Congenital hypothyroidism: Treatment and outcome

Current Opinion in Endocrinology and Diabetes

Volumn 12, Issue 1, 2005, Pages 42-52

  Rovet, Joanne ^a  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

Author keywords

Congenital hypothyroidism; Follow up; Newborn screening; Replacement therapy

Indexed keywords

THYROID HORMONE; THYROXINE;

BRAIN DEVELOPMENT; CONGENITAL HYPOTHYROIDISM; DISEASE SEVERITY; DRUG MEGADOSE; HUMAN; INTELLIGENCE QUOTIENT; MEDICAL RESEARCH; NEWBORN SCREENING; REVIEW; RISK FACTOR; THYROID HORMONE BLOOD LEVEL; TREATMENT OUTCOME;

EID: 14944381522     PISSN: 10683097     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.med.0000152669.91427.73     Document Type: Review

References (136)

1. LaFranchi S: Congenital hypothyroidism: etiologies, diagnosis, and management. Thyroid 1999; 9:735-740.
2. Van Vliet G: Neonatal hypothyroidism: treatment and outcome. Thyroid 1999; 9:79-84.
3. Vulsma T, Kempers MJE, van Tijn DA, et al. Congenital central hypothyroidism in children of mothers with gestational Graves' hyperthyroidism. In The Thyroid and Brain. Edited by Morreale de Escobar G, de Vijlder J, Butz S, et al. Stuttgart: Schattauer; 2003:121-129.
4. Brown RS, Bellisario RL, Botero D, et al. Incidence of transient congenital hypothyroidism due to maternal thyrotropin receptor-blocking antibodies in over one million babies. J Clin Endocrinol Metab 1996; 81:1147-1151.
5. Rovet J, Daneman D: Congenital hypothyroidism. A review of current diagnostic and treatment practices in relation to neuropsychologic outcome. Pediatr Drugs 2003; 5:141-149.
6. Crome L, Stern J: Pathology of Mental Retardation. Edinburgh: Churchill Livingstone; 1972.
7. Brooke CGD: The consequences of congenital hypothyroidism. Clin Endocrinol 1995; 42:432-438.
8. Fisher DA, Dussault JH, Foley TP, et al. Screening for congenital hypothyroidism: results of screening one million North American infants. J Pediatr 1979; 94:700-705.
9. Grüters A, Jenner A, Krude H: Long-term consequences of congenital hypothyroidism in the era of screening programmes. Best Pract Res Clin Endocrinol Metab 2002; 16:369-382.
10. Therrell BL: Newborn screening as we move to the twenty-first century. Southeast Asian J Trop Med Public Health 1999; 30(suppl 2):1-4.
11. Rovet J: Congenital hypothyroidism. Persisting deficits and associated factors. Child Neuropsychology 2003; 8:150-162. This paper examines outcome in three domains in children with congenital hypothyroidism identified by screening. Highlighted are a weakness in visuospatial processing that is associated with a prenatal thyroid hormone insufficiency, selective memory deficits associated with a postnatal thyroid hormone insufficiency, a sensorimotor weakness also associated with a postnatal insufficiency, and attention deficits reflecting abnormal thyroid hormone levels at time of testing.
12. Chan S, Rovet J: Thyroid hormones in fetal central nervous system. Fetal Matern Med Rev 2003; 14:177-208. This paper examines in detail the actions of thyroid hormone in the developing fetal brain in several conditions of thyroid hormone insufficiency.
13. Rovet JF: Congenital hypothyroidism: long-term outcome. Thyroid 1999; 9:741-748.
14. Rovet JF, Ehrlich R: The psychoeducational characteristics of children with early-treated congenital hypothyroidism. Pediatrics 2000; 105:515-522.
15. Bargagna S, Dinetti D, Pinchera A, et al. School attainments in children with congenital hypothyroidism detected neonatal screening and treated early in life. Eur J Endocrinol 1999; 140:407-413.
16. Glorieux J, Dussault J, Van Vliet F: Intellectual development at age 12 years in children with congenital hypothyroidism diagnosed by neonatal screening. J Pediatr 1992; 121:581-584.
17. Rochiccioli P, Roge B, Dechaux E, et al. School achievement in children with hypothyroidism detected at birth and search for predictive factors. Horm Res 1992; 38:236-240.
