Association between dietary behavior and puberty in girls.

INTRODUCTION: Over the decades the trends of early onset of puberty have been observed in children, particularly in girls. Research evidence has reported diet to be among the most important risk factors for puberty onset. This study evaluated the association between dietary behavior and puberty in girls. METHODS: We enrolled 201 girls with the main complaints of breast development as the cases at the Endocrine Department of Nanjing Children's Hospital. The cases were divided into breast development with central priming and breast development without central priming groups and were matched with 223 normal health girls with no breast development (control group). We used the modified Child Eating Behavior Questionnaire (CEBQ) to conduct a face-to-face interview about dietary behavior. Sample t-test or Mann Whitney U test or Chi-square test, the analysis of variance or Kruskal Wallis test, and least significant difference (LSD) were used to compare differences between the groups, Bonferroni was used to correct the p-value, and logistic regression was used to analyze risk factors for puberty onset. RESULTS: A total of 424 girls participated in this study, among them, 136 were cases with breast development with central priming, 65 were cases with breast development without central priming, and 223 were normal health girls with no breast development. Age of the participants ranged from 4.5 to 9.3 years. There were significant differences in food response (p < 0.001), dietary restriction (p < 0.001), frequencies of vegetable intake (χ2 = 8.856, p = 0.012), drinking milk (χ2 = 23.099, p = 0.001), and borderline statistical difference in a total score of unhealthy dietary behavior (p = 0.053) among the cases and controls. However, in the post hoc analysis, these dietary behaviors were significant differences between the girls with breast development with central priming and the control groups. Moreover, girls in the breast development with central priming group had significantly higher bone age (BA), uterine body length, ovarian volume, basal luteinizing hormone (LH), basal follicle-stimulating hormone (FSH), peak LH, peak FSH, estradiol (E2), and free triiodothyronine (FT3) compared to those in the breast development without central priming group. In the multivariate logistic regression, only uterine body length was associated with increased risk of breast development with central priming (OR = 1.516, 95%CI: 1.243-1.850). CONCLUSION: There were significant differences in dietary behaviors among girls with breast development with central priming and normal health girls with no breast development, and uterine body length was associated with an increasing risk of breast development with central priming among girls with breast development.

Case report: Development of central precocious puberty in a girl with late-diagnosed simple virilizing congenital adrenal hyperplasia complicated with Williams syndrome.

Congenital adrenal hyperplasia (CAH) and Williams Syndrome (WS; MIM # 194050) are distinct genetic conditions characterized by unique clinical features. 21-Hydroxylase deficiency (21-OHD; MIM #201910), the most common form of CAH, arises from mutations in the CYP21A2 gene, resulting in virilization of the external genitalia in affected females, early puberty in males, and short stature. Williams syndrome, caused by a microdeletion of 7q11.23, presents with distinctive facial features, intellectual disability, unique personality traits, early puberty, and short stature. This case report describe the clinical features of a 4-year-old girl referred due to progressive virilization and developmental delay. Genetic analysis confirmed concurrent CAH and WS, identifying a novel mutation in the CYP21A2 gene (c.1442T>C). Following corticosteroid therapy initiation, the patient developed central precocious puberty. This case report delves into the pubertal change patterns in a patient affected by overlapping genetic conditions, providing valuable insights in to the intricate clinical manifestation and management of these rare complex disorders.

Premature Pubarche: A Pragmatic Approach.

Premature pubarche (PP) is a common and usually benign variant of normal puberty most often seen in 5-year-old to 9-year-old children. Some providers routinely order laboratory testing and a bone age to try to rule out other diagnoses including nonclassic congenital adrenal hyperplasia and gonadal or adrenal tumors. I review the natural history of PP and studies which suggest that without clinical features such as rapid growth and progression or genital enlargement, it is unlikely that a treatable condition will be found. Therefore it is recommended that patients with PP not undergo testing unless there are red flags at the time of the initial visit.

Diagnosis, Treatment, and Outcomes of Males with Central Precocious Puberty.

