{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T20:33:05Z","timestamp":1772656385242,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Subclinical hypothyroidism (SCH) brain structure and resting state of functional activity have remained unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To investigate gray matter volume (GMV) and regional brain activity with the fractional amplitude of low-frequency fluctuations (fALFF) in subclinical hypothyroidism (SCH) patients before and after treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>We enrolled 54 SCH and 41 age-, sex-, and education-matched controls. GMV and fALFF of SCH were compared with controls and between pre- and post-treatment within SCH group. Correlations of GMV and fALFF in SCH with thyroid function status and mood scales were assessed by multiple linear regression analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to controls, GMV in SCH was significantly decreased in Orbital part of inferior frontal, superior frontal, pre-\/postcentral, inferior occipital, and temporal pole gyrus. FALFF values in SCH were significantly increased in right angular, left middle frontal, and left superior frontal gyrus. After treatment, there were no significant changes in GMV and the local brain function compared to pre-treatment, however the GMV and fALFF of the defective brain areas were improved. Additionally, decreased values of fALFF in left middle frontal gyrus were correlated with increased mood scales.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this study we found that patients with SCH, the gray matter volume in some brain areas were significantly reduced, and regional brain activity was significantly increased. After treatment, the corresponding structural and functional deficiencies had a tendency for improvement. These changes may reveal the neurological mechanisms of mood disorder in SCH patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.582519","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T06:27:29Z","timestamp":1614148049000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Gray Matter and Regional Brain Activity Abnormalities in Subclinical Hypothyroidism"],"prefix":"10.3389","volume":"12","author":[{"given":"Yang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaqiong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Tao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingguo","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su","family":"Lui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1210\/er.2006-0043","article-title":"The clinical significance of subclinical thyroid dysfunction","volume":"29","author":"Biondi","year":"2008","journal-title":"Endocr Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2008.01774.x","article-title":"The thyroid-brain interaction in thyroid disorders and mood disorders","volume":"20","author":"Bauer","year":"2008","journal-title":"J Neuroendocrinol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/S0149-7634(01)00037-9","article-title":"Thyroid hormones, brain function and cognition: a brief review","volume":"26","author":"Smith","year":"2002","journal-title":"Neurosci Biobehav Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2014.922042","article-title":"Iodine Deficiency and the Brain: Effects and Mechanisms","volume":"56","author":"Redman","year":"2016","journal-title":"Crit Rev Food Sci Nutr"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001647","article-title":"Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in bipolar depression","volume":"10","author":"Bauer","year":"2005","journal-title":"Mol Psychiatry"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4530(92)90060-K","article-title":"Major depression and subclinical (grade 2) hypothyroidism","volume":"17","author":"Joffe","year":"1992","journal-title":"Psychoneuroendocrinology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/BF00186625","article-title":"Subclinical hypothyroidism: neurobehavioral features and beneficial effect of L-thyroxine treatment","volume":"71","author":"Monzani","year":"1993","journal-title":"Clin Investig"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.150.3.508","article-title":"Subclinical hypothyroidism: a modifiable risk factor for depression","volume":"150","author":"Haggerty","year":"1993","journal-title":"Am J Psychiatry"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2006.02.001","article-title":"Subclinical hypothyroidism increases the risk for depression in the elderly","volume":"44","author":"Chueire","year":"2007","journal-title":"Arch Gerontol Geriatr"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2009.05.015","article-title":"Subclinical hypothyroidism (SCH) is not associated with metabolic derangement, cognitive impairment, depression or poor quality of life (QoL) in elderly subjects","volume":"50","author":"Park","year":"2010","journal-title":"Arch Gerontol Geriatr"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-145-8-200610170-00006","article-title":"Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction","volume":"145","author":"Roberts","year":"2006","journal-title":"Ann Intern Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/JGP.0b013e31820dcad5","article-title":"Thyroid hormones and depression: the Health in Men study","volume":"19","author":"Almeida","year":"2011","journal-title":"Am J Geriatr Psychiatry"},{"key":"B13","article-title":"Changes of event related potential and cognitive processes in patients with subclinical hypothyroidism after thyroxine treatment","volume":"36","author":"Jensovsky","year":"2002","journal-title":"Endocr Regul"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2012.32423","article-title":"Changes