Vivian L. Chin

Retinoic acid-induced CD38 expression in HL-60 myeloblastic leukemia cells regulates cell differentiation or viability depending on expression levels

Retinoic acid‐induced expression of the CD38 ectoenzyme receptor in HL‐60 human myeloblastic leukemia cells is regulated by RARα and RXR, and enhanced or prevented cell differentiation depending on the level of expression per cell. RARα activation caused CD38 expression, as did RXR activation but not as effectively. Inhibition of MAPK signaling through MEK inhibition diminished the induced expression by both RARs and RXRs. Expression of CD38 enhanced retinoic acid‐induced myeloid differentiation and G0 cell cycle arrest, but at higher expression levels, induced differentiation was blocked and retinoic acid induced a loss of cell viability instead. In the case of 1,25‐dihydroxyvitamin D3, induced monocytic differentiation was also enhanced by CD38 and not enhanced by higher expression levels, but without induced loss of viability. Expression levels of CD38 thus regulated the cellular response to retinoic acid, either propelling cell differentiation or loss of viability. The cellular effects of CD38 thus depend on its expression level. J. Cell. Biochem. 97: 1328–1338, 2006.

Gonadal dysfunction in Morbidly Obese Adolescent Girls

OBJECTIVE To describe gonadal dysfunction and evaluate polycystic ovary syndrome (PCOS) and its association with metabolic syndrome (MeS) among girls in a morbidly obese adolescent population. DESIGN In a cross-sectional study of 174 girls, height, weight, waist circumference, Tanner stage, reproductive hormones, carbohydrate and lipid markers, drug use, and menstrual history were obtained at baseline. Exclusion criteria were menarcheal age <2 years, hormonal contraceptive or metformin use, Tanner stage <4, and incomplete data on PCOS or MeS classification. SETTING University medical center outpatient clinic. PATIENT(S) Ninety-eight girls ages 13-19.6 years, Tanner 5, average body mass index of 46.6 kg/m(2), menarche at 11.4 years, and average menarcheal age of 5 years. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Polycystic ovary syndrome and MeS. RESULT(S) Ninety-eight girls were divided into four groups: PCOS by National Institutes of Health criteria (PCOSN, n = 24), irregular menses only (n = 25), elevated T (≥55 ng/dL) only (n = 6), and obese controls (n = 43). Metabolic syndrome by modified Cook criteria affected 32 girls or 33% overall: 6 of 24 PCOSN, 7 of 25 irregular menses only, 4 of 6 elevated T only, and 15 of 43 obese controls. Polycystic ovary syndrome by National Institutes of Health criteria and its individual components were not associated with MeS after adjusting for body mass index. CONCLUSION(S) Unlike obese adults, PCOSN and its individual components were not associated with MeS in the untreated morbidly obese adolescent population.

Bariatric Surgery in Adolescents: Is Routine Nutrient Supplementation Sufficient to Avoid Anemia Following Bariatric Surgery?

Background: Anemia following bariatric surgery is a known complication. To prevent nutrient deficiencies, adolescents require multivitamin/mineral supplementation following bariatric surgery. The purpose of this study was to investigate if routine multivitamin/mineral supplementation is sufficient to prevent anemia in adolescents undergoing bariatric surgery, particularly sleeve gastrectomy (SG), a procedure that may induce nutrient malabsorption. Methods: We conducted a retrospective review of pediatric patients who underwent SG (34 patients) and laparoscopic adjustable gastric banding (LAGB) (141 patients) (January 2006 through December 2013). We examined anemia marker levels (iron, ferritin, folate, B12, hemoglobin, and hematocrit) at first visit and 3, 6, and 12 months postsurgery by repeated-measures analysis adjusting for weight loss. Results: Following SG, folate levels decreased 3 and 6 months postsurgery but returned to baseline levels at 12 months. Furthermore, the SG group demonstrated lower folate levels compared with LAGB at 3 and 6 months. B12 levels decreased 6 months post-SG but returned to baseline at 12 months. Following LAGB, B12 levels decreased 12 months postsurgery compared with baseline. Ferritin levels decreased 3 months post-LAGB but returned to baseline levels at 6 months. There were no changes within groups or differences between groups in iron, hemoglobin, or hematocrit. Conclusions: While anemia did not occur in any patients while on recommended routine supplementation, folate levels were significantly reduced following SG and were lower in SG compared with LAGB patients. Additional folate supplementation seemed to improve folate levels, which highlights the importance of ongoing surveillance by primary care providers and the need for additional folate supplementation following SG.

