Onset Of Secondary Sexual Characteristics Research Articles

7802 A Review of 21 Cases of Kallmann Syndrome

Abstract Disclosure: T. Kashima: None. M. Ishimaru: None. E. Tanimoto: None. S. Fukui: None. C. Nakamura: None. N. Ujita: None. H. Miyagi: None. M. Igarashi: None. H. Doi: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None. Kallmann syndrome is the most common form of hypogonadotropic hypogonadism. The incidence is estimated to be 1 in 10,000 birth boys and 1 in 50,000 birth girls. The goals of treatment for childhood puberty are to induce the progression of secondary sexual characteristics close to physiological sexual maturity, to improve psychosocial problems caused by delayed puberty, and to achieve fertility. Methods.Twenty-one patients (fifteen males and six females) with a diagnosis of Kallmann syndrome who visited our Department between August 2004 and November 2023 were included in the study. The electronic medical records were reviewed retrospectively. Results.The median age at first visit was 15 years and 11 months (13 years and 3 months to 17 years and 7 months). The chief complained were secondary sexual characteristics not yet developed, olfactory disturbance, amenorrhea, decreased growth rate, and micropenis. Three adults had symptoms of Kallmann's syndrome and were seen for close examination. 6 had a history of hearing loss. Family history included 2 cases of hypogonadotropic hypogonadism and a sibling with Sjogren-Larsson syndrome. 9 cases had genetic testing, including KAL1, KAL2, FGF8, IL17D, 1 case each, and 2 gene variants of CHD2.At the time of initial examination, the median testicular volume in males was 1.0 mL (1.0-3.0 ml). Five of the six female patients had no breast enlargement.Endocrine examination revealed that the mean basic LH and LHRH test peak values were 0.25 and 3.40 mIU/mL, respectively; the mean basic FSH and peak FSH values were 0.91 and 4.47 mIU/m, respectively; the mean testosterone level in males was 0.09 ng/mL; and the mean estradiol level in females was 5.58 pg/mL.For the 20 patients, excluding children, gonadotropins (HCG+rFSH) for men and estrogen patches for women were both started at low doses and titrated up to Kaufman therapy in women. Median age at initiation of treatment was 16 years and 5 months (14 years and 1 month to 18 years and 6 months). Bone density increased after the start of treatment. One patient diagnosed with micropenis in infancy was treated with testosterone for micropenis at 2 years and 5 months. Two male patients had a baby with their partners. Discussion.The age of diagnosis (age of first examination) is considerably older than the average age of onset of secondary sexual characteristics, so it is necessary to educate the public so that patients can be examined earlier. The patient's fertility was partially confirmed, and a smooth transition to adult/reproductive medical care can be expected through earlier intervention. Presentation: 6/1/2024

P-598 Novel inactivating homozygous mutation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) and first live birth after in vitro maturation (IVM): a breakthrough

Abstract Study question How can pregnancy and live birth be achieved in patients with inactivating homozygous luteinizing hormone/choriogonadotropin receptor (LHCGR) mutation? Summary answer We report the first live birth after IVM in a patient with a novel homozygous inactivating LHCGR mutation (exon 6,c.470A>G). What is known already LH plays a fundamental role in female reproductive physiology and is responsible for steroidogenesis, oocyte maturation, ovulation and subsequent progesterone production by the corpus luteum. LH binds to the LHCGR located on the membrane of theca cells and mature granulosa cells. Inactivating mutations of the LHCG receptor lead to the impossibility to obtain final oocyte maturation both during natural cycles and after ovarian stimulation for in vitro fertilization purpose. Until now, egg donation represented the only option to treat their infertility. Study design, size, duration A case report. Participants/materials, setting, methods A 35 year-old nulliparous patient was referred to our university hospital for primary infertility. Main results and the role of chance The 35-year-old nulliparous patient presented with primary spaniomenorrhea but timely and spontaneous onset of secondary sexual characteristics. Serum LH levels were high (ranging from 15 to 30 IU/L) and to a lesser extent so were FSH levels. The ovarian reserve was normal for age, as assessed by serum AMH levels and ultrasound. There was no argument for polycystic ovarian syndrome, 21-hydroxylase deficiency, Cushing’s syndrome or hyperprolactinemia. Two previous attempts of controlled ovarian stimulation with gonadotropins and ovulation trigger with hCG and GnRH-agonist trigger had failed, resulting in low estradiol levels despite correct follicular growth on ultrasound and absence of ovulation after trigger. We identified by genetic analysis a novel homozygous inactivating LHCGR mutation (exon 6, c.470A>G) that had never been described previously. IVM was performed. A total of 7 oocytes were obtained after IVM, resulting in 4 Day 3 embryos. All embryos were frozen. Subsequently, 2 Day 3 embryos were replaced after endometrial preparation by hormone replacement therapy. The patient became pregnant and gave birth to a healthy baby. Two Day 3 embryos remain. Limitations, reasons for caution By definition, a case-report requires further studies to confirm our findings. Wider implications of the findings We describe a novel inactivating LHCGR mutation with subsequent live birth after IVM. As a growing number of gonadotropin receptor mutations are identified, this live birth successfully obtained places IVM as the only reliable option for these patients to conceive with their own eggs. Trial registration number not applicable

