Earlier Pubarche Research Articles

7534 Characterizing The Presentation Of Non-Classical Congenital Adrenal Hyperplasia

Abstract Disclosure: S. Patel: None. M. Skamagas: None. A.C. Levine: None. M. Yau: None. Introduction: 21-hydroxylase deficiency, due to CYP21A2 gene mutations, is the most common steroidogenic enzymatic defect causing congenital adrenal hyperplasia (CAH). Disease severity is categorized into the classical and milder, non-classical (NCAH) form. Many patients go undiagnosed due to variable presentation and delayed onset. We aim to investigate the specific presenting concerns, age of onset, and genotypes associated with NCAH. Methods: A retrospective chart review of 285 patients with CAH seen over the past 2 years at our academic pediatric and adult endocrine clinics was performed. Records were reviewed for presenting concerns and age of symptom onset. CYP21A2 gene analysis was performed commercially via multiplex ligation-dependent probe amplification or next generation sequencing. Results: Of the 165 patients classified with NCAH, genotypes were available for 124 patients. Of the patients with a V281L allele, 43 were homozygous and 49 were heterozygous. 7 patients had the P30L allele and 7 had other allele combinations. The overall most common presenting concerns were early pubarche (29%), hirsutism (28%), and irregular menses (26%). In V281L homozygotes, family history most commonly led to diagnosis (30%). In patients with V281L heterozygosity or the P30L allele, the predominant concern was early pubarche (37% and 43% respectively). 15% of patients were screened prenatally or only due to family history and were asymptomatic at diagnosis. Patients’ age at diagnosis ranged from 0-40 years, with the mean age at diagnosis for the total group being 13.3 ± 8.9 years. Mean age of onset in symptomatic V281L homozygotes (15.4 ± 7.9 years) trended toward an older age compared to symptomatic V281L heterozygotes (15.1 ± 10.5 years) (P value = 0.90). Those who were heterozygous for V281L/P30L or undetermined whether homozygous for V281L or heterozygous with a deletion were excluded from age of onset comparisons. Discussion: The mean age of symptom onset was in adolescence and did not differ significantly between V281L homozygotes and heterozygotes. Early pubarche is a frequent presenting symptom in children with NCAH, and our data support this finding. P30L has been associated with a more severe phenotype than V281L, and in our cohort, the only patient presenting in adrenal crisis had a genotype with a P30L mutation. As NCAH is one of the most common autosomal recessive disorders in humans and there is an allelic predominance of V281L in NCAH patients, it is not surprising that a large percentage of V281L homozygotes were diagnosed due to family history prior to developing symptoms. Such patients need to be followed clinically and our data describing symptom onset could be useful in counseling these families and those with prenatal diagnoses. Presentation: 6/1/2024

