Faculty Bibliography

Hypogonadal adolescent girls need estrogen therapy for the induction of puberty. For years, oral conjugated estrogens have been used for this purpose, starting at a very low dose, with gradual increments over time, to allow for the maturation of the reproductive organs, in order to mimic physiologic conditions. Several concerns, mainly due to first pass through the liver, are manifest with oral estrogen therapy. With the advent of transdermal estrogens and its improved efficacy profile as well as reduced side effects, it seems reasonable to consider it for pubertal induction. The primary objective of this study was to compare and contrast oral versus transdermal estrogen with regard to metabolism and physiology and to review current available data on transdermal estrogens with respect to exogenous pubertal induction.

Abstract The development of white matter signal abnormalities on magnetic resonance brain imaging (MRI) in children and young adults with congenital adrenal hyperplasia has been well documented. Existing theories regarding the development of these findings include effects of electrolyte imbalances, effects of disease-related hormone abnormalities, and non-physiologic long-term administration of corticosteroids. Many of the patients previously described were normal neurologically. We describe the case of white matter signal abnormalities in a neonate with salt-wasting congenital adrenal hyperplasia who presented with seizures during the first week of life, possibly due to a transient blood calcium disturbance. This case suggests that white matter changes are not simply the result of chronic insults and that they may not always be subclinical.

Abstract Objective: This study aims to describe the final adult height (FAH) and pubertal growth patterns in human immunodeficiency virus (HIV)-infected adolescents and to compare these to an age-matched population of seroreverting HIV-exposed, uninfected (HEU) adolescents. It further aims to evaluate the interplay of proinflammatory cytokines with insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), and IGFBP-1 during the pubertal growth spurt. Methods: HIV-infected (n=34) and HEU (n=12) adolescents who had achieved FAH were evaluated. Auxologic data, viral load, CD4+ T-lymphocyte (CD4) count, and the use of highly active antiretroviral therapy were obtained via a retrospective chart review. Serum interleukin (IL)-1alpha, IL-6, tumor necrosis factor (TNF)-alpha, IGFBP-1, IGFBP-3, and IGF-1 were assessed. Results: The mean FAH standard deviation score for the HIV-infected group was -0.78 (+/-1.1) compared to 0.05 (+/-0.78) for the HEU (p=0.034). There was a positive correlation between CD4 count and FAH (p=0.019). The mean age and magnitude of peak growth velocity (GV) was within normal limits. IL-1alpha, IL-6, TNF-alpha, IGFBP-3, and IGF-1 were not significantly correlated with HIV RNA or height. IGFBP-1 was detectable in 100% of poorly controlled HIV-infected patients and 25% of the HEU cohort (p=0.0003). Conclusions: The FAH of HIV-infected patients was significantly shorter than that of HEU patients, and it positively correlated with CD4 count. Our cohort demonstrated normal timing and magnitude of peak GV during puberty.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting adolescent females. Diagnosis of adolescent PCOS remains a challenge despite several existing criteria. One of the criteria includes ultrasound features, but this may under/over diagnose PCOS in adolescents. However, newer ultrasound modalities such as 3D sonograms may circumvent this limitation. Objective: To evaluate the role of ultrasonography in the diagnosis of adolescent PCOS by reviewing available studies that assessed the ovarian volume (OV) and other ovarian morphological features such as location and number of follicles, stromal area and volume. Methods: MEDLINE/PubMed database were searched to identify studies which assessed ovarian characteristics of adolescent PCOS patients (age, 10-19 years) by ultrasound. Studies on adults were also reviewed if study population included adolescents and stromal characteristics were assessed by 3D sonogram. Results: Four studies including 239 PCOS patients in the age group of 10-19yrs were identified. Two third of patients were overweight/ obese and one third of patients were non obese. Ethnic groups included CaucAsian (46%), Asian (32%), Hispanic (18%) and African American (3%). Most CaucAsians (96%) and Hispanics (95%) were overweight/obese and most Asians (89%) were non obese. Mean OV was 10.42cm3 for PCOS patients and 4.77cm3 for controls. The morphology of ovarian follicles was reported in two studies (n=84) which showed peripheral and multiple follicles (>10) in 85% of cases. Two studies that used 3D sonogram in adult PCOS (patients = 157, controls =107) partly included adolescents (age range 15-35yrs). Study population consisted of non obese CaucAsians (72%), and overweight/obese Asians (28%). Mean OV was 13.2cm3 for PCOS patients and 8.3cm3 for controls. Average numbers of follicles were >15 in all PCOS patients and stromal area to total ovarian area (S/A) ratio was significantly higher in PCOS patients than controls. One study reported Stromal volume (SV) and stromal/ovarian volume (SV/OV) ratio as significantly higher in PCOS patients (n=112) than controls (n=52) and ovarian vascularization significantly lower in controls than the patients. Indices such as S/A ratio,SV and SV/OV ratio were positively correlated with hyperandrogenemia. Conclusion:Pelvic ultrasound plays an increasingly important role in the diagnosis of PCOS in adolescent girls. Besides ovarian volume, ovarian morphology to look for peripherally located multiple follicles must be assessed with 2D ultrasound. 3D ultrasound allows for a more precise and objective assessment of not only ovarian morphology but also stromal area and volume, and overall blood flow patterns within the ovary. Further studies are warranted to evaluate the utility of 3D ultrasonographic assessment in adolescents with PCOS

