Associations of central precocious puberty with blood pressure trajectories: prospective cohort study.

BACKGROUND: Sex differences in blood pressure (BP) appear during childhood and adolescence, but the role of central precocious puberty (CPP) remains unclear. In this study, we aimed to examine the association of CPP with the risk of early hypertension and BP trajectories in girls and boys. METHODS: We analyzed trajectories of BP before and after puberty in girls aged 6-13 years (n = 305) and boys aged 10-15 years (n = 153) in the Taiwan Pubertal Longitudinal Study. The timing of puberty onset was defined as the month at which the children reached Tanner stage 2. We examined the association of CPP with the risk of early hypertension and BP trajectories before and after puberty onset. RESULTS: Among boys, CPP was found to be associated with early hypertension (odds ratio, 7.45 [95% CI, 1.15-48.06]), whereas no such association was observed among girls. Boys with CPP had higher systolic BP than did those with normal puberty onset before puberty onset (mean difference, 6.51 [95% CI, 0.58-12.43]) and after puberty onset (mean difference, 8.92 [95% CI, 8.58-15.26]). CONCLUSION: A large proportion of the higher systolic BP observed in boys with CPP compared with in those with normal puberty onset is accrued after puberty. IMPACT: We examined the sex-specific association of central precocious puberty with blood pressure trajectories to better understand whether central precocious puberty was associated with early hypertension. Central precocious puberty was associated with differences in systolic blood pressure trajectories, especially after puberty onset in boys. For boys only, central precocious puberty was associated with early hypertension. A large proportion of the higher systolic blood pressure observed in boys with central precocious puberty compared with in those with normal puberty onset was accrued after puberty. Interventions targeting central precocious puberty are likely to influence systolic blood pressure in early adulthood.

Congenital Adrenal Hyperplasia.

We describe congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, which is the most common primary adrenal insufficiency in children and adolescents. In this comprehensive review of CAH, we describe presentations at different life stages depending on disease severity. CAH is characterized by androgen excess secondary to impaired steroidogenesis in the adrenal glands. Diagnosis of CAH is most common during infancy with elevated 17-hydroxyprogesterone levels on the newborn screen in the United States. However, CAH can also present in childhood, with late-onset symptoms such as premature adrenarche, growth acceleration, hirsutism, and irregular menses. The growing child with CAH is treated with hydrocortisone for glucocorticoid replacement, along with increased stress doses for acute illness, trauma, and procedures. Mineralocorticoid and salt replacement may also be necessary. Although 21-hydroxylase deficiency is the most common type of CAH, there are other rare types, such as 11ß-hydroxylase and 3ß-hydroxysteroid dehydrogenase deficiency. In addition, classic CAH is associated with long-term comorbidities, including cardiometabolic risk factors, impaired cognitive function, adrenal rest tumors, and bone health effects. Overall, early identification and treatment of CAH is important for the pediatric patient.

Vaginal bleeding in children: A retrospective audit at a tertiary paediatric gynaecology service.

AIM: The aim of this study was to describe the clinical features and investigations of vaginal bleeding in prepubertal children. METHODS: We performed a retrospective case series of children under the age of 10 who presented with vaginal bleeding to our institution between 2018 and 2019. RESULTS: There were 32 cases identified during the timeframe, with a mean age of 5.5 years (standard deviation 3.2 years, range 5.5 days to 9.6 years). Vulvovaginitis was the most common diagnosis (n = 12, 37.5%), followed by precocious puberty (n = 5, 15.6%). Uncommon but serious causes were vaginal rhabdomyosarcoma (n = 1), and sexual abuse (one patient presenting with gonorrhoea and one with a non-accidental injury). Vaginoscopy was performed in nine patients (28.1%) for various reasons, and a vaginal foreign body was identified in two patients (6.3%). All the patients who had a serious cause of bleeding (neoplasm or sexual assault) or who required specific treatment (precocious puberty, lichen sclerosus, urethral prolapse) presented with red flags on history and/or examination: recurrent episodes of vaginal bleeding, heavy bleeding, associated general symptoms (poor feeding and growth), presence of thelarche, abdominal mass, associated profuse vaginal discharge and abnormal genital examination (skin changes, urethral prolapse or protruding mass from the vagina). CONCLUSIONS: A thorough history-taking and clinical examination aiming at identifying red flags may help to discriminate between benign causes of vaginal bleeding, where no further investigations are indicated, and alternative diagnoses with a poor outcome and/or requiring specific treatment and additional investigations.

