Faculty Bibliography

Background: PA, traditionally considered a benign process, is now viewed as a harbinger for future aberration such as polycystic ovary syndrome (PCOS) (1, 2). PA is the presence of pubic hair before age 8 yrs in girls, with DHEAS being the predominantly elevated androgen (3). While the role of androgens in bone growth has been well established in vitro (4), correlations between the elevated androgens and advanced bone age (ABA) observed in girls with PA have not been well delineated. The goal of this study was to identify the predominant androgen in a multiethnic cohort of girls with PA and to determine if that androgen was associated with ABA. Methods: A retrospective chart review was conducted on girls aged 5-7 that presented to our clinic between 2002-2010. The review included anthropometric data, androgen profile, bone age (BA), growth velocity and Tanner stage. Age-matched controls were also identified. Hormone concentrations were determined by radioimmunoassay and chromatography following extraction in our institution's endocrine laboratory. Mann-Whitney U tests and Spearman Correlation tests were used for statistical analyses. Results: Our cohort of 40 girls with PA were mostly Hispanic (58%) and African-American (25%) with a mean age of 6.89 +/- 0.80 yrs, BA of 7.83 +/-1.27 yrs, BMI 19.83 +/- 0.75, BMI Z-score 1.26 +/- 0.20, and growth velocity 7.03+/- 0.45 cm/yr. Testosterone was elevated in 60% of girls with PA (defined as >=10ng/dl for pre-pubertal girls) with DHEAS being elevated only in 30% of girls (>=75mug/dl for girls aged 6-8; >=55 mug/dl for girls <5 yr). Girls in the PA group had significantly elevated testosterone (11.55 +/- 4.83 ng/dL; p=0.04) and DHEAS (65.52 +/- 41.84 mug/dl; p=0.04) levels when compared to age-matched controls (n=7). The 17-OHP values in the two groups were not significantly different. 48% girls had an ABA (defined as BA >=1 yr of chronological age). There was a significant correlation between BA and serum testosterone while controlling for BMI (r=0.51, p=0.05). There was no significant association between BA and DHEAS, androstenedione, and 17-OHP.Conclusion: In our cohort of girls, testosterone emerged as the predominant elevated androgen. The adverse long-term effect of hyperandrogenism and consequent PCOS have been well established. Therefore monitoring girls with PA, elevated testosterone and ABA for emergence of aberrations in the hypothalamic gonadal axis may be prudent

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

BACKGROUND: The optimal dose and efficacy of (1)(3)(1)I treatment of children and adolescents with well-differentiated thyroid carcinoma (WDTC) and pulmonary metastases are not well established. A therapeutic challenge is to achieve the maximum benefit of (1)(3)(1)I to decrease disease-related morbidity and obtain disease-free survival while avoiding the potential complications of (1)(3)(1)I therapy. SUMMARY: We systematically reviewed the published literature on children and adolescents with WDTC and pulmonary metastases treated with (1)(3)(1)I to examine outcomes after (1)(3)(1)I administration and the risks and benefits of therapy. After reviewing 14 published articles, 9 articles met our inclusion criteria encompassing 112 pediatric and adolescent patients with WDTC and pulmonary metastases 21 years of age or younger at diagnosis spanning a follow-up period of 0.6-45 years. (1)(3)(1)I therapy after surgery and thyrotropin suppression resulted in complete, partial, and no disease response in 47.32%, 38.39%, and 14.29% of patients, respectively. Five studies provided data on disease response in relation to (1)(3)(1)I dose. In general, nonresponders received the highest (1)(3)(1)I doses and complete responders received a higher dose than partial responders. The disease-specific mortality rate was 2.68%. Survival was 97.32%. A second primary malignancy occurred in one patient. One out of 11 patients studied experienced radiation fibrosis. CONCLUSIONS: This review confirms that the majority of pediatric and adolescent patients with WDTC and pulmonary metastases treated with (1)(3)(1)I do not achieve complete response to therapy, yet disease-specific morbidity and mortality appear to remain low. It is therefore prudent to use caution in the repeated administration of (1)(3)(1)I to such patients to ensure that adverse effects of therapy do not cause more harm than good in a disease that has an overall favorable natural course. Long-term prospective studies are needed to analyze disease-specific morbidity and mortality, recurrence rate, dose-specific response, and dose-related adverse effects of (1)(3)(1)I in this patient population