18. Oerbeck B, Sundet K, Kase BF, et al. Congenital hypothyroidism: influence of disease severity and L-thyroxine treatment on intellectual, motor, and school-associated outcomes in young adults. Pediatrics 2003; 112:923-930. This is the first paper to compare outcome in young Norwegian adults with congenital hypothyroidism who were identified by screening with their siblings. The research is unique in maintaining most of the original sample.
19. Rovet J: In search of the optimal therapy for congenital hypothyroidism. J Pediatr 2004; 144:698-700.
20. Gunn AJ, Wake M, Cutfield WS: High and low dose initial thyroxine therapy for congenital hypothyroidism. J Paediatr Child Health 1996; 32:242-245.
21. Hindmarsh PC: Optimisation of thyroxine dose in congenital hypothyroidism. Arch Dis Child 2002; 86:73-75.
22. Hrytsiuk K, Gilbert R, Logan S, et al. Starting dose of levothyroxine for the treatment of congenital hypothyroidism: a systematic review. Arch Pediatr Adolesc Med 2002; 156:485-491.
23. Heyerdahl S: Longterm outcome in children with congenital hypothyroidism, degree of variability was seen. Acta Paediatr 2001; 90:1220-1222.
24. Fisher DA: The importance of early management in optimizing IQ in infants with congenital hypothyroidism [editorial]. J Pediatr 2000; 136:273-274.
25. Dubuis JM, Gloriueux J, Richer F, et al. Outcome of severe congenital hypothyroidism: closing the developmental gap with early high dose of levothyroxine treatment. J Clin Endocrinol Metab 1996; 81:222-227.
26. Rovet J, Alvarez M: Thyroid hormone and attention in children with congenital hypothyroidism. J Pediatr Endocrinol Metab 1996; 9:63-66.
27. Rovet J, Daneman D: Congenital hypothyroidism. A review of current diagnostic and treatment practices in relation to neuropsychologic outcome. Pediatr Drugs 2003; 5:141-149.
28. Ehrlich RM: Thyroxine dose for congenital hypothyroidism [editorial]. Clin Pediatr 1995; 34:514-520.
29. Rovet JF, Ehrlich RM: Long-term effects of L-thyroxine therapy for congenital hypothyroidism. J Pediatr 1995; 126:380-386.
30. Touati G, Leger J, Toublanc JE, et al. An initial dosage of 8 μg/kg is the appropriate for the vast majority of children with congenital hypothyroidism. In New Horizons in Neonatal Screening. Edited by Farriaux JP, Dhondt JL. Amsterdam: Elsevier 1994; 145-148.
31. Morreale de Escobar G, Obregon MJ, Escobar del Rey F: Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia? J Clin Endocrinol Metab 2000; 85:3975-3987.
32. Bernal J, Guadano-Ferraz A, Morte B: Perspectives in the study of thyroid hormone action on brain development and function. Thyroid 2003; 13:1005-1012. This paper reviews the molecular and physiologic processes involved in the role of thyroid hormone as an epigenetic factor in brain maturation. The paper provides evidence on thyroid hormone's role in brain gene expression and the mechanisms of action of thyroid hormone in brain gene expression.
33. Howdeshell KL: A model of the development of the brain as a construct of the thyroid system. Environ Health Perspect 2002; 110(suppl 3):337-348.
34. Zoeller RT, Rovet J: Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J Neuroendocrinol 2004; 18:809-818. We have summarized the role of thyroid hormone in brain development from both human and animal study perspectives, and show the critical role of timing in determining specific effects.
35. Bernal J, Nunez J: Thyroid hormones and brain development. Eur J Endocrinol 1995; 133:390-398.
36. Thompson CC, Potter GB: Thyroid hormone action in neural development. Cereb Cortex 2000; 10:939-945.
37. Shapiro S: Metabolic and maturational effects of thyroxine in the infant rat. Endocrinology 1966; 78:527-532.
38. Potter B, Mano M, Belling G, et al. Retarded fetal brain development resulting from severe dietary iodine deficiency in sheep. Neuropathol Appl Neurobiol 1982; 8:303-313.
39. Legrand J: Effects of thyroid hormones on central nervous system development. In Neurobehavioral Teratology. Edited by Yanat J. Amsterdam: Elsevier; 1984:331-363.
40. Rosman N, Malone M, Helfenstein M, et al. The effect of thyroid deficiency on myelination of the brain. Neurology 1972; 22:99-106.
