Bina Shah

Outcomes of Children and Adolescents with Well-Differentiated Thyroid Carcinoma and Pulmonary Metastases Following 131I Treatment: A Systematic Review

BACKGROUND The optimal dose and efficacy of ¹³¹I 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 ¹³¹I to decrease disease-related morbidity and obtain disease-free survival while avoiding the potential complications of ¹³¹I therapy. SUMMARY We systematically reviewed the published literature on children and adolescents with WDTC and pulmonary metastases treated with ¹³¹I to examine outcomes after ¹³¹I 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. ¹³¹I 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 ¹³¹I dose. In general, nonresponders received the highest ¹³¹I 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 ¹³¹I 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 ¹³¹I 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 ¹³¹I in this patient population.

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.

Elevated serum anti-Müllerian hormone in adolescents with polycystic ovary syndrome: relationship to ultrasound features

Abstract Context: Serum anti-Müllerian 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.

Endometrial Thickness, Uterine, and Ovarian Ultrasonographic Features in Adolescents with Polycystic Ovarian Syndrome

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.

Antenatal treatment of fetal goiter: a therapeutic challenge

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.

Evaluation of the Pro-inflammatory Cytokine Tumor Necrosis Factor-α in Adolescents with Polycystic Ovary Syndrome

BACKGROUND Patients with polycystic ovary syndrome (PCOS) often suffer from comorbidities associated with chronic inflammation characterized by elevations in pro-inflammatory cytokines. There is limited data on markers of chronic inflammation, in particular Tumor Necrosis Factor-alpha (TNF-α), in adolescents with PCOS. OBJECTIVES To compare serum levels of TNF-α in overweight or obese adolescents with PCOS and obese controls. In the PCOS group, to correlate serum TNF-α levels with body mass index (BMI) z-score, severity of hyperandrogenism, degree of insulin resistance, and ovarian ultrasonographic characteristics. METHODS We performed a cross-sectional retrospective analysis of clinical and biochemical findings in 23 overweight or obese adolescent females with PCOS (mean BMI z-score 2, mean age 15.2 yrs) and 12 obese age- and sex-matched controls (mean BMI z-score 2, mean age 14.1 y). All subjects were post-menarchal. Serum TNF-α levels were compared between groups. In the PCOS group, cytokine levels were correlated with BMI z-score, androgen levels, fasting insulin and glucose levels as well as ovarian ultrasonographic features. RESULTS Both groups were comparable in age, BMI z-score, fasting glucose, and fasting insulin. Mean free testosterone was 9.76 ± 5.13 pg/mL in the PCOS group versus 5 ± 2.02 pg/mL in the control group (P = .0092). Serum TNF-α was 7.4 ± 4 pg/mL in the PCOS group versus 4.8 ± 3.16 pg/mL in the control group (P = .0468). There was no significant correlation between serum TNF-α and BMI z-score, free testosterone, fasting insulin, or fasting glucose. No correlation existed between serum TNF-α and ovarian follicle number, distribution, or volume. CONCLUSIONS Serum TNF-α is elevated in overweight/obese adolescents with PCOS. Chronic inflammation in adolescents with PCOS render them at a potential increased risk for the development of atherosclerosis, type 2 diabetes, cancer, infertility, and other comorbidities. Every effort should be made to identify adolescents with PCOS early and initiate aggressive therapy to prevent future complications.

Letrozole Significantly Improves Growth Potential in a Pubertal Boy With Growth Hormone Deficiency

Clinical experience with using an aromatase inhibitor to suppress estrogen production during puberty for improvement of growth potential in adolescents with short stature is limited. This report documents treatment of such a patient with a combination of growth hormone and letrozole, a third-generation aromatase inhibitor. Our case demonstrates a favorable outcome on a short-term basis.

The Prevalence of Abnormal Liver Enzymes and Metabolic Syndrome in Obese Adolescent Females with Polycystic Ovary Syndrome

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.

Exogenous pubertal induction by oral versus transdermal estrogen therapy.

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.

Growth patterns in pubertal HIV-infected adolescents and their correlation with cytokines, IGF-1, IGFBP-1, and IGFBP-3

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)-1α, IL-6, tumor necrosis factor (TNF)-α, 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-1α, IL-6, TNF-α, 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.