Do children with congenital hypothyroidism exhibit abnormal cortical morphology?

Abstract

Background: Given thyroid hormone (TH)'s essential role in multiple aspects of early brain development, children with congenital hypothyroidism (CH) detected and treated early may still display subtle cognitive and behavioral impairments as well as brain abnormalities. However, effects on their cortical development are not yet known. We used an automated neuroimaging technique to determine if these children differ in cortical thickness (CT) from typically developing controls (TDC) and if the regions showing CT differences reflect severity of initial hypothyroidism and predict later neuropsychological functioning. Methods: FreeSurfer Image Analysis Suite was used on archived MRI scans from 41 CH and 42 TDC children aged 9-16 y. Vertex-based procedures were used to compare groups and perform correlations between CT and indices of disease severity and neuropsychological outcome. results: The CH group showed multiple regions of cortical thinning or cortical thickening within right and left hemispheres relative to TDC. CT values were significantly correlated with early T4 and thyroid-stimulating hormone (TSH) levels and current neuropsychological test indices. conclusion: The developing cortex is sensitive to early TH loss in CH. Different patterns of cortical thinning or cortical thickening among brain regions may reflect timing of TH deficiency relative to timing of cortical development.

Dorsal and ventral visual streams: Typical and atypical development

“…Importantly, the visual system is a known target for TH regulation during development (Berbel et al, 2010;Martinez-Galan, Escobar del Rey, Morreale de Escobar, Santacana, & RuizMarcos, 2004). As recently demonstrated by Clairman et al (2015), children who are deficient in TH during pregnancy, despite receiving early and continuous treatment after birth, experience aberrant neural development involving both cortical thinning and cortical thickening, including in regions belonging to both visual streams.…”

“…Nevertheless, because of their brief period of TH deficiency before treatment is received and takes effect, they still may show mild cognitive deficits, the nature and severity of which reflect the specific timing of their TH deficiency (Rovet, 2005). Structural neuroimaging studies of children with CH report that multiple brain regions show abnormal cortical thickness, including thinning of the superior parietal gyrus and precuneus, which belong to the dorsal stream, and inferior temporal gyrus belonging to the ventral visual stream (Clairman, Skocic, Lischinsky, & Rovet, 2015). Previous behavioral studies by our group and others suggest that visuospatial deficits in CH may be specific to the dorsal stream (Blasi et al, 2009;Leneman, Buchanan, & Rovet, 2001;Mirabella et al, 2005).…”

Preliminary Findings Show Maternal Hypothyroidism May Contribute to Abnormal Cortical Morphology in Offspring

“…It is relevant to note we recently reported that children with CH, who underwent a brief circumscribed period of TH insufficiency that occurred somewhat later and extended longer than in HYPO, also showed that cortical thinning and thickening relative to controls and effects reflected the severity of their hypothyroidism ( 45 ). Both CH and HYPO conditions showed thinning of the right precuneus and thickening in right occipital regions, while left precentral gyrus and right cuneus and postcentral gyrus thickening were correlated with late gestational or perinatal TH elevations in both populations.…”

“…Image analysis was performed on a Linux Fedora operating system using FreeSurfer Image Analysis Suite version 4.4 ( 53 ). When this study originally began, this version was the most current and used in other research in our lab ( 45 ). FreeSurfer consists of a series of automated algorithms that reproduce the brain’s inner and outer surfaces and measure distances between these surfaces on a point-to-point basis for the entire cortical mantle.…”

“…A number of neurodevelopmental conditions, such as autism spectrum disorder, attention-deficit hyperactive disorder, human X monosomy, fetal alcohol spectrum disorder, and William’s syndrome show a wide variety of CT abnormalities ( 35 – 42 ), which are typically attributed to defects in neuronal migration or cortical layering ( 43 , 44 ). Recently, we reported that children with congenital hypothyroidism (CH), who are TH-deficient in the period from late gestation until the first month or two of life, show cortical thinning and thickening in diverse regions with specific effects reflecting initial disease severity and predicting current neuropsychological functioning ( 45 ). By contrast, studies from the Netherlands examining children’s cortical morphology report normal CT and SA measurements if mothers had hypothyroxinemia in early pregnancy (i.e., low thyroxine or T4 but normal thyroid-stimulating hormone or TSH) ( 46 ) but cortical volumes were reduced if mothers’ free T4 levels were at the low or high extremes of the normal range ( 47 ).…”