Dataset Information

A mathematical model for predicting the adult height of girls with idiopathic central precocious puberty: A European validation.

ABSTRACT:

Background

A previous single-center study established a mathematical model for predicting the adult height (AH) in girls with idiopathic central precocious puberty (CPP).

Objective

To perform internal and external validations by comparing the actual AH to the calculated AH established by this model and to update it.

Methods

The original formula, calculated AH (cm) = 2.21 (height at initial evaluation, SD) + 2.32 (target height, SD) - 1.83 (luteinizing hormone/follicle-stimulating hormone peaks ratio) + 159.68, was established in a sample of 134 girls (group 4) and was applied to additional girls with CPP seen in the same center (group 1, n = 35), in Germany (group 2, n = 43) and in the Netherlands (group 3, n = 72). This formula has been updated based on these extended data, and both versions are available at the following location: http://www.kamick.org/lemaire/med/girls-cpp15.html.

Results

Despite the differences among the 4 groups in terms of their characteristics at the initial evaluation and the percentages of patients treated with the gonadotropin-releasing hormone analogue, they have similar calculated and actual AHs. The actual AHs are 162.2±7.0, 163.0±7.6, 162.4±7.7 and 162.1±5.6 cm in groups 1 to 4, respectively. They are highly correlated with the AHs calculated by the formula established in the original group (group 4), with R at 0.84, 0.67 and 0.69 in groups 1 to 3, respectively. When the actual AHs and the AHs predicted by the Bayley and Pinneau method are compared, the R is 0.76, 0.51 and 0.64 in groups 1 to 3, respectively. The absolute differences between actual AHs and the calculated AHs are greater than 1 SD (5.6 cm) in 15%, 35% and 28% of the patients in groups 1 to 3, respectively.

Conclusion

This study validates and updates the previously established formula for predicting AH in girls with CPP. This updated formula can help clinicians to make treatment decisions.

SUBMITTER: Lemaire P

PROVIDER: S-EPMC6178384 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

A mathematical model for predicting the adult height of girls with idiopathic central precocious puberty: A European validation.

Lemaire Pierre P Duhil de Bénazé Gwénaëlle G Mul Dick D Heger Sabine S Oostdijk Wilma W Brauner Raja R

PloS one 20181009 10

<h4>Background</h4>A previous single-center study established a mathematical model for predicting the adult height (AH) in girls with idiopathic central precocious puberty (CPP).<h4>Objective</h4>To perform internal and external validations by comparing the actual AH to the calculated AH established by this model and to update it.<h4>Methods</h4>The original formula, calculated AH (cm) = 2.21 (height at initial evaluation, SD) + 2.32 (target height, SD) - 1.83 (luteinizing hormone/follicle-stimu ...[more]

PMID: 30300409

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Project description:BackgroundRecent studies demonstrated that changes in DNA methylation (DNAm) and inactivation of two imprinted genes (MKRN3 and DLK1) alter the onset of female puberty. We aimed to investigate the association of DNAm profiling with the timing of human puberty analyzing the genome-wide DNAm patterns of peripheral blood leukocytes from ten female patients with central precocious puberty (CPP) and 33 healthy girls (15 pre- and 18 post-pubertal). For this purpose, we performed comparisons between the groups: pre- versus post-pubertal, CPP versus pre-pubertal, and CPP versus post-pubertal.ResultsAnalyzing the methylome changes associated with normal puberty, we identified 120 differentially methylated regions (DMRs) when comparing pre- and post-pubertal healthy girls. Most of these DMRs were hypermethylated in the pubertal group (99%) and located on the X chromosome (74%). Only one genomic region, containing the promoter of ZFP57, was hypomethylated in the pubertal group. ZFP57 is a transcriptional repressor required for both methylation and imprinting of multiple genomic loci. ZFP57 expression in the hypothalamus of female rhesus monkeys increased during peripubertal development, suggesting enhanced repression of downstream ZFP57 target genes. Fourteen other zinc finger (ZNF) genes were related to the hypermethylated DMRs at normal puberty. Analyzing the methylome changes associated with CPP, we demonstrated that the patients with CPP exhibited more hypermethylated CpG sites compared to both pre-pubertal (81%) and pubertal (89%) controls. Forty-eight ZNF genes were identified as having hypermethylated CpG sites in CPP.ConclusionMethylome profiling of girls at normal and precocious puberty revealed a widespread pattern of DNA hypermethylation, indicating that the pubertal process in humans is associated with specific changes in epigenetically driven regulatory control. Moreover, changes in methylation of several ZNF genes appear to be a distinct epigenetic modification underlying the initiation of human puberty.

Project description:OBJECTIVE:To compare the serum inhibin B, anti-Müllerian hormone (AMH) and leptin concentrations in girls with idiopathic central precocious puberty (CPP) to their concomitant characteristics and evaluate the capacity of each of these hormones to predict the age at first menstruation in those who were untreated and who completed their puberty. METHODS:This single-center study included 94 girls selected from a cohort of 493 girls seen between 1981 and 2012 and diagnosed with idiopathic CPP for whom a remaining serum sample collected at the initial evaluation was available. Of these 25 were untreated and completed their puberty. RESULTS- CORRELATIONS AT INITIAL EVALUATION:In the whole cohort the inhibin B concentration displayed significant positive correlations with the age at the onset of puberty and at initial evaluation; bone age; breast Tanner stage; serum basal estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and AMH concentrations, LH peak and LH/FSH peak ratio. The AMH concentration displayed a significant positive correlation with serum estradiol and a negative correlation with basal FSH concentration. The leptin concentration displayed significant positive correlations with the age at initial evaluation, bone age, and body mass index and a negative correlation with the FSH peak. RESULTS- PREDICTION OF AGE AT FIRST MENSTRUATION:In 25 untreated girls, the inhibin B concentration was negatively correlated with the age at first menstruation (r = -0.61, p = 0.001) and the time between the onset of puberty and first menstruation (r = -0.59, p = 0.002). Inhibin B concentrations <30 pg/mL were associated with a time between the onset of puberty and first menstruation ?3 years in 14/15 patients with a sensitivity of 0.67 and a specificity of 0.75. The age at first menstruation was estimated using a formula: min (11.15-0.510 LH/FSH peak ratio, 11.57-0.025 inhibin B)available at: http://www.kamick.org/lemaire/med/girls-cpp18.html. CONCLUSION:We established formulas based on the serum inhibin B concentrations and LH/FSH peak ratio at the initial evaluation, alone or in combination, to predict the age at first menstruation in girls with CPP. These formulas can assist with determining the indications for treatment in CPP.

Dataset Information

A mathematical model for predicting the adult height of girls with idiopathic central precocious puberty: A European validation.

Background

Objective

Methods

Results

Conclusion

Publications

A mathematical model for predicting the adult height of girls with idiopathic central precocious puberty: A European validation.

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