The Increased Prevalence of Precocious Puberty in Female Children and its Association with the Link to Increased Sexual Imbalances in Later Life

Precocious puberty, the premature onset of secondary sexual characteristics before the age of 8 in girls, has emerged as a growing concern in pediatric endocrinology. The prevalence of precocious puberty has witnessed a noticeable rise in recent decades, attributed to various environmental, genetic, and lifestyle factors. This surge in early maturation poses significant challenges not only to affected individuals and their families but also to healthcare systems worldwide. Moreover, beyond the immediate physical changes, there exists a complex interplay between precocious puberty and future sexual imbalances. Studies suggest that early puberty may predispose females to a myriad of health issues, including increased risk of metabolic disorders, psychological challenges, and reproductive complications later in life. Furthermore, the societal implications of this trend cannot be overlooked, as it may exacerbate existing gender disparities and contribute to broader socio-cultural issues. Understanding the link between precocious puberty and future sexual imbalances is crucial for developing effective preventive strategies and providing comprehensive care to affected individuals. This necessitates interdisciplinary research efforts encompassing endocrinology, psychology, genetics, and public health. In conclusion, this review shall highlight the urgent need for continued investigation into the escalating prevalence of precocious puberty in female children and its far-reaching implications for sexual health and well-being across the lifespan. By elucidating the underlying mechanisms and risk factors, healthcare professionals can better address this growing public health concern and mitigate its long-term consequences on individuals and societies alike.

FRI490 Association Between TSH Levels And Early Development Of Secondary Sexual Characteristics Among Children With Congenital Hypothyroidism

Abstract Disclosure: M.M. Nunez Stosic: None. T. Seeherunvong: None. Although hypothyroidism typically delays puberty, early pubertal development in patients with hypothyroidism and markedly elevated TSH levels has been reported. Recent studies investigated the association between thyroid function and timing of puberty among normal children. Jung et al. reported an association between serum TSH and LH levels in girls with central precocious puberty. By contrast Wilken et al. found an association between serum T4 level and onset of pubarche but not thelarche among female subjects. We investigated the association between serum TSH levels and onset of secondary sexual characteristics among patients with congenital hypothyroidism. A retrospective study was conducted including girls and boys aged ≥6 years and ≤ 18 years with confirmed primary congenital hypothyroidism who were seen in our pediatric endocrinology clinic at University of Miami, between May 2012 and May 2022. Age of onset of secondary sexual characteristics (SSC) such as body odor, acne, axillary hair, pubic hair, breast/testicular development was recorded. Early onset of SSC was defined by its presence in girls younger than 8 years and in boys younger than 9 years. Onset of SSC was considered early normal if it occurred between 8-9.5 years in girls and between 9-10.5 years in boys. A third group of patients were those with onset of SSC after 9.5 years in girls and after 10.5 years in boys. We recorded the serum TSH levels from age 6-8 years in girls and from 7-9 years in boys. We determined the average TSH levels and the proportion of the serum TSH level above normal range. IBM SPSS Statistics software version 28.0.0.0(190) was used for data analysis. Fifty-seven subjects with a history of congenital hypothyroidism, 36 girls (63.2%) and 21 boys (36.8%) were included in the study. Seventeen patients (29.8%) had early or early normal onset of SSC. The prevalence was more frequent among girls than boys, 14% and 3% respectively (p value= 0.046). Among all 57 subjects, only 9 had normal serum TSH. The mean proportion of TSH levels above normal limit was 62.4% in patients with early or normal early onset of SSC. By contrast, the mean proportion of serum TSH level above normal limit was 53.7% in those patients who had neither early nor early normal onset of SSC (p value=0.044). In summary, early and early normal onset of SSC was associated with higher TSH levels in children with congenital hypothyroidism. Further studies with a larger number of subjects will be needed to define further the specific SSC most associated with an abnormally elevated TSH. Presentation: Friday, June 16, 2023