Context: Bisphenol A (BPA) is an environmental endocrine disruptor that has been linked to many reproductive disorders in animal models and humans. One such disorder is polycystic ovary syndrome (PCOS), which has been correlated with increased BPA levels in adult women. However, little is known about the role of serum BPA in adolescents with PCOS and its correlation with the metabolic profile. Objectives: To measure BPA levels in adolescent with PCOS as compared to a body mass index (BMI)-matched control group. To correlate serum BPA levels with disease severity, as measured by biochemical and radiologic features. Design: A retrospective chart review of clinical, biochemical, and ultrasonographic data in adolescents with PCOS and controls. Serum BPA was measured and compared between groups and correlated with biochemical (testosterone, insulin resistance) and ovarian ultrasound findings. Setting: Urban tertiary academic medical center. Participants: Study groups included 15 overweight/obese adolescent females with PCOS (mean age 15.27 years, mean BMI 32.84) and 14 BMI-matched female controls (mean age 14.1 years, mean BMI 31). Results: Biochemical data showed a mean free testosterone of 7.06 pg/mL and mean LH:FSH ratio of 1.93 in the PCOS group as compared to mean testosterone of 4.51 pg/mL and mean LH:FSH ratio of 1.12 in the control group (P=0.08 and 0.012, respectively). The index of insulin resistance (HOMA-IR) was 1.65 in the PCOS group and 1.82 in the control group (P=0.75). Serum BPA levels were 0.624 +/-1.29 ng/mL in the PCOS group versus 0.28 +/-0.11 ng/mL in controls (P=0.325). No correlation was found between serum BPA levels and biochemical and radiologic markers of PCOS severity. Conclusions: The results of this exploratory study pose many interesting questions about BPA exposure in adolescents. Although the results are not statistically significant, both adult studies and animal models have shown a strong correlation between serum BPA and severity of PCOS. The weaker relationship in adolescents may be explained in part by shorter duration of exposure to BPA in years. Further studies are warranted to clarify the correlation of PCOS and the endocrine disruptor BPA in a larger setting