Central precocious puberty (CPP) among males is less frequent than among females but more likely to have an underlying pathologic cause. Diagnosis of CPP is often straightforward among males because increased testicular volume, the first sign of puberty, can be verified although careful central nervous system (CNS) assessment is generally necessary. Treatment with gonadotropin-releasing hormone agonist (GnRHa) is indicated, given in conjunction with any therapy needed for CNS lesions. Monitoring of treatment usually can consist of evaluating growth and physical puberty and with testosterone levels as the only lab data. Short-term and long-term outcome data indicate efficacy and safety, although data are limited. Such data need to be reported.

Isolated Vaginal Bleeding Before the Onset of Puberty.

Isolated vaginal bleeding before the onset of puberty is a rare presentation of isosexual precocity. In most cases, isolated vaginal bleeding without an abnormal genital examination is self-limited with resolution usually within 1 to 3 episodes. Watchful waiting is appropriate in most patients who do not have persistent bleeding, other signs of puberty, or signs/symptoms of an underlying etiology. Workup for patients with concerning features may include puberty hormone levels and/or transabdominal and transperineal ultrasound.

Heterozygous gain of function variant in GUCY1A2 may cause autonomous ovarian hyperfunction.

PURPOSE: The purpose of this study was to characterize the phenotype associated with a de novo gain-of-function variant in the GUCY1A2 gene. METHODS: An individual carrying the de novo heterozygous variant c.1458G>T p.(E486D) in GUCY1A2 was identified by exome sequencing. The effect of the corresponding enzyme variant α2E486D/ß1 was evaluated using concentration-response measurements with wild-type enzyme and the variant in cytosolic fractions of HEK293 cells, UV-vis absorbance spectra of the corresponding purified enzymes, and examination of overexpressed fluorescent protein-tagged constructs by confocal laser scanning microscopy. RESULTS: The patient presented with precocious peripheral puberty resembling the autonomous ovarian puberty seen in McCune-Albright syndrome. Additionally, the patient displayed severe intellectual disability. In vitro activity assays revealed an increased nitric oxide affinity for the mutant enzyme. The response to carbon monoxide was unchanged, while thermostability was decreased compared to wild type. Heme content, susceptibility to oxidation, and subcellular localization upon overexpression were unchanged. CONCLUSION: Our data define a syndromic autonomous ovarian puberty likely due to the activating allele p.(E486D) in GUCY1A2 leading to an increase in cGMP. The overlap with the ovarian symptoms of McCune-Albright syndrome suggests an impact of this cGMP increase on the cAMP pathway in the ovary. Additional cases will be needed to ensure a causal link.

Females with Breast Development before Three Years of Age.

Breast development in a girl 3 years of age or younger is a commonly encountered scenario. Nearly all of these cases will either regress or fail to progress during follow-up, confirming a diagnosis of premature thelarche (PT). Studies show that these girls will have onset of true puberty and menses at a normal age. The authors present evidence that laboratory testing, particularly basal and gonadotropin hormone-releasing hormone -stimulated gonadotropin levels, will show overlap between girls with PT and the rare patients with the onset of central precocious puberty before age 3, mainly of whom have hypothalamic hamartomas.

Congenital adrenal hyperplasia complicated by gonadotropin-dependent precocious puberty.

Precocious puberty, characterised by the early appearance of secondary sexual characteristics, poses challenges in diagnosis and management. Here, we describe a case of precocious puberty diagnosed in a boy in middle childhood, who presented with progressive phallus enlargement, pubic hair development and increased aggressive behaviour. Hormonal evaluation confirmed the diagnosis of congenital adrenal hyperplasia (CAH), complicated by gonadotropin-dependent precocious puberty. The case highlights the importance of assessment of testicular volume in a patient presenting with precocious puberty. Symmetrical testicular enlargement in a patient with CAH suggests premature activation of the hypothalamic-pituitary-gonadal axis. The patient received glucocorticoid therapy to suppress androgen production related to CAH and gonadotropin-releasing hormone analogue therapy to control premature activation of the hypothalamic-pituitary-gonadal axis. Follow-up visits showed regression of secondary sexual characteristics and improved growth velocity.

The effect of gonadoliberin analog treatment in precocious puberty on polycystic ovarian syndrome prevalence in adulthood.

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 long-term follow-up focused on screening for PCOS would seem beneficial.

Swedish cohort study found that half of the girls with shunted hydrocephalus had precocious or early puberty.

