Abstract
Magnetic resonance imaging (MRI) data of children with late diagnosed congenital hypothyroidism and cognitive alterations such as abnormal verbal memory processing suggest altered telencephalic commissural connections. The corpus callosum (CC) is the major inter-hemispheric commissure that contra-laterally connects neocortical areas. However, in late diagnosed neonates with congenital hypothyroidism, the possible effect of early transient and chronic postnatal hypothyroidism still remains unknown. We have studied the development of the anterior, middle and posterior CC, using in vivo MRI and electron microscopy in hypothyroid and control male rats. Four groups of methimazole (MMI) treated rats were studied. One group, as a model for early transient hypothyroidism, was MMI-treated from postnatal day (P) 0 to P21; some of these rats were also treated with L-thyroxine (T4) from P15 to 21. Another group modeling chronic hypothyroid, were treated with MMI from P0 to 150 and from embryonic day 10 to P170. The results obtained from these groups were compared with same age control rats. The normalized T2 signal obtained using MRI was higher in MMI-treated rats and correlated with a low number and percentage of myelinated axons. The number and density of myelinated axons decreased in transient and chronic hypothyroid rats at P150. The g-ratio (inner to outer diameter ratio) and the estimated conduction velocity of myelinated axons were similar between MMI-treated and controls, but the conduction delay decreased in the posterior CC of MMI-treated rats compared to controls. These data show that early postnatal transient and chronic hypothyroidism alters CC maturation in a way that may affect the callosal transfer of information. These alterations cannot be reversed after delayed T4-treatment. Our data support the findings of neurocognitive delay in late T4-treated children with congenital hypothyroidism.
Highlights
IntroductionCongenital hypothyroidism is commonly caused by agenesis, dysgenesis (including ectopia) and dysfunction of the thyroid gland, causing neurological and psychiatric deficits, such as intellectual disability, spasticity, and disturbances in gait and co-ordination (Dussault and Ruel, 1987; Rovet et al, 1992; Rovet, 1999, 2002; Brown, 2012; Clairman et al, 2015; Krude et al, 2015; Léger, 2015; Aycan et al, 2017).Screening programs are crucial for the early detection and treatment of congenital hypothyroidism in an attempt to avoid the severe neurological and mental diseases that results from late diagnosis, neurological deficits may persist even when congenital hypothyroidism is diagnosed at birth (Rovet et al, 1992; Rovet, 2005)
Our results show that both postnatal transient and postnatal chronic hypothyroidism cause a greater decrease of myelinated axon number and percentage in posterior than in anterior and middle corpus callosum (CC), and that this decrease is not recovered when T4-treatment is delayed
In all MMI rats, mean unmyelinated and myelinated axon diameter decreases in the posterior CC, except in the case of MMIE10 rats in which it remains low in all zones of the CC. g-Ratio is similar between MMI and C rats
Summary
Congenital hypothyroidism is commonly caused by agenesis, dysgenesis (including ectopia) and dysfunction of the thyroid gland, causing neurological and psychiatric deficits, such as intellectual disability, spasticity, and disturbances in gait and co-ordination (Dussault and Ruel, 1987; Rovet et al, 1992; Rovet, 1999, 2002; Brown, 2012; Clairman et al, 2015; Krude et al, 2015; Léger, 2015; Aycan et al, 2017).Screening programs are crucial for the early detection and treatment of congenital hypothyroidism in an attempt to avoid the severe neurological and mental diseases that results from late diagnosis, neurological deficits may persist even when congenital hypothyroidism is diagnosed at birth (Rovet et al, 1992; Rovet, 2005). Despite a generalized implementation of screening programs in developed countries, the incidence of primary transient congenital hypothyroidism is on the increase in some countries, cases with mild dysfunction of the thyroid gland (Pearce et al, 2010; Léger et al, 2015) The causes for this remain under discussion but may be related to delays in the onset of L-thyroxine (T4) treatment (Rovet et al, 1992), screening thresholds (Olivieri et al, 2013; Léger et al, 2014) and to iodine deficiency during lactation and early infancy (Morreale de Escobar and Escobar del Rey, 1980, 2003; Sava et al, 1984; Köhler et al, 1996; Pearce et al, 2004; Berbel et al, 2007; Walker et al, 2007; Berbel and Morreale de Escobar, 2011). In southern Italy, a mildly iodine-deficient region, hypothyroidism associated with postpartum thyroiditis can affect up to 3.9% of women (StagnaroGreen et al, 2011b), and more importantly, postpartum thyroiditis is usually only diagnosed by the sixth month postpartum (Lazarus, 2011; Stagnaro-Green et al, 2011b), effectively at the end of the nursing period recommended by the WHO and UNICEF (Stagnaro-Green et al, 2011a)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
