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      Suppression of TSH in Congenital Hypothyroidism Is Significantly Related to Serum Levels and Dosage of Thyroxine

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          Abstract

          Aim: To assess thyrotropin (thyroid-stimulating hormone; TSH) suppression and serum thyroxine (T<sub>4</sub>) concentrations in infants with congenital hypothyroidism in relation to T<sub>4</sub> dose and pretreatment parameters. Method: A retrospective study of all cases treated in a single centre since neonatal screening began was performed. Results: In 54 infants treated with a mean daily T<sub>4</sub> dose of 9.8 µg/kg, the TSH concentration was suppressed (<6 mU/l) in 65% of the cases by 6 months with the serum T<sub>4</sub> level at the upper end of the infant reference range. Infants who suppressed their TSH later did not differ in pretreatment serum TSH or T<sub>4</sub> concentration. T<sub>4</sub> dose and serum T<sub>4</sub> level were lower in infants whose TSH was not suppressed. Conclusions: TSH suppression in congenital hypothyroidism is significantly related to serum levels and dosage of T<sub>4</sub>. We suggest that a delay in TSH suppression is mainly due to undertreatment.

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          Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism.

          Patients with hypothyroidism are usually treated with thyroxine (levothyroxine) only, although both thyroxine and triiodothyronine are secreted by the normal thyroid gland. Whether thyroid secretion of triiodothyronine is physiologically important is unknown. We compared the effects of thyroxine alone with those of thyroxine plus triiodothyronine (liothyronine) in 33 patients with hypothyroidism. Each patient was studied for two five-week periods. During one period, the patient received his or her usual dose of thyroxine. During the other, the patient received a regimen in which 50 microg of the usual dose of thyroxine was replaced by 12.5 microg of triiodothyronine. The order in which each patient received the two treatments was randomized. Biochemical, physiologic, and psychological tests were performed at the end of each treatment period. The patients had lower serum free and total thyroxine concentrations and higher serum total triiodothyronine concentrations after treatment with thyroxine plus triiodothyronine than after thyroxine alone, whereas the serum thyrotropin concentrations were similar after both treatments. Among 17 scores on tests of cognitive performance and assessments of mood, 6 were better or closer to normal after treatment with thyroxine plus triiodothyronine. Similarly, among 15 visual-analogue scales used to indicate mood and physical status, the results for 10 were significantly better after treatment with thyroxine plus triiodothyronine. The pulse rate and serum sex hormone-binding globulin concentrations were slightly higher after treatment with thyroxine plus triiodothyronine, but blood pressure, serum lipid concentrations, and the results of neurophysiologic tests were similar after the two treatments. In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland.
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            Influence of timing and dose of thyroid hormone replacement on development in infants with congenital hypothyroidism.

            To test whether early treatment with a high initial dose of levothyroxine can prevent suboptimal mental development in all neonates with congenital hypothyroidism (CH). Sixty-one patients, 27 with severe CH and 34 with mild CH, were treated either early ( or =13 days) with either a high initial dose of levothyroxine (> or =9.5 microg/kg/d) or a low initial dose (<9.5 microg/kg/d). With these criteria, 4 treatment groups were formed. The results of the Bayley test, performed at the age of 10 to 30 months and expressed as mental developmental index (MDI) and psychomotor developmental index (PDI), were related to socioeconomic status, treatment group, initial free thyroxine (FT(4)) concentration, and mean FT(4) concentration during the first 3 months of treatment (FT(4)-A) and the ensuing 9 months (FT(4)-B). Mean (+/- SD) MDI was 113 +/- 14, and mean PDI was 114 +/- 12. In the severe CH group, only the patients treated early with a high initial dose had normal MDI scores (124 +/- 16), whereas the scores of the other groups ranged from 97 to 103. In contrast, all patients in the mild CH group had normal scores (range, 122-125), except those in the group treated late with a low initial dose, whose score was 110 +/- 10. Forty-three percent of the variance in MDI and PDI scores was explained by treatment factors, such as the treatment group, initial FT(4) concentration, FT(4)-A, and FT(4)-B. Our data suggest that optimal treatment includes achievement of euthyroidism before the third week of life by initiation of therapy before 13 days with a levothyroxine dose above 9.5 microg/kg/d and maintenance of FT(4) concentrations in the upper normal range during the first year. Thus treated, patients with CH can achieve normal psychomotor development at 10 to 30 months, irrespective of the severity of the disease.
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              Outcome of severe congenital hypothyroidism: closing the developmental gap with early high dose levothyroxine treatment

              J Dubuis (1996)
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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
                1663-2818
                1663-2826
                2003
                2003
                20 February 2003
                : 59
                : 2
                : 85-90
                Affiliations
                aChildren’s Hospital, Leicester Royal Infirmary, Leicester, and bDepartment of Epidemiology and Public Health, University of Leicester, Leicester, UK
                Article
                68576 Horm Res 2003;59:85–90
                10.1159/000068576
                12589112
                cf0378aa-9aee-415b-841f-dfa2dc2c521a
                © 2003 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.

                History
                : 28 June 2002
                : 28 October 2002
                Page count
                Figures: 1, Tables: 4, References: 30, Pages: 6
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Thyroxine serum levels,Thyrotropin suppression,Congenital hypothyroidism, infants

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