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.

ODP376 Accuracy of Doppler Assessment of the Uterine Arteries for the Diagnosis of Pubertal Onset in Girls: A Scoping Review

Abstract Introduction The uterine artery pulsatility index (PI) assessed by Doppler ultrasonography (US) reflects the blood flow impedance in the vessel distal to the sampling point and tends to decrease with the onset of puberty, being suggested as a parameter to define pubertal development. Objective To evaluate the accuracy of the uterine artery PI for the diagnosis of puberty in girls. Methods A PRISMA-ScR-compliant scoping review was performed in the MEDLINE and Embase databases with "puberty" and "Doppler ultrasonography" as search terms. Studies that included girls aged 0-18 years who underwent pelvic US with Doppler of the uterine arteries and calculation of the PI were considered eligible. Results Ten studies comprising 1385 girls aged 1.2-18 years were included. The selected studies were published between 1996 and 2021 and included participants from five countries (Italy, Brazil, Iran, Belgium and Denmark). Six studies included girls who were referred for evaluation of pubertal disorders, mainly thelarche or early-onset pubarche, while four studies selected only healthy girls. Nine studies found a significant difference in Doppler and PI according to pubertal stage, with PI cutoff points ranging from 2.5 to 4.6 for the diagnosis of onset of puberty, with a sensitivity of 77-94%, specificity of 85-100% and accuracy of 79-98%. Conclusion Doppler assessment of the uterine arteries with PI calculation is a useful noninvasive tool in the diagnosis of onset of secondary sexual characteristics in girls. Presentation: No date and time listed

Case report: A rare case of central precocious puberty due to hypothalamic hamartoma

Precocious puberty defined by the onset of secondary sexual characteristics before 8 years in girls and 9 years in boys. It is more common in females than males and is usually sporadic. Depending on the primary source of hormonal production, precocious puberty is classified as central and peripheral. Precocious puberty in infants is very rare. While investigating a case of precocious puberty, it is essential to progress systematically, with an identification of isolated or complete precocious puberty followed by bone age estimation, relevant hormonal assays, including GnRH stimulation, as well as neuroimaging when indicated. We present a case of isosexual (central) precocious puberty in a 1 year, 3-month-old girl, who was symptomatic for 1 year of age and was diagnosed to have hypothalamic hamartoma after methodical evaluation and responded to treatment with GnRH agonists.

The value of urinary gonadotropins in the diagnosis of central precocious puberty: a meta-analysis

BackgroundThe gonadotropin-releasing hormone (GnRH) stimulation test is time-consuming, invasive, and costly. However, it is the diagnostic gold standard for central precocious puberty (CPP), which in girls is defined as the onset of secondary sexual characteristics before the age of 8 years accompanied by breast buds, accelerated growth, and advanced bone age. This meta-analysis was performed to compare the diagnostic value of urinary gonadotropins and the GnRH stimulation test for CPP.MethodsWe searched six databases for relevant literature. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we estimated the sensitivity, specificity, area under the summary receiver operating characteristic curve (AUC), and publication bias.ResultsSix eligible trials fulfilled the inclusion criteria. In the meta-analysis of urinary luteinizing hormone (ULH), after excluding the data of one study, we obtained an AUC of 0.90 (sensitivity = 0.81, specificity = 0.85). The meta-analysis of the ULH to urinary follicle-stimulating hormone (UFSH) ratio revealed an AUC of 0.8116 (sensitivity = 0.79, specificity = 0.84).ConclusionBoth the ULH level and ULH:UFSH ratio are effective and available approaches for CPP diagnosis.Trial RegistrationINPLASY 2021120076.

