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 (T4) 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 T4 (free T4) 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 T4 (free T4)/TSH or TSH/T4/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 T4/free T4 levels in the upper half of the normal age-related reference range. Some newborns and infants will have persistently high TSH levels despite normalized T4/free T4 serum concentrations.

Keywords:
Congenital hypothyroidism, Screening, Management
1.
Fisher DA: Effectiveness of newborn screening programs for congenital hypothyroidism: prevalence of missed cases. Pediatr Clin North Am 1987;34:881–890.
2.
LaFranchi SH, Hanna CE, Krainz PL, Skeels MR, Miyahira RS, Sesser DE: Screening for congenital hypothyroidism with specimen collection at two time periods. Results of the Northwest Regional Screening Program. Pediatrics 1985;76:734–740.
3.
Delange F: Neonatal screening for congenital hypothyroidism. Results and perspectives. Horm Res 1997;48:51–56.
4.
Fisher DA: Screening for congenital hypothyroidism: status report. Trends Endocrinol 1991;129–134.
5.
Tylek-Lemanska D, Kumorowicz-Kopiec M, Starzyk J: Screening for congenital hypothyroidism: the value of retesting after four months in neonates with low or very low birth weight. J Med Screening 2005;12:166–169.
6.
van Tijn DA, de Vijlder JJ, Verbeeten B Jr, Verkerk PH, Vulsma T: Neonatal detection of congenital hypothyroidism of central origin. J Clin Endocrinol Metab 2005;90:3350–3359.
7.
Olivieri A, Stazi MA, Mastroiacovo P, Fazzini C, Medda E, Spagnolo A, De Angelis S, Grandolfo ME, Taruscio D, Cordeddu V, Sorcini M, Study Group for Congenital Hypothyroidism: A population based study on the frequency of additional congenital malformations in infants with congenital hypothyroidism: Data from the Italian Registry for Congenital Hypothyroidism (1991–1998). J Clin Endocrinol Metab 2002;87:557–562.
8.
American Academy of Pediatrics, Rose SR, and the Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown RS, Public Health Committee, Lawson Wilkins Pediatric Endocrine Society, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, Varma SK: update of newborn screening and therapy for congenital hypothyroidism. Pediatrics 2006;117:2290–2303.
9.
Perry R, Hollmann A, Wood A, Donaldson M: Ultrasound of the thyroid gland in the newborn. Arch Dis Child 2002;87:209–211.
10.
Ohnishi H, Sato H, Noda H, Inomata H, Sasaki N: Color Doppler ultrasonography: diagnosis of ectopic thyroid gland in patients with congenital hypothyroidism caused by thyroid dysgenesis. J Clin Endocrinol Metab 2003;88:5145–5149.
11.
Calvo R, Obregon MJ, Ruiz de Ona C, Escobar del Rey F, Morreale de Escobar G: Congenital hypothyroidism as studied in rats: crucial role of maternal thyroxine but not of 3,5,38-triiodothyronine in the protection of the fetal brain. J Clin Invest 1990;86:889–894.
12.
Bongers Schokking JJ, de Muinck Keizer-Schrama SMPF: Influence of timing and dose of thyroid hormone replacement on mental, psychomotor and behavioral development in children with congenital hypothyroidism. J Pediatr 2005;147:768–772.
13.
LaFranchi S: Congenital hypothyroidism, etiologies, diagnosis and management. Thyroid 1999;9:735–740.
14.
Fisher DA: Management of congenital hypothyroidism. J Clin Endocrinol Metab 1991;72:523–527.
15.
Selva KA, Harper A, Downs A, Blasco PA, LaFranchi SH: Neurodevelopmental outcomes in congenital hypothyroidism: comparison of initial T4 dose and time to reach target T4 and TSH. J Pediatr 2005;147:775–781.
16.
Bakker B, Kempers MJ, De Vijlder JJ, Van Tijn DA, Wiedijk BM, Van Bruggen M, Vulsma T: Dynamics of the plasma concentrations of TSH, FT4 and T3 following thyroxine supplementation in congenital hypothyroidism. Clin Endocrinol 2002;57:529–535.