7696 Ovarian Steroid Cell Tumor Presenting as Non-classical Adrenal Hyperplasia

Abstract Disclosure: V. Reddy: None. A. Gowda: None. V. Vattipally: None. D. Kunduru: None. IntroductionSteroid cell tumors(SCT) of the ovary make up less than 0.1% of all ovarian tumors. The three subtypes are stromal luteoma, Leydig cell tumor, and steroid cell tumor-not otherwise specified (NOS) which is the commonest subtype. Androgen excess is seen in 75% tumors and presents with virilization. Tumors are usually benign but maybe malignant in 25-43% cases. Factors predicting malignancy include size >7 cm, mitotic activity, necrosis, hemorrhage, and nuclear atypia. Case ReportA 29 y/o Caucasian female presented with secondary amenorrhea and hirsutism. History includes DM2,hypothyroidism,depression and morbid obesity. She reported early pubarche by age 8,menarche at age 13 and developed hirsutism and irregular menstrual cycles from age 15. No workup due to poor follow up until she saw PCP at age 21.She was diagnosed with PCOS and started on Metformin. Eventually referred to endocrinology at age 27, since amenorrhea and hirsutism persisted. On exam she had significant male pattern hair loss and hirsutism over face and body.She reported three first trimester miscarriages.Labs showed testosterone 370 ng/dl, 17 OHP 808 ng/dl, DHEAS 47 ng/dl, Estradiol 117 pg/ml, FSH 2.2 mIU/ml, LH 2.5 mIU/ml, androstenedione 319 ng/dl.Transvaginal US was unremarkable. She was diagnosed with non classical adrenal hyperplasia (NCAH) and started on treatment with prednisone 5 mg daily, drospirenone and spironolactone 100 mg daily.3 months later, labs showed 50% lowering of testosterone to 199 ng/dl and 17 OHP to 407 ng/dl.There was continued biochemical and clinical improvement at the next visit with 17 OHP 73 ng/dl and testosterone 55 ng/dl. Labs done 21 months after initial presentation, showed sudden dramatic rise in 17 OHP to 1148 ng/dl and testosterone to 639 ng/dl. Normal AFP, HCG, CEA, CA125, CA19-9, Inhibin A. CT showed 10.4 cm solid right ovarian mass and underwent right salpingo-oophorectomy. Pathology showed steroid cell tumor, NOS. Labs 1 month postoperatively showed complete normalization of testosterone to <3 ng/dl, 17 OHP to 11 ng/dl and DHEAS 0.66 ng/dl. Steroid therapy was tapered and discontinued. DiscussionWe present the case of a patient with ovarian SCT presenting as NCAH.SCTs are very rare accounting for only 0.1% of all ovarian tumors. Since they commonly secrete androgens, they present similarly to CAH or PCOS and may rarely even co-exist with CAH. Differentiating between NCAH and SCT is difficult especially when there is initial response to steroid therapy and imaging is unremarkable as with our patient. It is important to consider SCT in patients with hyperandrogenism even in the setting of elevated 17 OHP levels. Care should be taken to follow up both clinical and metabolic metrics closely and investigate if any change is noticed. Early diagnosis can prevent irreversible symptoms of hyperandrogenism. Presentation: 6/1/2024

7696 Ovarian Steroid Cell Tumor Presenting As Non-classical Adrenal Hyperplasia

Abstract Disclosure: V. Reddy: None. A. Gowda: None. V. Vattipally: None. D. Kunduru: None. Ovarian Steroid Cell Tumor Presenting as Non-classical Adrenal Hyperplasia IntroductionSteroid cell tumors(SCT) of the ovary make up less than 0.1% of all ovarian tumors. The three subtypes are stromal luteoma, Leydig cell tumor, and steroid cell tumor-not otherwise specified (NOS) which is the commonest subtype. Androgen excess is seen in 75% tumors and presents with virilization. Tumors are usually benign but maybe malignant in 25-43% cases. Factors predicting malignancy include size >7 cm, mitotic activity, necrosis, hemorrhage, and nuclear atypia. Case ReportA 29 y/o Caucasian female presented with secondary amenorrhea and hirsutism. History includes DM2,hypothyroidism,depression and morbid obesity. She reported early pubarche by age 8,menarche at age 13 and developed hirsutism and irregular menstrual cycles from age 15. No workup due to poor follow up until she saw PCP at age 21.She was diagnosed with PCOS and started on Metformin. Eventually referred to endocrinology at age 27, since amenorrhea and hirsutism persisted. On exam she had significant male pattern hair loss and hirsutism over face and body.She reported three first trimester miscarriages.Labs showed testosterone 370 ng/dl, 17 OHP 808 ng/dl, DHEAS 47 ng/dl, Estradiol 117 pg/ml, FSH 2.2 mIU/ml, LH 2.5 mIU/ml, androstenedione 319 ng/dl.Transvaginal US was unremarkable. She was diagnosed with non classical adrenal hyperplasia (NCAH) and started on treatment with prednisone 5 mg daily, drospirenone and spironolactone 100 mg daily.3 months later, labs showed 50% lowering of testosterone to 199 ng/dl and 17 OHP to 407 ng/dl.There was continued biochemical and clinical improvement at the next visit with 17 OHP 73 ng/dl and testosterone 55 ng/dl. Labs done 21 months after initial presentation, showed sudden dramatic rise in 17 OHP to 1148 ng/dl and testosterone to 639 ng/dl. Normal AFP, HCG, CEA, CA125, CA19-9, Inhibin A. CT showed 10.4 cm solid right ovarian mass and underwent right salpingo-oophorectomy. Pathology showed steroid cell tumor, NOS. Labs 1 month postoperatively showed complete normalization of testosterone to <3 ng/dl, 17 OHP to 11 ng/dl and DHEAS 0.66 ng/dl. Steroid therapy was tapered and discontinued. DiscussionWe present the case of a patient with ovarian SCT presenting as NCAH.SCTs are very rare accounting for only 0.1% of all ovarian tumors. Since they commonly secrete androgens, they present similarly to CAH or PCOS and may rarely even co-exist with CAH. Differentiating between NCAH and SCT is difficult especially when there is initial response to steroid therapy and imaging is unremarkable as with our patient. It is important to consider SCT in patients with hyperandrogenism even in the setting of elevated 17 OHP levels. Care should be taken to follow up both clinical and metabolic metrics closely and investigate if any change is noticed. Early diagnosis can prevent irreversible symptoms of hyperandrogenism. Presentation: 6/1/2024