Case 308: Van Wyk-Grumbach Syndrome.

HISTORY: An 11-year-old girl presented to the pediatric gastroenterology outpatient department of our institution with gradually increasing painless abdominal distention. The distention started 2 years earlier and was not associated with any other constitutional symptoms, vomiting, diarrhea, jaundice, hematemesis, or melaena. She reported early satiety and heaviness in the lower abdomen. The abdominal swelling was predominantly in the infraumbilical region and was soft at palpation. She was the first child of nonconsanguineous parents and had an uneventful perinatal course after a normal vaginal delivery. Her developmental milestones were normal. She had an average scholastic performance at school. There was no history of visual problems, seizures, or inappropriate behaviors. She had an early menarche 2 years previously. Her menstrual cycles were regular, and there was no abnormal vaginal discharge. Her breast development was normal (Tanner stage III), while pubic and axillary hair were absent (Tanner stage I). She was short for her age (104 cm; normal range, 120-154 cm). There was no history of short stature among her siblings or parents. Laboratory investigations were performed to measure thyroid-stimulating hormone (1354.34 µIU/mL; normal range, 0.35-5.5 µIU/mL), triiodothyronine (<2.5 ng/dL [0.0385 pmol/L]; normal range, 100-200 ng/dL [1.54-3.08 pmol/L]), thyroxine (1.35 µg/dL [17.37 nmol/L]; normal range, 5-12 µg/dL [64.35-154.44 nmol/L]), ß-human chorionic gonadotropin (<1.2 mIU/mL; normal, <5 mIU/mL), luteinizing hormone (0.08 mIU/mL; normal range, 0.1-6.0 mIU/mL), and follicle-stimulating hormone (6.93 mIU/mL; normal range, 0.3-2.0 mIU/mL) levels. Complete blood count was normal. An abdominal mass was suspected, and abdominopelvic CT was performed and followed by US; these examinations revealed multiple large cysts in both ovaries. The uterus was pubertal in shape, and endometrial thickness was 9 mm, representing normal follicular phase measurement. Serum CA-125 and inhibin levels were normal. To evaluate short stature, radiographs of the hand and pelvis were obtained as part of a limited skeletal survey, keeping in mind the possible skeletal changes associated with hypothyroidism. In view of the hypothyroidism, US of the neck was also performed. Treatment was started based on the clinical and radiologic parameters, and the child's condition improved with medical treatment.

Extent of Extraskeletal Manifestations of Fibrous Dysplasia/McCune-Albright Syndrome in Patients with Mazabraud's Syndrome.

Mazabraud's syndrome (MZB) is a rare condition in which fibrous dysplasia of bone/the McCune-Albright syndrome (FD/MAS) co-exists with intramuscular myxomas. Both FD and the myxomas harbor the GNAS-mutation. Recent studies have shown that extraskeletal, GNAS-related features are associated with a more severe phenotype of FD/MAS. However, patients with MZB are often only seen by orthopedic surgeons. We therefore evaluated MZB patients seen in tertiary referral centers from the Netherlands (LUMC), USA (National Institutes of Health) and France (INSERM UMR 1033 (Lyos), Hôpital Edouard Herriot). All FD/MAS patients known in these centers with an additional diagnosis of a myxoma were included. Demographic information and data on disease extent and extraskeletal manifestations of FD/MAS such as precocious puberty (PP) or café-au-lait patches (CAL) were retrieved from patient's medical records. Thirty MZB patients were included: 20 women (67%) and 10 men (33%). Patients received a diagnosis of MZB (median 42 years, range 16-19) significantly later than the diagnosis of FD/MAS (median 30 years, range 0-60), p < 0.01. Twenty-six patients were diagnosed with polyostotic disease (87%). In 97% the myxoma was located near the skeletal FD lesion. The combination of MZB and MAS was made in 13 patients in whom PP (n = 7), CAL (n = 7), GH-excess (n = 3) and hyperthyroidism (n = 3) were present. Other extraskeletal features were (multinodular) goiter (n = 2) and thyroid cysts (n = 1). Furthermore, in this cohort of patients with MZB several (pre-)malignant tumors were observed; ductal carcinoma in situ of the breast in 3 patients (10%), breast cancer in 1 patient (3.3%), intra pancreatic mucinous neoplasms in 3 patients (10%) and liver adenomas in 2 patients (6.6%). A total of 47% of patients with MZB had an additional extraskeletal feature such as an endocrinopathy. In MZB, 87% of patients suffer from polyostotic FD, 43% of patients have extraskeletal GNAS-features such as an hyperfunctioning endocrinopathy and 30% (pre-)malignant tumors. We therefore advocate that MZB patients should undergo a complete screening and long-term follow-up for extent of bone disease, but also extraskeletal GNAS features of FD/MAS.