AIM: We aimed to evaluate the occurrence of, and risk factors for precocious and early puberty in a retrospective cohort study of girls with shunted infantile hydrocephalus. METHODS: The study population comprised 82 girls with infantile hydrocephalus, born between 1980 and 2002, and treated with a ventriculoperitoneal shunt. Data were available for 39 girls with myelomeningocele and 34 without. Medical records were analysed regarding clinical data and timing of puberty. Precocious and early puberty was defined as the appearance of pubertal signs before 8 years and 0 months and 8 years and 9 months, respectively. RESULTS: Median age at last admission was 15.8 years (range 10.0-18.0). In total, 15 girls (21%) had precocious puberty, and another 21 (29%) had early puberty. Three or more shunt revisions had been performed in 26/36 girls with early or precocious puberty and in 3/37 girls without (p = 0.01). The number of shunt revisions correlated negatively with age at the start of puberty in the girls with myelomeningocele (Spearman's correlation coefficient = -0.512, p = 0.001). CONCLUSION: Girls with shunted infantile hydrocephalus have a high risk of precocious or early puberty. Repeated shunt revisions seemed to be associated with early puberty.

Effects of the COVID-19 pandemic on the incidence of central precocious puberty; a narrative review.

Central precocious puberty (CPP) is the premature activation of the hypothalamus-pituitary-gonadal axis, resulting in the early development of secondary sexual characteristics. CPP classically occurs before the age of 8 years in girls and 9 years in boys. The aetiology of this precocious onset of puberty is governed by complex mechanistic interactions between genetic and environmental factors. The rates of CPP have been documented to have been rising before the COVID-19 pandemic; despite this, the incidence of CPP has increased exponentially since the start of the pandemic. There are multiple theories potentially explaining this change in incidence of CPP over COVID-19. These include the direct effect of SARS-coV-2 infection, increasing body mass index of adolescents over sequential lockdowns, changes in sleep patterns, increased use of electronic devices and levels of stress, and additionally potential earlier detection of signs of CPP by parents and carers. Whilst there is evidence from observational cohorts, case studies and animal models for each of these factors, it is difficult to definitively prove which has had the greatest impact due to the mainly retrospective nature of the human research that has been conducted. Moreover, studies set in diverse settings with varying population make comparison complex. Additionally, each country responded differently to the COVID-19 pandemic and the lockdowns varied between locations, hence the effect of lockdown was not equal or universal. Despite this, similar trends have been identified, with various lifestyle changes that occurred over the pandemic being potentially influential factors on the development of CPP.

Long-term health consequences of central precocious/early puberty (CPP) and treatment with Gn-RH analogue: a short update.

BACKGROUND: The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to comprehensively analyze and summarize research articles to elucidate the potential link between precocious or early pubertal onset (CPP) and crucial health factors. METHODS: We conducted a systematic review of studies published from -January 2000 to March 2023, sourced from databases of Medline, PubMed, Google Scholar and Web of Science. We assessed the relationship between CPP and final adult height (FHt), bone health, reproductive function, body mass index, metabolic and cardiovascular abnormalities, and increased cancer risk. RESULTS: Upon reviewing and analyzing selected studies, the following key findings emerged: (a) treating CPP in girls before age 6-7 and in boys before age 9 improves FHt; (b) bone mineral density (BMD) decreases during GnRHa treatment but normalizes afterward, with no lasting effects on peak bone mass during puberty; (c) GnRH treatment does not negatively affect menstrual cycles; however, untreated CPP increases the risk of premature or early-onset menopause; (d) the incidence of PCOS/hyperandrogenemia may be slightly elevated in women with a history of CPP, but overall reproductive function remains largely unaffected; (e) earlier thelarche and menarche may enhance susceptibility to breast carcinogenesis; (f) CPP contributes to an increased risk of obesity and type 2 diabetes in both genders; (g) early menarche may slightly increase the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk of depression and anxiety disorders. CONCLUSION: Monitoring and early diagnosis of these conditions are of paramount importance for successful management.

[McCune-Albright syndrome: a case report and literature review]. / Syndrome de McCune-Albright : à propos d'un cas et revue de la littérature.

