Abnormal free T4 associated with lower brain perfusion in adults
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High and low free thyroxine levels are associated with lower global brain perfusion in adults and could lead to brain diseases, such as dementia, according to a presenter.
“Thyroid function has previously been associated with dementia and neurocognitive disorders,” Oscar H. Roa Dueñas, MD, a PhD candidate at Erasmus University Medical Center in The Netherlands, told Healio. “It is, however, not yet known through which mechanisms. In our study, we show that free thyroxine levels are associated with brain perfusion in middle-aged and elderly people. Low brain perfusion has been shown to be associated with neurocognitive diseases. Therefore, brain perfusion could be a promising mediator in the association between thyroid function and subsequent neurocognitive diseases.”
Roa Dueñas and colleagues analyzed data from 5,142 adults participating in the Rotterdam Study in The Netherlands (mean age, 63.8 years; 55.4% women). Thyroid function measurements were collected between 1997 and 2007. Normal free T4 was defined as between 11 pmol/L and 25 pmol/L. Associations involving thyroid-stimulating hormone were analyzed using natural logarithmic transformation. All participants underwent an MRI between 2005 and 2015 to assess global brain perfusion. Of the study cohort, 3,105 underwent an arteriolar and venular retinal calibers assessment.
Participants with a low free T4 level of 10 pmol/L had a mean 0.8 mL less brain perfusion and those with a high free T4 of 25 pmol/L had 2.44 mL less brain perfusion compared with adults with free T4 of 15 pmol/L. No association was observed between TSH and brain perfusion.
“Based on our results, both higher and lower free T4 levels, even within the normal range, are related to suboptimal cerebral blood perfusion,” Roa Dueñas said. “This may suggest an optimum free T4 level when considering treatment targets in hypothyroidism patients. However, we have not investigated levothyroxine users specifically, and we therefore need to be cautious drawing any conclusions.”
Of those who underwent an arteriolar and venular retinal calibers assessment, each natural log increase in TSH was associated with 0.92 m narrower arteriolar retinal vessels. The association persisted after adjusting for systolic and diastolic blood pressure. Participants who were positive for thyroid peroxidase (TPO) antibodies had 1.78 m narrower arteries than those who were negative for TPO antibodies. No associations were observed between thyroid function and venular retinal vessels.
Roa Dueñas said the causality of the associations should be investigated before exploring whether interventions in thyroid function could reduce the risk for neurocognitive and neurovascular disorders.
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Thyroid hormones play an important role in the normal function of a number of key organ systems. Either deficiency or excess in thyroid hormone leads to end-organ dysfunction and ultimately symptoms that cause patients to present to their physicians for treatment.
However, the mechanisms underlying the detrimental effects of hyperthyroidism and hypothyroidism, in particular neurocognitive effects, are not all well understood. Roa Dueñas and colleagues aimed to measure the association between thyroid function and brain circulation as a potential mechanism underlying the link between thyroid disease and brain diseases, like stroke and dementia. Indeed, the primary finding that both high and low levels of free thyroxine are associated with lower global brain perfusion in an inverted U-shaped relationship points to a possible mechanism.
The study did not address neurocognitive or cerebrovascular outcomes, such as stroke, although this has been addressed in other studies. One might hypothesize based on these results that those with underlying cerebrovascular disease, such as prior stroke or vascular dementia, may be particularly sensitive to small changes in thyroid hormone levels. It also suggests a possible mechanism underlying why some patients with thyroid disease experience more subtle but persistent neurocognitive symptoms, including brain fog. Further studies of thyroid hormone levels and cerebral perfusion, including those with patient-centered outcomes, may be of interest to those managing and living with thyroid disease and neurocognitive symptoms.
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Roa Dueñas O, et al. OR-24. Presented at: American Thyroid Association Annual Meeting; Sept. 30-Oct. 3, 2021 (virtual meeting).
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