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      Episodes of Overtreatment during the First Six Months in Children with Congenital Hypothyroidism and Their Relationships with Sustained Attention and Inhibitory Control at School Age

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          Abstract

          Background/Aims: Contradictory results regarding the optimal initial dose of levothyroxine in children with congenital hypothyroidism (CH) hamper the clinical management of these children during their early infancy. We explore the relationships between the initial dose of levothyroxine and endocrine control during the first 6 months and cognition at school age. Subjects and Methods: Fifty children with CH, 14 boys (10 ± 3.1 years) and 36 girls (9.7 ± 2.6 years), at the Pediatric Endocrine Unit of the Hospital Gregorio Marañón in Madrid were studied. Neurocognitive evaluation was carried out exploring alertness and inhibitory control. The number of episodes of overtreatment during the first 6 months, the initial dose of levothyroxine, etiology and sex were the predictor variables. Results: Inhibitory control was significantly lower in children with CH than in controls. An interaction with gender and etiology was obtained. Alertness had an inverse relationship with the number of episodes of overtreatment with no interaction with gender or etiology. Conclusion: Episodes of overtreatment and not the initial dose of levothyroxine are a risk factor for deficit in alertness whereas subtle inhibitory control deficit seems to be a permanent problem with the current therapeutic approach.

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          Thyroid hormone receptors in brain development and function.

          Juan Bernal (2007)
          Thyroid hormones are important during development of the mammalian brain, acting on migration and differentiation of neural cells, synaptogenesis, and myelination. The actions of thyroid hormones are mediated through nuclear thyroid hormone receptors (TRs) and regulation of gene expression. The purpose of this article is to review the role of TRs in brain maturation. In developing humans maternal and fetal thyroid glands provide thyroid hormones to the fetal brain, but the timing of receptor ontogeny agrees with clinical data on the importance of the maternal thyroid gland before midgestation. Several TR isoforms, which are encoded by the THRA and THRB genes, are expressed in the brain, with the most common being TRalpha1. Deletion of TRalpha1 in rodents is not, however, equivalent to hormone deprivation and, paradoxically, even prevents the effects of hypothyroidism. Unliganded receptor activity is, therefore, probably an important factor in causing the harmful effects of hypothyroidism. Accordingly, expression of a mutant receptor with impaired triiodothyronine (T(3)) binding and dominant negative activity affected cerebellar development and motor performance. TRs are also involved in adult brain function. TRalpha1 deletion, or expression of a dominant negative mutant receptor, induces consistent behavioral changes in adult mice, leading to severe anxiety and morphological changes in the hippocampus.
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            Attentional networks

            Michael Posner, Stanislas Dehaene (1994)
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              The functional integration of the anterior cingulate cortex during conflict processing.

              Michael Posner, John Fossella, Kevin G. Guise … (2008)
              Although functional activation of the anterior cingulate cortex (ACC) related to conflict processing has been studied extensively, the functional integration of the subdivisions of the ACC and other brain regions during conditions of conflict is still unclear. In this study, participants performed a task designed to elicit conflict processing by using flanker interference on target response while they were scanned using event-related functional magnetic resonance imaging. The physiological response of several brain regions in terms of an interaction between conflict processing and activity of the anterior rostral cingulate zone (RCZa) of the ACC, and the effective connectivity between this zone and other regions were examined using psychophysiological interaction analysis and dynamic causal modeling, respectively. There was significant integration of the RCZa with the caudal cingulate zone (CCZ) of the ACC and other brain regions such as the lateral prefrontal, primary, and supplementary motor areas above and beyond the main effect of conflict and baseline connectivity. The intrinsic connectivity from the RCZa to the CCZ was modulated by the context of conflict. These findings suggest that conflict processing is associated with the effective contribution of the RCZa to the neuronal activity of CCZ, as well as other cortical regions.
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                Author and article information

                Journal
                Journal ID (publisher-id): HRP
                Journal ID (nlm-ta): Horm Res Paediatr
                Journal ID (doi): 10.1159/issn.1663-2818
                Title: Hormone Research in Paediatrics
                Publisher: S. Karger AG
                ISSN (Print): 1663-2818
                ISSN (Electronic): 1663-2826
                Publication date Subscription-year: 2010
                Publication date (Print): July 2010
                Publication date (Electronic): 16 April 2010
                Volume: 74
                Issue: 2
                Pages: 114-120
                Affiliations
                aFaculty of Psychology, University of Havana, Cuba; bPaediatric Endocrine Unit and cLaboratory of Metabolic Disorders, University Hospital Gregorio Marañón, Madrid, Spain
                Author notes
                *Miguel A. Alvarez, Faculty of Psychology, University of Havana, Mazon y San Rafael 10400 (Cuba), Tel. +53 755 3034, Fax +53 755 1820, E-Mail malv@infomed.sld.cu
                Article
                Publisher ID: 313370 Other ID: Horm Res Paediatr 2010;74:114–120
                DOI: 10.1159/000313370
                PubMed ID: 20395659
                SO-VID: c02c1b95-45b8-46d3-95c3-80557eff9c1b
                Copyright © © 2010 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 26 June 2009
                Date accepted : 12 November 2009
                Page count
                Figures: 3, Tables: 1, References: 47, Pages: 7
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Keywords: Congenital hypothyroidism,Endocrine control,Neurocognition
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes, Neurology, Nutrition & Dietetics, Sexual medicine, Internal medicine, Pharmacology & Pharmaceutical medicine
                Keywords: Congenital hypothyroidism, Endocrine control, Neurocognition

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