McCune-Albright syndrome is an inherited disease characterized by the association of fibrous dystrophy of bone, café-au-lait skin spots and precocious puberty revealing endocrine hyperactivity. Genetically, this disease is due to a mutation of the Gs protein responsible for activation of adenylate cyclase with excessive production of cAMP. The particular morphology of café-au-lait spots should suggest early diagnosis. Its treatment depends on the endocrinopathy from which the patient suffers and the extent of the fibrous dysplasia. Bisphosphonates have proven their effectiveness on bone pain and the limitation of fibrous dysplasia. Surgery retains its place in complicated forms. We report a rare case of McCune-Albright syndrome complicated by a femur fracture in a 12-year-old girl and we discuss the clinical and paraclinical characteristics of this pathological entity.

Central precocious puberty secondary to peripheral precocious puberty due to a pineal germ cell tumor: a case and review of literature.

BACKGROUND: The pineal lesion affecting melatonin is a rare cause of central precocious puberty by decreasing the inhibition of hypothalamic-pituitary-gonadal axis. Germ cell tumor secreting human chorionic gonadotropin is a rare cause of peripheral puberty. CASE PRESENTATION: A 5.8-year-old male presented facial hair and phallic growth, deepened voice, and accelerated growth velocity for 6 months. The elevated human chorionic gonadotropin level with undetectable gonadotropin levels indicated peripheral precocious puberty. Brain imaging revealed a pineal mass and further pathology indicated the diagnosis of teratoma. During chemoradiotherapy with operation, the elevated human chorionic gonadotropin level reduced to normal range, while the levels of gonadotropins and testosterone increased. Subsequently, progressing precocious puberty was arrested with gonadotrophin-releasing hormone analog therapy. Previous cases of transition from peripheral precocious puberty to central precocious puberty were reviewed. The transitions were caused by the suddenly reduced feedback inhibition of sex steroid hormones on gonadotropin releasing hormone and gonadotropins. CONCLUSIONS: For patients with human chorionic gonadotropin-secreting tumors, gonadotropin levels increase prior to sex steroid decrease, seems a sign of melatonin-related central PP related to melatonin.

Metabolic/endocrine disorders in survivors of childhood-onset and cranial radiotherapy- treated ALL/NHL: a meta-analysis.

BACKGROUND: Cranial radiotherapy (CRT) is recommended to high-risk pediatric patients with acute lymphoblastic leukemia or aggressive non-Hodgkin's lymphoma (ALL/NHL). However, effects of CRT treatment on the development of metabolic/endocrine disorders remain unclear. This meta-analysis aimed to identify metabolic and endocrine disturbances in survivors of childhood-onset and CRT-treated ALL/NHL. METHODS: Different online databases were searched using restricted search fields. Follow-up data and outcome measurements, including the prevalence of growth hormone (GH) deficiency, hypothyroidism, vitamin D deficiency, overweight/obesity, and hypogonadism were recorded. The height data was indicated by height-standard deviation score (height-SDS). Statistical estimates such as odds ratio (OR) and weighted standard mean difference (SMD) were compared between additional CRT treatment group and non-CRT treatment group. Study-to-study heterogeneity was calculated by calculating I-squared statistic, and fixed/random effect was applied to synthesize and analyze extracted data. RESULTS: Fifteen studies were included (4269 patients in total). Adult height SDS was lower in CRT-treated patients (pooled SMD = -0.581, 95% CI: -0.649--0.512), and CRT-treated patients were likely to develop short stature (pooled OR = 2.289, 95% CI:1.674-3.130). Regardless of the study year, which potentially reflects the state-of-the-art CRT technique, the prevalence of short stature and GH deficiency was time-independent. Additionally, previous CRT can increase the risk of precocious puberty (pooled OR = 2.937, 95% CI: 1.281-6.736), hypothyroidism (pooled OR = 2.057, 95% CI:1.510-2.801), and hypogonadism (pooled OR = 3.098, 95% CI:2.521-3.807). However, the risk of being overweight/obese was similar between the patients with and without CRT (pooled OR = 1.278, 95% CI: 0.675-2.421). CONCLUSION: Childhood-onset and CRT-treated ALL/NHL survivors are likely to have shorter height, precocious puberty, hypothyroidism, and hypogonadism.

Premature pubarche during minipuberty - literature review and two case reports.

