressing pituitary-gonadal axis in short-term trials is also addressed. Short- and long-term safety was summarized. Expert commentary: Long experience on triptorelin depot use in children with CPP is available. Outcome differences on AH are reported; they may be due to heterogenicity of treated patients; some items remain to be optimized. No long term-adverse events on reproductive function are reported; additional studies would clarify if CPP per sè or triptorelin depot administration may increase hyperandrogenism and/or polycystic ovary syndrome risk in adulthood. The quarterly formulation seems to be able to suppress pituitary-gonadal axis and pubertal development and to determine similar end-results as monthly formulation, but additional trials are needed. Few data are available for the 22.5 mg/6 month formulation. Triptorelin depot treatment of CPP should be restricted to tertiary pediatric endocrinology centers, considering that some uncertainties still exist and that rare but serious adverse events may occur. [ABSTRACT FROM AUTHOR]

Background: Children with central precocious puberty (CPP) are treated with gonadotropin-releasing hormone agonists (GnRHa) to suppress puberty. Optimizing treatment outcomes continues to be studied. The relationships between growth, rate of bone maturation (bone age/chronological age [ΔBA/ΔCA]), luteinizing hormone (LH), predicted adult stature (PAS), as well as variables influencing these outcomes, were studied in children treated with depot leuprolide (LA Depot) Methods: Subjects (64 girls, seven boys) with CPP received LA Depot every 3 months for up to 42 months. Multivariate regression analyses were conducted to examine the predictors affecting ΔBA/ΔCA, PAS and growth rate. Results: Ninety percent of subjects (18 of 20) were suppressed (LH levels <4 IU/L) at 42 months. Over 42 months, the mean growth rate declined 2 cm/year, the mean BA/CA ratio decreased 0.21 and PAS increased 8.90 cm for girls (n=64). PAS improved to mid-parental height (MPH) in 46.2% of children by 30 months of treatment. Regression analysis showed that only the Body Mass Index Standardized Score (BMI SDS) was significantly associated (β+0.378 and +0.367, p≤0.05) with growth rate. For PAS, significant correlations were with MPH (β+0.808 and +0.791, p<0.001) and ΔBA/ΔCA (β+0.808 and +0.791, p<0.001). For ΔBA/ΔCA, a significant association was found only with BA at onset of treatment (β−0.098 and −0.103, p≤0.05). Peak-stimulated or basal LH showed no significant influence on growth rate, ΔBA/ΔCA or PAS. Conclusions: Growth rate and bone maturation rate normalized on treatment with LA Depot. LH levels were not significantly correlated with growth rate, ΔBA/ΔCA or PAS, suggesting that suppression was adequate and variations in gonadotropin levels were below the threshold affecting outcomes. [ABSTRACT FROM AUTHOR]

Background: Hypothalamic hamartoma (HH) represents the commonest cause of organic central precocious puberty (CPP). Follow-up of these patients in adulthood is scarce. Objective: To describe the anthropometric, metabolic, and reproductive parameters of patients with CPP due to HH before and after treatment with gonadotropin-releasing hormone analog (GnRHa). Methods: We performed a retrospective and cross-sectional study in a single tertiary center including 14 patients (7 females) with CPP due to HH. Results: The mean duration of GnRHa treatment was 7.7 ± 2.4 years in boys and 7.9 ± 2.1 years in girls. GnRHa treatment was interrupted at the mean chronological age (CA) of 12.1 ± 1.1 years in boys and 10.7 ± 0.5 years in girls. At the last visit, the mean CA of the male and female patients was 21.5 ± 3.2 and 24 ± 3.9 years, respectively. Eleven of the 14 patients reached normal final height (FH) (standard deviation score -0.6 ± 0.9 for males and -0.6 ± 0.5 for females), all of them within the target height (TH) range. The remaining 3 patients had predicted height within the TH range. The mean body mass index and the percentage of body fat mass was significantly higher in females, with a higher prevalence of metabolic disorders. All patients presented normal gonadal function in adulthood, and 3 males fathered a child. Conclusion: All patients with CPP due to HH reached normal FH or near-FH. A higher prevalence of overweight/obesity and hypercholesterolemia was observed in the female patients. Finally, no reproductive disorder was identified in both sexes, indicating that HH per se has no deleterious effect on the gonadotropic axis in adulthood. [ABSTRACT FROM AUTHOR]

