MTC complications
Thyroid gland, illustration.

Hyperthyroidism appears to be associated with learning and memory impairments due to decreased expression of the GRIN2B subunit of the N-methyl-D-aspartate (NMDA) receptor in the hippocampus. These findings are consistent with previous studies that report hippocampal pathway alterations in patients with thyroid disease, such as medullary thyroid carcinoma (MTC), according to a recently published study in Brain Research.

Although there is evidence that associates hyperthyroidism with reduced grey matter volume in brain areas involved in memory and learning, the pathophysiology and impact of thyroid hormones in neuronal networks are not yet fully understood. 

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Several studies have investigated the impact of thyroid hormones on neural pathways involved in memory. For example, the expression of cyclin-dependent kinase 5 (Cdk5), involved in the regulation of neuronal plasticity and neuronal plasticity, was proven to be aberrant in patients with MTC. 

Similarly, previous studies have shown a negative correlation between thyroid hormone levels and the expression of several NMDA receptor subunits, which are crucial for memory development.

Therefore, the authors aimed to further investigate the mechanisms behind memory and learning alterations in patients with thyroid diseases by determining the levels of NMDA receptor subunits, Cdk5, as well as other genes with a role in hippocampal-dependent learning in rats treated with tyrosine. 

The rats were divided into 3 groups a control group, a sham group, and a hyperthyroid group. The latter two received L-thyroxine or saline for 21 days, followed by a cognitive assessment using Morris water maze testing to asses spatial memory.

The cognitive assessment revealed that hyperthyroid rats had deteriorated spatial memory in comparison to the control group. Results revealed that only GRIN2B expression was significantly decreased in rats receiving l-thyroxine, Cdk5, GRIN2A, BDNF, and cFOS levels did not appear to be affected by thyroid hormone administration.

“It is not enough to research memory performance, researchers also need to evaluate other cognitive performance and molecular mechanism that underlies diminished memory performance,” the authors concluded.


Sahin L, Keloglan Müsüroglu S, Selin Cevik O, et al . Hyperthyroidism leads learning and memory impairment possibly via GRIN2B expression alterations. Brain Res. Published online December 20, 2022. doi:10.1016/j.brainres.2022.148209