Age at pubarche and the risk of developing cardiometabolic complications among 50–52-year-old men from Krakow Longitudinal Study (Poland)

Despite contradictory observations, it has been postulated that early age of adrenarche predisposes to an increased risk of cardiometabolic complications in further ontogeny due to greater body fatness. The aim of this study was to test the above postulates. We present the results of research on 67 men aged 50–52 – participants of the Krakow Longitudinal Study conducted in the years 1976–2022 – from two birth cohorts 1970 and 1972. Boys were examined annually, aged 6–18, initially 940 people, at the age of eighteen – 358. They were examined again as adult men in 2004 (age 32–34) – 122 people and again in 2022 (age 50–52 years) 67 men. Based on the pubarcheal age, 50-year-olds were divided into 3 groups: early (11 people), average maturing (44 people) and (12 people), where the following were compared: resting systolic and diastolic blood pressure, basic parameters lipid profile – total cholesterol and its fractions, triglycerides, fasting glucose, body height and weight, waist and hip circumferences, indicators – Body Mass Index (BMI), Waist–hip Ratio (WHR), the thickness of 6 skinfolds and the prevalence of metabolic syndrome. The results of the analyses showed that: (1) there is a clear gradation, i.e., the earlier the age of pubarche, the worse the metabolic health of men; (2) compared to the other groups, the total adiposity in men with early pubarche is slightly higher, with clearly marked abdominal obesity; BMI and WHR showed a contrasting picture. At this stage of the analyses, it is difficult to clearly judge whether the cause of the increased cardiometabolic risk in the studied men with early pubarche is related to earlier age of adrenarche and the mechanisms and stimuli causing it, or to greater adiposity.

Puberty in girls with Prader-Willi syndrome: cohort evaluation and clinical recommendations in a Latin American tertiary center.

Prader-Willi syndrome (PWS) is a genetic disorder characterized by hypothalamic-pituitary deficiencies including hypogonadism. In girls with PWS, hypogonadism can present early in childhood, leading to genital hypoplasia, delayed puberty, incomplete pubertal development, and infertility. In contrast, girls can present with premature activation of the adrenal axis leading to early pubarche and advanced bone age. We aim to evaluate the progression of puberty and adrenarche signals in girls with PWS. A longitudinal retrospective cohort study included girls with PWS followed at a Pediatric Endocrinology Outpatient Clinic in a Tertiary University Hospital in Sao Paulo, Brazil from 2002 to 2022. Data collected via chart review included clinical information on birth history, breast and pubic hair Tanner stages, presence of genital hypoplasia, age at menarche, regularity of menstrual cycles, body mass index (BMI) z-score, final height, age of initiation of estrogen replacement and growth hormone replacement, as well as results for PWS genetic subtype; biochemical investigation (LH, FSH, estradiol, DHEA-S); radiographic bone age and pelvic ultrasound. A total of 69 girls were included in the study and the mean age of puberty onset was 10.2 years in those who started puberty after the age of 8 years. Breast Tanner stage IV was reached by 29.1% girls at a mean age of 14.9 years. Spontaneous menarche was present in 13.8% and only one patient had regular menstrual cycles. Early adrenarche was seen in 40.4% of cases. Our study demonstrated in a large sample that girls with PWS often present with delayed onset of puberty despite frequent premature adrenarche. Based on our results, we suggest an estrogen replacement protocol for girls with PWS to be started at the chronological age or bone age of 12-13 years, taking into consideration the uterus size. Further prospective studies are needed.