Purpose: Reported changes in body mass index (BMI) in central precocious puberty (CPP) during and after gonadotropin-releasing hormone analog (GnRHa) treatment are inconsistent. We, therefore, investigated auxological parameters in GnRHatreated girls with idiopathic CPP (ICPP) until attainment of near final height (NFH). Methods: From the medical records of 59 ICPP girls who attained NFH after GnRHa therapy, auxological changes were compared between overweight (BMI=85th percentile) and normal-weight (BMI<85th percentile) groups. BMIs were changed into standard deviation scores (BMISDSs) for subject chronologic age (BMISDS-CA) and bone age (BMISDS-BA). Results: The incidence of overweight including obesity was high at the start of therapy (35.6%). The predicted adult height (PAH) at start of therapy was significantly shorter than the midparental height (MPH), whereas PAH at end of therapy approached MPH, and NFH was greater than MPH. Height velocity (HV) in the overweight group was higher during GnRHa therapy than that in the normal-weight group, but those in the two groups were not different after therapy until NFH. Both BMISDS-CA and BMISDS-BA increased significantly during therapy, but both BMISDSs decreased significantly after therapy until NFH. At NFH, neither BMISDS was different from that at baseline. In the normal-weight group, both BMISDSs increased during therapy and were maintained until NFH. In the overweight group, neither BMISDS changed during therapy, but there was a decrease after therapy until NFH. Conclusion: The different patterns of BMISDS change during and after GnRHa therapy until NFH between the 2 groups were related to the different HV during GnRHa therapy. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the influence of obesity on the clinical course and effect of gonadotropin-releasing hormone analog (GnRHa) treatment in girls with central precocious puberty (CPP). Methods: Medical records of 182 girls with CPP treated with GnRHa were reviewed. They were divided into 2 groups: normal weight (n=108) and overweight/obesity (n=74). Chronological age (CA), bone age (BA), difference between BA and CA (BA- CA), standard deviation score (SDS) of height, body mass index (BMI), predicted adult height (PAH), and laboratory findings were compared at baseline, after 1 year, and at the end of GnRHa treatment in both groups. Results: Mean BMI SDS at baseline was 0.08±0.60 in the normal weight group and 1.55±0.36 in the overweight/obesity group. Initial CA, BA, midparental height, and PAH were similar between the 2 groups. BA-CA after treatment was significantly decreased compared to baseline in both groups (P<0.001). Between the 2 groups, a decrease in BA--CA during treatment showed no significant difference. PAH at the end of treatment was significantly increased compared to baseline in both groups (P<0.001). PAH at the end of treatment in the overweight/obesity group (159.88±3.41 cm) was similar to that of the normal weight group (159.19±3.25 cm). Comparing the 2 groups according to change in BMI after treatment, there were no differences in ΔPAH, ΔBA--CA, and Δheight SDS for BA. Conclusion: GnRHa treatment in obese girls with CPP improved the height outcome and had similar results in normal weight CPP girls. Obesity might not affect the efficacy of GnRHa in girls with CPP. [ABSTRACT FROM AUTHOR]

