Till Ittermann1, Katharina Wittfeld2,3, Matthias Nauck4,5, Robin Bülow6, Norbert Hosten6, Henry Völzke1, Hans J Grabe2,3. 1. 1 Institute for Community Medicine , Site Rostock/Greifswald, Greifswald, Germany . 2. 2 Institute for Psychiatry and Psychotherapy , Site Rostock/Greifswald, Greifswald, Germany . 3. 3 German Center for Neurodegenerative Diseases (DZNE) , Site Rostock/Greifswald, Greifswald, Germany . 4. 4 Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald , Greifswald, Germany . 5. 5 DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine Greifswald , Greifswald, Germany . 6. 6 Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald , Greifswald, Germany .
Abstract
BACKGROUND: Previous patient studies suggest that thyroid dysfunction affects volumes of particular regions of the brain. So far, population-based data related to this topic are lacking. The aim of this study was to investigate associations of serum levels of thyrotropin (TSH), free triiodothyronine, and free thyroxine (fT4) with total brain volume, gray matter volume, white matter volume (WMV), and hippocampal volume (HV) in a population-based study. METHODS: Data on 2557 individuals were pooled from two independent population-based surveys of the Study of Health in Pomerania conducted in Northeast Germany. Brain volumes were determined from images derived from 1.5 T magnetic resonance imaging. Low and high TSH were defined using the cutoffs 0.40 and 3.29 mIU/L, respectively. Associations between thyroid hormone levels and segmented brain volumes were analyzed by linear regression models. Further, voxel-based morphometry was conducted to search for associations with thyroid hormone levels in a hypothesis-free way throughout the whole brain. All models were adjusted for confounders. RESULTS: Only 9/70 individuals with high TSH had low free triiodothyronine or fT4 levels. Individuals with high TSH had significantly lower total brain volume (β = -26.9 [confidence interval (CI) -49.0 to -4.8]; p = 0.017), WMV (β = -16.1 [CI -29.4 to -2.7]; p = 0.018), and HV (β = -223 [CI -395 to -50]; p = 0.011) than individuals with TSH within the reference range, while low TSH was not significantly associated with any of the brain volumes. Voxel-based morphometry analyses revealed a significant positive association with serum fT4 levels in the left middle frontal gyrus. CONCLUSIONS: In conclusion, the results of this study indicate that the subclinical hypothyroid state may lead to a reduced brain volume affecting particularly HV in younger subjects and WMV, which might correspond to subtle microstructural changes in white matter fiber tracts or myelination of the axones. Gray matter seems not to be affected by subclinical hypothyroid states.
BACKGROUND: Previous patient studies suggest that thyroid dysfunction affects volumes of particular regions of the brain. So far, population-based data related to this topic are lacking. The aim of this study was to investigate associations of serum levels of thyrotropin (TSH), free triiodothyronine, and free thyroxine (fT4) with total brain volume, gray matter volume, white matter volume (WMV), and hippocampal volume (HV) in a population-based study. METHODS: Data on 2557 individuals were pooled from two independent population-based surveys of the Study of Health in Pomerania conducted in Northeast Germany. Brain volumes were determined from images derived from 1.5 T magnetic resonance imaging. Low and high TSH were defined using the cutoffs 0.40 and 3.29 mIU/L, respectively. Associations between thyroid hormone levels and segmented brain volumes were analyzed by linear regression models. Further, voxel-based morphometry was conducted to search for associations with thyroid hormone levels in a hypothesis-free way throughout the whole brain. All models were adjusted for confounders. RESULTS: Only 9/70 individuals with high TSH had low free triiodothyronine or fT4 levels. Individuals with high TSH had significantly lower total brain volume (β = -26.9 [confidence interval (CI) -49.0 to -4.8]; p = 0.017), WMV (β = -16.1 [CI -29.4 to -2.7]; p = 0.018), and HV (β = -223 [CI -395 to -50]; p = 0.011) than individuals with TSH within the reference range, while low TSH was not significantly associated with any of the brain volumes. Voxel-based morphometry analyses revealed a significant positive association with serum fT4 levels in the left middle frontal gyrus. CONCLUSIONS: In conclusion, the results of this study indicate that the subclinical hypothyroid state may lead to a reduced brain volume affecting particularly HV in younger subjects and WMV, which might correspond to subtle microstructural changes in white matter fiber tracts or myelination of the axones. Gray matter seems not to be affected by subclinical hypothyroid states.
Authors: Karen Lariosa-Willingham; Kimmo K Lehtimäki; Diana Miszczuk; Dmitri Leonoudakis; Timo Bragge; Laura Tolppanen; Antti Nurmi; Megan Flanagan; Janelle Gibson; David Wilson; Jennifer Stratton Journal: BMC Neurosci Date: 2022-05-25 Impact factor: 3.264
Authors: Peter T Nelson; Dennis W Dickson; John Q Trojanowski; Clifford R Jack; Patricia A Boyle; Konstantinos Arfanakis; Rosa Rademakers; Irina Alafuzoff; Johannes Attems; Carol Brayne; Ian T S Coyle-Gilchrist; Helena C Chui; David W Fardo; Margaret E Flanagan; Glenda Halliday; Suvi R K Hokkanen; Sally Hunter; Gregory A Jicha; Yuriko Katsumata; Claudia H Kawas; C Dirk Keene; Gabor G Kovacs; Walter A Kukull; Allan I Levey; Nazanin Makkinejad; Thomas J Montine; Shigeo Murayama; Melissa E Murray; Sukriti Nag; Robert A Rissman; William W Seeley; Reisa A Sperling; Charles L White; Lei Yu; Julie A Schneider Journal: Brain Date: 2019-06-01 Impact factor: 15.255
Authors: Tom Chambers; Richard Anney; Peter N Taylor; Alexander Teumer; Robin P Peeters; Marco Medici; Xavier Caseras; D Aled Rees Journal: J Clin Endocrinol Metab Date: 2021-03-08 Impact factor: 5.958
Authors: Norbert Hosten; Robin Bülow; Henry Völzke; Martin Domin; Carsten Oliver Schmidt; Alexander Teumer; Till Ittermann; Matthias Nauck; Stephan Felix; Marcus Dörr; Marcello Ricardo Paulista Markus; Uwe Völker; Amro Daboul; Christian Schwahn; Birte Holtfreter; Torsten Mundt; Karl-Friedrich Krey; Stefan Kindler; Maria Mksoud; Stefanie Samietz; Reiner Biffar; Wolfgang Hoffmann; Thomas Kocher; Jean-Francois Chenot; Andreas Stahl; Frank Tost; Nele Friedrich; Stephanie Zylla; Anke Hannemann; Martin Lotze; Jens-Peter Kühn; Katrin Hegenscheid; Christian Rosenberg; Georgi Wassilew; Stefan Frenzel; Katharina Wittfeld; Hans J Grabe; Marie-Luise Kromrey Journal: Healthcare (Basel) Date: 2021-12-24