Diagnosis and management of precocious sexual maturation: an updated review

Cheuiche, Amanda Veiga; Silveira, Letícia Guimarães da; Paula, Leila Cristina Pedroso de; Lucena, Iara Regina Siqueira; Silveiro, Sandra Pinho

doi:10.1007/s00431-021-04022-1

Cited by 100 publications

(83 citation statements)

References 141 publications

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“…Precocious puberty (PP) is defined as is the onset of secondary sexual attributes before the age of 8 years in girls and 9 years in boys. PP is categorized either as Central PP (CPP), when premature maturation of the hypothalamic-pituitary-gonadal axis is present or as Peripheral PP (PPP), when an excessive secretion of sex hormones is recorded, regardless of gonadotropin secretion [ 3 ]. The prevalence of PP is not well-documented.…”

Section: Introductionmentioning

confidence: 99%

Diet-Induced Hypothalamic Inflammation, Phoenixin, and Subsequent Precocious Puberty

et al. 2021

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Recent studies have shown a rise in precocious puberty, especially in girls. At the same time, childhood obesity due to overnutrition and energy imbalance is rising too. Nutrition and fertility are currently facing major challenges in our societies, and are interconnected. Studies have shown that high-fat and/or high-glycaemic-index diet can cause hypothalamic inflammation and microglial activation. Molecular and animal studies reveal that microglial activation seems to produce and activate prostaglandins, neurotrophic factors activating GnRH (gonadotropin-releasing hormone expressing neurons), thus initiating precocious puberty. GnRH neurons’ mechanisms of excitability are not well understood. In this review, we study the phenomenon of the rise of precocious puberty, we examine the physiology of GnRH neurons, and we review the recent literature regarding the pathophysiological mechanisms that connect diet-induced hypothalamic inflammation and diet-induced phoenixin regulation with precocious puberty.

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Section: Introductionmentioning

confidence: 99%

Diet-Induced Hypothalamic Inflammation, Phoenixin, and Subsequent Precocious Puberty

et al. 2021

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“…Some studies have reported that there was a high correlation between the secondary sexual characteristics and bone age or bone maturation state in children and adolescents (6)(7)(8)(9). Testing of secondary sexual characteristics is relatively simple and feasible compared to X-ray photography; thus, it is worth exploring whether those characteristics can be used to predict bone age, so as to evaluate the BDS in children and adolescents.…”

Section: Introductionmentioning

confidence: 99%

Nomogram for Predicting Bone Development State of Female Children and Adolescents–A Fast Screening Approach Based on Pubes Stages for Growth and Development

Yang

Wang

Wu³

et al. 2021

Front. Pediatr.

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Objective: To develop a nomogram for predicting bone development state (BDS) of female children and adolescents in a large scale.Methods: Four hundred forty-seven female students were designated as the training cohort to develop the predictive model, whereas 196 female students were used as the validation cohort to verify the established model. Bone age, height, body mass, body fat percentage, and secondary sexual characteristics were recorded, and BDS was determined with the chronological age and bone age. Multivariate logistic regression was conducted to determine the factors, and nomogram was developed and validated with the training and validation cohorts, respectively.Results: One hundred forty-seven female students were identified as BDS abnormal in the training cohort (32.9%), and 104 were determined in the validation cohort (53.1%). Age, height, weight, and pubes stage were selected for the predictive model. A nomogram was developed and showed a good estimation, with a C-index of 0.78 and a good calibration in the training cohort. Application of the nomogram to the validation cohort showed a similar C-index of 0.75 and a good calibration.Conclusion: A nomogram for predicting bone development was developed, which can provide a relatively good estimation of BDS for female children and adolescents in Chinese metropolis.

