Aim: To assess the management and outcome of the congenital hypothyroidism (CH) patients followed at our institution since the introduction of systemic neonatal screening for CH. Study Design: The records of 139 CH patients referred to our center between 1978 and 2014 were retrospectively reviewed. Biochemical and imaging data at diagnosis, initial treatment and growth were analyzed. Results: 111 patients had thyroid dysgenesis (64 ectopy, 46 athyreosis and 1 hypoplasia) and 28 patients had a gland in situ (17 dyshormonogenesis/goiter and 11 normal-sized gland). Levothyroxine treatment was initiated at a median age of 11 days with a mean dose of 11.4 µg/kg/day. Compared to those with ectopy, patients with athyreosis had higher thyroid-stimulating hormone (TSH) and lower thyroxine at diagnosis as well as more delayed bone maturation. Between 1978 and 2014, we observed earlier treatment and earlier TSH normalization. Birth auxology was slightly above the mean of the reference population. Growth at 1 and 6 years and school progression at 11 years were similar to those of the reference population. Conclusion: Ectopy is the commonest cause of CH. Children with CH treated early with a mean levothyroxine dose of 11.4 µg/kg/day had a median TSH of 3.07 mU/l at 1 month of age and normal growth.

Keywords:
Congenital hypothyroidism, Diagnosis, Imaging, Outcome, Growth
1.
Grosse SD, van Vliet G: Prevention of intellectual disability through screening for congenital hypothyroidism: how much and at what level? Arch Dis Child 2011;96:374-379.
2.
Léger J, Olivieri A, Donaldson M, Torresani T, Krude H, van Vliet G, et al: European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. Horm Res Paediatr 2014;81:80-103.
3.
Castanet M, Polak M, Bonaïti-Pellié C, Lyonnet S, Czernichow P, Léger J, et al: Nineteen years of national screening for congenital hypothyroidism: familial cases with thyroid dysgenesis suggest the involvement of genetic factors. J Clin Endocrinol Metab 2001;86:2009-2014.
4.
Perry R, Heinrichs C, Bourdoux P, Khoury K, Szöts F, Dussault JH, et al: Discordance of monozygotic twins for thyroid dysgenesis: implications for screening and for molecular pathophysiology. J Clin Endocrinol Metab 2002;87:4072-4077.
5.
Abramowicz MJ, Duprez L, Parma J, Vassart G, Heinrichs C: Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. J Clin Invest 1997;99:3018-3024.
6.
Vilain C, Rydlewski C, Duprez L, Heinrichs C, Abramowicz M, Malvaux P, et al: Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8. J Clin Endocrinol Metab 2001;86:234-238.
7.
Gaudino R, Garel C, Czernichow P, Léger J: Proportion of various types of thyroid disorders among newborns with congenital hypothyroidism and normally located gland: a regional cohort study. Clin Endocrinol (Oxf) 2005;62:444-448.
8.
Marinovic D, Garel C, Czernichow P, Léger J: Additional phenotypic abnormalities with presence of cysts within the empty thyroid area in patients with congenital hypothyroidism with thyroid dysgenesis. J Clin Endocrinol Metab 2003;88:1212-1216.
9.
Lucas-Herald A, Jones J, Attaie M, Maroo S, Neumann D, Bradley T, et al: Diagnostic and predictive value of ultrasound and isotope thyroid scanning, alone and in combination, in infants referred with thyroid-stimulating hormone elevation on newborn screening. J Pediatr 2014;164:846-854.
10.
Perry RJ, Hollman AS, Wood AM, Donaldson MDC: Ultrasound of the thyroid gland in the newborn: normative data. Arch Dis Child Fetal Neonatal Ed 2002;87:F209-F211.
11.
Chanoine JP, Toppet V, Body JJ, van Vliet G, Lagasse R, Bourdoux P, et al: Contribution of thyroid ultrasound and serum calcitonin to the diagnosis of congenital hypothyroidism. J Endocrinol Invest 1990;13:103-109.
12.
Villar J, Cheikh Ismail L, Victora CG, Ohuma EO, Bertino E, Altman DG, et al: International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet 2014;384:857-868.
13.
Cole TJ, Freeman JV, Preece MA: British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Stat Med 1998;17:407-429.
14.
Enseignement.be: Indicateurs de l'enseignement. Available at http://enseignement.be/index.php?page=0&navi=2264 (accessed April 15, 2015).
15.
Jones JH, Attaie M, Maroo S, Neumann D, Perry R, Donaldson MDC: Heterogeneous tissue in the thyroid fossa on ultrasound in infants with proven thyroid ectopia on isotope scan - a diagnostic trap. Pediatr Radiol 2010;40:725-731.
16.
Scott DA, Wang R, Kreman TM, Sheffield VC, Karniski LP: The Pendred syndrome gene encodes a chloride-iodide transport protein. Nat Genet 1999;21:440-443.
17.
Grasberger H, Mimouni-Bloch A, Vantyghem MC, van Vliet G, Abramowicz M, Metzger DL, et al: Autosomal dominant resistance to thyrotropin as a distinct entity in five multigenerational kindreds: clinical characterization and exclusion of candidate loci. J Clin Endocrinol Metab 2005;90:4025-4034.
18.