Background: The influence of gonadotropin-releasing hormone analogue (GnRHa) treatment on body mass index (BMI) evolution in girls with idiopathic central precocious puberty (CPP) is unclear. Hence, we aimed to evaluate the effect of GnRHa treatment on BMI-standard deviation score (SDS) from diagnosis of idiopathic CPP until adult height. Methods: An observational study of girls diagnosed with CPP in Spain was carried out between January 2008 and December 2014. A computer program was designed to process clinical and biological data from patients treated in 55 departments of pediatric endocrinology throughout the country. The inclusion criteria were (1) girls diagnosed with CPP before 8 years of age; (2) born after 1992; (3) with a difference between bone and chronological age of at least 1 year, and (4) with a luteinizing hormone peak >7 U/l during luteinizing hormone-releasing hormone testing. The influence of GnRHa treatment on BMI-SDS evolution was analyzed. Results: Data from 333 girls (22.2% adopted) were evaluated. We report follow-up data at 6, 12, 24, 36, 48 and 60 months and adult height from 269, 232, 198, 153, 105, 56 and 49 girls, respectively. During treatment, there was an increase in BMI SDS of 0.43 ± 1.17 (95% CI: 0.20-0.64). At adult height (n = 49), BMI-SDS was 1.51 ± 1.38, which was 0.60 ± 1.09 higher than at diagnosis (95% CI: 0.43-0.75). Conclusions: During treatment with GnRHa, girls experience a significant increase in BMI-SDS that persists after therapy is stopped and adult height has been reached. [ABSTRACT FROM AUTHOR]

Background: In girls with Idiopathic Central Precocious Puberty (ICPP) concern has been raised by the potential impact of GnRH-analogues (GnRHa) treatment on body weight. We evaluated the effect of GnRHa on Body Mass Index (BMI) in girls with ICPP according to weight status at diagnosis. Methods: One hundred seventeen ICPP girls were divided according to pretreatment weight status in: normal weight (NW), overweight (OW) and obese (OB). BMI at one and two years of treatment was assessed. BMI-SDS of 60 patients who reached adult height (AH) was compared to that of 33 ICPP untreated girls. Results: NW girls significantly increased their baseline BMI-SDS at 1 and 2 years of treatment. OW girls only had a significant increment at one year of treatment while OB girls showed no BMI-SDS change. Patients evaluated at AH (at least four years after GnRHa withdrawal) showed a significant decrease on BMI compared to baseline and a significantly lower BMI than the untreated group. Conclusion: In ICPP girls the BMI increase under GnRHa was inversely related to the pretreatment weight status. In the long term follow-up, no detrimental effect of GnRHa on body weight was observed. BMI-SDS was lower in treated than in untreated girls. [ABSTRACT FROM AUTHOR]

Copyright of Revista Mexicana de Pediatria is the property of Sociedad Mexicana de Pediatria and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Central precocious puberty (CPP) is caused by the premature reactivation of the hypothalamic-pituitary-gonadal axis. Genetic, nutritional, and environmental factors play a crucial role in determining pubertal timing. Recently mutations in kisspeptin (KISS1), kisspeptin receptor (KISS1R), and makorin RING finger protein 3 (MKRN3) genes have been identified as genetic causes of CPP. In particular, the MKRN3 gene is known to affect pubertal initiation. The MKRN3 gene is located on chromosome 15q11-q13 in the Prader-Willi syndrome (PWS) critical region. MKRN3 deficiency, due to a loss of function mutation, leads to the withdrawal of hypothalamic inhibition and prompts pulsatile gonadotropin-releasing hormone secretion, resulting in precocious puberty. The exact functions of these genes associated with CPP are still not well understood. Larger studies are required to discover the mechanisms involved in pubertal development. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to assess the effect of gonadotropin-releasing hormone (GnRH) agonist therapy on body mass index (BMI) and growth in girls diagnosed with idiopathic central precocious puberty (CPP). Materials and Methods: Hospital records of 32 girls with idiopathic CPP who have been receiving GnRH agonist therapy for at least 12 months were retrospectively reviewed and auxological, clinical and laboratory parameters of the patients were recorded. BMI, body mass index standard deviation score (BMI SDS) for chronological age body mass index standard deviation score (CA-BMI SDS), BMI SDS for bone age body mass index standard deviation score (BA-BMI SDS), ratios of obesity and overweight were assessed before treatment and on the 12th month of therapy in patients diagnosed with idiopathic CPP. Results: The study comprised of 32 girls diagnosed with idiopathic CPP. BMI values showed statistically significant increase in the 1st year of treatment (19.16 ± 2.8 vs. 20.7 ± 3.4, P = 0.001). Despite a mild increase in CA-BMI SDS in the 1st year of treatment versus before treatment, it was no statistically significant (1.0 ± 0.8 vs. 1.1 ± 0.9, P = 0.061). However, significant increase was observed in BA-BMI SDS in the 1st year of treatment versus before treatment (0.8 ± 0.7 vs. 0.4 ± 0.8, P < 0.001). Before treatment, 37.5% (12/32) of the patients were overweight and 21.9% (5/32) were obese, whereas in the 1st year, 34.4% (11/32) of the patients were overweight and 31.3% were obese (P = 0.001). Conclusion: Whilst 1/3 of the cases diagnosed with idiopathic CPP were overweight and obese at the time of diagnosis, GnRH agonist therapy caused statistically significant weight gain in patients diagnosed with CPP. Therefore, these patients should be closely monitored and weight control should be provided by diet and exercise programs in the course of treatment. [ABSTRACT FROM AUTHOR]