A case of complete androgen insensitivity syndrome with a novel androgen receptor mutation.

Abstract We report a case of a 14-year-old girl with primary amenorrhea and phenotypic as well as hormonal features of complete androgen insensitivity syndrome (CAIS), who tested positive for a novel missense androgen receptor gene mutation resulting in serine-to-isoleucine change at position 703 in exon 4 in the ligand-binding domain. The interesting features of this case include a persistence of Müllerian derivatives, Sertoli cell adenoma, Tanner III pubic hair, and a normal bone mineral density. These features are not typically described in CAIS. This novel mutation associated with a unique clinical presentation serves to significantly enrich the literature on this rare and fascinating disorder of androgen insensitivity syndrome.

Screening for autoimmune thyroiditis and celiac disease in minority children with type 1 diabetes

Abstract Background: Hashimoto’s thyroiditis (HT) and celiac disease (CD) are commonly associated with type 1 diabetes (T1DM). There is no consensus on screening, however, the American Diabetes Association (ADA) and the International Society for Pediatric and Adolescent Diabetes (ISPAD) recommend testing for thyroid function (TFT), thyroid antibodies and anti-tissue transglutaminase antibodies (TTG) IgA soon after diagnosis. TFT should be repeated every 1–2 years while TTG IgA should be tested for within 2 and 5 years. We hypothesize that the rate of HT and CD in our T1DM children is lower, so screening may need to be revised to reflect their underlying risk. Methods: An Institutional Review Board (IRB)-approved retrospective chart review was conducted on children with T1DM in the past 10 years. Age, sex, race, A1C, TFT, thyroid and celiac antibodies were obtained. t-Tests, the Wilcoxon-Mann-Whitney test and stepwise regression were performed. Results: Of 222 children with T1DM, with a mean age of 15.8±5.53 years, followed for 6.1±4.0 years, 53% female, mean A1C 11.1±1.9% and 87% African American (AA). Three had Graves’ disease (1.3%), three had HT (1.3%) and 97% were euthyroid. TFT were assessed on average every 1.3 years and thyroid antibodies every 2.5 years. Positive thyroid antibody was found in 11%, negative in 57% and unknown in 32%. The positive antibody group had higher mean A1C and TSH. No biopsy confirmed cases of CD (0%) were found when screened every 2.3 years. Conclusions: The number of individuals who screened positive for hypothyroid HT and CD was lower than expected in our population. Further studies are needed to assess the optimal screening frequency for HT and CD in minority children with T1DM.

Long-term follow-up of gonadal dysfunction in morbidly obese adolescent boys after bariatric surgery.

Abstract Background Elevated body mass index (BMI) is associated with hypogonadism in men but this is not well described in adolescents. The aim is to evaluate gonadal dysfunction and the effects of weight loss after gastric banding in obese adolescent boys. Methods Thirty-seven of 54 boys (age 16.2±1.2 years, mean BMI 48.2 kg/m2) enrolled at the Center for Adolescent Bariatric Surgery at Columbia University Medical Center had low total testosterone for Tanner 5 <350 ng/dL. Sixteen had long-term hormonal data for analysis at baseline (T0), 1 year (T1) and 2 years (T2) post-surgery. T-tests, chi-squared (χ2) tests, correlation and linear mixed models were performed. Results At T0, the hypogonadal group had higher systolic blood pressure (SBP) (75th vs. 57th percentile, p=0.02), fasting insulin (19 vs. 9 μIU/mL, p=0.0008) and homeostatic index of insulin resistance (HOMA-IR) (4.2 vs. 1.9, p=0.009) compared to control group. Total testosterone was negatively correlated with fasting insulin and HOMA-IR. In the long-term analysis, BMI, weight, waist circumference (WC), and % excess weight decreased at T1 and T2 compared to T0. Mean total testosterone at T0, T1 and T2 were 268, 304 and 368 ng/dL, respectively (p=0.07). There was a statistically significant negative correlation between BMI and testosterone after 2 years (r=−0.81, p=0.003). Conclusions Low testosterone levels but unaltered gonadotropins are common in this group and associated with insulin resistance. While a significant increase in testosterone was not found over time, the negative relationship between BMI and testosterone persisted, suggesting there may be an optimal threshold for testosterone production with respect to BMI. Long-term studies are needed.

