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Maurício Martins da Silva Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

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Lueni Lopes Felix Xavier Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

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Carlos Frederico Lima Gonçalves Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

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Ana Paula Santos-Silva Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
NUMPEX, Campus Duque de Caxias, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

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Francisca Diana Paiva-Melo Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

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Mariana Lopes de Freitas Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

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Rodrigo Soares Fortunato Laboratory of Molecular Radiobiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

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Leandro Miranda-Alves Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

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Andrea Claudia Freitas Ferreira Laboratory of Endocrine Physiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
NUMPEX, Campus Duque de Caxias, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

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Bisphenol A (BPA) is the most common monomer in polycarbonate plastics and an endocrine disruptor. Though some effects of BPA on thyroid hormone (TH) synthesis and action have been described, the impact of this compound on thyroid H2O2 generation remains elusive. H2O2 is a reactive oxygen species (ROS), which could have deleterious effect on thyrocytes if in excess. Therefore, herein we aimed at evaluating the effect of BPA exposition both in vivo and in vitro on H2O2 generation in thyrocytes, besides other essential steps for TH synthesis. Female Wistar rats were treated with vehicle (control) or BPA 40 mg/kg BW for 15 days, by gavage. We then evaluated thyroid iodide uptake, mediated by sodium-iodide symporter (NIS), thyroperoxidase (TPO) and dual oxidase (DOUX) activities (H2O2 generation). Hydrogen peroxide generation was increased, while iodide uptake and TPO activity were reduced by BPA exposition. We have also incubated the rat thyroid cell line PCCL3 with 10−9 M BPA and evaluated Nis and Duox mRNA levels, besides H2O2 generation. Similar to that found in vivo, BPA treatment also led to increased H2O2 generation in PCCL3. Nis mRNA levels were reduced and Duox2 mRNA levels were increased in BPA-exposed cells. To evaluate the importance of oxidative stress on BPA-induced Nis reduction, PCCL3 was treated with BPA in association to N-acetylcysteine, an antioxidant, which reversed the effect of BPA on Nis. Our data suggest that BPA increases ROS production in thyrocytes, what could lead to oxidative damage thus possibly predisposing to thyroid disease.

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Caroline Culen University Clinic of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Diana-Alexandra Ertl University Clinic of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Katharina Schubert University Clinic of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Lisa Bartha-Doering University Clinic of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Gabriele Haeusler University Clinic of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Turner syndrome (TS), although considered a rare disease, is the most common sex chromosome abnormality in women, with an incident of 1 in 2500 female births. TS is characterized by distinctive physical features such as short stature, ovarian dysgenesis, an increased risk for heart and renal defects as well as a specific cognitive and psychosocial phenotype. Given the complexity of the condition, patients face manifold difficulties which increase over the lifespan. Furthermore, failures during the transitional phase to adult care result in moderate health outcomes and decreased quality of life. Guidelines on the optimal screening procedures and medical treatment are easy to find. However, recommendations for the treatment of the incriminating psychosocial aspects in TS are scarce. In this work, we first reviewed the literature on the cognitive and psychosocial development of girls with TS compared with normal development, from disclosure to young adulthood, and then introduce a psychosocial approach to counseling and treating patients with TS, including recommendations for age-appropriate psychological diagnostics. With this work, we aim to facilitate the integration of emphasized psychosocial care in state-of-the-art treatment for girls and women with TS.

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Maria Luisa Brandi Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
Fondazione Italiana Ricerca sulle Malattie dell’Osso (FIRMO Onlus), Florence, Italy

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Stefania Bandinelli Geriatric Unit, Azienda Sanitaria Toscana Centro, Florence, Italy

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Teresa Iantomasi Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

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Francesca Giusti Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

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Eleonora Talluri Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

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Giovanna Sini Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

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Fabrizio Nannipieri Clinical Research, Abiogen Pharma, Pisa, Italy

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Santina Battaglia Clinical Research, Abiogen Pharma, Pisa, Italy

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Riccardo Giusti Clinical Research, Abiogen Pharma, Pisa, Italy

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Colin Gerard Egan CE Medical Writing SRLS, Pisa, Italy

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Luigi Ferrucci Longitudinal Study Section, Translation Gerontology Branch, National Institute on Aging, Baltimore, Maryland, USA

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Objective

This study aimed to evaluate the association between the endocrine-disrupting chemical, bisphenol A (BPA) on circulating levels of 25-hydroxy vitamin D (25(OD)D) and other vitamin D metabolites in an elderly population in Italy.

