Thyroid Status and Brain Circulation: The Rotterdam Study

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Context: Whether thyroid dysfunction is related to altered brain circulation in the general population remains unknown. Objective: We determined the association of thyroid hormones with different markers of brain circulation within community-dwelling elderly people. Methods: This was a population-based study of 3 subcohorts of the Rotterdam Study, starting in 1989, 2000, and 2006. A total of 5142 participants (mean age, 63.8 years; 55.4% women), underwent venipuncture to measure serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Between 2005 and 2015, all participants underwent phase-contrast brain magnetic resonance imaging to assess global brain perfusion (mL of blood flow/100 mL of brain/minute). Arteriolar retinal calibers were assessed using digitized images of stereoscopic fundus color transparencies in 3105 participants as markers of microcirculation. We investigated associations of TSH, FT4 with brain circulation measures using (non)linear regression models. Results: FT4 (in pmol/L) levels had an inverse U-shaped association with global brain perfusion, such that high and low levels of FT4 were associated with lower global brain perfusion than middle levels of FT4. The difference in global brain perfusion between high FT4 levels (25 pmol/L) and middle FT4 levels (FT4 = 15 pmol/L; P nonlinearity =. 002) was up to -2.44 mL (95% CI -4.31; -0.56). Higher and lower levels of FT4, compared with middle FT4 levels, were associated with arteriolar retinal vessels (mean difference up to -2.46 μm, 95% CI -4.98; 0.05 for lower FT4). Conclusion: These results suggest that thyroid dysfunction could lead to brain diseases such as stroke or dementia through suboptimal brain circulation that is potentially modifiable.

Original languageEnglish
Pages (from-to)E1293-E1302
JournalJournal of Clinical Endocrinology and Metabolism
Issue number3
Early online date11 Oct 2021
Publication statusPublished - Mar 2022

Bibliographical note

Funding Information:
This work was supported by the European Union's Horizon 2020 research and innovation program (grant number 667375) ("CoSTREAM"); the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO) (grant numbers 948-00-010, 918- 46-615); The Netherlands Organization for Health Research and Development (ZonMw); The Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. The funding source had no role in study design, collection, analysis, interpretation of data, writing of the report or decision to submit the article for publication.

Publisher Copyright:
© 2021 The Author(s) 2021.


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