41. Iniguez M, De Lecea L, Guadano-Ferraz A, et al. Cell-specific effects of thyroid hormone on RC3/neurogranin expression in rat brain. Endocrinology 1996; 137:1032-1041.
42. Auso E, Lavado-Aturic R, Cuevas E, et al. A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration. Endocrinology 2004; 145:4037-4047. This paper describes results from an experimental approach to assess the effects of mild and transient maternal hypothyroxinemia on fetal corticogenesis. Results found effects on cytoarchitecture and radial distribution of neurons in somatosensory cortex and hippocampus in 83% of experimental animals.
43. Lavado-Autric R, Auso E, Garcia-Velasco JV, et al. Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny. J Clin Invest 2003; 111:1073-1082.
44. Madeira MD, Cadete-Leite A, Andrade JP, et al. Effects of hypothyroidism upon the granular layer of the dentate gyrus in male and female adult rats: a morphometric study. J Comp Neurol 1991; 314:171-186.
45. Xiao Q, Nikodem VM: Apo ptosis in the developing cerebellum of the thyroid hormone deficient rat. Front Biosci 1998; 3:A52-A57.
46. Gilbert ME, Paczkowski C: Propylthiouracil (PTU)-induced hypothyroidism in the developing rat impairs synaptic transmission and plasticity in the dentate gyrus of the adult hippocampus. Brain Res Dev Brain Res 2003; 145:19-29.
47. Sui L, Gilbert ME: Pre- and postnatal propylthiouracil-induced hypothyroidism impairs synaptic transmission and plasticity in area CA1 of the neonatal rat hippocampus. Endocrinology 2003; 144:4195-4203.
48. Rusch A, Erway LC, Oliver D, et al. Thyroid hormone receptor beta-dependent expression of a potassium conductance in inner hair cells at the onset of hearing. Proc Natl Acad Sci U S A 1998; 95:15758-15762.
49. Kelley MW, Turner JK, Reh TA: Ligands of steroid/thyroid receptors induce cone photoreceptors in vertebrate retina. Development 1995; 121:3777-3785.
50. Ng L, Hurley JB, Dierks B, et al. A thyroid hormone receptor that is required for the development of green cone photoreceptors. Nat Genet 2001; 27:94-98.
51. Francois M, Bonfils P, Leger J, et al. Role of congenital hypothyroidism in hearing loss in children. J Pediatr 1994; 123:444-446.
52. Rovet J, Walker W, Bliss B, et al. Long-term sequelae of hearing impairment in congenital hypothyroidism. J Pediatr 1996; 128:776-783.
53. Mirabella G, Westall C, Asztalos E, et al. The development of contrast sensitivity in infants with prenatal and neonatal thyroid hormone insufficiencies. Pediatr Res [in press]. We showed that offspring of hypothyroid women and children with congenital hypothyroidism have a vision defect reflecting reduced contrast sensitivity. This defect was most evident when maternal hypothyroidism or congenital hypothyroidism was severe.
54. Ipina SL, Ruiz-Marcos A: Dendritic structure alterations induced by hypothyroidism in pyramidal neurons of the rat visual cortex. Brain Res 1986; 394:61-67.
55. Gould E, Butcher LL: Developing cholinergic basal forebrain neurons are sensitive to thyroid hormone. J Neurosci 1989; 9:3346-3358.
56. Bates JM, St Germain DL, Galton VA: Expression profiles of the three iodothyronine deiodinases, D1, D2, and D3, in the developing rat. Endocrinology 1999; 140:844-851.
57. Kester MH, Martinez de Mena R, Obregon MJ, et al. Iodothyronine levels in the human developing brain: major regulatory roles of iodothyronine deiodinases in different areas. J Clin Endocrinol Metab 2004; 89:3114-3116. This paper charts the ontogenic changes in thyroid hormones and deiodinase enzymes in different brain regions in normal fetuses and preterm infants. The data show that the human cerebral cortex needs thyroid hormone before the fetal thyroid is functional and that this must be supplied by the mother.
58. Friesema EC, Grueters A, Biebermann H, et al. Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet 2004; 364:1435-1437. This paper is critical in examining the structure and function of a thyroid hormone transporter and its role in X-linked psychomotor retardation caused by a defect in entry of T3 into neurons.