A Unique Case of Bilateral Hürthle Cell Adenoma in an Adolescent

Background: Hürthle cell (HC) neoplasms are rare among pediatric thyroid cancers. HC adenomas (HCA) are typically benign and localized unilaterally without recurrence, and they are thus treated by hemithyroidectomy. HC carcinomas (HCC) can be bilateral and are more aggressive, necessitating total thyroidectomy. Diagnosis relies upon surgical histopathology demonstrating invasion for classification as HCC or lack of invasion in HCA, since fine needle aspiration fails to differentiate between the two. Methods: We report a case of a 14-year-old adolescent female with bilateral HCA. She had an initial left hemithyroidectomy for a large nodule measuring 2 × 1.5 × 1.2 cm3 in the left lobe, while smaller subcentimeter nodules remained under surveillance in the right. One year later, a nodule in the right lobe doubled in size, necessitating a right hemithyroidectomy which also revealed HCA. Conclusion: To our knowledge, this is the first reported case of bilateral HCA in pediatrics. It highlights the importance of close surveillance of persistent small nodules, even in patients with previously documented benign lesions such as HCA, which are typically thought to be unilateral and localized. Both HCA and HCC remain unpredictable in behavior, and treatment of HCA should be individualized.

Alterations in Glucose Effectiveness and Insulin Dynamics: Polycystic Ovary Syndrome or Body Mass Index

Background/Aims: To delineate the relationship of polycystic ovary syndrome (PCOS), obesity, and hyperandrogenism (HA) with glucose and insulin dynamics in adolescents across a broad body mass index (BMI). Methods: Seventy-four PCOS subjects (aged 16 years) and 82 controls (aged 16 years) were evaluated by an oral glucose tolerance test. Subjects were categorized by BMI: normal weight (21 ± 0.4), overweight/obesity (OO; 33 ± 1.0), and severe obesity (SO; 48 ± 1.4). Indices of glucose and insulin dynamics were determined. Multiple linear regression analysis was used to evaluate the contribution of PCOS, HA, and BMI to these indices. Results: BMI was significantly associated with systolic and diastolic blood pressure and insulin resistance. A significant interaction between BMI and PCOS and indices of post-glucose load was observed. The mean difference in peak glucose, early glucose response, area under the curve for glucose, and glucose effectiveness (SgIo) between PCOS and control subjects was significantly different between OO and SO. In PCOS subjects, testosterone was positively associated with BMI, fasting insulin, early insulin response, and diastolic blood pressure, and negatively associated with SgIo. Conclusions: Abnormal glucose dynamics in adolescents with PCOS is mainly due to SO. The combination of PCOS and SO has a synergistic effect on glucose dynamics when compared to all other groups.

Exenatide Effects on Cardiometabolic Risk and Weight in Adolescents with Morbid Obesity and Type 2 Diabetes Mellitus: Two Case Reports

Objective Glucagon-like peptide-1 (GLP-1) receptor agonists improve glycemic control and cardiometabolic risk factors in adults with type 2 diabetes mellitus, but pediatric data is sparse. Research design and methods This is the first report to describe the effects of GLP-1 receptor agonist Exenatide on metabolic risk and weight in adolescents with morbid obesity (BMI>35kg/m2) and type 2 diabetes in the first 6 months after treatment initiation. Two patients with morbid obesity who failed conventional therapy with insulin glargine and Metformin were treated with the addition of Exenatide. Metabolic parameters were obtained at 3 and 6 months post intervention. Results Improvements in cardiometabolic risk factors, such as fasting glucose and triglyceride levels, as well as HbA1c, were reached at 6 months compared to baseline. Conclusions Our cases highlight the therapeutic potential of exenatide for adolescent patients with morbid obesity and type 2 diabetes.

Evaluation of puberty by verifying spontaneous and stimulated gonadotropin values in girls

Abstract Background: Changes in pharmacological agents and advancements in laboratory assays have changed the gonadotropin-releasing hormone analog stimulation test. Objective: To determine the best predictive model for detecting puberty in girls. Subjects: Thirty-five girls, aged 2 years 7 months to 9 years 3 months, with central precocious puberty (CPP) (n=20) or premature thelarche/premature adrenarche (n=15). Methods: Diagnoses were based on clinical information, baseline hormones, bone age, and pelvic sonogram. Gonadotropins and E2 were analyzed using immunochemiluminometric assay. Logistic regression for CPP was performed. Results: The best predictor of CPP is the E2-change model based on 3- to 24-h values, providing 80% sensitivity and 87% specificity. Three-hour luteinizing hormone (LH) provided 75% sensitivity and 87% specificity. Basal LH lowered sensitivity to 65% and specificity to 53%. Conclusions: The E2-change model provided the best predictive power; however, 3-h LH was more practical and convenient when evaluating puberty in girls.