Purpose: There is controversy surrounding the growth outcomes of treatment with gonadotropin-releasing hormone agonist (GnRHa) in central precocious puberty (CPP). We analyzed height preservation after treatment with GnRHa with and without growth hormone (GH) in girls with CPP . Methods: We reviewed the medical records of 82 girls with idiopathic CPP who had been treated with GnRHa at Severance Children's Hospital from 2004 to 2014. We assessed the changes in height standard deviation score (SDS) for bone age (BA), and compared adult height (AH) with midparental height (MPH) and predicted adult height (PAH) during treatment in groups received GnRHa alone (n=59) or GnRHa plus GH (n=23). Results: In the GnRHa alone group, the height SDS for BA was increased during treatment. AH (160.4±4.23 cm) was significantly higher than the initial PAH (156.6±3.96 cm) (P<0.001), and it was similar to the MPH (159.9±3.52 cm). In the GnRHa plus GH group, the height SDS for BA was also increased during treatment. AH (159.3±5.33 cm) was also higher than the initial PAH (154.6±2.55 cm) (P<0.001), which was similar to the MPH (158.1±3.31 cm). Height gain was slightly higher than that in the GnRHa alone group, however it statistically showed no significant correlation with GH treatment. Conclusion: In CPP girls treated with GnRHa, the height SDS for BA was increased, and the AH was higher than the initial PAH. Combined GH treatment showed a limited increase in height gain. [ABSTRACT FROM AUTHOR]