59. Thorpe-Beeston JG, Nicolaides KH, McGregor AM: Fetal thyroid function. Thyroid 1992; 2:207-217.
60. Calvo RM, Jauniaux E, Gulbis B, et al. Fetal tissues are exposed to biologically relevant free thyroxine concentrations during early phases of development. J Clin Endocrinol Metab 2002; 87:1768-1777.
61. Robbins J, Lakshmanan M: The movement of thyroid hormones in the central nervous system. Acta Med Austriaca 1992; 19:21-25.
62. Chanoine JP, Alex S, Fang SL, et al. Role of transthyretin in the transport of thyroxine from the blood to the choroids plexus, the cerebrospinal fluid, and the brain. Endocrinology 1992; 130:933-938.
63. Schreiber G, Aldred AR, Jaworowski A, et al. Thyroxine transport from blood to brain via transthyretin synthesis in choroid plexus. Am J Physiol 1990; 258:R338-R345.
64. Dratman MB, Crutchfield FL, Schoenhoff MB: Transport of iodothyronines from bloodstream to brain: contributions by blood:brain and choroid plexus: cerebrospinal fluid barriers. Brain Res 1991; 554:229-236.
65. Lauder JM, Krebs H: Do neurotransmitters, neurohumors, and hormones specify critical periods? In: Developmental Neurophysiology. Edited by Greenough WT, Juraska JM. New York: Academic Press 1986; 120-174.
66. Virgili M, Saverino O, Vaccari M, et al. Temporal, regional and cellular selectivity of neonatal alteration of the thyroid state on neurochemical maturation in the rat. Exp Brain Res 1991; 83:556-561.
67. Puymirat J, Luo M, Dussault HL: Immunocytochemical localization of thyroid hormone nuclear receptors in cultured hypothalamic dopaminergic neurons. Neuroscience 1989; 30:443-449.
68. Virgili M, Saverino O, Vaccari M, et al. Temporal, regional and cellular selectivity of neonatal alteration of the thyroid state on neurochemical maturation in the rat. Exp Brain Res 1991; 83:556-561.
69. Claustre J, Balende C, Pujol JF: Influence of thyroid hormone status on tyrosine hydroxylase in central and peripheral catecholaminergic structures. Neurochem Int 1996; 28:277-281.
70. Rozanov CB, Dratman MB: Immunohistochemical mapping of brain triiodothyronine reveals prominent localization in central noradrenergic systems. Neuroscience 1996; 74:897-915.
71. Glorieux J, Dussault JH, Morisette J, et al. Follow-up at ages 5 and seven years on mental development with hypothyroidism detected by Quebec Screening Program. J Pediatr 1985; 107:913-915.
72. New England Congenital Hypothyroidism Collaborative: Neonatal hypothyroidism screening: status of patients at six years of age. J Pediatr 1985; 107:915-919.
73. Murphy G, Hulse JA, Jackson D, et al. Early treated hypothyroidism: development at 3 years. Arch Dis Child 1986; 61:761-765.
74. Moschini L, Costa P, Marinell E, et al. Longitudinal assessment of children with congenital hypothyroidism detected by neonatal screening. Helv Paediatr Acta 1986; 41:415-425.
75. Illig R, Largo RH, Qin Q, et al. Mental development in congenital hypothyroidism after neonatal screening. Arch Dis Child 1987; 62:1050-1055.
76. Illicki A, Larrson A: Psychological development at 7 years of children with congenital hypothyroidism. Acta Paediatr Scand 1991; 80:199-204.
77. Simons WF, Fuggle PW, Grant DB, et al. Intellectual development at 10 years in early treated congenital hypothyroidism. Eur J Pediatr 1991; 150:570-574.
78. Rovet J, Ehrlich R, Sorbara D: Neurodevelopment in infants and preschool children with congenital hypothyroidism. Etiological and treatment factors affecting outcome. J Pediatr Psychology 1992; 17:187-213.
79. Grüters A, Liesenkoetter KP, Zapico M, et al. Results of a screening programme for congenital hypothyroidism in Berlin. Exp Clin Endocrinol Diabetes 1997; 105:28-31.
80. Salerno M, Militerni R, Di Maio S, et al. Intellectual outcome at 12 years of age in congenital hypothyroidism. Eur J Endocrinol 1999; 141:105-110.
