The pleiotropic function of thyroid hormones (TH) is mediated by an organ
specific expression of thyroid hormone transporters, deiodinases and TH
receptors. In a series of studies we used the model of an experimentally induced
hyper- or hypothyroidism in human volunteers to delineate TH action on the
brain. A battery of neuropsychological testing paradigms was employed and
complemented by structural and functional multimodal neuroimaging.
Experimentally induced mild thyrotoxicosis for 6 weeks was associated with
changes in brain structure (determined with voxel-based morphometry), resting
state functional connectivity, and task-related functional activation in a
working memory paradigm. Partial withdrawal of TH replacement in patients
without thyroid (subclinical hypothyroidism) likewise lead to changes on
multiple functional and structural brain measures. Importantly, the series of
studies reviewed here identified the cerebellum as one crucial site of
action.
Background: Thyroid hormone action is mediated by two forms of thyroid hormone receptors (α,β) with differential tissue distribution. Thyroid hormone receptor β (TRβ) mutations lead to resistance to thyroid hormone action in tissues predominantly expressing the β form of the receptor (pituitary, liver). This study seeks to identify effects of mutant TRβ on pituitary size.
Methods: High-resolution 3D T1-weighted magnetic resonance images were acquired in 19 patients with RTHβ in comparison to 19 healthy matched controls. Volumetric measurements of the pituitary gland were performed independently and blinded by four different raters (two neuroradiologists, one neurologist, one neuroscientist).
Results: Patients with mutant TRβ (Resistance to Thyroid Hormone β,RΤΗβ) showed elevated fT3/4 levels with normal TSH levels, whereas healthy controls showed normal thyroid hormone levels. Imaging revealed smaller pituitary size in RTHβ patients in comparison to healthy controls (F(1,35)=7.05, p=0.012, partial η2 =0.17).
Conclusion: RTHβ subjects have impaired sensitivity to thyroid hormones, along with decreased size of the pituitary gland.
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