The prevalence of precocious puberty among children in Qufu City, Shandong Province, China, a population-based study

ObjectiveWe sought to investigate the prevalence of precocious puberty in children aged 6–10 years in Qufu City, Shandong Province, China.MethodsA total of 5,169 primary school students from grades 1–3 were recruited by population-based multi-stage stratified cluster random sampling. Professional pediatricians conducted physical examinations in October 2020. Precocious puberty is defined as the onset of secondary sexual characteristics in boys aged < 9 years or girls < 8 years or menstruation in girls < 10 years old. Tanner staging was used to record the development of breast and pubic hair in girls and testicular volume and pubic hair in boys. According to the standards of the International Obesity Task Force, we diagnosed overweight, obesity, or severe obesity. In obese girls, a combination of palpation and ultrasound was used to evaluate breast development. The difference was tested by chi-squared test, and all data were statistically analyzed using IBM SPSS version 25.0.ResultsThe unadjusted and adjusted prevalence rates of precocious puberty were 5.01% (11.53% for girls and 1.41% for boys) and 6.29% (14.23% for girls and 1.54% for boys), respectively. The prevalence of precocious puberty in urban (5.34%) dwellers was much higher than that in suburban residents (2.36%, P < 0.05). The prevalence of precocious puberty in the overweight (21.43% for girls and 1.97% for boys), obesity (35.48% for girls and 4.6% for boys), and severe obesity (32.35% for girls and 3.38% for boys) groups were higher than that in the normal weight group (4% for girls and 0.54% for boys, P < 0.05).ConclusionThe prevalence of precocious puberty is high, and overweight and obesity are related to precocious puberty in Qufu, Shandong Province, China.

P-625 In vitro maturation of oocytes: a breakthrough for treating infertility in inactivating mutation of the luteinizing hormone/choriogonadotropin receptor

Abstract Study question How can pregnancy and live birth be achieved in patients with inactivating homozygous luteinizing hormone/choriogonadotropin receptor (LHCGR) mutation? Summary answer We report the first live birth after in vitro maturation (IVM) in a patient with a novel homozygous inactivating LHCGR mutation (exon 6, c.470 A>G). What is known already LH plays a fundamental role in female reproductive physiology and is responsible for steroidogenesis, oocyte maturation, ovulation and subsequent progesterone production by the corpus luteum. LH binds to the LHCGR located on the membrane of theca cells and mature granulosa cells. Inactivating mutations of the LHCGR lead to the impossibility to obtain final oocyte maturation both during natural cycles and after ovarian stimulation for in vitro fertilization purposes. Therefore, egg donation represents the only option for treating their infertility. Study design, size, duration A case report. Participants/materials, setting, methods A 35 year-old nulliparous patient referred to our university hospital for primary infertility. Main results and the role of chance The 35-year-old nulliparous patient presented with primary spaniomenorrhea but timely and spontaneous onset of secondary sexual characteristics. Serum LH levels were high (ranging from 15 to 30 IU/L) and to a lesser extent so were FSH levels. The ovarian reserve was normal for age, as assessed by serum AMH levels and ultrasound. There was no argument for polycystic ovarian syndrome, 21-hydroxylase deficiency, Cushing’s syndrome or hyperprolactinemia. Two previous attempts of controlled ovarian stimulation with gonadotropins and ovulation trigger with hCG and GnRH-agonist trigger had failed, resulting in low estradiol levels despite correct follicular growth on ultrasound and absence of ovulation after trigger. However, genetic analysis identified a novel homozygous inactivating LHCGR mutation (exon 6, c.470A>G) which had never been described previously. IVM was performed. A total of 7 oocytes were obtained after IVM, resulting in 4 Day 3 embryos. All embryos were frozen. Subsequently, 2 Day 3 embryos were replaced after endometrial preparation by hormone replacement therapy. The patient became pregnant and gave birth to a healthy baby. Two Day 3 embryos remain. Limitations, reasons for caution By definition, a case-report requires further studies to confirm our findings. Wider implications of the findings We describe a novel inactivating LHCGR mutation with subsequent live birth after IVM. As a growing number of gonadotropin receptor mutations are identified, this successfully achieved live birth places IVM as the only reliable option for these patients to conceive with their own eggs. Trial registration number Not applicable.