New insights into precocious puberty and ADHD: a nationwide cohort study.

BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children; however, studies delineating the association between ADHD and central precocious puberty are limited. This study aimed to understand whether children with ADHD are at a higher risk of central precocious puberty. METHODS: This population-based retrospective cohort study was conducted using the National Health Insurance Research Database of Taiwan to investigate the association between ADHD and the incidence of central precocious puberty between 2000-2015. We identified ADHD individuals treated with methylphenidate, atomoxetine or not. The control cohort consisted of individuals without ADHD. The outcome measure was central precocious puberty diagnosis. RESULTS: Among 290,148 children (mean age: 5.83 years), central precocious puberty incidence was 4.24 and 1.95 per 105 person-years in the ADHD and control groups, respectively. Children with ADHD treated with medication had a higher risk than those without ADHD. However, medication use did not affect the incidence of central precocious puberty among children with ADHD. CONCLUSION: This study showed an association between ADHD and a higher risk of central precocious puberty. Early referral of children with ADHD to a pediatric endocrinologist for evaluation may facilitate correct diagnoses and early interventions. IMPACT: ADHD is associated with a higher risk of central precocious puberty. This study provides relevant findings, as it is the first nationwide, population-based cohort study to investigate the association between ADHD and the risk of central precocious puberty with a 15-year follow-up. Early referral of children with ADHD to a pediatric endocrinologist for the evaluation of suspected precocious puberty could facilitate correct diagnosis. Early intervention treatment with gonadotropin-releasing hormone agonist might improve final height in children with central precocious puberty.

[OPTIC DISC EDEMA IN McCUNE-ALBRIGHT SYNDROME].

INTRODUCTION: Craniofacial polyostotic fibrous dysplasia, as part of McCune-Albright syndrome, can have severe complications including vision loss. Also, patients with this syndrome are at greater risk of secondary intra-cranial pressure elevation due to medication side effects. BACKGROUND: : A 6-year-old girl with McCune-Albright syndrome and polyostotic craniofacial fibrous dysplasia and optic canal narrowing, developed signs of slowly progressive optic nerve compression on clinical examination including deteriorating visual acuity, positive relative afferent pupillary defect )RAPD) and bilateral optic disc swelling. Imaging using optical coherence tomography (OCT) revealed progressive retinal nerve fiber layer thickening. Prior to deterioration, the dose of triptorelin, a gonadotrophin-releasing hormone analogue, she was treated with for precocious puberty, was increased. Medication cessation was followed by improvement in clinical and imaging findings. CONCLUSIONS: : McCune-Albright syndrome patients with craniofacial involvement and/or gonadotrophin-releasing hormone analogue treatment should be monitored regularly for clinical signs of optic neuropathy together with routine OCT imaging.

Child-related and parental predictors for thelarche in a general population of girls: the PANIC study.

BACKGROUND: Obesity has been associated with earlier thelarche, whereas other predictors for it remain unclear. METHODS: We studied child-related and parental predictors for earlier thelarche in 195 girls aged 6-8 years followed up for 2 years. A physician evaluated breast development by inspection and palpation. Body fat percentage (BF%) was measured by dual-energy X-ray absorptiometry, diet by food records, and physical activity and sedentary time by body movement and heart rate monitors. Parental education, smoking, and alcohol consumption and household income were assessed by questionnaires. Gestational age, birth weight, and maternal prepregnancy BMI were obtained from hospital registers. Predictors for thelarche were examined using logistic regression analysis adjusted for age and follow-up time. RESULTS: The incidence of thelarche during 2 years increased by 11% (OR 1.11, CI 1.06-1.17, p < 0.001) for 1 unit increase in baseline BF%. Girls with a smoking parent had a 2.64 (95% CI 1.21-5.77, p = 0.015) times higher incidence of thelarche than other girls. The associations of lower parental education and higher maternal prepregnancy BMI with the higher incidence of thelarche were largely explained by BF%. Other possible predictors were not associated with thelarche. CONCLUSIONS: Higher BF% and exposure to tobacco smoke are independent predictors for earlier thelarche.

