In this study, we investigated alteration in GMD among representative TAO patients with or without DON. Compared to N-DON, GMD was decreased significantly in DON, mainly in the right middle temporal gyrus, left middle frontal gyrus, left superior frontal gyrus, and right middle frontal orbicular gyrus. The cortical visual processing network includes dorsal and ventral pathways. The middle temporal gyrus is a key node in the dorsal pathway, which involves in visuospatial functions and visual motion [29-31]. The middle frontal gyrus and superior frontal gyrus take part in the oculomotor control, which is closely related to dorsal and ventral pathways. [32-34].
Thyroid dysfunction could influence a wide range of visual pathways, including retina cone opsin expression, myelination in optic nerve[9-11], and visual gyrus[12, 13]. Besides, abnormal limbic regions caused by dysfunction of thyroid are mostly temporal and frontal lobes [36, 37], which is consistent with our findings.
Previous studies have indicated that both hypothyroidism and hyperthyroidism can lead to brain abnormalities in structure and function[12, 40]. A study on 2557 individuals suggested that patients with hypothyroidism had significantly lower total brain volume than the normal. Hypothyroidism could cause a reduction in grey matter volume (GMV) in the left postcentral gyrus and cerebellum. Reduction in white matter volume was also observed in the cerebellum, right superior frontal gyrus, middle frontal gyrus, right anterior central gyrus, and right temporal gyrus. Through VMB analysis, hyperthyroid patients exhibit reduced GMV in the hippocampus, parahippocampal gyrus, calcarine, lingual gyrus, and left temporal pole, which are critical for memory, attention, emotion, vision, and motor planning.
For brain connection, thyroid dysfunction also leads to abnormal functional connectivity (FC) in the brain. Resting-state magnetic resonance imaging (rs-MRI) identified a significant decrease in hippocampus volume and functional FC in regions of the right front-parietal network, medial visual network, and motor network in hypothyroid patients . Compared with healthy controls, patients with hyperthyroidism exhibited increased FC in the bilateral anterior insula (AI), bilateral posterior insula (PI) and left anterior lobe of the cerebellum (ALC); whereas decreased FC in the bilateral lateral prefrontal cortex (LPFC), right medial temporal gyrus (MTG) and bilateral posterior cingulate cortex (PCC). Even more, short-term hyperthyroidism could lead to abnormal connection in brain.
No study on the effect of dynamic thyroid function on brain structure has been reported. Krausz Y et al. compared regional cerebral blood flow (rCBF) between hypothyroid patients and health subjects during euthyroid state after treatment. Compared with controls, rCBF in hypothyroid patients before treatment was lower in the right parietooccipital gyri, cuneus, posterior cingulate, lingual gyrus, fusiform, insula, and pre- and postcentral gyri. Perfusion failed to recover to normal when the thyroid function returns to normal state . These findings were validated by later researches. According to the above discussion, the brain function of patients with hypothyroidism can not be completely recovered after a thyroid hormone supplement, which indicates that the dynamic abnormality of thyroid hormone may lead to brain dysfunction.
The pathogenesis of DON remains unclear. The DON was caused by compression associated with edema and increased volume of orbital tissue. Muscle index[3, 4] was applied to evaluate crowded orbital apex, with several contradictions in the follow-up studies [4-6]. Recently, researchers proposed that the maximum diameter of rectus muscle was an important quantifiable predictor of compressive optic neuropathy in TAO . In our study, the difference in orbital apex crowding between the two groups was minimized. Therefore, under the circumstance of excluding crowded orbital apex, the DON group experienced a decrease in gray matter density in different brain areas, which was similar to that caused by dysthyroid function.It is well accepted that thyroid dysfunction is closely related to the development and in proportion to the severity of TAO. So, Thyroid abnormalities might be related to abnormal changes in the brain regions of patients with DON. In this study,there was no significant difference in T3, T4, and TSH between the two groups, but 6 patients (18.75%) had been diagnosed with hypothyroidism. This may be because we can not reflect the long-term dynamic changes of thyroid hormone levels when we detect thyroid hormone levels at a time point. Therefore, it is necessary to further study the long-term dynamic thyroid hormone level of large sample
This study had several limitations. First, the sample size of each group was relatively small. Further studies are required to reproduce our findings by recruiting a large cohort of patients. Second, this study was cross-sectional, which made it difficult to evaluate if increased GMD of the higher vision cortex could be influenced by prolonged illness duration.