Precocious puberty in relation to the COVID-19 pandemic. A survey among Argentine pediatric endocrinologists

Introduction. Puberty is manifested initially by the onset of secondary sexual characteristics as a result of hormonal changes that progressively lead to complete sexual maturity. In Argentina and worldwide, the lockdown resulting from the SARS-CoV-2 pandemic may have interfered in the onset and timing of pubertal development. Objective. To describe the perception of pediatric endocrinologists in Argentina regarding consultations for suspected precocious and/or rapidly progressive puberty during the pandemic. Materials and methods. Descriptive, observational, cross-sectional study. Anonymous survey among pediatric endocrinologists members of the Sociedad Argentina de Pediatría and/or the Asociación de Endocrinología Pediátrica Argentina administered in December 2021. Results. Out of 144 pediatric endocrinologists, 83 completed the survey (rate of response: 58%). All of them considered that consultation for precocious or early puberty increased, either in terms of early thelarche (84%), early pubarche (26%), and/or precocious puberty (95%). Ninety-nine percent agreed that this has occurred to a greater extent in girls. All survey respondents also consider that the diagnosis of central precocious puberty has increased. In total, 96.4% of respondents consider that the number of patients treated with GnRH analogs has increased. Conclusion. Our results about the perception of pediatric endocrinologists are consistent with data published in other regions on the increase in the diagnosis of precocious puberty during the COVID-19 pandemic. We underscore the need to develop national registries of central precocious puberty, and to disseminate the evidence for a timely detection and management.

047 Multifactorial obesity: The influence of obesity on pubertal development and the HPG axis

Around 370 million children worldwide are overweight or obese [DiCesare], which poses a serious threat to global health perspective. Obesity is a disease, which means that once obese, the biological systems change to a different setpoint which makes losing weight with lifestyle intervention only very difficult. We know that nutritional status is an important regulator of growth and puberty. This presentation will focus on the impact of obesity in children on growth and puberty. BMI gain as well as obesity are related to an increased height gain during childhood and taller stature. However, not at birth or at 18 years. One of the explanations is that obese children stop growing earlier because they have an advanced bone age. Several hormones are suggested as possible mediators for this effect on growth and bone age: insulin, leptin or sex steroids like androgens or estrogens. No definite candidate has been identified yet, but both leptin and estrogen are important hormones in activating the hypothalamic-pituitary-gonadal axis. Leptin is a hormone produced by fat tissue. It informs the brain on the body’s energy storage. When there is too little, the body will not enter puberty, which costs a lot of energy. Estrogen is produces by gonads, but also by adipose tissue by aromatization of androgens into estrogens. Adrenal androgen levels are increased in children with obesity. Data from large cohort studies show that BMI and obesity are associated with early start of puberty, early pubarche and younger age of menarche. Physicians treating children and adolescents need to bear in mind that childhood obesity is associated with alterations in growth and pubertal development [ 1 Di Cesare M. Sorić M. Bovet P. Miranda J.J. Bhutta Z. Stevens G.A. Laxmaiah A. et al. The epidemiological burden of obesity in childhood: a worldwide epidemic requiring urgent action. BMC Med. 2019; 17: 212 Crossref PubMed Scopus (269) Google Scholar , 2 de Groot C.J. van den Berg A. Ballieux B. Kroon H.M. Rings E.H.H.M. Wit J.M. et al. Determinants of advanced bone age in childhood obesity. Horm Res Paediatr. 2017; 87: 254-263 Crossref PubMed Scopus (21) Google Scholar , 3 He Q. Karlberg J. Bmi in childhood and its association with height gain, timing of puberty, and final height. Pediatr Res. 2001; 49 Crossref PubMed Scopus (319) Google Scholar , 4 Sørensen K. Mouritsen A. Aksglaede L. Hagen C.P. Mogensen S.S. Juul A. Recent secular trends in pubertal timing: implications for evaluation and diagnosis of precocious puberty. Horm Res Paediatr. 2012; 77: 137-145 Crossref PubMed Scopus (215) Google Scholar , 5 Eckert-Lind C. Busch A.S. Petersen J.H. Biro F.M. Butler G. Bräuner E.V. Juul A. Worldwide secular trends in age at pubertal onset assessed by breast development among girls: A systematic review and meta-analysis. JAMA Pediatr. 2020; 174: e195881 Crossref PubMed Scopus (84) Google Scholar ].

PUBERTY IN A SAMPLE OF BRAZILIAN SCHOOLBOYS: ONSET AND ANTHROPOMETRIC CHARACTERISTICS.