Methods

This was a retrospective analysis of the InCHIANTI Biobank in Italy. The association between vitamin D metabolites namely 1,25(OH)D, 25(OH)D, parathyroid hormone (PTH) and BPA levels were evaluated. Multiple regression models were used to examine the association between predictor variables with 1,25(OH)D or 25(OH)D levels.

Results

Samples from 299 individuals aged 72.8 ± 15.7 years were examined. Mean levels of BPA, 1,25(OH)D and 25(OH)D were 351.2 ± 511.6 ng/dL, 43.7 ± 16.9 pg/mL and 20.2 ± 12.1 ng/mL, respectively. One hundred eighty individuals (60.2%) were deficient (<20 ng/mL) in 25(OH)D and this population also presented higher BPA levels (527.9 ± 1289.5 ng/dL vs 86.9 ± 116.8 ng/dL, P  < 0.0001). Univariate analysis revealed that BPA levels were negatively correlated with both 1,25(OH)D (r= −0.67, P  < 0.0001) and 25(OH)D (r= −0.69, P  < 0.0001). Multivariate regression revealed that PTH (β: −0.23, 95% CI: −0.34, −0.13, P  < 0.0001) and BPA (β: −0.25, 95% CI: −0.3, −0.19, P  < 0.0001) remained significantly associated with 25(OH)D levels while BPA was also associated with 1,25(OH)D levels (β: −0.19, 95% CI: −0.22, −0.15, P  < 0.0001). Receiver operating characteristic curve analysis showed that a BPA concentration of >113 ng/dL was the best cut-off to predict individuals deficient in 25(OH)D (area under the curve: 0.87, 95% CI: 0.82–0.90, P  < 0.0001).

Conclusion

The strong negative association between BPA and vitamin D in this elderly population warrants further investigation, particularly since this population is already at greatest risk of hypovitaminosis and fracture.

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Stine Linding Andersen Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

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Stig Andersen Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Geriatrics, Aalborg University Hospital, Aalborg, Denmark

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The management of hyperthyroidism in pregnant patients has been a topic of raised clinical awareness for decades. It is a strong recommendation that overt hyperthyroidism of Graves’ disease in pregnant women should be treated to prevent complications. The consequences of hyperthyroidism in pregnancy are less studied than hypothyroidism, and a literature review illustrates that the main burden of evidence to support current clinical guidance emerges from early observations of severe complications in Graves’ disease patients suffering from untreated hyperthyroidism in the pregnancy. On the other hand, the more long-term consequences in children born to mothers with hyperthyroidism are less clear. A hypothesis of fetal programming by maternal hyperthyroidism implies that excessive levels of maternal thyroid hormones impair fetal growth and development. Evidence from experimental studies provides clues on such mechanisms and report adverse developmental abnormalities in the fetal brain and other organs. Only few human studies addressed developmental outcomes in children born to mothers with hyperthyroidism and did not consistently support an association. In contrast, large observational human studies performed within the last decade substantiate a risk of teratogenic side effects to the use of antithyroid drugs in early pregnancy. Thus, scientific and clinical practice are challenged by the distinct role of the various exposures associated with Graves’ disease including the hyperthyroidism per se, the treatment, and thyroid autoimmunity. More basic and clinical studies are needed to extend knowledge on the effects of each exposure, on the potential interaction between exposures and with other determinants, and on the underlying mechanisms.

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Stefan Pilz Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Armin Zittermann Clinic for Thoracic and Cardiovascular Surgery, Herz- und Diabeteszentrum NRW, Ruhr University Bochum, Bad Oeynhausen, Germany

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Christian Trummer Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Verena Theiler-Schwetz Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Elisabeth Lerchbaum Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Martin H Keppel University Institute for Medical and Chemical Laboratory Diagnostics, Paracelsus Medical University, Salzburg, Austria

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Martin R Grübler Department of Cardiology, Swiss Cardiovascular Center Bern, Bern University Hospital, University of Bern, Bern, Switzerland

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Winfried März Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, Ruperto-Carola University of Heidelberg, Heidelberg, Germany
Synlab Medical Center of Human Genetics Mannheim, Mannheim, Germany