81. Connelly JF, Rickards AL, Coakley JC, et al. Newborn screening for congenital hypothyroidism, Victoria, Australia, 1977-1997. Part 2: Treatment, progress and outcome. J Pediatr Endocrinol Metab 2001; 14:1611-1634.
82. Derksen-Lubsen G, Verkerk PH: Neuropsychologic development in early-treated congenital hypothyroidism: analysis of literature data. Pediatr Res 1996; 39:561-566.
83. Rovet J: Long-term neuropsychological sequelae of early-treated congenital hypothyroidism: effects in adolescence. Acta Paediatr 1999; 432:88-95.
84. Heyerdahl S, Oerbeck B: Congenital hypothyroidism: developmental outcome in relation to levothyroxine treatment variables. Thyroid 2003; 13:1029-1038. This review summarizes outcome studies in congenital hypothyroidism versus control and in mild versus severe congenital hypothyroidism, and examines the relationship between treatment and outcome variables with a view to addressing the issue of what constitutes optimal treatment. The authors recommend the documentation of a broad array of outcome variables and multicenter studies to increase sample size.
85. Kreisner E, Schermann L, Cargo-Neto E, et al. Predictors of intellectual outcome in a cohort of Brazilian children with congenital hypothyroidism. Clin Endocrinol 2004; 60:250-255. This study examined outcome in 31 consecutive newborns with permanent primary congenital hypothyroidism from Porto Alegre Brazil. The authors report impaired intellectual development in 26% of patients and attribute findings to poor follow-up and lack of maternal schooling, as well as initial disease severity.
86. Rovet J, Ehrlich R, Sorbara D: Intellectual outcome in children with fetal hypothyroidism. Implications for neonatal diagnosis. J Pediatr 1987; 110:700-704.
87. Bargagna S, Canepa G, Costagli C, et al. Neuropsychological follow-up in early-treated congenital hypothyroidism: a problem-oriented approach. Thyroid 2000; 10:243-249.
88. Tillotson SL, Fuggle PW, Smith I, et al. Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect. BMJ 1994; 309:440-445.
89. Heyerdahl S: Development of children with congenital hypothyroidism diagnosed by neonatal screening in Norway. In Advances in Neonatal Screening. Edited by Therrell BL. Amsterdam: Excerpta Medica; 1987:81-84.
90. Virtanen M, Maenpaa J, Santavuori P, et al. Congenital hypothyroidism: age at start of treatment versus outcome. Acta Paediatr Scand 1983; 72:197-201.
91. Toublanc JE, Rives S, Acousta A, et al. Psychomotor and intellectual development in 52 children with congenital hypothyroidism screened at birth. Factors likely to have an effect on prognosis. Arch Fr Pediatr 1990; 47:191-195.
92. Salerno M, DiMaio S, Militerni R, et al. Prognostic factors in the intellectual development at 7 years of age in congenital hypothyroidism. J Endocrinol Invest 1995; 18:774-779.
93. Kuscera S: Intellectual development of children with congenital hypothyroidism (CH) detected by newborn screening. In: The Thyroid and Brain. Edited by Morreale de Escobar G, de Vijlder J, Butz S, et al. Stuttgart: Schattauer; 2003:310-311.
94. Irie M, Nakajima H, Inomata H, et al. Screening of neonatal hypothyroidism in Japan. In Advances in Neonatal Screening. Edited by Therrell B. Amsterdam: Excerpta Medica; 1987:41-47.
95. Alm J, Larsson A, Zetterstrom R: Congenital hypothyroidism in Sweden. Acta Paediatr Scand 1981; 70:907-912.
96. Labarta JL, Mayayo E, Puga B, et al. Psychomotor development in congenital hypothyroidism: Spanish experience. In The Thyroid and Brain. Edited by Morreale de Escobar G, de Vijlder J, Butz S, et al. Stuttgart: Schattauer; 2003:259-272. This paper reviews findings from three studies in Spain, two multicenter and one from the children's hospital in Zaragoza. Results showed that although children with congenital hypothyroidism have a favorable outcome, they do not reach their intellectual potential. Disease severity as indicated by initial thyroxine levels was the most important prognostic factor.
97. Heyerdahl S, Kase BF, Lie SO: Intellectual development in children with congenital hypothyroidism in relation to recommended thyroxine treatment. J Pediatr, 118:850-857.
98. Cermack GA, Foley TP: Longitudinal assessment of L-thyroxine therapy for congenital hypothyroidism. J Pediatr 1990; 117:211-219.
