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      Effects of Early High-Dose Levothyroxine Treatment on Auditory Brain Event-Related Potentials at School Entry in Children with Congenital Hypothyroidism

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          Aims: We tested whether brain event-related potentials (ERPs) are normal in children with congenital hypothyroidism (CH) after early high-dose levothyroxine treatment. Methods: Auditory ERPs were recorded in 33 normal controls and in 15 children with CH at 5 years 9/12. Based on bone maturation at diagnosis, the CH group was divided into severe (n = 8) and moderate (n = 7) subgroups. CH patients were treated at a median age of 14 days with a mean initial dose of levothyroxine of 11.6 µg/kg·day. Two ERP components (N100 and N200) were measured and clinical follow-up variables collected. Results: The functional anatomical and cognitive organisation of the auditory system, as revealed by the analyses of ERP measures, did not differ between CH and controls, or between severe and moderate CH subjects. However, N200 latency was globally longer in the CH than in the control group (p = 0.01) and was positively correlated with the over-treatment index (r = 0.61; p < 0.05) and verbal IQ. N200 amplitude was negatively correlated with initial dose (r = –0.74; p < 0.005). Conclusion: These data suggest that sensitive tools such as ERPs can reveal differences between CH and controls and relate these differences to the adequacy of treatment of CH.

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          Most cited references 28

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          A behavior rating scale for the preschool child.

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            Generators of the late cognitive potentials in auditory and visual oddball tasks.

            Recordings directly within the brain can establish local evoked potential generation without the ambiguities always associated with extracranial electromagnetic measures. Depth recordings have found that sensory stimuli activate primary cortex and then material-specific encoders. Sensory-specific areas remain active for long periods, but by about 200 ms are joined by activation in widespread brain systems. One system is related to the orientation of attention. It is centered in paralimbic and attentional frontoparietocingular cortex, and associated with the P3a. A second system associated with P3b envelopes cognitive contextual integration. It engages the ventral temporofrontal event-encoding cortices (inferotemporal, perirhinal, and ventrolateral prefrontal), association cortices (superior temporal sulcal and posterior parietal), and the hippocampus. Thus, even in simple tasks, activation is widespread but concentrated in particular multilobar systems. With this information, the late cognitive potentials can be used to monitor the probable location, timing and intensity of brain activation during cognitive tasks.
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              Perspectives in the study of thyroid hormone action on brain development and function.

              The purpose of this review is to provide an up-to-date report on the molecular and physiologic processes involved in the role of thyroid hormone as an epigenetic factor in brain maturation. We summarize the available data on the control of brain gene expression by thyroid hormone, the correlation between gene expression and physiologic effects, and the likely mechanisms of action of thyroid hormone on brain gene expression. In addition we propose a role for unliganded thyroid hormone receptors in the pathogenesis of hypothyroidism. Finally, we review recent data indicating that thyroid hormone receptors have an impact on behavior.

                Author and article information

                Horm Res Paediatr
                Hormone Research in Paediatrics
                S. Karger AG
                October 2006
                20 October 2006
                : 66
                : 5
                : 240-248
                Departments of aPsychiatry and bPediatrics, Ste Justine Hospital and Research Center, Université de Montréal, Montréal, Canada; cInstituto de Neurología y Neurocirugía, La Habana, Cuba
                95069 Horm Res 2006;66:240–248
                © 2006 S. Karger AG, Basel

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                Page count
                Figures: 2, Tables: 1, References: 48, Pages: 9
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