ABSTRACTObjective: To determine the age of puberty onset in boys and collect anthropometric data of participants at different puberty stages.Methods: This is a cross-sectional study that assessed 430 boys in a random sample representing 48,390 students from public and private schools from the city of Uberaba, Southeast Brazil. The inclusion criteria were males, aged between 5 and 18 years, and absence of previous diseases. Participants and their guardians filled a semistructured questionnaire with questions relevant to their and their parents’ puberty. We set the significance at p<0.05 and calculated the 95% confidence intervals.Results: The mean age found in the puberty stage G2 was 11.2±1.8 (95% of participants in stage G2 were 9.2-13.4 years old). Pubarche data showed a mean of age of 11.0±1.6 years (95% of the participants experienced pubarche when they were 8.0-14.0 years old). When compared to the confidence intervals of two classical studies on the subject, our results showed a trend toward earlier pubarche. In addition, the mean age of this event in the children’s parents was of 12.1±1.4 years, which was significantly higher than the age of the children’s pubarche (p<0.001).Conclusions: These results indicate a secular decreasing trend in pubarche age and an earlier puberty onset. Considering these parameters, is important to design public policies aimed at preventing these early events.

Pubertal timing in boys and girls born to mothers with gestational diabetes mellitus: a systematic review.

ContextThe incidence of gestational diabetes mellitus (GDM) has been on the rise, driven by maternal obesity. In parallel, pubertal tempo has increased in the general population, driven by childhood obesity.ObjectiveTo evaluate the available evidence on pubertal timing of boys and girls born to mothers with GDM.Data sourcesWe searched MEDLINE, EMBASE, CINAHL Plus, Cochrane library and grey literature for observational studies up to October 2019.Study selection and extractionTwo reviewers independently selected studies, collected data and appraised the studies for risk of bias. Results were tabulated and narratively described as reported in the primary studies.ResultsSeven articles (six for girls and four for boys) were included. Study quality score was mostly moderate (ranging from 4 to 10 out of 11). In girls born to mothers with GDM, estimates suggest earlier timing of pubarche, thelarche and menarche although for each of these outcomes only one study each showed a statistically significant association. In boys, there was some association between maternal GDM and earlier pubarche, but inconsistency in the direction of shift of age at onset of genital and testicular development and first ejaculation. Only a single study analysed growth patterns in children of mothers with GDM, describing a 3-month advancement in the age of attainment of peak height velocity and a slight increase in pubertal tempo.ConclusionsPubertal timing may be influenced by the presence of maternal GDM, though current evidence is sparse and of limited quality. Prospective cohort studies should be conducted, ideally coupled with objective biochemical tests.

Associations of Maternal Gestational Weight Gain and Obesity With the Timing of Pubertal Onset in Daughters.

Early puberty is associated with adverse health outcomes, but little is known regarding early-life determinants influencing pubertal timing. We examined the associations between maternal gestational weight gain (GWG) and the timing of the onset of breast development (thelarche) and pubic hair development (pubarche) in a cohort of 2,070 girls born in a Kaiser Permanente Northern California facility between 2005 and 2006. Using Weibull regression models accommodating interval censoring and adjusting for important confounders, we found that excess GWG was associated with increased risk of early thelarche (hazard ratio (HR) = 1.50, 95% confidence interval (CI): 1.26, 1.78) and early pubarche (HR = 1.35, 95% CI: 1.10, 1.66). Inadequate GWG was associated with early thelarche (HR = 1.36, 95% CI: 1.08, 1.71). The associations between excess or inadequate GWG and risk of earlier thelarche were stronger if mothers were obese before or at the beginning of pregnancy (body mass index ≥30 kg body weight per m height squared) (HR = 2.01, 95% CI: 1.53, 2.63; HR = 2.08, 95% CI: 1.45, 2.98, respectively). Similar associations were found for pubarche outcome. Inclusion of girls' prepubertal body mass index slightly attenuated these associations, but they remained significant. Monitoring of maternal weight before and throughout pregnancy might help prevent early pubertal onset and subsequent negative health outcomes.