Thyrotropinomas tend to be aggressive, invasive tumors that are difficult to resect because of their marked fibrosis and their proximity to vital structures such as the optic chiasm. The latter characteristic also limits the use of radiation therapy. In the few cases reported of children younger than 18 years whose thyrotropinomas were treated surgically, the results were disappointing. We present here the case of a 16-year-old boy with a thyrotropin-secreting pituitary macroadenoma who underwent partial resection via a transsphenoidal approach and was left with significant residual tumor and continued hyperthyroidism. He subsequently received 4 years of long-acting release somatostatin therapy, during which he has remained euthyroid without requiring antithyroid medication. To our knowledge, this is thus far the longest duration of somatostatin therapy in the pediatric age group. This regimen also achieved a decrease in compression of the optic nerve and prevented further tumor growth. We review here the current literature on somatostatin analog treatment including molecular mechanisms and promising new treatment modalities, such as the heterodimerization of dopamine and somatostatin receptors. We conclude that this has been a useful adjuvant treatment for our adolescent patient

OBJECTIVE: Our aim was to evaluate uterine and ovarian ultrasonographic features including endometrial thickness (ET) in adolescent females with PCOS, which is limited in this population. METHODS: We performed a retrospective chart review of young females (n=51) ranging in age from 10 to 18 years with the diagnosis of PCOS. Clinical, biochemical and pelvic sonography data were reviewed. Sonographic data included uterine parameters of ET, length, and volume as well as ovarian volume and follicular morphologic features. RESULTS: Data in 51 girls were analyzed. Menstrual periods were reported as irregular in 26/51 (50.9%), amenorrheic in 19/51 (37.2%), regular in 4/51 (7.8%) and metrorrhagia in 2/51 (3.9%). Uterine features revealed that the endometrial stripe was enlarged (>7mm) in 16/51 (31.4%) of girls, all with homogeneous appearance. The uterine length was lower than normal in 22/51 (43.1%) of girls, normal in 21/51 (41.2%), and higher than normal in 8/51 (15.7%). Uterine volume was normal in 31/51 (60.7%) and higher in 20/51 (39.3%) of girls. Enlarged ovarian volume was found in 22/51 (43%) of patients. Mean ovarian volumes were 16.1cm(3) and 13.1cm(3) in bilateral and unilaterally enlarged ovaries, respectively. The morphology of ovarian follicles was studied in a subset of 40 patients. The location of ovarian follicles was peripheral in 81% and mixed in 19%. The number of follicles was also examined in 43 patients. They were few (<5) in 12%, moderate (5-10) in 5% and multiple (>10) in 84% cases. There was the presence of at least one >10mm cyst in 25% of girls. CONCLUSION: Majority of the adolescents with PCOS demonstrated multiple peripheral ovarian follicles, with large ovarian volumes in some, indicating an important role of ultrasonography in the diagnosis of PCOS, even at a younger age. Endometrial thickness, uterine length, ovarian size, and follicular morphology should be carefully examined in cases of adolescent PCOS

OBJECTIVES: We sought to determine the prevalence of abnormal liver enzymes suggestive of nonalcoholic steatohepatitis and metabolic syndrome in obese adolescent females with polycystic ovary syndrome. DESIGN: A retrospective chart review. PARTICIPANTS: Patients included 39 obese (body mass index Z score >/= 2) adolescent females with a diagnosis of polycystic ovary syndrome. Clinical and biochemical data in these patients were reviewed. MAIN OUTCOME MEASURES: Aspartate and alanine aminotransferase levels, lipid panel, blood pressure, body mass index, and glucose intolerance were the main outcome measures of the study. RESULTS: The study showed that 15.4 % (6 of 39) of patients had elevated aminotransferase levels, suggestive of nonalcoholic steatohepatitis, and 43.6 % (17 of 39) of patients qualified as having metabolic syndrome. Finally, 10.2 % (4 of 39) of patients were found to have both liver dysfunction and metabolic syndrome. CONCLUSION: Liver dysfunction consistent with nonalcoholic steatohepatitis and metabolic syndrome are prevalent in obese adolescent females with polycystic ovary syndrome. Therefore, early screening and further work-up for both disease states are warranted in cases of young adolescent females with polycystic ovary syndrome