Central Precocious Puberty in a Three-Year-Old Girl

Precocious puberty is defined as the onset of secondary sexual characteristics before 8 years of age in girls and 9 years in boys. Central Precocious Puberty (CPP) is caused by early activation of the hypothalamic-pituitary-gonadal axis. Laboratory test of LH, FSH, and Estradiol is recommended for monitoring suppressive effects from GnRHa therapy in the early three months and every six months. This study aimed to report a case of CPP in a 3-year and 3-month-old girl. A 3-year and 3-month-old girl went to the hospital with vaginal bleeding (menstruation), breast development, and pubic and axilla hair for 7-month-old. Physical examination found moderately ill with obesity, body weight 20 kg, height 98 cm. Tanner stage was A2M3P2, café au lait was found in the left forehead with size 7x3.5 cm. In March 2015 before GnRHa therapy, LH, FSH and Estradiol level increased with levels of 4.32 mlU/mL, 6.01 mlU/mL, and 67 pg/mL, and after 3 months of the treatment was 0.87 mlU/mL, 2.51 mlU/mL and <20 pg/mL. Pelvic ultrasonography showed suggestive precocious puberty, bone age 5-year and 9-month (Greulich and Pyle), CT-Scan of the brain showed hypothalamic tumor suspected hypothalamic hamartoma. This patient was treated with a GnRHa injection every 4 weeks. Leuprorelin is a synthetic non-peptide analogue of natural GnRH. The diagnosis was based on medical history, physical examination, laboratory, and radiological findings. The prognosis of the patient was good.

CHARACTERIZING PRIMARY AMENORRHEA IN A LARGE DIVERSE COHORT

To our knowledge, no recent large studies in the US have reexamined the etiologies of primary amenorrhea; particularly, in the context of increasing obesity rates and diverse ethnic backgrounds. The purpose of this study is to identify and characterize underlying causes of primary amenorrhea amongst a large, diverse cohort. We performed a retrospective chart review of the Kaiser Permanente Southern California database for patients with primary amenorrhea using ICD9 and ICD10 diagnosis codes 626.0 and N91.0, selecting for females ages 0-21 years old at first diagnosis from 2008-2019. Charts were then reviewed to determine which patients met diagnostic criteria for primary amenorrhea, as defined by the American Academy of Pediatrics (AAP): lack of menarche by age 15 years old or by >3 years after onset of secondary sexual characteristics. BMI-for-age percentile (BMIPCT) was used per CDC and AAP guidelines for patients ages 2-19 to account for differences in body composition with sex and age. Medical records were reviewed for demographics and clinical characteristics. Data were analyzed using ANOVA and Tukey analysis; p<0.05. Out of 936 patients from initial search, 748 were diagnosed with primary amenorrhea by chart review. Of those diagnosed, 45% identified as Hispanic (n=340), 32% as White (n=238), 10% as Black (n=73), and 7% as Asian (n=51). The remaining 6% (n=46) identified as Native American/Alaskan, Pacific Islander, Multiple, Other, or Unknown were excluded from final statistical analyses due to small sample size. Within ethnicity groups, patients were normally distributed by age. There was no significant difference in age of presentation between ethnicity groups. BMIPCT ranged from <1 to >99 with a median percentile of 69. The mean BMIPCT was 71 for Hispanic, 46 for White, 63 for Black, and 45 for Asian patients. There was a significant difference for both BMI and BMIPCT when comparing Hispanic vs. White (P<.001) and Hispanic vs. Asian patients (P<.001). A similar trend was seen comparing Black vs. Asian (P<.001) and Black vs. White patients (P<.001). There was no significant difference comparing Hispanic vs. Black, nor White vs. Asian patients. Hispanic and Black populations have significantly higher BMI and BMI-for-age percentiles at time of primary amenorrhea diagnosis when compared to White and Asian populations. However, there is no difference in age of presentation between ethnicity groups. Traditionally, the most common diagnosis underlying primary amenorrhea is hypogonadotropic hypogonadism or gonadal dysgenesis, followed by Mullerian anomaly, physiologic delay, and polycystic ovarian syndrome. Over the past 10 years, limited research in Europe and Asia evaluating differing ethnicities suggest alternative etiologies for primary amenorrhea.