Body mass index growth trajectories, early pubertal maturation, and short stature.

BACKGROUND: Childhood body mass index (BMI) trajectory classes are rarely linked to early puberty risk, particularly among Chinese children. We estimated early puberty risk across BMI trajectory classes, investigated factors contributing to pubertal development, and examined differences in final adult height between children exhibiting early and nonearly pubertal maturation across the classes. METHODS: The Taiwan Children Health Study recruited 10-year-old children in 2010 from 14 Taiwanese communities and resurveyed them at age 11, 12, and 18 years. The study comprised 3109 children (50.4% boys) with available data for BMI (age 6-11 years) and pubertal stages (age 11, 12, and 18 years). RESULTS: Classes 1-4 were persistently healthy weight, rapid BMI growth, chronically overweight/obese, and early transient overweight/obese. Children in class 3 exhibited the highest risk of early pubertal maturation. Puberty genetic score, low sleep quality, and high fat-free mass collectively explained 15% of the variance in Tanner stages among class 3 children. Early pubertal maturation was considered to cause short and tall stature in boys and girls, respectively. CONCLUSIONS: Modifying sleep quality and fat-free mass may reduce early puberty risk in children with chronic overweight/obesity. Vigorous physical activity may reduce adiposity and increase the final adult height in the children.

Unfavorable Hormonal and Psychologic Profile in Adult Women with a History of Premature Adrenarche and Pubarche, Compared to Women with Polycystic Ovary Syndrome.

If circulating adrenal androgens levels rise before the age of 8 years in girls, this phenomenon is termed premature adrenarche (PA), while the concomitant appearance of pubic hair is called premature pubarche (PP). Girls with PA-PP display an unfavorable hormonal profile compared to their normal peers and have an increased risk of developing polycystic ovary syndrome (PCOS) features peripubertally. However, the sequelae of premature adrenarche remains unclear. We assessed metabolic, hormonal, psychologic profiles, and ovarian morphology in 21 women of mean age (±SD) 21.3±3.3 years, BMI: 23.6±4.4 kg/m2 with PA-PP, 45 women with PCOS and 26 controls, matched for age and BMI. PA-PP women displayed a favorable lipid profile compared to PCOS and controls. Insulin resistance index (HOMA-IR), however, were similar in PA-PP and PCOS women (2.09±1.42, 2.08±0.83) and higher than controls (1.13±0.49, p <0.05). Circulating androstenedione levels did not differ between PA-PP and PCOS women (0.11±0.05 vs. 0.12±0.03), but was higher than that of controls (0.02±0.0 nmol/l, p <0,05). Ovarian volume was increased in PA-PP and PCOS (11.14±3.3 vs. 10.99±4.61) compared to controls (6.74±1.83 cm3). PA-PP women had a higher score of state/trait anxiety and depressive and eating disorder symptoms than controls, with a pattern that matched that of PCOS women. Only 14% of the PA-PP group fulfilled the Rotterdam PCOS criteria. Some women with a history of PA-PP displayed hormonal and psychologic profile similar to PCOS, and accordingly a regular monitoring of these girls during adulthood is advised.

Early menarche is associated with insulin resistance in advanced maternal age before delivery.

Purpose: With the wide implementation of the universal two-child policy in China, the number of pregnant women in advanced maternal age (AMA) will increase gradually. We aimed to assess the association between age at menarche (AAM) and insulin resistance (IR) before delivery in AMA. Methods: A total of 80 pregnant women in AMA were consecutively enrolled before delivery in Zhongda hospital. Pregnant women were stratified into early menarche group and late menarche group according to the age of regular menstruation (about 13 years). At delivery, serum glucose and lipid levels were measured. IR was calculated by the method of homeostasis model assessment 2(HOMA2). Results: The fasting blood insulin (17.68(9.72-36.71) and 10.35(7.76-15.10), respectively; p = .006) and HOMA-IR (2.08(1.18-4.37) and 1.24(0.89-1.78), respectively; p = .005) were higher in early menarche group than in late menarche group. AAM was inversely associated with HOMA-IR in AMA (r= -0.27, p = .014). In the multivariable analysis, AAM in late menarche group was negatively related to the level of HOMA-IR compared to those in early menarche group (ß= -2.275, p≤.0001). Conclusions: Taken together, our findings suggest that AAM was inversely associated with HOMA-IR in AMA. Furthermore, pregnant women in AMA with early menarche might have higher HOMA-IR levels than those with late menarche. Clinical trial registration: Chinese Clinical Trial Registry (No. ChiCTR-RRC-16008714), retrospectively registered.

