Background/Aims: Controversy exists regarding the diagnosis and treatment of mild congenital hypothyroidism (MCH). We studied the value of 123I imaging in patients with MCH. Methods: Retrospective chart review of infants and children <4 years of age who underwent 123I imaging: group 1 = MCH [thyroid-stimulating hormone (TSH) <25 µIU/ml, normal free T4/T3], group 2 = severe congenital hypothyroidism (TSH ≥25 µIU/ml), and group 3 = MCH in infancy imaged after treatment withdrawal at age 3 years. Data collected included 4- and 24-hour 123I uptake, TSH, free T4/total T3 at imaging, age at imaging, and levothyroxine (L-T4) dose at 1 year of. Results: Thirty-six patients underwent 123I imaging. In group 1 (n = 20, median TSH: 8.49 µIU/ml), 85% had abnormal imaging consistent with dyshormonogenesis. Two patients were referred after 1 year of age. The median age at imaging for the remaining 18 patients was 54 days. Median L-T4 dose at 1 year of age for these 18 patients was 2.8 μg/kg, which is consistent with dyshormonogenesis. Ninety-one percent of group 2 (n = 11, median TSH: 428.03 µIU/ml) had abnormal imaging. The median age at imaging was 13 days. Four patients in group 3 had abnormal 123I imaging and restarted treatment. Conclusion:123I imaging is a valuable tool for evaluation, diagnosis, and treatment of MCH.

Keywords:
Congenital hypothyroidism, Thyroid imaging, 123Iodine, Dyshormonogenesis, Mild congenital hypothyroidism
1.
LaFranchi SH: Approach to the diagnosis and treatment of neonatal hypothyroidism. J Clin Endocrinol Metab 2011;96:2959-2967.
2.
Harris KB, Pass KA: Increase in congenital hypothyroidism in New York State and the United States. Mol Genet Metab 2007;91:268-277.
3.
LaFranchi SH: Increasing incidence of congenital hypothyroidism: some answers, more questions. J Clin Endocrinol Metab 2011;96:2395-2397.
4.
Olivieri A, Corbetta C, Weber G, Vigone MC, Fazzini C, Medda E: Congenital hypothyroidism due to defects of thyroid development and mild increase of TSH at screening: data from the Italian National Registry of Infants With Congenital Hypothyroidism. J Clin Endocrinol Metab 2013;98:1403-1408.
5.
Corbetta C, Weber G, Cortinovis F, Calebiro D, Passoni A, Vigone MC, Beck-Peccoz P, Chiumello G, Persani L: A 7-year experience with low blood TSH cutoff levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH). Clin Endocrinol (Oxf) 2009;71:739-745.
6.
Bongers-Schokking JJ, Koot HM, Wiersma D, Verkerk PH, Keizer-Schrama S: Influence of timing and dose of thyroid hormone replacement on development in infants with congenital hypothyroidism. J Pediatr 2000;136:292-297.
7.
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;147:775-780.
8.
Albert BB, Heather N, Derraik JGB, Cutfield WS, Wouldes T, Tregurtha S, Mathai S, Webster D, Jeffries C, Gunn AJ, Hofman PL: Neurodevelopmental and body composition outcomes in children with congenital hypothyroidism treated with high-dose initial replacement and close monitoring. J Clin Endocrinol Metab 2013;98:3663-3670.
9.
Van Vilet G, Czernichow P: Screening for neonatal endocrinopathies: rationale, methods and results. Semin Neonatol 2004;9:75-85.
10.
Vincent MA, Rodd C, Dussault JH, Van Vilet G: Very low birth weight newborns do not need repeat screening for congenital hypothyroidism. J Pediatr 2002;140:311-314.
11.
Rapaport R, Sills I, Patel U, Oppenheimer E, Skuza K, Horlick M, Goldstein S, Dimartino J, Saenger P: Thyrotropin-releasing hormone stimulation tests in infants. J Clin Endocrinol Metab 1993;77:889-894.
12.