Invited Commentary: Childhood Adiposity and the Onset of Puberty-It Turns Out There Is More to Be Learned.

The literature on the relationship between adiposity and the onset of puberty is extensive, both in size and in the length of time this question has been alive in the biomedical literature. It is easy to wonder, then, whether there is anything new to be learned in this crowded field. In this issue of the Journal, Deardorff et al. (Am J Epidemiol. 2022;191(1):7-16) show that it is still possible to innovate in this area. The authors report on the relationship between body mass index at age 5 years and a variety of markers of the onset of puberty. Consistent with the current literature, they show no association between body mass index at age 5 and pubertal onset in boys. They also show an association between obesity at age 5 with earlier onset of secondary sexual characteristics in girls, making an important subject-matter contribution that addresses many of the concerns of the existing literature in assigning causality. At the same time, the authors make an important, although less evident contribution to the practice of epidemiology for studies where the assessment of pubertal status is of interest.

6-Year-Old Girl With a Luteinized Follicular Ovarian Cyst and an Estradiol Level &amp;gt; 1,000 PG/ML

Background: Precocious puberty in girls is defined as onset of secondary sexual characteristics, such as breast development, before 8 years of age. To differentiate between central and peripheral precocious puberty, laboratory and imaging evaluation is helpful. When gonadotropins are low but estradiol is elevated, results may suggest a primary ovarian source of estrogen production. Small ovarian cysts are not uncommon, are benign and self-resolve. However, large ovarian cysts are rare, let alone ones requiring surgical removal. Clinical Case: A 6 year 7 month old girl presented with several days of breast tenderness and palpable bilateral breast tissue noted by her mother. There was no history of vaginal bleeding. There were no reported exposures to estrogen-containing products. Her mother reached menarche at age 14 years. The patient was born full term and was otherwise healthy. On exam, her height was at the 90-95th %ile (mid-parental height at the 95th %ile) and her growth velocity was 10.9 cm/yr. She had Tanner 2 breasts (1 cm breast bud on the left and 1.5 cm on the right), Tanner 1 pubic hair and no axillary hair, body odor, acne or café-au-lait macules. A bone age was read as 6 years at a chronological age of 6 years 7 months. A laboratory evaluation revealed an estradiol of 1,029 pg/mL (<15 pg/mL), LH <0.02 mIU/mL, FSH <0.09 mIU/mL, 17-hydroxyprogesterone (17-OHP) 410 ng/dL (<91 ng/dL), AFP 2.3 ng/mL (<6.1 ng/mL), beta-hCG <2 mIU/mL, TSH 2.41 mIU/L (0.5-3.2 mIU/L), and free T4 0.9 ng/dL (0.9-1.4 ng/dL). Pelvic ultrasound revealed a large unilocular cystic structure measuring 6.5 x 4.1 x 6.1 cm in the left adnexal region with no left ovary visualized. The right ovary appeared prepubertal. The uterus was prepubertal in appearance with endometrial thickness of 2 mm. Abdominal ultrasound showed no evidence of a suprarenal mass. A laparoscopic cyst resection was completed, given the risk of left ovarian torsion. Cytology was negative; pathology revealed a luteinized follicular cyst. Repeat labs in one month showed a prepubertal estradiol level of 6.7 pg/mL with LH 0.02 mIU/mL and FSH 0.38 mIU/mL. 17-OHP normalized to 29 ng/dL. Breast tissue had regressed. Conclusion: This case describes the rare finding of a large luteinized follicular ovarian cyst that required surgical removal in a 6-year-old girl in the setting of a significantly elevated estradiol level. Luteinized follicular cysts have been described in newborns, though rare. To our knowledge, this is the first described case of a luteinized follicular cyst in this patient’s age group. Laboratory and imaging evaluation should be considered in girls presenting with precocious puberty, despite the extent of thelarche, as the clinical examination does not always correlate with degree of estradiol elevation. This is especially important if clinical changes are acute and other features are consistent with puberty, such as rapid linear growth.