Tall stature in children and adolescents.

Tall stature is usually defined as a height beyond 97th percentile or more than 2 SD above the mean height for age and sex in a defined population. Familiar tall stature, also known as constitutional tall stature, is the most common cause of tall stature. Overnutrition, obesity, also usually causes overgrowth. Tall stature by itself is not a pathological condition, however, there are a number of disorders associated with tall stature. Some genetic disorders and syndromes may be associated with mental retardation and various complications. Therefore, recognition of tall stature and revealing the underlying pathogenic causes and making the diagnosis are important not to miss the serious conditions and to provide adequate medical care and genetic counseling. Pathological causes for tall statute include endocrine disorders, such as excessive growth hormone secretion, hyperthyroidism, precocious puberty and lipodystrophy, chromosome disorders, such as Trisomy X (47, XXX female), Klinefelter Syndrome (47, XXY), XYY syndrome (47, XYY male) and fragile X syndrome, and syndromes and metabolic disorders, such as Marfan Syndrome, Beckwith-Wiedemann Syndrome, Simpson-Golabi-Behmel Syndrome, Sotos Syndrome and homocystinuria. Children may require growth-reductive treatment if the predicted adult height would be excessive and unacceptable. Some hormonal, high doses of sex steroids, or surgical, bilateral percutaneous epiphysiodesis of the distal femur and proximal tibia and fibula, treatment is currently available to reduce adult height.

Epileptic Encephalopathy, Myoclonus-Dystonia, and Premature Pubarche in Siblings with a Novel C-Terminal Truncating Mutation in ATRX Gene.

The X-linked alpha thalassemia mental retardation (ATR-X) syndrome is a genetic disorder caused by X-linked recessive mutations in ATRX gene, related to a wide spectrum of clinical manifestations, such as alpha thalassemia, developmental delay, genital abnormalities, and gastrointestinal disorders. Patients with ATR-X syndrome can suffer from different types of epileptic seizures, but a severe epileptic encephalopathy pattern has not been described to date. We describe, for the first time, two brothers with genetically confirmed ATR-X syndrome who presented with drug-resistant epileptic encephalopathy, with tonic and polimorphic seizures reported in the elder brother and epileptic spasms in the younger brother. Moreover, both brothers showed a peculiar movement disorder with myoclonus-dystonia, worsened during periods of distress or pain. These cases expand the clinical spectrum of ATR-X syndrome and open new opportunities for the molecular diagnosis of ATRX mutations in male patients with severe epileptic encephalopathies and movement disorders.

Hidradenitis suppurativa in a prepubertal case series: a call for specific guidelines.

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease associated with a high physical and psychological burden. It is a disorder of the infundibular segment of the pilosebaceous unit, characterized by subcutaneous nodules, abscesses, sinus tracts and scar formation on the intertriginous and apocrine-bearing areas. HS is quite rare in young and prepubertal children. It usually begins after puberty, but several reports of prepubertal HS onset have been described. These cases are strongly linked to hormonal disorders and genetic susceptibility. Specific guidelines for prepubertal patients are still lacking, so further studies are warranted to better delineate a tailored approach. This paper aims to summarize the most significant aspects, as well as the most recent information about the epidemiology, pathogenesis, clinical features, diagnosis, comorbidities and treatment of paediatric HS. In addition, we report our clinical experience in managing HS in a group of eight prepubertal patients based on systemic antibiotics (azithromycin) and zinc oral supplementation.

Body mass index at the presentation of premature adrenarche is associated with components of metabolic syndrome at puberty.