Rapaport R: Congenital hypothyroidism: an evolving common clinical conundrum. J Clin Endocrinol Metab 2010;95:4223-4225.
13.
Simpster T, Rapaport R: Update on some aspects of neonatal thyroid disease. J Clin Res Pediatr Endocrinol 2010;2:95-99.
14.
Rapaport R, Akler G, Regelmann MO, Greig F: Time for thyrotropin releasing hormone to return to the United States of America. Thyroid 2010;20:947-948.
15.
Brown RS: Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics 2006;117;2290-2303.
16.
Leger J, Olivieri A, Donaldson M, Torresani T, Krude H, van Vliet G, Polak M, Butler G; ESPE-PES-SLEP-JSPE-APEG-APPES-ISPAE; Congenital Hypothyroidism Consensus Conference Group: European Society for Paediatric Endocrinology Consensus Guidelines on Screening, Diagnosis, and Management of Congenital Hypothyroidism. Horm Res Pediatr 2014;81:80-103.
17.
Perry RJ, Maroo S, Maclennan AC, Jones JH, Donaldson MD: Combined ultrasound and isotope scanning is more informative in the diagnosis of congenital hypothyroidism than single scanning. Arch Dis Child 2006;91:972-976.
18.
Chang Y, Lee DH, Hong YH, Hong HS, Choi DL, Seo DY: Congenital hypothyroidism: analysis of discordant US and scintigraphic findings. Radiology 2011;258:872-879.
19.
Bradford RK, Tulchinsky M: Subcutaneous injection of 99mTc-pertechnetate for neonatal thyroid scintigraphy. Clin Nucl Med 2013;38:1015-1018.
20.
Balon HR, Silberstein EB, Meier DA, Charkes D, Sarkar SD, Royal HD, Donohoe KJ: Society of Nuclear Medicine Procedure Guideline for Thyroid Scintigraphy. 2006, http://snmmi.files.cms-plus.com/docs/Thyroid_Scintigraphy_V3.pdf.
21.
Gelfand MJ, Parisi MT, Treves ST: Pediatric radiopharmaceutical administered doses: 2010 North American consensus guidelines. J Nucl Med 2011;52:318-322.
22.
Arnold G, Belfort M, Bellisario R, Caggana M, Clark D, Comeau Anne, Hannon H, Harris KB, Kaslovsky R, Kronn D, Kus C, Martin D, Morrissey M, New M, Pass KA, Quarrier J, Schedlbauer L, Sharp J, Shepard B, Willey AM: Newborn Screening in New York State: A Guide for Health Professionals. Albany, New York State Department of Health, 2003.
23.
Djemli A, Van Vliet G, Belgoudi J, Lambert M, Delvin EE: Reference intervals for free thyroxine, total triiodothyronine, thyrotropin and thyroglobulin for Quebec newborns, children and teenagers. Clin Biochem 2004;37:328-330.
24.
Fogelman I, Maisey MN, Clarke SE: An Atlas of Clinical Nuclear Medicine, ed 2. London, CRC Press, 1994.
25.
Schoen EJ, Clapp W, To TT, Fireman BH: The key role of newborn thyroid scintigraphy with isotopic iodide (123I) in defining and managing congenital hypothyroidism. Pediatrics 2004;114:e683-e688.
26.
Fisher DA: Management of congenital hypothyroidism. J Clin Endocriol Metab 1991;72:523-529.
27.
Rabbiosi S, Vigone MC, Cortinovis F, Zamproni I, Fugazzola L, Persani L, Corbetta C, Chiumello G, Weber G: Congenital hypothyroidism with eutopic thyroid gland: analysis of clinical and biochemical features at diagnosis and after re-evaluation. J Clin Endocriol Metab 2013;98:1395-1402.
28.
Hanukoglu A, Perlman K, Shamis I, Brnjac L, Rovet J, Daneman D: Relationship of etiology to treatment in congenital hypothyroidism. J Clin Endocrinol Metab 2001;26:186-191.
29.
