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Abstract
Purpose: Patients with hyperthyroidism have frequent neuropsychiatric symptoms such as lack of attention, concentration, poor memory, impaired executive functions, depression, and anxiety. These neurocognitive impairments such as memory, attention, and executive functions appear to be associated with dysfunction in brain regions. This study was conducted to investigate the metabolic changes in the brain subcortical regions, i.e., posterior parietal cortex and dorsolateral prefrontal cortex (DLPFC), in patients with hyperthyroidism before and after antithyroid treatment using proton magnetic resonance spectroscopy (1H MRS).Materials and Methods: We collected neuropsychological and 1H MRS data from posterior parietal cortex and DLPFC, in both control (N = 30) and hyperthyroid (N = 30) patients. In addition, follow-up data were available for 19 patients treated with carbimazole for 30 weeks. The relative ratios of the neurometabolites were calculated using the Linear Combination Model (LCModel). Analysis of co-variance using Bonferroni correction was performed between healthy controls and hyperthyroid patients, and a paired t-test was applied in patients at baseline and follow-up. Spearman’s rank-order correlation was used to analyze bivariate associations between thyroid hormone levels and metabolite ratios, and the partial correlation analysis was performed between neuropsychological scores and metabolite ratios, with age and sex as covariates, in the patients before and after treatment.Results: Our results revealed a significant decrease in choline/creatine [glycerophosphocholine (GPC) + phosphocholine (PCh)/creatine (tCr)] in both the posterior parietal cortex and DLPFC in hyperthyroid patients, and these changes were reversible after antithyroid treatment. The posterior parietal cortex also showed significantly reduced glutamate/creatine (Glu/tCr), (glutamate + glutamine)/creatine (Glx/tCr), and increased glutathione/creatine (GSH/tCr) ratios in the hyperthyroid patients over control subjects. In DLPFC, only (N-acetyl aspartate + N-acetyl aspartyl-glutamate)/creatine (NAA + NAAG)/tCr was increased in the hyperthyroid patients. After antithyroid treatment, (GPC + PCh)/tCr increased, and Glx/tCr decreased in both brain regions in the patients at follow-up. Gln/tCr in the posterior parietal cortex was decreased in patients at follow-up. Interestingly, (GPC + PCh)/tCr in DLPFC showed a significantly inverse correlation with free tri-iodothyronine (fT3) in hyperthyroid patients at baseline, whereas NAA/tCr showed positive correlations with fT3 and free thyroxine (fT4) in hyperthyroid patients before and after antithyroid treatment, in the posterior parietal cortex. In DLPFC, only (NAA + NAAG)/tCr showed positive correlations with fT3 and fT4 in the patients before treatment.Conclusion: The overall findings suggest that all the brain metabolite changes were not completely reversed in the hyperthyroid patients after antithyroid treatment, even after achieving euthyroidism.
Highlights
Thyroid hormones play an important role in the development and maturation of the brain and neuronal differentiation in humans (Zoeller and Rovet, 2004; Bernal, 2007)
Our findings showed significantly reduced Glu/total creatine (tCr) and Glx/tCr ratios in the posterior parietal cortex in hyperthyroid patients compared to healthy controls
We found a positive correlation between N-acetyl aspartate (NAA)/tCr and fT3 and fT4 in the posterior parietal cortex in patients at baseline and followup, and positive correlations between (NAA + NAAG)/tCr and fT3 and fT4 in dorsolateral prefrontal cortex (DLPFC) in patients at baseline only
Summary
Thyroid hormones play an important role in the development and maturation of the brain and neuronal differentiation in humans (Zoeller and Rovet, 2004; Bernal, 2007) Dysfunction of these hormones may influence deficits in physiology, cognitive function, and emotional behavior (Bauer et al, 2008). Several studies have demonstrated that hyperthyroidism is commonly coupled with a range of neuropsychiatric symptoms, namely, nervousness, irritability, depression, anxiety, memory impairment, lack of concentration, and declined executive functions (Fahrenfort et al, 2000; Vogel et al, 2007; Yuan et al, 2019) The neurocognitive functions such as attention and concentration are associated with the cerebral cortex such as prefrontal and parietal cortices, which are highly sensitive to thyroid hormone concentration (Heuer, 2007). We speculate that excess thyroid hormone influences brain function but may lead to metabolic abnormalities in the mature brain structures, namely, posterior parietal cortex and dorsolateral prefrontal cortex (DLPFC), critical for cognitive functions
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