A pivotal event in the onset of puberty in humans is the reemergence of the pulsatile release of the gonadotropin-releasing hormone (GnRH) from hypothalamic neurons. Pathways governing GnRH ontogeny and physiology have been discovered by studying animal models and humans with reproductive disorders. Recent human studies implicated the activation of kisspeptin and its cognate receptor (KISS1/KISS1R) and the inactivation of MKRN3 in the premature reactivation of GnRH secretion, causing central precocious puberty (CPP). MKRN3, an imprinted gene located on the long arm of chromosome 15, encodes makorin ring finger protein 3, which is involved in ubiquitination and cell signaling. The MKRN3 protein is derived only from RNA transcribed from the paternally inherited copy of the gene due to maternal imprinting. Currently, MKRN3 defects represent the most frequent known genetic cause of familial CPP. In this review, we explored the clinical, hormonal and genetic aspects of children with sporadic or familial CPP caused by mutations in the kisspeptin and MKRN3 systems, essential genetic factors for pubertal timing. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives 1. To determine BMI, obesity/overweight rates, glucose and lipids at baseline, during GnRHa treatment and shortly after therapy discontinuation in female children with CPP and EP. 2. To compare this response to that seen in a similar group of untreated patients. Methods A retrospective analysis of 71 children with either CPP (n = 37) or EP (n = 34) was undertaken. Forty three were treated with a GnRHa for at least 2 years, while 28 were followed without treatment. Results At the time of diagnosis, a higher BMI (z-score of 1.1 ± 0.8 vs. 0.6 ± 0.7, p = 0.004) and a higher prevalence of obesity/overweight (72.9 vs. 35.3%, p = 0.001) was observed in subjects with CPP when compared to those with EP. Children with EP had higher fasting glucose and total cholesterol than those with CPP. BMI z-score, obesity/overweight rates, fasting glucose and lipids did not change significantly in girls with CPP or EP during 3 yrs of follow up, regardless of treatment. Weight z-scores were higher at 3 years in treated than in untreated girls with CPP (p = 0.02), while it was higher in untreated than in GnRHa-treated patients with EP at baseline, 1, 2 and 3 years (p = 0.007, p = 0.002, p = 0.02 and p = 0.04, respectively) and remained so shortly after stopping therapy (p = 0.03). Conclusions There is a high prevalence of obesity/overweight in girls with CPP and EP at diagnosis. However, this risk is greater in CPP than in EP girls. BMI, Obesity/overweight rates, fasting glucose and lipids remained stable in CPP and EP girls regardless of therapy. Weight z-scores were found to be higher in treated CPP girls and in untreated girls with EP. [ABSTRACT FROM AUTHOR]

Objective: The combination therapy of gonadotropin-releasing hormone analogues (GnRHa) and recombinant human growth hormone (rhGH) has been used to increase growth in children with premature sexual maturation and attenuated growth. The aim of this report was to study the benefit over cost of combined treatment in girls with central precocious puberty (CPP) and poor height prognosis and in girls with idiopathic short stature (ISS) and early puberty. Should this expensive treatment be given to such patients? Subjects and methods: Two patient groups were included: five girls with central precocious puberty (CPP) who reached final height (FH) at 16.3±1.2 years and eight girls with ISS who reached FH at 14.7±0.8 years. Patients were treated for 3.5±0.6 years. Results: In both groups, FH improved significantly; in CPP from -1.3 to -0.5 standard deviation score (SDS) (p=0.030) and in ISS from -2.6 to -1.7 SDS (p=0.012). Only girls with CPP reached their target height (-0.5 vs. -0.6 SDS) (p=0.500). Conclusions: Both groups had a total height gain of 5 cm. Each centimetre cost about €2700 per patient. This treatment should be considered only in patients with extremely low height prediction and very early pubertal onset. [ABSTRACT FROM AUTHOR]

Hypothalamic hamartomas (HHs) are tumors generally associated with isolated central precocious puberty (CPP). To our knowledge, we report a unique case of a girl with HH associated with CPP and growth hormone deficiency. This case highlights the complex interaction between HHs and the hypothalamic-pituitary-gonadal axis. It also emphasizes the value of close follow-up of growth velocity in these patients even after treatment of the CPP. [ABSTRACT FROM AUTHOR]