OBJECTIVE: Pre-natal ultrasonography presents an opportunity for in-utero therapy of a fetal goiter. Because of the morbidity associated with a large goiter and the risks of repeated intra-amniotic injections, controversy arose about the precise indications of this mode of treatment. We describe our observations in treating a 22-week-old fetus with a large goiter because of dyshormogenesis, monitored with serial 3D high frequency, high resolution ultrasonography and amniotic hormonal measurements. Fetal hypothyroidism was confirmed by cordocentesis and amniotic hormone levels. After assessment of relevant risk factors and the criteria for in-utero intervention, including goiter volume, amniotic fluid index, polyhydramnios and tracheal compression, we determined that hormonal therapy was warranted. Levothyroxine was injected every 7-10 days, and its efficacy monitored by ultrasound changes and amniotic hormone sampling. RESULTS: Reduction in goiter volume restored normal neck flexion relieving the pressure on the trachea, polyhydramnios was prevented and amniotic hormone levels were normalised. The infant was euthyroid at birth, however, by age 4 days hypothyroidism was diagnosed, and treatment with l-thyroxine started. CONCLUSION: Advances in fetal ultrasonography permit judicious therapy of an enlarging goiter in a hypothyroid fetus, which may contribute to enhancing cognitive development. We discuss the value of amniotic hormone sampling, the objectives and risks of in-utero intervention in the light of recent literature and our own observations

Objective: To assess the quality of diagnostic work-up received by patients with 'possible' polycystic ovary syndrome (PCOS).Design: A retrospective chart review.Setting: A hospital based Pediatric Clinic in New York City.Patients: Sixty female patients aged 13-19 years, with a primary ICD-9 diagnosis of ovarian dysfunction (256), menstrual irregularity (626), or hirsutism (704.1) were randomly selected for evaluation. In addition, 18 patients who were assigned the same ICD-9 codes at the Pediatric Endocrine Clinic were assessed.Main Outcome: Rates of assessment for diagnostic criteria of PCOS and selected co-morbidities.Results: Twenty-five percent (15/60) of the patients were evaluated for PCOS according to the Rotterdam Criteria, and only 2 were evaluated for common co-morbidities associated with PCOS. Of the 28 patients who presented with two or more signs of PCOS (menstrual irregularity plus either obesity, hirsutism and/or acne), 15 were evaluated for PCOS (54%), but only 7% were assessed for common co-morbidities.All patients referred to the Pediatric Endocrine Clinic received appropriate evaluation for PCOS. In addition, 89% of the study group underwent further assessment for selected complications of PCOS.Conclusions: Patients presenting to an inner-city pediatric clinic with 'possible' PCOS often do not receive a complete diagnostic evaluation. In addition, those evaluated for PCOS are often not adequately screened for the known health consequences associated with this condition. These findings suggest that PCOS is under evaluated and possibly under diagnosed in this pediatric population, which raises serious concerns regarding the potential for major longterm public health consequences.Conflict of interest:None declared

BACKGROUND/AIMS: Studies in adult population have suggested that leptin might play a role in inducing obesity related hypertension mediated by the sympathetic nervous system. This association has not been established for adolescents. Our study is designed to explore the relationship between leptin and norepinephrine levels in pediatric patients and to identify any contributors to hypertension for this population. METHODS: Thirty-nine obese adolescents, divided into four groups by gender and hypertension status were included in the study. Leptin and norepinephrine levels were measured during oral glucose tolerance tests (OGTT) to optimize hormonal secretion. T tests were used to compare baseline levels of glucose, insulin, leptin and norepinephrine at 0 hour point of OGTT between the hypertensive and normotensive patients for both genders. Analysis of covariance (ANCOVA) was used for comparison of subsequent levels between the hypertensive and normotensive groups for in both genders, with the corresponding baseline level as the covariance. Models with and without BMI adjustment were created and their results were found to be consistent. Correlation between leptin and norepinephrine was examined at each time point and through analysis of area under the curve (AUC). RESULTS: Contrary to the previous findings obtained in adult patients, our results did not show any direct relationships between levels of leptin and norepinephrine. A slight decrease in norepinephrine level at 1 hour in the normotensive male group and a significant increase in leptin level at 1 hour in the hypertensive female group was observed. CONCLUSION: Our preliminary data suggest that norepinephrine and leptin levels at 0 and 1 hour during routine OGTT, for males and females, respectively, may help identify a subgroup of obese adolescents who have higher risk for hypertension and cardiovascular complications.