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      Update on the Management of Congenital Hypothyroidism

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      Hormone Research in Paediatrics

      S. Karger AG

      Congenital hypothyroidism, Screening, Management

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          Abstract

          Background: Congenital hypothyroidism (CH) is the most frequent congenital endocrine disorder. The diagnosis in industrialized countries is usually made with population-based newborn screening that measures thyroid-stimulating hormone (TSH) or TSH and total thyroxine (T<sub>4</sub>) in dried blood spots in the first 3 days of life. In newborns with a screening result suspicious for hypothyroidism, the diagnosis of primary CH is confirmed when serum TSH levels are above and T<sub>4</sub> (free T<sub>4</sub>) levels are below the age-related reference ranges. Hypothalamic-pituitary hypothyroidism is more difficult to diagnose. Most infants with this diagnosis are missed in screening programs unless T<sub>4</sub> (free T<sub>4</sub>)/TSH or TSH/T<sub>4</sub>/thyroxine binding globulin is simultaneously measured. If hypothyroidism is confirmed by laboratory analysis, imaging studies should be performed immediately; however, it is not acceptable to delay hormone replacement therapy if imaging studies are not readily available. Conclusions: The goal of treatment of CH is to avoid disturbed mental development, and initial treatment can be adjusted to physiological conditions. To match the higher thyroid hormone concentrations in the first weeks of life, substitution with l-thyroxine should aim to achieve serum T<sub>4</sub>/free T<sub>4</sub> levels in the upper half of the normal age-related reference range. Some newborns and infants will have persistently high TSH levels despite normalized T<sub>4</sub>/free T<sub>4</sub> serum concentrations.

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          Most cited references 22

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          Neurodevelopmental outcomes in congenital hypothyroidism: comparison of initial T4 dose and time to reach target T4 and TSH.

          To compare neurodevelopmental outcomes in severe and moderate congenital hypothyroidism (CH) among 3 different initial L-thyroxine doses and to examine the effect of the time to thyroid function normalization on neurodevelopmental outcomes. Neurodevelopmental assessments of 31 subjects included the Mullen Scales of Early Learning, Wechsler Preschool and Primary Scale of Intelligence-Revised, Wechsler Intelligence Scale for Children, Wide-Range Achievement Test, and Child Behavioral Checklist. Subjects started on higher initial L-thyroxine doses (50 mug) had full-scale IQ scores 11 points higher than those started on lower (37.5 mug) initial doses. However, verbal IQ, performance IQ, and achievement scores did not differ among the 3 treatment cohorts. Subjects with moderate CH had higher full-scale IQ scores than subjects with severe CH, regardless of the initial treatment dose. Subjects who took longer than 2 weeks to normalize thyroid function had significantly lower cognitive, attention, and achievement scores than those who achieved normal thyroid function at 1 or 2 weeks of therapy. Initial L-thyroxine dose and faster time to normalization of thyroid function are important to optimal neurodevelopmental outcome. In severe CH, it is important to choose an initial dose at the higher end of the recommended range to achieve these goals.
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            Influence of timing and dose of thyroid hormone replacement on mental, psychomotor, and behavioral development in children with congenital hypothyroidism.

            To evaluate the influence of initial and postinitial treatment factors on cognitive, psychomotor, and psychological outcome in schoolchildren with congenital hypothyroidism (CH). We studied 45 patients (19 with severe CH and 26 with mild CH) and 37 control children by correlating initial and postinitial treatment factors (free thyroxine and thyroid-stimulating hormone [TSH] concentrations, and the percentage of overtreatment and undertreatment periods) with the results of neuropsychological tests and behavior (as reported on the Teacher Report Form [TRF]). The global IQ of the children with CH was comparable to that of the controls; visuomotor and verbal scores were lower, and total TRF scores were higher. Ethnic group, previous development, and overtreatment predicted IQ and verbal scores, with higher scores seen for the overtreated patients than for the control children and those patients who had not been overtreated. As initial treatment was less satisfactory, total TRF scores were higher. Our study suggests that initial and postinitial suboptimal treatment of CH leads to abnormalities in IQ and specific fields. Overtreatment may advance cognitive development in 5-1/2- to 7-year-olds. Suboptimal initial treatment may lead to behavioral problems. We recommend that TSH concentrations be maintained within the normal range in patients with CH.
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              Familial neonatal transient hypothyroidism due to maternal TSH-binding inhibitor immunoglobulins.

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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                978-3-8055-8475-3
                978-3-8055-8476-0
                1663-2818
                1663-2826
                2007
                December 2007
                10 December 2007
                : 68
                : Suppl 5
                : 107-111
                Affiliations
                Charité, Institute for Experimental Pediatric Endocrinology, Berlin, Germany
                Article
                110591 Horm Res 2007;68:107–111
                10.1159/000110591
                18174723
                © 2007 S. Karger AG, Basel

                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.

                Page count
                Tables: 2, References: 33, Pages: 5
                Categories
                Pediatric Workshop 4

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