Trends in the Incidence of central precocious puberty and normal variant puberty among children in denmark, 1998 to 2017

BACKGROUND Central precocious puberty (CPP) in girls seriously affects their physical and mental development in childhood. The method of diagnosis—gonadotropin-releasing hormone (GnRH)–stimulation test or GnRH analogue (GnRHa)–stimulation test—is expensive and makes patients uncomfortable due to the need for repeated blood sampling. OBJECTIVE We aimed to combine multiple CPP–related features and construct machine learning models to predict response to the GnRHa-stimulation test. METHODS In this retrospective study, we analyzed clinical and laboratory data of 1757 girls who underwent a GnRHa test in order to develop XGBoost and random forest classifiers for prediction of response to the GnRHa test. The local interpretable model-agnostic explanations (LIME) algorithm was used with the black-box classifiers to increase their interpretability. We measured sensitivity, specificity, and area under receiver operating characteristic (AUC) of the models. RESULTS Both the XGBoost and random forest models achieved good performance in distinguishing between positive and negative responses, with the AUC ranging from 0.88 to 0.90, sensitivity ranging from 77.91% to 77.94%, and specificity ranging from 84.32% to 87.66%. Basal serum luteinizing hormone, follicle-stimulating hormone, and insulin-like growth factor-I levels were found to be the three most important factors. In the interpretable models of LIME, the abovementioned variables made high contributions to the prediction probability. CONCLUSIONS The prediction models we developed can help diagnose CPP and may be used as a prescreening tool before the GnRHa-stimulation test.

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Clinical characteristics and treatment patterns with histrelin acetate subcutaneous implants vs. leuprolide injections in children with precocious puberty: a real-world study using a US claims database

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0721 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Lawrence A. Silverman ◽

Xu Han ◽

Huan Huang ◽

Aimee M. Near ◽

Yiqun Hu

Keyword(s):

Precocious Puberty ◽

Central Precocious Puberty ◽

Treatment Costs ◽

Interquartile Range ◽

Duration Of Treatment ◽

Claims Database ◽

Total Treatment ◽

Patient Groups ◽

Hormone Analogs ◽

Index Treatment

Abstract Objectives Gonadotropin-releasing hormone analogs are the treatment of choice for central precocious puberty (CPP). This study characterizes patients treated with histrelin implant or leuprolide injection. Methods A US claims database was used to identify patients aged ≤20 years with ≥1 histrelin or leuprolide claim (index treatment) between April 2010 and November 2017 and continuous enrollment ≥3 months before and ≥12 months after the index treatment date. Results Overall, 4,217 patients (histrelin, n=1,001; leuprolide, n=3,216) were identified. The percentage of patients with CPP diagnosis was greater in the histrelin (96.5%) vs. leuprolide (68.8%; p<0.0001) cohort. In patients with CPP (histrelin, n=966; leuprolide, n=2,214), mean age at treatment initiation was similar for histrelin (9.0 ± 2.0 years) and leuprolide (9.1 ± 2.3 years), with >50% of patients aged 6–9 years. Mean treatment duration was significantly longer for histrelin (26.7 ± 14.8 months) vs. leuprolide (14.1 ± 12.1 months; p<0.0001), and was longer in younger patient groups. More patients switched from leuprolide to histrelin (12.3%) than vice versa (3.6%; p<0.0001). Median annual total treatment costs were slightly lower for the histrelin cohort ($23,071 [interquartile range, $16,833–$31,050]) than the leuprolide cohort ($27,021 [interquartile range, $18,314–$34,995]; p<0.0001). Conclusions Patients with CPP treated with histrelin had a longer duration of treatment, lower rates of index treatment discontinuation, and lower annual treatment costs vs. those treated with leuprolide.

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Central precocious puberty in a girl with LEGIUS syndrome: an accidental association?

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01004-9 ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Valentina Orlandi ◽

Paolo Cavarzere ◽

Laura Palma ◽

Rossella Gaudino ◽

Franco Antoniazzi

Keyword(s):

Genetic Analysis ◽

Precocious Puberty ◽

Central Precocious Puberty ◽

Neurofibromatosis Type ◽

Case Presentation ◽

New Variant ◽

Legius Syndrome ◽

Timing Of Puberty ◽

First Time

Abstract Background Central precocious puberty is a condition characterized by precocious activation of the hypothalamic-pituitary-gonadal axis. It may be idiopathic or secondary to organic causes, including syndromes such as Neurofibromatosis type 1 (NF1). Case presentation We presented a girl of 6 years and 10 months with almost 11 café-au-lait skin macules, without other clinical or radiological signs typical of NF1, and with a central precocious puberty. Genetic analysis evidenced the new variant NM-152594.2:c.304delAp. (Thr102Argfs*19) in SPRED1 gene, which allowed to diagnose Legius syndrome. Conclusions We report for the first time a case of central precocious puberty in a girl with Legius syndrome. The presence of central precocious puberty in a child with characteristic café-au-lait macules should suggest pediatricians to perform genetic analysis in order to reach a definitive diagnosis. Further studies on timing of puberty in patients with RASopathies are needed to better elucidate if this clinical association is casual or secondary to their clinical condition.

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