Background: Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder, with an incidence of 1:15,000. More than 90% of cases result from mutations of CYP21, leading to 21-OH-ase deficiency with inadequate cortisol production and increased ACTH with resultant hyperplasia of the adrenal glands in both genders and female masculinization of the external genitalia (clitoral enlargement, labioscrotal fusion). Delaying diagnosis in males can precipitate adrenal crisis. There are limited reports in the literature which investigate this entity and the utility of adrenal ultrasound (US) in the early diagnosis of CAH. Definitive diagnosis of CAH is made by biochemical studies, but results are not immediately available. Objectives: Our objectives were to assess the usefulness of neonatal US of the adrenal glands as an additional rapid study in the diagnosis of CAH and to review the literature on the sonographic criteria for the diagnosis. Design: Retrospective review and analysis of adrenal sonographic images were performed by two radiologists on two separate occasions. The size, morphology, and echogenicity of each adrenal gland were evaluated. The diagnosis of CAH was confirmed with biochemical and genetic studies. The adrenal gland was considered enlarged if adrenal gland length 20mm, width 4 mm. Study Subjects: We reviewed the adrenal US of 7 neonates (5 males, 2 females) with CAH. Six subjects were identified with Salt-wasting (SW) CAH and 1 with Simple-virilizing (SV) CAH. Fourteen adrenal US images were reviewed. Results: The morphologic characteristics of the adrenal glands were described. Five patients had surface-pattern of cerebriform appearance with bilateral (b/l) adrenal gland enlargement. One patient had a lobular surface appearance and the other patient had lobular/smooth appearance. Corticomedullary differentiation and echogenicity were preserved in all patients. The size (length and width) of adrenal glands were reviewed for 12 images. One patient was excluded; he had normal length and width measurements because of prior treatment. The majority of cases (11/12 images in 6 neonates) had abnormal length measurements (range: 20mm-35mm, mean 26.7mm). More than half of subjects also had (7/11 images, 4 neonates) abnormal adrenal gland width (range: 4mm-6mm). Four out of eleven images (2 neonates) had adrenal gland width measurements within normal range (3mm). Conclusions: We support the findings that characteristic bilateral adrenal gland enlargement and cerebriform/lobulated tubular appearance are associated in neonates with CAH. Our data supports the premise that adrenal US can be utilized as an additional rapid diagnostic tool in neonates suspected for CAH. The sonographic criteria for the enlargement of adrenal glands need to be revised

We present a case of pelvic venous congestion in a 13-year-old girl who complained of pelvic pain for 9 months. The diagnosis of pelvic congestion syndrome was suggested by imaging modalities, including sonography, CT and MRI, with classically described imaging findings. The girl underwent diagnostic laparoscopy, where visual inspection demonstrated congested pelvic veins and endometriosis. After removal of endometrial implants, the child's pain persisted and she subsequently underwent venography and embolization of the ovarian veins. We found no literature describing pelvic venous congestion (PVC) in children. Knowledge that PVC exists in children is important, particularly for pediatric radiologists who are imaging patients with complaints of pelvic pain

Aims: Previous studies have demonstrated an increase in the amount of radiation administered when utilising the radial artery versus the femoral artery for access. However, radiation exposure between experienced radial and femoral operators is not well defined. Methods and results: We retrospectively analysed 1,922 patients who underwent coronary angiography with or without percutaneous coronary intervention (PCI) and had radiation dose data available for analysis at a tertiary care center from October 2010 to June 2011. Experienced operators were defined as those that perform more than >75 PCIs a year with more 95% of cases performed using the transradial or transfemoral approach for at least 5 years. The outcomes of interest were fluoroscopy time (FT) and dose area product (DAP). Analysis was performed separately for diagnostic only procedures and procedures PCI. Data is presented as median [interquartile range], and statistical analysis was performed using the Mann-Whitney U test. Of the 1,922 patients, 1,565 (81.4%) cases were performed by experienced femoral operators and 357 (18.6%) cases were performed experienced radial operators. The majority of these cases (65.3%) underwent a diagnostic coronary angiogram only (989 femoral and 266 radial). For diagnostic coronary angiography, both total dose area product (DAP) and fluoroscopy time (FT) were significantly higher in transradial versus transfemoral approaches (6038 [3158-8884] vs. 5240 [3517-7429] Gym², p<0.001 and 6.2 [4.0-10.2] vs. 3.6 [2.7-5.4] min, p=0.02). For procedures involving PCI, DAP was not significantly different in transradial versus transfemoral approaches (16,842 [12,017-24,532] vs. 15,577 [10,089-22,203] Gym², p=0.06) although FT was significantly higher (20.4 [13.3-29.6] vs. 14.0 [9.9-20.71] min, p<0.001). Conclusions: In a contemporary cohort of patients undergoing coronary angiography with or without PCI, the transradial approach was associated with higher radiation exposure when compared with transfemoral approach, even in cases performed by experienced operators. While transradial procedures has other advantages (reduced access site complications/bleeding), the amount of radiation administered should be borne in mind while caring for such patients