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Marlene Pandis Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Vitamin D testing and treatment is a subject of controversial scientific discussions, and it is challenging to navigate through the expanding vitamin D literature with heterogeneous and partially opposed opinions and recommendations. In this narrative review, we aim to provide an update on vitamin D guidelines and the current evidence on the role of vitamin D for human health with its subsequent implications for patient care and public health issues. Vitamin D is critical for bone and mineral metabolism, and it is established that vitamin D deficiency can cause rickets and osteomalacia. While many guidelines recommend target serum 25-hydroxyvitamin D (25[OH]D) concentrations of ≥50 nmol/L (20 ng/mL), the minimum consensus in the scientific community is that serum 25(OH)D concentrations below 25–30 nmol/L (10–12 ng/mL) must be prevented and treated. Using this latter threshold of serum 25(OH)D concentrations, it has been documented that there is a high worldwide prevalence of vitamin D deficiency that may require public health actions such as vitamin D food fortification. On the other hand, there is also reason for concern that an exploding rate of vitamin D testing and supplementation increases costs and might potentially be harmful. In the scientific debate on vitamin D, we should consider that nutrient trials differ from drug trials and that apart from the opposed positions regarding indications for vitamin D treatment we still have to better characterize the precise role of vitamin D for human health.

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Kennett Sprogøe Ascendis Pharma A/S, Hellerup, Denmark

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Eva Mortensen Ascendis Pharma, Inc., Palo Alto, California, USA

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David B Karpf Ascendis Pharma, Inc., Palo Alto, California, USA

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Jonathan A Leff Ascendis Pharma, Inc., Palo Alto, California, USA

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The fundamental challenge of developing a long-acting growth hormone (LAGH) is to create a more convenient growth hormone (GH) dosing profile while retaining the excellent safety, efficacy and tolerability of daily GH. With GH receptors on virtually all cells, replacement therapy should achieve the same tissue distribution and effects of daily (and endogenous) GH while maintaining levels of GH and resulting IGF-1 within the physiologic range. To date, only two LAGHs have gained the approval of either the Food and Drug Administration (FDA) or the European Medicines Agency (EMA); both released unmodified GH, thus presumably replicating distribution and pharmacological actions of daily GH. Other technologies have been applied to create LAGHs, including modifying GH (for example, protein enlargement or albumin binding) such that the resulting analogues possess a longer half-life. Based on these approaches, nearly 20 LAGHs have reached various stages of clinical development. Although most have failed, lessons learned have guided the development of a novel LAGH. TransCon GH is a LAGH prodrug in which GH is transiently bound to an inert methoxy polyethylene glycol (mPEG) carrier. It was designed to achieve the same safety, efficacy and tolerability as daily GH but with more convenient weekly dosing. In phase 2 trials of children and adults with growth hormone deficiency (GHD), similar safety, efficacy and tolerability to daily GH was shown as well as GH and IGF-1 levels within the physiologic range. These promising results support further development of TransCon GH.

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Anastasia K Armeni Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, University of Patras Medical School, Patras, Greece

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Konstantinos Assimakopoulos Department of Psychiatry, University of Patras Medical School, Patras, Greece

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Dimitra Marioli Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, University of Patras Medical School, Patras, Greece

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Vassiliki Koika Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, University of Patras Medical School, Patras, Greece

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Euthychia Michaelidou Department of Biology, University of Patras, Patras, Greece

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Niki Mourtzi Department of Biology, University of Patras, Patras, Greece

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Gregoris Iconomou Department of Psychiatry, University of Patras Medical School, Patras, Greece

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Neoklis A Georgopoulos Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, University of Patras Medical School, Patras, Greece

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Over the past decades, research attention has increasingly been paid to the neurobiological component of sexual behavior. The aim of the present study was to investigate the correlation of estrogen receptor α (ERA) gene polymorphism (rs2234693-PvuII) (T→C substitution) and oxytocin receptor gene polymorphism (rs53576) (G→A substitution) with sexuality parameters of young, healthy women. One hundred thirty-three Greek heterosexual women, students in higher education institutions, 20–25 years of age, sexually active, with normal menstrual cycles (28–35 days), were recruited in the study. Exclusion criteria were chronic and/or major psychiatric diseases, use of oral contraceptive pills (OCs), polycystic ovary syndrome (PCOS), thyroid diseases as well as drugs that are implicated in hypothalamus–pituitary–gonadal axis. T allele (wildtype) of rs2234693 (PvuII) polymorphism of ERA gene was correlated with increased levels of arousal and lubrication, whereas A allele (polymorphic) of rs53576 (OXTR) polymorphism was correlated with increased arousal levels. The simultaneous presence of both T allele of rs2234693 (PvuII) and A allele of rs53576 (OXTR) polymorphisms (T + A group) was correlated with increased arousal, orgasm levels as well as female sexual function index full score. To our knowledge, this is the first study to investigate the interaction between ERA and OXTR with regard to sexual function in women. Female sexuality is a complex behavioral trait that encompasses both biological and psychological components. It seems that variability in female sexual response stems from genetic variability that characterizes endocrine, neurotransmitter and central nervous system influences.