Andersen AN, Gianaroli L, Felberbaum R, de Mouzon J, Nygren KG; European IVF-monitoring programme (EIM), European Society of Human Reproduction and Embryology (ESHRE): Assisted reproductive technology in Europe, 2001. Results generated from European registers by ESHRE. Hum Reprod 2005;20:1158-1176.
19.
Ferraretti AP, Goossens V, Kupka M, Bhattacharya S, de Mouzon J, Castilla JA, et al: Assisted reproductive technology in Europe, 2009: results generated from European registers by ESHRE. Hum Reprod 2013;28:2318-2331.
20.
Blondel B, Bréart G, du Mazaubrun C, Badeyan G, Wcislo M, Lordier A, et al: The perinatal situation in France. Trends between 1981 and 1995 (in French). J Gynecol Obstet Biol Reprod (Paris) 1997;26:770-780.
21.
Fisher DA: The importance of early management in optimizing IQ in infants with congenital hypothyroidism. J Pediatr 2000;136:273-274.
22.
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.
23.
Simoneau-Roy J, Marti S, Deal C, Huot C, Robaey P, van Vliet G: Cognition and behavior at school entry in children with congenital hypothyroidism treated early with high-dose levothyroxine. J Pediatr 2004;144:747-752.
24.
Léger J, Larroque B, Norton J; Association Française pour le Dépistage et la Prévention des Handicaps de l'Enfant: Influence of severity of congenital hypothyroidism and adequacy of treatment on school achievement in young adolescents: a population-based cohort study. Acta Paediatr 1992, 2001;90:1249-1256.
25.
Dimitropoulos A, Molinari L, Etter K, Torresani T, Lang-Muritano M, Jenni OG, et al: Children with congenital hypothyroidism: long-term intellectual outcome after early high-dose treatment. Pediatr Res 2009;65:242-248.
26.
Kempers MJE, van der Sluijs Veer L, Nijhuis-van der Sanden RWG, Lanting CI, Kooistra L, Wiedijk BM, et al: Neonatal screening for congenital hypothyroidism in the Netherlands: cognitive and motor outcome at 10 years of age. J Clin Endocrinol Metab 2007;92:919-924.
27.
Mathai S, Cutfield WS, Gunn AJ, Webster D, Jefferies C, Robinson E, et al: A novel therapeutic paradigm to treat congenital hypothyroidism. Clin Endocrinol (Oxf) 2008;69:142-147.
28.
Bubuteishvili L, Garel C, Czernichow P, Léger J: Thyroid abnormalities by ultrasonography in neonates with congenital hypothyroidism. J Pediatr 2003;143:759-764.
29.
Van Vliet G, Deladoëy J: Diagnosis, treatment and outcome of congenital hypothyroidism. Endocr Dev 2014;26:50-59.
30.
Castanet M, Goischke A, Léger J, Thalassinos C, Rodrigue D, Cabrol S, et al: Natural history and management of congenital hypothyroidism with in situ thyroid gland. Horm Res Paediatr 2015;83:102-110.
31.
Castanet M, Lyonnet S, Bonaïti-Pellié C, Polak M, Czernichow P, Léger J: Familial forms of thyroid dysgenesis among infants with congenital hypothyroidism. N Engl J Med 2000;343:441-442.
32.
Devos H, Rodd C, Gagné N, Laframboise R, van Vliet G: A search for the possible molecular mechanisms of thyroid dysgenesis: sex ratios and associated malformations. J Clin Endocrinol Metab 1999;84:2502-2506.
33.
Eugène D, Djemli A, van Vliet G: Sexual dimorphism of thyroid function in newborns with congenital hypothyroidism. J Clin Endocrinol Metab 2005;90:2696-2700.
34.
Salerno M, Micillo M, Di Maio S, Capalbo D, Ferri P, Lettiero T, et al: Longitudinal growth, sexual maturation and final height in patients with congenital hypothyroidism detected by neonatal screening. Eur J Endocrinol 2001;145:377-383.
35.
Leger J, Czernichow P: Congenital hypothyroidism: decreased growth velocity in the first weeks of life. Biol Neonate 1989;55:218-223.
36.
Van Vliet G, Larroque B, Bubuteishvili L, Supernant K, Léger J; Association Française pour le Dépistage et la Prévention des Handicaps de l'Enfant: Sex-specific impact of congenital hypothyroidism due to thyroid dysgenesis on skeletal maturation in term newborns. J Clin Endocrinol Metab 2003;88:2009-2013.
37.
Kempers MJE, van der Sluijs Veer L, Nijhuis-van der Sanden MWG, Kooistra L, Wiedijk BM, Faber I, et al: Intellectual and motor development of young adults with congenital hypothyroidism diagnosed by neonatal screening. J Clin Endocrinol Metab 2006;91:418-424.
38.
Bongers-Schokking JJ, Resing WCM, de Rijke YB, de Ridder MAJ, de Muinck Keizer-Schrama SMPF: Cognitive development in congenital hypothyroidism: is overtreatment a greater threat than undertreatment? J Clin Endocrinol Metab 2013;98:4499-4506.
39.
Azar-Kolakez A, Ecosse E, Dos Santos S, Léger J: All-cause and disease-specific mortality and morbidity in patients with congenital hypothyroidism treated since the neonatal period: a national population-based study. J Clin Endocrinol Metab 2013;98:785-793.
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2016
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