Delvecchio M, Faienza MF, Acquafredda A, Zecchino C, Peruzzi S, Cavallo L: Longitudinal assessment of levo-thyroxine therapy for congenital hypothyroidism: relationship with aetiology, bone maturation and biochemical features. Horm Res 2007;68:105-112.
30.
Hyman SJ, Greif F, Holzman I, Patel A, Wallach E, Rapaport R: Late rise of thyroid stimulating hormone in ill newborns. J Pediatr Endocrinol Metab 2007;20:501-510.
31.
Maniatis AK, Taylor L, Letson GW, Bloch CA, Kappy MS, Zeitler P: Congenital hypothyroidism and the second newborn metabolic screening in Colorado, USA. J Pediatr Endocrinol Metab 2006;19:31-38.
32.
Kaplan M, Kauli R, Lubin E, Grunebaum M, Laron Z: Ectopic thyroid gland: a clinical study of 30 children and review. J Pediatr 1978;92:205-209.
33.
Daliva AL, Linder B, DiMartino-Nardi J, Saenger P: Three-year follow-up of borderline congenital hypothyroidism. J Pediatr 2000;136:53-56.
34.
Mengreli C, Kanaka-Gantenbein C, Girginoudis P, Magiakou M,Christakopoulou I, Giannoulia-Karantana A, Chrousos GP, Dacou-Voutetakis C: Screening for congenital hypothyroidism: the significance of threshold limit in false-negative results. J Clin Endocrinol Metab 2010;95:4283-4290.
35.
Calaciura F, Motta RM, Miscio G, Fichera G, Leonardi D, Carta A, Trischitta V, Tassi V, Sava L, Vigneri R: Subclinical hypothyroidism in early childhood: a frequent outcome of transient neonatal hypothyroidism. J Clin Endocrinol Metab 2002;87:3209-3214.
36.
Leonardi D, Polizzotti N, Carta A, Gelsomino R, Sava L, Vigneri R, Calaciura F: Longitudinal study of thyroid function in children with mild hyperthyrotropinemia at neonatal screening for congenital hypothyroidism. J Clin Endocrinol Metab 2008;93:2679-2685.
37.
Grüters A, Krude H: Detection and treatment of congenital hypothyroidism. Nat Rev Endocrinol 2012;8:104-113.
38.
Cavarzere P, Castanet M, Polak M, Raux-Demay M, Cabrol S, Carel JC, Leger J, Czernichow P: Clinical description of infants with congenital hypothyroidism and iodide organification defects. Horm Res 2008;70:240-248.
39.
Tonacchera M, Banco ME, Montanelli L, DiCosmo C, Agretti P, De Marco G, Ferrarini E, Ordookhani A, Perri A, Chiovato L, Santini F, Vitti P, Pinchera A: Genetic analysis of the PAX8 gene in children with congenital hypothyroidism and dysgenetic or eutopic thyroid glands: identification of a novel sequence variant. Clin Endocrinol 2007;67:34-40.
40.
Iwatani N, Mabe H, Devriendt K, Kodama M, Miike T: Deletion of NKX2-1 gene encoding thyroid transcription factor-1 in two siblings with hypothyroidism and respiratory failure. J Pediatr 2000;137:272-276.
41.
Krude H, Schutz B, Biebermann H, von Moers A, Schnabel D, Neitzel H, Tönnies H, Weise D, Lafferty A, Schwarz S, DeFelice M, von Deimling A, van Landeghem F, DiLauro R, Grüters A: Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency. Clin Invest 2002;109:475-480.
42.
Castanet M, Park SM, Smith A, Bost M, Léger J, Lyonnet S, Pelet A, Czernichow P, Chatterjee K, Polak M: A novel loss of function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis, and cleft palate. Hum Mol Genet 2002;11:2051-2059.
43.
Baris I, Arisoy AE, Smith A, Agostini M, Mitchell CS, Park SM, Halefoglu AM, Zengin E, Chatterjee VK, Battaloglu E: A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis. J Clin Endocrinol Metab 2006;91:4183-4187.
© 2014 S. Karger AG, Basel
2014
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.