PHYSICAL AND SEXUAL DEVELOPMENT OF ADOLESCENT GIRLS WITH RECURRENT URINARY TRACT INFECTIONS

THE AIM: to study the peculiarities of physical and sexual development of adolescent girls with recurrent urinary tract infections.PATIENTS AND METHODS. Examined 70 adolescent girls aged 16 – 18 years with exacerbation of chronic pyelonephritis (CP): 1 group (n=43) – with rare relapse history (relapses pyelonephritis from 1 to 3 times during the period of the disease, rCP) and group 2 (n=27) with frequent relapses (more than 3 times a year, fCP). The control group (n=30) consisted of practically healthy adolescent girls of the same age. Anthropometry, evaluation of sexual development, specialized gynecological examination, determination of serum hormones, ultrasound examination of the reproductive organs were carried out. Statistical processing of research results was performed using the software packages Statistica 6.0 ("StatSoft Inc", USA) and statistical analysis Microsoft Office Excel 2003" ("Microsoft Corporation", USA).RESULTS. It was revealed that in patients with rCP, compared with girls of the 1st and control groups, there was a lower growth, a decrease in the basic pelvic dimensions, against the background of a tendency to increase weight, there were some variants of sexual disorders, more often than in other groups there were early pubarche and later menarche. Established significant increase in the level of LH, testosterone and DHEA-S in the background of hypoprogesteronemia. The rate of hyperpolymenorrhea, uterine bleeding and primary oligomenorrhea was significantly higher, were often found emerging polycystic ovary syndrome and chronic vulvovaginitis.CONCLUSION. Patients with frequent recurrence of urinary tract infections have a variety of constitutional features, a tendency to metabolic syndrome development, expressed hormonal status violations. The detected increase in testosterone levels contributes to the emerging polycystic ovaries syndrome development.

Present Knowledge on the Etiology and Treatment of Adrenarche.

Premature adrenarche (PA) has been assumed to be a benign variant of normal pubertal development. Yet, current collective information suggests associations between PA and potential risks for development of polycystic ovary syndrome and adult diseases such as the metabolic syndrome. Adrenarche refers to the increased secretion of the adrenal androgen precursors DHEA, DHEAS, and androstenedione, which normally occurs in children at age 6-8 years. PA may be identified clinically by early pubarche, which is defined as the development of pubic or axillary hair before 8 years in girls or 9 years in boys. This paper will consider adrenal steroidogenesis, genetic markers, neurobiological changes, skeletal maturation, and associations with adult disorders. The differential diagnosis will be reviewed because PA remains a diagnosis of exclusion. Finally, synthesis of current knowledge regarding PA, suggestions for evaluation, management, and treatment are offered.

High DHEAS Is Associated With Earlier Pubertal Events in Girls But Not in Boys.

Context:Premature adrenarche (PA) has been associated with increased metabolic risk.Objective:To describe the risk of precocious thelarche (PT; <8 years), pubarche (PP; girls <8 years, boys <9 years), and gonadarche (PG; <9 years) in children with high dehydroepiandrosterone sulphate (DHEAS [HD]) vs those with normal DHEAS (ND).Setting and Intervention:Longitudinal Chilean cohort (n = 1052, 49.9% girls). Annual clinical examination including secondary sex characteristics by Tanner staging. Logistic regression models were adjusted by age and BMI.Main Outcome:Assess the relationship between DHEAS and premature thelarche, gonadarche, and pubarche in both sexes.Results:At age of DHEAS determination, overweight/obesity was present in 44.3% of boys and 42.9% of girls. Incidences of any precocious event were observed in 17.2% of boys and in 25.4% of girls, presented as 8.7% of PG and 8.5% of PP in boys and as 21.3% of PT and 4.1% of PP in girls. In crude and adjusted models in boys, HD did not increase the risk of earlier pubertal events. Conversely, girls with HD had a 2.6 times greater risk of early thelarche and a three times greater risk of early pubarche compared with girls with ND concentrations.Conclusion:In Chilean adolescents, precocious events of pubertal development were in line with the worldwide secular trend of earlier sexual maturation. HD was only associated with PT and PP in girls. Continuous follow-up of this cohort is a unique opportunity to prospectively address and analyze the interrelationships among HD, early growth, and adiposity as determinants of gonadarche, pubertal rate/sequence progression, and ovarian function.