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Adriano N Cury Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Verônica T Meira Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Osmar Monte Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil
Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Marília Marone Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Nilza M Scalissi Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Cristiane Kochi Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Luís E P Calliari Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Carlos A Longui Pediatric Endocrinology Unit, Endocrinology and Metabolism, Nuclear Medicine Laboratory, Pediatrics Department, Irmandade da Santa Casa de Misericórdia de São Paulo, 01221-020 São Paulo, Brazil

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Background/aims

Treatments for Graves' disease (GD) in children and adolescents include oral antithyroid drugs (ATDs), near total thyroidectomy, and radioactive iodine (RAI). ATDs remain the preferred choice in this age group, but because persistent remission occurs in 30% of cases, RAI is becoming a common option for definitive therapy.

Methods

We performed a review of 65 medical records of GD patients under age 19 years who were followed between 1985 and 2005.

Results

The prevalence of GD was higher in females (3:1) and during puberty (for both genders). If no remission was detected during ATD treatment, RAI was indicated when the following criteria were present: non-compliance, relapse, or side effects that were related to ATDs, large goiter, and long-term use of ATDs. The majority of patients developed hypothyroidism within 6 months after RAI. A progressive higher dose regimen was implemented in the last 10 years of the study period. A second RAI dose was necessary in eight cases. During the follow-up period, three pregnancies occurred. One patient with a thyroid nodule and benign cytology was detected.

Conclusions

RAI therapy is effective and safe in the treatment of GD in children and adolescents.

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Aldo Bonaventura Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

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Fabrizio Montecucco Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

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Franco Dallegri Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

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The prevalence of type 2 diabetes mellitus (T2DM) is increasing all over the world. Targeting good glycemic control is fundamental to avoid the complications of diabetes linked to hyperglycemia. This narrative review is based on material searched for and obtained via PubMed up to April 2015. The search terms we used were: ‘hypoglycemia, diabetes, complications’ in combination with ‘iatrogenic, treatment, symptoms.’ Serious complications might occur from an inappropriate treatment of hyperglycemia. The most frequent complication is iatrogenic hypoglycemia that is often associated with autonomic and neuroglycopenic symptoms. Furthermore, hypoglycemia causes acute cardiovascular effects, which may explain some of the typical symptoms: ischemia, QT prolongation, and arrhythmia. With regards to the latter, the night represents a dangerous period because of the major increase in arrhythmias and the prolonged period of hypoglycemia; indeed, sleep has been shown to blunt the sympatho-adrenal response to hypoglycemia. Two main strategies have been implemented to reduce these effects: monitoring blood glucose values and individualized HbA1c goals. Several drugs for the treatment of T2DM are currently available and different combinations have been recommended to achieve individualized glycemic targets, considering age, comorbidities, disease duration, and life expectancy. In conclusion, according to international guidelines, hypoglycemia-avoiding therapy must reach an individualized glycemic goal, which is the lowest HbA1c not causing severe hypoglycemia and preserving awareness of hypoglycemia.

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Ashley N Reeb Department of Otolaryngology, Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

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Andrea Ziegler Department of Otolaryngology, Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

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Reigh-Yi Lin Department of Otolaryngology, Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

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Follicular thyroid cancer (FTC) is the second most common type of thyroid cancers. In order to develop more effective personalized therapies, it is necessary to thoroughly evaluate patient-derived cell lines in in vivo preclinical models before using them to test new, targeted therapies. This study evaluates the tumorigenic and metastatic potential of a panel of three human FTC cell lines (WRO, FTC-238, and TT1609-CO2) with defined genetic mutations in two in vivo murine models: an orthotopic thyroid cancer model to study tumor progression and a tail vein injection model to study metastasis. All cell lines developed tumors in the orthotopic model, with take rates of 100%. Notably, WRO-derived tumors grew two to four times faster than tumors arising from the FTC-238 and TT2609-CO2 cell lines. These results mirrored those of a tail vein injection model for lung metastasis: one hundred percent of mice injected with WRO cells in the tail vein exhibited aggressive growth of bilateral lung metastases within 35 days. In contrast, tail vein injection of FTC-238 or TT2609-CO2 cells did not result in lung metastasis. Together, our work demonstrates that these human FTC cell lines display highly varied tumorigenic and metastatic potential in vivo with WRO being the most aggressive cell line in both orthotopic and lung metastasis models. This information will be valuable when selecting cell lines for preclinical drug testing.

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