BACKGROUND: Activating mutations of the ABCC8 gene can lead to permanent neonatal diabetes mellitus (PNDM). Glucose variability in infants with NDM treated with insulin can be extreme. We report long-term glycemic control in a patient with PNDM on sulfonylurea therapy, despite initial allergic reaction. METHODS: A Chinese girl presented on the first day of life with persistent hyperglycemia. Despite treatment with various insulin regimens, hemoglobin (Hb)A1c (normal 4.8%-6.3%) increased from 5.0% at 14 days of age to a peak of 9.7% at 15 months of age. Her average insulin dose was 0.5 units/kg/day. Genetic analysis revealed two novel ABCC8 gene activating mutations encoding the beta-cell sulfonylurea-1 receptor of the ATP-sensitive potassium channel. At age 3 years 2 months, transition from insulin to the oral sulfonylurea glyburide was initiated. After 8 days, she developed urticaria, palmar erythema, and a diffuse maculopapular rash, which resolved when medication was discontinued. At age 3 years 11 months, glyburide was reintroduced at a very low dose and was increased with concomitant weaning of insulin over the following 6 months. RESULTS: Normoglycemia (HbA1c 5.6%) was achieved on glyburide without any further allergic reaction at the age of 4 years 5 months with improved metabolic control. For the next 3 years, HbA1c measurements, and glucose means and variability were significantly lower compared with values during insulin therapy. CONCLUSIONS: As compared with subcutaneous insulin, oral sulfonylureas improved long-term metabolic control in a patient with NDM caused by novel activating mutations in the ABCC8 gene. Desensitization permitted safe oral sulfonylurea therapy in our patient with NDM despite initial allergic reaction. Fewer episodes of hypoglycemia occurred on sulfonylurea than on insulin therapy, which is an advantage in a very young child.

CONTEXT: Serum anti-Mullerian hormone (AMH) is linked to the ovarian follicle pool. Little is known about the relationship between serum AMH and ovarian ultrasound (US) features in adolescents with polycystic ovary syndrome (PCOS). OBJECTIVES: To confirm that serum AMH is elevated in adolescents with PCOS and to correlate serum AMH with ovarian US features in this population are the objectives of this study. DESIGN: A retrospective chart review of clinical, biochemical, and ultrasonographic data in adolescents with PCOS and normal controls is the design of the study. Serum AMH was measured and compared between groups and correlated with ovarian US findings. SETTING: The study was done in two urban tertiary academic medical centers. PARTICIPANTS: Study groups included 23 adolescent females with PCOS and 12 age and BMI-matched female controls. Main outcome measures: We hypothesized that serum AMH would be elevated in the PCOS group compared with the controls and would positively correlate with the follicle number, distribution, and ovarian volume. RESULTS: Serum AMH was 6.78+/-3.55 ng/mL in the PCOS group vs. 3.38+/-1.48 ng/mL in the controls (p=0.0004). AMH positively correlated with ovarian volume (left ovary r=0.65, p=0.0007, right ovary r=0.55, p=0.0065) and peripheral follicle distribution (p=0.0027). Ten or more follicles were observed in 83% of USs. CONCLUSIONS: There is a positive relationship between serum AMH and ovarian volume as well as peripheral follicular distribution in adolescents with PCOS. Our findings support the use of serum AMH as a useful marker to reflect ovarian US features typical of PCOS in cases where accurate USs are not available and for follow-up.