Background: Hypothyroidism may profoundly alter mental function and influence mood and cognition, but the neural correlates of these impairments and of thyroid hormone treatment are not well understood.
Methods: We prospectively studied 24 subjects, 14 previously untreated newly diagnosed hypothyroid patients (age 42±12 yrs; 11 female, 3 men) and 10 euthyroid control subjects (41±12 yrs). All patients underwent comprehensive neuropsychiatric assessment, blood laboratory testing, and positron emission tomography with [F-18]fluorodeoxyglucose, before and after achieving euthyroid status with levothyroxine treatment. Regional normalized brain activity was assessed by statistical parametric mapping (SPM2).
Results: Before treatment, hypothyroid patients demonstrated significantly decreased glucose metabolism relative to the control group in the anterior (subgenual/perigenual) and posterior cingulate cortex, the prefrontal cortex and subcortical structures including the dorsal and ventral striatum, the putamen and the amygdala. Hypothyroid patients showed a significant increase of regional normalized brain activity after treatment. No significant differences were found between the hypothyroid and control groups after treatment, indicating a normalization of brain metabolism. At baseline decreased prefrontal metabolism was associated with the severity of somatic complaints. Increase of prefrontal metabolism was associated with normalization of TSH and metabolism in the posterior cingulate cortex correlated with improvement in a standardized measure of short-term memory.
Conclusion: This is the first PET study demonstrating in vivo regionally specific effects of primary hypothyroidism on cerebral glucose metabolism especially in the perigenual anterior cingulate/medial frontal gyrus and its normalization with levothyroxine treatment. Furthermore, associations between abnormalities of regional brain metabolism and neuropsychological impairments can be demonstrated in adults with hypothyroidism.
Ethical approval by IRB University of California Los Angeles (UCLA).