17.
Bongers Schokking JJ, de Muinck Keizer-Schrama SMPF: Influence of timing and dose of thyroid hormone replacement on mental, psychomotor and behavioral development in children with congenital hypothyroidism. J Pediatr 2005;147:768–772.
18.
Grant DB: Growth in early treated congenital hypothyroidism. Arch Dis Child 1994;70:464–468.
19.
Derksen-Lubsen G, Verkerk PH: Neuropsychologic development in early treated congenital hypothyroidism: analysis of literature data. Pediatr Res 1996;39:561–565.
20.
Delange F, DeVijlder J, Morreale De Escobar G, Rochiccioli P, Varrone S: Significance of early diagnostic data in congenital hypothyroidism: report of the Subcommittee on Neonatal Hypothyroidism of the European Thyroid Association; in Delange F, Fisher DA, Glinoer D (eds): Research in Congenital Hypothyroidism. New York, Plenum Press, NATO ASI Ser 1989, vol 161, pp 225–234.
21.
Heyerdahl S, Kase BF, Lie SO: Intellectual development of children with congenital hypothyroidism in relation to recommended thyroxine treatment. J Pediatr 1991;118:850–855.
22.
Dubuis JM, Glorieux J, Richer F, Deal CL, Dussault JH, Van Vliet G: Outcome of severe congenital hypothyroidism: closing the developmental gap with early high dose levothyroxine treatment. J Clin Endocrinol Metab 1996;81:222–227.
23.
Fisher DA: The importance of early management in optimizing IQ in infants with congenital hypothyroidism (editorial). J Pediatr 2000;136:273–279.
24.
Boileau P, Bain P, Rivas S, Toublanc JE: Earlier onset of treatment or increment in LT4 dose in screened congenital hypothyroidism: which was the more important factor for IQ at 7 years? Horm Res 2004;61:228–234.
25.
Kohler B, Schnabel D, Biebermann H, Grueters A: Transient congenital hypothyroidism and hyperthyrotropinemia: normal thyroid function and physical development at the ages of 6–14 years. J Clin Endocrinol Metab 1996;81:1563–1568.
26.
DuPrez L, Parma J, Van Sande J, Rodien P, Dumont JE, Vassart G, Abramowicz M: TSH receptor mutations and thyroid disease. Trends Endocrinol 1998;9:133–142.
27.
Corvillain B, Van Sande J, Dumont JE, Vassart G: Somatic and germline mutations of the TSH receptor and thyroid diseases. Clin Endocrinol 2001;55:143–148.
28.
Miki K, Nose O, Miyai K, Yabuuchi H, Harada T: Transient infantile hyperthyrotropinemia. Arch Dis Child 1989;64:1177–1182.
29.
Tyfield LA, Abusrewil SSA, Jones SR, Savage DCL: Persistent hyperthyrotropinemia since the neonatal period in clinical euthyroid children. Eur J Pediatr 1991;150:308.
30.
Matsuura N, Yamada Y, Nohara Y, Konishi J, Kasagi K, Endo K, Kojima H, Wataya K: Familial, neonatal transient hypothyroidism due to maternal TSH-binding inhibitor immunoglobulins. N Engl J Med 1980;303:738–741.
31.
Iseki M, Shimizu M, Oikawa T, Hojo H, Arikawa K, Ichikawa Y, Momotani N, Ito K: Sequential serum measurements of thyrotropin binding inhibiting immunoglobulin G in transient neonatal hypothyroidism. J Clin Endocrinol Metab 1983;57:384–389.
32.
Tonacchera M, Van Sande J, Parma J, Duprez L, Cetani F, Costagliola S, Dumont JE, Vassart G: TSH receptor and disease. Clin Endocrinol 1996;44:621–633.
33.
Fisher DA, Schoen EJ, LaFranchi S, Mandel SH, Nelson JC, Carlton EI, Goshi JH: The hypothalamic-pituitary-thyroid negative feedback control axis in children with treated congenital hypothyroidism. J Clin Endocrinol Metab 2000;85:2722–2727.
© 2007 S. Karger AG, Basel
2007
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.