When male seahorses take the female contraceptive pill ...

17α-ethinylestradiol (EE2), the female contraceptive pill, has been detected in mediterranean coasts where seahorse populations, Hippocampus guttulatus, live. Low environmental concentrations have the potential to disrupt growth but also endocrine metabolism, and this imbalance is all the more critical in early life stage. To investigate the impact of EE2 in reared seahorses, we exposed aged 2months and sexually undifferentiated seahorses to an environmental concentration of 21ng/L of EE2 for a period of 30days. EE2 exposure led to a 19% reduction in weight, but also a mortality rate of 27%. This exposure predicted demasculinization of male individuals with a late onset of secondary sexual characteristics. EE2 exposure led to an increase of the free androgen index, but significant reductions of estradiol and testosterone in males were observed. This low estrogen concentration seemed to impact the positive feedback on luteinizing hormone (LH) with a decrease in LH production. Added to this, synthetic estrogen had a negative impact on the production and the release of follicle-stimulating hormone. Contrary to all expectations, females demonstrated a significant decrease in vitellogenin, following exposure to EE2 at 21ng/L, while no changes were detected in males. This first study on the European long-snouted seahorses confirmed the deleterious impact of the female contraceptive pill with a real impact on growth, sexual differentiation, and maturation in young immature seahorses.

Postinjection Muscle Fibrosis from Lupron.

We describe the case of a 6.5-year-old girl with central precocious puberty (CPP), which signifies the onset of secondary sexual characteristics before the age of eight in females and the age of nine in males as a result of stimulation of the hypothalamic-pituitary-gonadal axis. Her case is likely related to her adoption, as children who are adopted internationally have much higher rates of CPP. She had left breast development at Tanner Stage 2, adult body odor, and mildly advanced bone age. In order to halt puberty and maximize adult height, she was prescribed a gonadotropin releasing hormone analog, the first line treatment for CPP. She was administered Lupron (leuprolide acetate) Depot-Ped (3 months) intramuscularly. After her second injection, she developed swelling and muscle pain at the injection site on her right thigh. She also reported an impaired ability to walk. She was diagnosed with muscle fibrosis. This is the first reported case of muscle fibrosis resulting from Lupron injection.

The Enigmatic Pursuit of Puberty in Girls

* Abbreviations: BCERC — : Breast Cancer and the Environment Research Centers NHANES — : National Health and Nutrition Examination Survey PROS — : Pediatric Research in Office Settings Nuances of puberty, the actual trigger, influencing factors, secular and tempo changes, continue to plague us. Uncertainty, as in quantum physics, may continue. Niels Bohr concluded decades ago that what you see depends on how you look. In the robust Breast Cancer and the Environment Research Centers (BCERC) study in this issue of Pediatrics by Biro et al, onset of Tanner 2 breast development is the main end point.1 This article adds to studies providing the unsettling findings that the age of onset of breast development, in synch with, though not entirely explained by, the “obesity epidemic,” has continued to drop. It will inspire continued investigations of causes and implications for psychosocial public health. Remedies will follow. The 1997 cross-sectional Pediatric Research in Office Settings (PROS) study on 17 000 US girls, followed by nationally representative data from the National Health and Nutrition Examination Survey III (NHANES), reported earlier onset of secondary sexual characteristics in girls over the previous several decades.2 The considerable controversy and angst generated by these findings led to lay and scientific essays and studies here and abroad. … Address correspondence to Marcia E. Herman-Giddens, PA, DrPH, 1450 Russell Chapel Rd, Pittsboro, NC 27312. E-mail: mherman-giddens{at}unc.edu