99. American Academy of Pediatrics, Section on Endocrinology and Committee on Genetics, and American Thyroid Association Committee on Public Health: Newborn screening for congenital hypothyroidism: recommended guidelines. Pediatrics 1993; 91:1203-1209.
100. Working Group on Congenital Hypothyroidism of the European Society for Paediatric Endocrinology: Guidelines for neonatal screening programmes for congenital hypothyroidism. Eur J Pediatr 1993; 152:974-975.
101. Rovet JF: Neurobehavioral consequences of congenital hypothyroidism identified by newborn screening. In Therapeutic Outcome of Endocrine Disorders. Efficacy, Innovation, and Quality of Life. Edited by Stabler, B, Bercu BB. New York: Springer-Verlag; 2000:235-254.
102. Rovet J: Children with CH and their siblings. Do they really differ? Pediatrics. [in press]. I found that when children with congenital hypothyroidism were tested at the exact same age and with the same test, those with athyrosis or ectopic glands (but not dyshormonogenesis) scored, on average, 6 points below siblings in IQ.
103. Hanukoglu A, Perlman K, Shamis I, et al. Relationship of etiology to treatment in congenital hypothyroidism. J Clin Endocrinol Metab 2001; 86:186-191.
104. Song S, Daneman D, Rovet J: The influence of etiology and treatment factors on intellectual outcome in congenital hypothyroidism. J Dev Behav Pediatr 2001; 22:376-384.
105. Sack J, Frucht H, Amadeo O, et al. Breast milk thyroxine and not cow's mild may mitigate and delay the clinical picture of neonatal hypothyroidism. Acta Paediatr Scand 1981; 277:54-56.
106. Rovet JF: Does breast feeding protect the hypothyroid infant diagnosed by newborn screening? Am J Dis Child 1990; 144:319-323.
107. New England Congenital Hypothyroidism Collaborative: Elementary school performance of children with congenital hypothyroidism. J Pediatr 1990; 116:27-32.
108. Léger J, Larroque B, Norton J, et al. Influence of severity of congenital hypothyroidism and adequacy of treatment on school achievement in young adolescents: a population-based cohort study. Acta Paediatr 2001; 90:1249-1256.
109. Chiovato L, Bargagna S: Congenital hypothyroidism: treat children but don't forget their parents [commentary]. Eur J Endocrinol 1999; 14:101-104.
110. Alvarez M, Carvajal F, Renon A, et al. Differential effect of fetal, neonatal and treatment variables on neurodevelopment in infants with congenital hypothyroidism. Horm Res 2004; 61:17-20. Results from infants with congenital hypothyroidism tested on four occasions between 3 and 18 months were submitted to regression analysis examining aspects of fetal hypothyroidism, initial severity, treatment age, dosage, and efficacy of therapy. Results found that fetal and neonatal hypothyroidism have different effects on brain maturation sites during the first 2 years and some deficits are likely unavoidable.
111. Bongers-Schokking JJ, Koot HM, Wiersma D, et al. Influence of timing and dose of thyroid hormone replacement on development in infants with congenital hypothyroidism. J Pediatr 2000; 136:292-297.
112. Simoneau-Roy J, Marti S, Deal C, et al. Cognition and behavior at school entry in children with congenital hypothyroidism treated early with high-dose levothyroxine. J Pediatr 2004; 144:747-752. This paper studied a small sample of school-age children with congenital hypothyroidism who received a high starting dosage of thyroxine and showed a moderate but nonsignificant lowering of IQ, specific deficits, and behavioral consequences of subsequent under- and overtreatment.
113. Salerno M, Militerni R, Bravaccio C, et al. Effect of different starting doses of levothyroxine on growth and intellectual outcome at four years of age in congenital hypothyroidism. Thyroid 2002; 12:45-52.
114. Laureau E, Hebert R, Vanasse M, et al. Somatosensory evoked potentials and auditory brain-stem responses in congenital hypothyroidism. II. A cross-sectional study in childhood. Correlations with hormonal levels and developmental quotients. Electroencephalogr Clin Neurophysiol 1987; 67:521-530.
115. Alvarez M, Guell R, Daniel L: Neurocognitive condition of 8 year old children with congenital hypothyroidism treated early. Rev Neurol 1999; 28:701-706.