The aim of this study was to analyze the relationship between premature adrenarche (PA) and metabolic syndrome (MeS) parameters at presentation and during puberty. This study comprised 47 girls with PA. Age- and puberty-matched 22 healthy girls without PA were the control group. Patients were evaluated at admission (first evaluation) and later in puberty (second evaluation). Anthropometric measurements, lipid levels, and hormonal parameters were studied and oral glucose tolerance test was performed. Indices for insulin resistance (IR) were calculated. The study group was divided in subgroups according to body mass index (BMI) and compared with the control group. The age of the PA group at first evaluation was 8.0 ± 1.1 years; mean height SDS and BMI SDS were 0.4 ± 1.2 and 0.6 ± 0.9, respectively. Age of PA group at the second evaluation was 12.9 ± 2.4 years. Frequency of obesity and overweight was 14.9 and 23.4%. Dyslipidemia ratio was 28.3%. PA group had significantly higher BMI than controls. Mean insulin concentration was higher and mean glucose and FGIR were lower in PA group and also dyslipidemia ratio was 5.3 times higher in PA than controls (p = 0.040). In PA group, overweight/obese subjects had still higher BMI at second evaluation and also higher fasting glucose, insulin, HOMA-IR. However, PA children with exaggerated DHEAS concentrations compared to those without had similar BMI SDS, insulin sensitivity, and secretion indices and lipid profile at second evaluation. BMI SDS at first evaluation was positively correlated with HOMA-IR at puberty; however, there is no correlation between DHEAS at first evaluation and HOMA-IR at puberty.Conclusion: BMI at adrenarche is more important than prepubertal adrogen concentrations such as DHEAS, while predicting the IR in puberty. Long-term follow-up of children supports the observation that PA per se may be related to IR; however, the risk increases with obesity. What is Known: • Premature adrenarche (PA) is receiving more attention as evidence emerges for a relation between early androgen excess and metabolic syndrome. • The onset of the adrenal androgen production before 8 years in girls defined as PA. Pubarche, axillary hair, apocrine body odor, acne are typical phenotypic features of PA. What is New: • Body mass index at adrenarche is an important risk factor for development of insulin resistance in pubertal ages. • Degree of dehydroepiandrosterone sulfate elevation was not shown as a risk factor for insulin resistance.

The usefulness of circulating levels of leptin, kisspeptin, and neurokinin B in obese girls with precocious puberty.

This study investigated the relationships of circulating leptin, kisspeptin, and neurokinin B (NKB) levels with precocious puberty (PP) in overweight/obese girls and evaluated the usefulness of these markers in the initiation of puberty. One hundred and twenty-eight girls aged 7.0-8.9 years with PP (group A, normal-weight; group B, overweight/obese) and 30 age-matched normal controls (NC) were enrolled. Serum levels of leptin, kisspeptin, and NKB were measured by commercial kits. Serum leptin levels were higher in group A (4.21 ng/mL) and B (5.64 ng/mL) compared to the NC (2.35 ng/mL, p < .001). Serum kisspeptin levels were lower in group A (0.59 ng/mL) than in group B (0.66 ng/mL, p = .018). Serum NKB levels were not different among the three groups. The predictive value of leptin (AUC =0.791) was lower than that of IGF-1 (AUC =0.917, p = .009), although both were significant markers for PP in the regression analysis. BMI z-score (AUC =0.806) was a predictive factor of PP. In conclusion, a higher level of leptin, IGF-1, and fatness in overweight/obese girls with PP compared to the NC confirms their roles in the regulation of puberty. Further research is needed if the effects of kisspeptin and NKB on puberty are limited at the levels of neurons or target tissue.

Current review of prepubertal vaginal bleeding.

PURPOSE OF REVIEW: Prepubertal vaginal bleeding raises many concerns and evaluation and diagnosis may prove difficult for many providers. We aim to provide a comprehensive review and recent updates for those practitioners who care for these patients. RECENT FINDINGS: Prompt management in the case of prepubertal vaginal bleeding is indicated, especially to rule out malignancy or abuse. If a child is reluctant to undergo examination, or if the extent of injury or source of bleeding cannot be determined, examination under anesthesia and vaginoscopy is recommended. Use of vaginoscopy allows for clear visualization of the vagina and cervix without distorting hymenal anatomy, as well as diagnosis and removal of a foreign body and evaluation of mucosal damage caused. In the case of sexual abuse, providers specifically trained in pediatrics need to be present, and safety of the patient should always be ensured. SUMMARY: Careful history taking and targeted examination may lead to diagnosis in the case of prepubertal vaginal bleeding. However, in more difficult cases, practitioners should not hesitate to examine a patient in the operating room using general anesthesia to elicit the cause. Although sexual abuse and malignancy are always on the differential, most causes of bleeding are benign and easily treated.