Background Gonadotropin-releasing hormone agonist (GnRHa)-stimulated luteinizing hormone (LH) is the standard hormonal assessment for both diagnosis and therapeutic monitoring of children with central precocious puberty (CPP). Use of unstimulated (random) LH levels may be helpful in diagnosis and has gained popularity in monitoring GnRHa therapy despite lack of validation against stimulated values. The objective of this investigation was to assess the suitability of random LH for monitoring pubertal suppression during GnRHa treatment. Methods Data from a multi-year, multicenter, open-label trial of annual histrelin implants for CPP was used for our analysis. Children meeting clinical and hormonal criteria for CPP, either naïve to GnRHa therapy or previously treated with another GnRHa for at least 6 months who were being treated at academic pediatric centers were included in the study. Subjects received a single 50-mg subcutaneous histrelin implant annually until final explant at an age determined at the discretion of each investigator. Monitoring visits for physical examination and GnRHastimulation testing were performed at regular intervals. The main outcome measure was pubertal suppression during treatment defined by peak LH < 4 mIU/mL after GnRHa stimulation. Results During histrelin treatment, 36 children underwent a total of 308 monitoring GnRHa stimulation tests. Unstimulated and peak LH levels were positively correlated (r = 0.798), and both declined from the first to second year of treatment. Mean ± SD peak LH level during therapy was 0.62 ± 0.43 mIU/mL (range, 0.06-2.3), well below the normal prepubertal mean. Mean random LH was 0.35 ± 0.25 mIU/mL (range, 0.04-1.5), 10-fold higher than the normal prepubertal mean. The random LH levels were above the prepubertal upper threshold (<0.3 mIU/mL) in 48.4% of all tests and in 88.9% of subjects at some point during therapy. Conclusions In contrast with GnRHa-stimulated LH, unstimulated LH values frequently fail to demonstrate suppression to prepubertal values during GnRHa therapy for CPP, despite otherwise apparent pubertal suppression, and are thus unsuitable for therapeutic monitoring. [ABSTRACT FROM AUTHOR]

Background/Aim: TTF1 and EAP1 are transcription factors that modulate gonadotropin-releasing hormone expression. We investigated the contribution of TTF1 and EAP1 genes to central pubertal disorders. Patients and Methods: 133 patients with central pubertal disorders were studied: 86 with central precocious puberty and 47 with normosmic isolated hypogonadotropic hypogonadism. The coding region of TTF1 and EAP1 were sequenced. Variations of polyglutamine and polyalanine repeats in EAP1 were analyzed by GeneScan software. Association of TTF1 and EAP1 to genes implicated in timing of puberty was investigated by meta-network framework GeneMANIA and Cytoscape software. Results: Direct sequencing of the TTF1 did not reveal any mutation or polymorphisms. Four EAP1 synonymous variants were identified with similar frequencies among groups. The most common EAP1 5′-distal polyalanine genotype was the homozygous 12/12, but the genotype 12/9 was identified in 2 central precocious puberty sisters without functional alteration in EAP1 transcriptional activity. TTF1 and EAP1 were connected, via genetic networks, to genes implicated in the control of menarche. Conclusion: No TTF1 or EAP1 germline mutations were associated with central pubertal disorders. TTF1 and EAP1 may affect puberty by changing expression in response to other members of puberty-associated gene networks, or by differentially affecting the expression of gene components of these networks. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: We studied the effect of gonadotropin-releasing hormone analogues (GnRHa) on weight gain as a possible side effect. Methods: We analyzed longitudinally changes in BMI-SDS in 92 children [median age 8.0 years (IQR 7.1-8.9), 88% females, mean BMI-SDS 0.69 ± 1.30] with idiopathic central precocious puberty or early puberty treated with GnRHa. Furthermore, 25 overweight children with GnRHa were compared to 25 overweight children without GnRHa matched by age, gender, degree of overweight, and pubertal stage. Results: The matched overweight children without GnRHa demonstrated a significant increase in their BMI-SDS in the course of 1 year (+0.18 ± 0.22). Normal-weight children treated with GnRHa demonstrated a significant increase in BMI-SDS in the course of 1 year (+0.32 ± 0.66) in contrast to overweight children treated with GnRHa who showed a stable BMI-SDS (-0.02 ± 0.27). This significant difference in changes in BMI-SDS between normal-weight and overweight children treated with GnRHa was also observed at the end of GnRHa treatment and 6 months later (p < 0.001). Conclusions: Change in weight status differed between overweight and normal-weight children during GnRHa treatment. We found no increased risk for the side effect of weight gain in overweight children treated with GnRHa. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]