Association of prenatal and childhood PBDE exposure with timing of puberty in boys and girls

BackgroundPolybrominated diphenyl ether (PBDE) flame retardants are endocrine-disrupting chemicals that exhibit estrogenic and androgenic properties and may affect pubertal timing. MethodsStudy subjects were participants between 1999 and 2013 in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal cohort study of predominantly Mexican origin families in Northern California. We measured serum concentrations of four PBDEs (BDE-47, -99, -100, -153) in blood collected from mothers during pregnancy (N=263) and their children at age 9years (N=522). We determined timing of pubertal onset in 309 boys and 314 girls using clinical Tanner staging every 9months between 9 and 13years of age, and timing of menarche by self-report. We used Poisson regression for relative risk (RR) of earlier puberty and parametric survival analysis for time ratios (TR) of pubertal milestones. ResultsPrenatal concentrations of all 4 congeners and ƩPBDEs were associated with later menarche in girls (RRearlier menarche=0.5, 95% confidence interval (CI): 0.3, 0.9 for ƩPBDEs) but earlier pubic hair development in boys (RRearlier pubarche=2.0, 95% CI: 1.3, 3.3 for ƩPBDEs). No associations were seen between prenatal exposure and girls' breast or pubic hair development or boys' genital development. Childhood PBDE exposure was not associated with any measure of pubertal timing, except for an association of BDE-153 with later menarche. ConclusionsWe found that prenatal PBDE exposure was associated with later menarche in girls but earlier pubarche in boys, suggesting opposite pubertal effects in girls and boys.

Thyroid Hormones and Timing of Pubertal Onset in a Longitudinal Cohort of Females, Northern California, 2006-11.

Pubertal timing is regulated by a complex interplay of hormones. Few studies have evaluated the role of thyroid hormones in pubertal onset. We investigated the associations between blood concentrations of free and total thyroxine (FT4, TT4), free triiodothyronine, and thyroid stimulating hormone and pubertal onset among females. Participants included 323 Kaiser Permanente Northern California members followed at annual intervals during 2004-11, who provided a blood sample during the first 3 years of the study. Thyroid hormone concentrations were measured in serum in the first blood specimen available for each participant. Pubertal onset was defined as Tanner stage ≥2 for breast (thelarche) and pubic hair (pubarche) development. Associations between thyroid hormones and pubertal onset were assessed by multivariable logistic regression and Cox proportional hazards modelling. At blood draw, participants were age 6.5-10.1 (median 7.7) years, 10% had reached thelarche, and 12% had reached pubarche. Participants were followed 0-5 years after blood draw (median 4). At most recent clinical visit, participants were age 6.7-14.7 (median 12.3) years, 92% had reached thelarche, and 89% had reached pubarche. No associations were identified between having reached thelarche or pubarche at time of blood draw and thyroid hormones. Examined longitudinally, higher concentrations of pre-pubertal FT4 and TT4 were associated with earlier pubarche (adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.06, 1.86; per ng/dL and aHR 1.07, 95% CI 1.02, 1.12; per μg/dL respectively). Higher pre-pubertal concentrations of FT4 and TT4 are associated with earlier pubarche.

Is anti-Mullerian hormone an indicator of potential polycystic ovary syndrome in prepubertal girls with simple obesity?

The aim of this anti-Mullerian hormone (AMH) levels in prepubertal obese girls are a predictive marker for polycystic ovary syndrome (PCOS) and to investigate the relationship between insulin resistance and AMH. Sixty girls with premature pubarche or obesity and 20 healthy controls between the ages of 6-9 were enrolled. Of the patients, 22 (36.7%) were in the obese group (Group 1), 28 (46.7%) in the early pubarche group (Group 2) and 10 (16.6%) in the early pubarche + obese group (Group 3). Comparison of the subjects' fasting insulin and homeostatic model assessment insulin resistance (HOMA-IR) demonstrated significantly higher values for group 1 compared to group 2 (p=0.001 and 0.001) and, likewise, significantly higher values for group 3 compared to group 2. There was no significant differences between all groups for AMH levels. AMH levels were not significantly different in the obese girls compared to the other groups. There was also no relationship between AMH and insulin resistance in any of the groups. Further studies, however, are needed due the limited number of subjects in this study and in the absence of adequate relevant data.

Younger pubertal age is associated with allergy and other atopic conditions in girls.