INTRODUCTION: Isolated premature pubarche (PP) in infancy may be the reason for many diagnostic difficulties. This is due to the low incidence and, therefore, the limited number of studies on this subject and the lack of strict laboratory standards because of the physiological variability of gonadotropic hormone and androgen concentrations during minipuberty. MATERIAL AND METHODS: We aimed to present current knowledge about PP in infancy based on the literature review and 2 cases of male infants with scrotal hair during minipuberty. RESULTS: Isolated hair in the pubic region in a boy during the period of minipuberty requires differential diagnosis. After excluding serious aetiology, it seems to be a mild, self-limiting variant of precocious puberty. The phenomenon is probably a result of increased sensitivity of the hair follicles to transiently increased androgen concentration. CONCLUSIONS: Isolated pubic hair in infancy as a mild, self-limiting variant of precocious puberty in infants should be a diagnosis of exclusion. The condition resolves spontaneously, but it absolutely requires further follow-up to exclude serious aetiology in the case of puberty progression.

Analysis of risk factors of precocious puberty in children.

BACKGROUND: The purpose of this study is to explore the related factors of precocious puberty in children. METHODS: 1239 children who underwent physical examination in our hospital from January 2020 to December 2022 were analyzed, including 198 precocious children and 1041 normal children. According to the age of 198 precocious children and 1041 normal children, 205 normal children were selected, and the remaining 836 normal children were excluded. They were divided into precocious group and normal group. The general data of the two groups were recorded. Logistic regression was used to analyze the influencing factors of precocious puberty in children. RESULTS: There were statistically significant differences (P < 0.05) between the two groups in sex, bone age, daily exercise time, E2, FSH, LH, leptin, mother's menarche time, living environment, consumption of nutritional supplements, consumption of foods containing pigments and preservatives, consumption of high-protein foods, and sleeping time. The multifactor logistic regression analysis shows that the risk factors of children's precocious puberty included gender (female), bone age (> 10 years old), and daily exercise time (< 0.9 h), E2 (≥ 66.00pmol/L), FSH (≥ 6.00U/L), LH (≥ 3.50U/L), leptin (≥ 8.00 µ G/L), mother's menarche time (< 12 years old), living environment (chemical industry zone), consumption of nutritional supplements (often), consumption of high-protein food (often), and sleep time (< 10 h). CONCLUSION: In conclusion, children's gender, bone age, exercise habits, E2, FSH, LH, leptin, mother's menarche time, living environment, eating habits, sleep time and other factors are closely related to precocious puberty in children. Reminding parents to actively prevent related factors in clinical work is helpful to prevent the occurrence of precocious puberty in children.

Precocious puberty in patients with Pompe disease.

Introduction: The life expectancy of Pompe disease patients has increased due to improved neonatal screening and enzyme replacement therapy. Nevertheless, the potential effect of frequent medical device exposure on pubertal development in these patients is not well understood, so further investigation is warranted. Methods: In this cross-sectional study, we assessed the growth and puberty of nine Pompe disease patients. In addition, to determine the effects of frequent plastic medical device exposure in these patients, we measured urinary phthalate metabolites before and one day after enzyme replacement therapy. Results: Five out of nine patients (55%) with Pompe disease on enzyme replacement therapy had precocious puberty. Patients with precocious puberty had significantly shorter predicted adult heights compared to those with normal puberty (p = 0.014). The levels of mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) increased after enzyme replacement therapy, but the average levels of phthalate metabolites did not significantly differ between patients with normal and precocious puberty. Conclusion: Pompe disease patients on enzyme replacement therapy tend to have precocious puberty, which may reduce their adult height. There are no significant differences in urinary phthalate metabolites between normal and precocious puberty patients. Regular follow-up of growth and puberty in Pompe disease patients is important to improve their health outcomes.

Clinical Review: Prepubertal Bleeding.

BACKGROUND: Prepubertal bleeding is a common presentation in the pediatric office and can be distressing for patients and families. A comprehensive approach to diagnosis and management allows clinicians to identify patients at risk for worrisome pathology and arrange timely care. OBJECTIVE: We aimed to review the key features of clinical history, physical exam, and diagnostic workup of a child presenting with prepubertal bleeding. We reviewed potential pathologies requiring urgent investigations and management, such as precocious puberty and malignancy, as well as more common etiologies, including foreign bodies and vulvovaginitis. CONCLUSION: Clinicians should approach each patient with the goal of excluding diagnoses that require urgent interventions. A thoughtful clinical history and physical exam can inform appropriate investigations to optimize patient care.