116. Gottschalk B, Richman R, Lewandowski L: Subtle speech and motor deficits of children with congenital hypothyroidism treated early. Dev Med Child Neurol 1994; 36:216-220.
117. Fuggle PW, Grant DB, Smith I, et al. Intelligence motor skills and behaviour at 5 years in early-treated congenital hypothyroidism. Eur J Pediatr 1991; 150:570-574.
118. Kooistra L, Laane C, Vulsma T, et al. Motor and cognitive development in children with congenital hypothyroidism. J Pediatr 1994; 124:903-909.
119. Gauchard GC, Deviterne D, Leheup B, et al. Effect of age at thyroid stimulating hormone normalization on postural control in children with congenital hypothyroidism. Dev Med Child Neurol 2004; 46:107-113. Children whose TSH normalized past 3 months of age had persisting deficits in postural, educational, and psychomotor aptitudes.
120. Leneman M, Buchanan L, Rovet J: Where and what visuospatial processing in children with congenital hypothyroidism. J Int Neuropsychol Soc 2001; 7:556-562.
121. Kooistra L, van der Meere JJ, Vulsma T, et al. Sustained attention problems in children with early treated hypothyroidism. Acta Paediatr 1996; 84:425-429.
122. Rovet J, Hepworth S: Attention problems in adolescents with congenital hypothyroidism: A multicomponential analysis. J Int Neuropsychol Soc 2001; 7:734-744.
123. Rovet J, Hepworth S: Dissociating attention deficits in children with ADHD and congenital hypothyroidism using multiple CPTs. J Child Psychol Psychiatry 2001; 42:1049-1056.
124. Rovet J: Behavioral and cognitive abnormalities associated with congenital hypothyroidism. In Thyroid Disorders in Infancy and Childhood. Edited by Hauser P, Rovet J. Washington DC: American Psychiatric Press; 1998:85-126.
125. Rovet J: Long-term follow-up of children born with sporadic congenital hypothyroidism. Ann Endocrinol 2003; 64:58-61.
126. Toublanc JE, Riblier E, Rives S: Results of national evaluation tests (primary schools) of CE2 and 6th classes of 73 students with congenital hypothyroidism screened at birth. Arch Paediatr 1998; 5:255-263.
127. Rovet J: Congenital hypothyroidism and nonverbal learning disabilities. In: Syndrome of NLD: Manifestations in Neurological Disease, Disorder, and Dysfunction. Edited by Rourke B. New York: Guilford Press 1995; 255-281.
128. Kooistra L, Stemerdink N, van der Meere J, et al. Behavioural correlates of early-treated congenital hypothyroidism. Acta Paediatr 2001; 90:1141-1146.
129. Kooistra L, Vulsma T, van der Meere J: An investigation of impulsivity in children with early-treated congenital hypothyroidism. Dev Neuropsychol 2004; 26:595-610. A study using computer-driven experimental memory tests in 7.5-year-old children with congenital hypothyroidism showed slow and variable performance but no evidence of poor impulse control or short-term memory problems.
130. Buj V: Average IQ values in various European countries. Personal Individ Diff 1981; 2:168-169.
131. Holmes BJ: Individually-administered intelligence tests: an application of anchor test norming and reporting procedures in British Columbia. Vancouver: Educational Research Institute of British Columbia:11. Report of Student Achievement report no. 81, 1981.
132. Hollowell JG, Staeling NW, Hannon WH, et al. Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from National Health and Nutrition Examination Surveys I and III (1971-1974 and 1988-1994). J Clin Endocrinol Metab 1998; 83:3398-3400.
133. Vitti P, Delange F, Pinchera A, et al. Europe is iodine deficient. Lancet 2003; 361:1226.
134. Vitti P: Neuropsychological assessment in humans living in mild to moderate iodine deficiency. In The Thyroid and Brain. Edited by Morreale de Escobar G, de Vijlder J, Butz S, et al. Stuttgart: Schattauer; 2003:57-63.
135. Flynn JR: Massive IQ gains in 14 nations: what IQ tests really measure. Psychol Bull 1987; 101:171-191.
136. Alexander EK, Marqusee E, Lawrence J, et al. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med 2004; 351:241-249. This paper, which titrated dose levels of pregnant women with preexisting hypothyroidism to ongoing changes in thyroid hormone status during pregnancy, has important implications for treating women with congenital hypothyroidism of reproductive age.