Secondary Sexual Characteristics in Boys: Data From the Pediatric Research in Office Settings Network

Data from racially and ethnically diverse US boys are needed to determine ages of onset of secondary sexual characteristics and examine secular trends. Current international studies suggest earlier puberty in boys than previous studies, following recent trend in girls. Two hundred and twelve practitioners collected Tanner stage and testicular volume data on 4131 boys seen for well-child care in 144 pediatric offices across the United States. Data were analyzed for prevalence and mean ages of onset of sexual maturity markers. Mean ages for onset of Tanner 2 genital development for non-Hispanic white, African American, and Hispanic boys were 10.14, 9.14, and 10.04 years and for stage 2 pubic hair, 11.47, 10.25, and 11.43 years respectively. Mean years for achieving testicular volumes of ≥ 3 mL were 9.95 for white, 9.71 for African American, and 9.63 for Hispanic boys; and for ≥ 4 mL were 11.46, 11.75, and 11.29 respectively. African American boys showed earlier (P < .0001) mean ages for stage 2 to 4 genital development and stage 2 to 4 pubic hair than white and Hispanic boys. No statistical differences were observed between white and Hispanic boys. Observed mean ages of beginning genital and pubic hair growth and early testicular volumes were 6 months to 2 years earlier than in past studies, depending on the characteristic and race/ethnicity. The causes and public health implications of this apparent shift in US boys to a lower age of onset for the development of secondary sexual characteristics in US boys needs further exploration.

Early onset of puberty in young girls: an Italian cross-sectional study.

International literature and clinical practice have referred to Marshall and Tanner data to define the physiological age at onset of puberty. A study in the United States (1997) showed an anticipation in pubertal onset, whereas several European studies did not confirm this trend. To describe the onset of secondary sexual characteristics in a large Italian population of girls and to compare it to reference literature data. A cross-sectional study on 7311 2-14-yr-old girls who spontaneously requested a clinical evaluation for routine health check-up or acute illness by family pediatrician's offices in a northern Italian region (Lombardy), between September 2005 and November 2006. Trained family pediatricians performed a complete physical examination; pubertal status was evaluated following Tanner's criteria; breast development was assessed by palpation. Mean age of thelarche (B2), pubarche (PH2), menarche were 9.75, 10.09, and 12.49 yr, respectively. The prevalence of B2 and PH2 at ages 7-7.99 was 5.9% and 5.6%, respectively, at ages 8-8.99 was 15.5% and 13.8%, respectively. Mean time lapse from B2 to B3 and B2 to menarche was 1.46 and 2.74 yr, respectively. Mean age at menarche of our population and their respective mothers was almost identical. Our population presented earlier clinical signs of pubertal development than those defined by Marshall and Tanner. Mean age of menarche was not different in comparison to the previous generation. A different progression of pubertal development was found, in which the shift to B3 may have more clinical relevance.

Multifunctional role of steroidogenic factor 1 and disorders of sex development

Disorders of sex development (DSD) involve several conditions that result from abnormalities during gonadal determination and differentiation. Some of these disorders may manifest at birth by ambiguous genitalia; others are diagnosed only at puberty, by the delayed onset of secondary sexual characteristics. Sex determination and differentiation in humans are processes that involve the interaction of several genes such as WT1, NR5A1, NR0B1, SOX9, among others, in the testicular pathway, and WNT4, DAX1, FOXL2 and RSPO1, in the ovarian pathway. One of the major proteins in mammalian gonadal differentiation is the steroidogenic nuclear receptor factor 1 (SF1). This review will cover some of the most recent data on SF1 functional roles and findings related to mutations in its coding gene, NR5A1.