Opposing effects of thyroid hormones on hypothalamic subunits and limbic structures in hyperthyroidism patients: A comprehensive volumetric study

Thyroid hormones play a critical role in brain development, but paradoxically, patients with hyperthyroidism often exhibit cognitive decline and irritability. This study aims to explore the pattern of atrophy in hyperthyroid patients, changes in specific areas of the brain, including hypothalamic subfields and limbic structures, and their relationships with hormonal levels and psychometric tests. This prospective cross-sectional study involves 19 newly diagnosed, untreated hyperthyroid patients, and 15 age and gender-matched control subjects. The participants underwent psychometric and cognitive tests and volumetric MRI. The hypothalamic subfield (anterior-inferior, anterior-superior, superior-tubular, inferior-tubular, and posterior hypothalamus) and limbic structures (fornix, basal forebrain, nucleus accumbens, and septal nucleus) were segmented using voxel-based morphometry, surface-based morphometry, and deep learning algorithms. The groups were compared using the t-test, and correlation analyses were performed between clinical parameters and volumetric measurements. The correlation between hormonal parameters and volumetric measurements in patient and control groups was assessed with the Meng test. Hyperthyroid patients displayed widespread grey matter loss and sulcal shallowing in the left hemisphere. However, no local gyrification index changes or cortical thickness variations were detected. The limbic structures and hypothalamic subunits did not show any volume discrepancies. Free thyroxine in the patient group negatively correlated with bilateral anterior-inferior and right septal nucleus, but positively correlated with left anterior-inferior in the control group. Thyroid stimulating hormone in the patient group showed a positive correlation with bilateral fornix volume, a correlation absent in the control group. Disease duration negatively correlated with right anterior-inferior, right tubular inferior, and right septal nucleus. Changes in cognitive and psychometric test scores in the patient group correlated with the bilateral septal nucleus volume. Hyperthyroidism primarily leads to a reduction in grey matter volume and sulcal shallowing. Thyroid hormones have differing volumetric effects in limbic structures and hypothalamic subunits under physiological and hyperthyroid conditions.