RELATIONSHIP BETWEEN SERUM LEPTIN LEVELS AND WEIGHT GAIN IN GIRLS WITH CENTRAL PRECOCIOUS PUBERTY AT 1-YEAR FOLLOW-UP.

OBJECTIVE: Patients with central precocious puberty (CPP) may have increased serum leptin levels; however, it is not well known whether this increase differs between patients with and without obesity. Our objectives were to describe the changes in serum leptin in girls with CPP in the first 12 months after diagnosis based on body mass index (BMI) and to explore whether serum leptin level at CPP diagnosis is related to BMI z-score (BMIz) after a 1-year follow-up. METHODS: A prospective cohort study was performed. We included 42 girls with idiopathic CPP in Tanner stages II and III. Anthropometric measurements were performed, and serum leptin was measured at study initiation and after 12 months. Patients were stratified according to BMI category (30 with a BMI in the <94th percentile and 12 with a BMI in the >95th percentile). Study variables were compared. Correlations among leptin, BMIz, and body fat were assessed. RESULTS: Leptin increased gradually during the first year of treatment. In girls with a BMI in the <94th percentile at diagnosis, body fat percentage increased gradually during the first year of follow-up. CONCLUSION: Girls with a BMI in the <94th percentile have a greater risk of weight increase. Leptin level >10.5 ng/dL at diagnosis is a risk factor for weight gain after 1 year. ABBREVIATIONS: BMI = body mass index BMIz = BMI z-score CPP = central precocious puberty GnRHa = gonadotropin-releasing hormone analogue.

Early menarche is associated with non-alcoholic fatty liver disease in adulthood.

BACKGROUND: The aim of this study was to examine the association between early menarche (<12 years) and non-alcoholic fatty liver disease (NAFLD) in premenopausal women and to explore whether it is mediated by adult obesity and insulin resistance. METHODS: We analyzed data of premenopausal women, aged ≥15 years, from the Korea National Health and Nutrition Examination Survey (2007-2009). We divided the women into three groups: early menarche, reference (12.00-15.99 years), and late menarche. The presence of NAFLD was determined using hepatic steatosis index >36.0. RESULTS: Of the 4,387 women evaluated, 673 (15.4%) met the criteria for NAFLD. The prevalence of NAFLD was higher in both women with early and late menarche compared with the reference (early, 23.4%; reference, 14.0%; late, 19.9%, P < 0.001). After adjustment of confounders including age, the OR for NAFLD in early menarche compared with the reference was 3.04 (95%CI: 1.99-4.65). Further adjustment of mediators, such as central obesity or insulin resistance, attenuated the association to 1.91-2.17. There was no association, however, between late menarche and NAFLD after adjustment of confounders. CONCLUSIONS: Early menarche was associated with an increased risk of NAFLD in young and middle-aged premenopausal Korean women.

Treatment of Girls and Boys with McCune-Albright Syndrome with Precocious Puberty - Update 2017.

The most common endocrinopathy associated with McCune-Albright Syndrome (MAS) is peripheral precocious puberty (PP) which occurs far more often in girls than in boys. We will discuss the latest advancements in the treatment of precocious puberty in MAS that have been achieved during the past 10 years. However, due to the rarity of the condition and the heterogeneity of the disease, research in this field is limited particularly in regards to treatment in boys. In girls, a period of watchful waiting is recommended prior to initiating therapy due to extreme variability in the clinical course. This article will review in detail current pharmacologic treatment in girls, which typically consists of either inhibiting estrogen production or blocking estrogen action at the level of the end-organ. The two treatments with the most evidence at this time are Tamoxifen (which is an estrogen receptor modulator) and Letrozole (which is a 3rd generation aromatase inhibitor). This article will also review the current treatment strategies in boys which typically include using an androgen receptor blocker and an aromatase inhibitor. Due to the rarity of the condition, large multicenter collaborative studies are needed to further investigate efficacy and safety with the goal of establishing the gold standard for treatment of PP in children with MAS.