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“…PUBERTY is a biologically complex process during which individuals acquire secondary sexual characteristics and reproductive capacity [1,2]. Precocious puberty (PP) is defined as the earlier progression of this process in both boys and girls at a chronological age earlier than the lower limit of the reference age in the general population to which they belong [1,2], and it is divided into two types: gonadotropin-dependent and -independent PP [2]. Gonadotropin-dependent PP is caused by the premature maturation of the hypothalamus-pituitary-gonadal axis and is responsible for the majority of PP cases, particularly in girls [1,2].…”

mentioning

confidence: 99%

“…Precocious puberty (PP) is defined as the earlier progression of this process in both boys and girls at a chronological age earlier than the lower limit of the reference age in the general population to which they belong [1,2], and it is divided into two types: gonadotropin-dependent and -independent PP [2]. Gonadotropin-dependent PP is caused by the premature maturation of the hypothalamus-pituitary-gonadal axis and is responsible for the majority of PP cases, particularly in girls [1,2].…”

mentioning

confidence: 99%

“…In contrast to gonadotropin-dependent PP, gonadotropinindependent PP, in which sex steroids are excessively produced independent of gonadotropin secretion, is less common and may be associated with tumors including androgen-producing adrenal tumors and Leydig cell tumors. Beta-human chorionic gonadotropin (β-hCG)producing tumors have also been implicated in gonadotropin-independent PP due to their stimulation of testosterone production by Leydig cells [2]. Although germ cell tumors are the predominant cause of β-hCGproducing tumors, hepatoblastoma has also been shown to induce gonadotropin-independent PP by secreting β-hCG [3][4][5]; however, there is limited evidence to show that gonadotropin-independent PP is caused by β-hCGproducing tumors other than germ cell tumors or hepatoblastoma.…”

mentioning

confidence: 99%

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Beta-human chorionic gonadotropin-producing neuroblastoma: an unrecognized cause of gonadotropin-independent precocious puberty

et al. 2022

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The pathogenesis of gonadotropin-independent precocious puberty (PP) includes both congenital and acquired forms, the latter of which may be associated with neoplasms, such as sex-steroid hormone-producing tumors. Beta-human chorionic gonadotropin (β-hCG)-producing tumors also cause gonadotropin-independent PP by stimulating the production of testosterone in Leydig cells. Germ cell tumors and hepatoblastoma both produce β-hCG; however, there is limited evidence to show that gonadotropin-independent PP is caused by other β-hCG-producing tumors. We herein report the first case of β-hCG-producing neuroblastoma associated with the development of gonadotropin-independent PP. A 2-year-old boy presented with an increased penile length, enlargement of the testes, pigmentation of the external genitalia, and growth acceleration. Imaging, blood, and urinary examinations revealed the presence of neuroblastoma in the right adrenal region. Decreased levels of luteinizing hormone and follicle-stimulating hormone with an increased testosterone level were indicative of gonadotropin-independent PP. Since serum β-hCG was elevated, β-hCG-producing neuroblastoma was suspected. Histological findings of the resected tumor were compatible with neuroblastoma. An immunohistochemical analysis using serial sections revealed staining for β-hCG in synaptophysin-positive cells. Furthermore, immunofluorescence showed the co-staining of β-hCG with neuron-specific enolase. These results suggested that β-hCG was produced by tumor cells. Surgical removal of the tumor promptly normalized serum β-hCG and testosterone levels. In conclusion, we propose the addition of neuroblastoma to the list of differential diagnoses of gonadotropin-independent PP with β-hCG positivity in serum that includes germ cell tumors and hepatoblastoma.

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Diagnosis and management of precocious sexual maturation: an updated review

Cited by 100 publications

References 141 publications

Diet-Induced Hypothalamic Inflammation, Phoenixin, and Subsequent Precocious Puberty

Diet-Induced Hypothalamic Inflammation, Phoenixin, and Subsequent Precocious Puberty

Nomogram for Predicting Bone Development State of Female Children and Adolescents–A Fast Screening Approach Based on Pubes Stages for Growth and Development

Beta-human chorionic gonadotropin-producing neuroblastoma: an unrecognized cause of gonadotropin-independent precocious puberty

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