Early menarche is linked to higher incidence of adult asthma, suggesting that earlier puberty may influence type 2 immune response characteristics of allergic diseases. We examined the hypothesis that timing of breast and pubic hair development, which precede menarche, is associated with increased childhood atopic conditions. Girls were enrolled at 6-8 yr of age (2004-2007) in the Breast Cancer and the Environment Research Program Puberty Study and were followed through 2011. Pubertal stages were assessed and atopic conditions were queried annually. Associations of age at pubertal stage 2 for breast or pubic hair development with atopic conditions were assessed using prevalence ratios (PR) or odds ratios (OR) and 95% confidence intervals (CI) from log-binomial regression and generalized estimating equation models, controlling for body mass index and other covariates. A total of 1055 girls with medical and pubertal stage data were included. Asthma (ever vs. never) was associated with younger pubarche (≤10 vs. >10 yr, PR = 1.15, CI: 1.04-1.28 adjusted for race/ethnicity and site; PR = 1.13, CI: 1.01-1.25 further adjusted for BMI), but not thelarche. In longitudinal models, risk of developing allergies increased with younger age at pubarche (adjusted OR = 1.60, CI: 1.10-2.34; ≤10 vs. >10 yr). Risks were highest among black girls with earlier pubarche (n = 248/326); for allergies, their fully adjusted OR was 2.35, CI: 1.06-5.19 for pubarche ≤10 vs. >10 yr. Atopic conditions during childhood are associated with younger age at pubarche, independent of obesity, and these relationships may vary by racial/ethnic groups.

Menstrual Disorders

Menstrual Disorders

Age of Onset of Polycystic Ovarian Syndrome in Girls May Be Earlier Than Previously Thought

Objectives To study the age at diagnosis of polycystic ovarian syndrome (PCOS) in a pediatric population. To compare risk factors involved in causing PCOS in preadolescent and adolescent girls. To review the current literature on the reported age of PCOS in girls. Design A retrospective chart review and systematic review of the literature. Participants Patients included 58 girls (age ≤18 yrs) with a diagnosis of PCOS based on the Rotterdam criteria. Girls were grouped as preadolescents (<13 yrs) or adolescents (13–18 yrs). Clinical and biochemical data were reviewed from the time of diagnosis. Main Outcome Measures Age at diagnosis. Differences in risk factors for PCOS (Ethnicity, obesity, family history of PCOS, birth weight, age at pubarche, thelarche and menarche, evidence of hyperandrogenism and/or insulin resistance) were compared between the two groups. Results There were 26% (15/58) preadolescent girls (9–12 yrs) vs 74% (43/58) adolescents (13–18 yrs). There was no significant difference between the two groups in ethnicity, BMI z-score, family history of maternal PCOS, birth weight, hyperandrogenism, or insulin resistance. Preadolescents with PCOS had significantly earlier onset of pubarche and thelarche than adolescents with PCOS, by 1.9 and 1.5 yrs, respectively ( P = 0.018, 0.030). In addition to earlier puberty, PCOS developed 2.1 years sooner after thelarche in preadolescents than in adolescents. ( P = 0.008) Preadolescents were significantly taller for age than adolescents (72nd % vs 43rd %) ( P = 0.005). A review of the 28 studies published in the last 3 years that included PCOS patients with age <=18 yrs described only 6.4% (27/425) of pediatric subjects with age <13 yrs. Four were primarily pediatric studies that included patients under the age of 13 yrs, with 9.4% (12/127) of the patients <13 yrs. Conclusion Increased awareness of PCOS in young females is needed. PCOS may occur at a younger age in girls who develop early pubarche and thelarche. Therefore, the diagnosis and workup should be considered in young girls with risk factors suggestive of PCOS.

Medical Considerations of Long-Term Survival of Werdnig–Hoffmann Disease

To report intercurrent nonrespiratory complications of unprecedented survival for Werdnig-Hoffman disease (spinal muscular atrophy type 1 [SMA 1]). A retrospective chart review and caregiver questionnaire for 103 consecutively referred SMA 1 patients for whom death was prevented during infancy. Overall, 15 of 63 (23.8%) respondents had severe, symptomatic bradycardias. Thirteen of 25 males had bilateral cryptorchidism, and two were unilateral. Ten of 42 (24%) respondents had recurrent oral candidiasis, and eight (19.0%) had recurrent nonoral candidiasis. All patients had hip dislocation/subluxation. They had collapsing spines and scoliosis by 1 yr of age. Ninety-six had indwelling gastrostomy/nasogastric tubes before 24 mos of age. Twenty-six underwent fundoplication to decrease reflux. Fifty-seven were on modified elemental diets with reported benefits. About one half had early pubarche. Three patients had episodes of acute pancreatitis. One untreated patient died of candidal endocarditis at 4 mos of age, and a second child had mitral valve candidiasis on autopsy. Prolonged survival of SMA 1 results in a high incidence of concomitant medical conditions that need to be addressed.