of subtests of Wechsler Memory Scale and cognitive function in subjects with subclinical hypothyroidism following treatment with levothyroxine","volume":"8","author":"Aghili","year":"2012","journal-title":"Arch Med Sci"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(97)00089-4","article-title":"Psychopathological and cognitive features in subclinical hypothyroidism","volume":"21","author":"Baldini","year":"1997","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"B16","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.ajp.2013.12.004","article-title":"Low mood and response to Levothyroxine treatment in Indian patients with subclinical hypothyroidism","volume":"8","author":"Vishnoi","year":"2014","journal-title":"Asian J Psychiatr"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e0154846","DOI":"10.1371\/journal.pone.0154846","article-title":"Subclinical Hypothyroidism after 131I-Treatment of Graves\u2019 Disease: A Risk Factor for Depression","volume":"11","author":"Yu","year":"2016","journal-title":"PLoS One"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0011","article-title":"Health status, mood, and cognition in experimentally induced subclinical hypothyroidism","volume":"92","author":"Samuels","year":"2007","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"B19","article-title":"Prevalence of depression in patients affected by subclinical hypothyroidism","volume":"52","author":"Demartini","year":"2010","journal-title":"Panminerva Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1017\/S1461145706006481","article-title":"Brain SPECT study of common ground between hypothyroidism and depression","volume":"10","author":"Krausz","year":"2007","journal-title":"Int J Neuropsychopharmacol"},{"key":"B21","article-title":"Regional cerebral blood flow in patients with mild hypothyroidism","volume":"45","author":"Krausz","year":"2004","journal-title":"J Nucl Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-2235","article-title":"Brain glucose metabolism in hypothyroidism: a positron emission tomography study before and after thyroid hormone replacement therapy","volume":"94","author":"Bauer","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl215","article-title":"fMRI revealed neural substrate for reversible working memory dysfunction in subclinical hypothyroidism","volume":"129","author":"Zhu","year":"2006","journal-title":"Brain J Neurol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2011.01.065","article-title":"Comparison of grey matter atrophy between patients with neuromyelitis optica and multiple sclerosis: a voxel-based morphometry study","volume":"81","author":"Duan","year":"2012","journal-title":"Eur J Radiol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2010.04.006","article-title":"Cerebral and cerebellar gray matter reduction in first-episode patients with major depressive disorder: a voxel-based morphometry study","volume":"80","author":"Peng","year":"2011","journal-title":"Eur J Radiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2008.04.012","article-title":"An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF","volume":"172","author":"Zou","year":"2008","journal-title":"J Neurosci Methods"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1348\/000712606X146197","article-title":"A classification of handedness using the Annett Hand Preference Questionnaire","volume":"98","author":"Dragovic","year":"2007","journal-title":"Br J Psychol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e25159","DOI":"10.1371\/journal.pone.0025159","article-title":"Increased activity imbalance in fronto-subcortical circuits in adolescents with major depression","volume":"6","author":"Jiao","year":"2011","journal-title":"PLoS One"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2014.10.017","article-title":"Clinical, cognitive, and functional connectivity correlations of resting-state intrinsic brain activity alterations in unmedicated depression","volume":"172","author":"Tadayonnejad","year":"2015","journal-title":"J Affect Disord"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/BF02984562","article-title":"Cerebral blood flow abnormalities induced by transient hypothyroidism after thyroidectomy\u2013analysis by tc-99m-HMPAO and SPM96","volume":"18","author":"Nagamachi","year":"2004","journal-title":"Ann Nucl Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0452","article-title":"Diminished Quality of Life and Increased Brain Functional Connectivity in Patients with Hypothyroidism After Total Thyroidectomy","volume":"26","author":"Shin","year":"2016","journal-title":"Thyroid"},{"key":"B32","article-title":"Technetium-99m ethyl cysteinate dimer (ECD) cerebral accumulation and symptom and sign severity during hypothyroidism","volume":"31","author":"Schraml","year":"2010","journal-title":"Neuro Endocrinol Lett"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e12587","DOI":"10.1111\/jne.12587","article-title":"Alteration in intrinsic and extrinsic functional connectivity of resting state networks associated with subclinical hypothyroidism","volume":"30","author":"Kumar","year":"2018","journal-title":"J Neuroendocrinol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1162\/jocn_a_00595","article-title":"The role of right prefrontal and medial cortex in response inhibition: interfering with action restraint and action cancellation using transcranial magnetic brain stimulation","volume":"26","author":"Dambacher","year":"2014","journal-title":"J Cognit Neurosci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2009.09.006","article-title":"Functional neuroimaging of self-referential encoding with age","volume":"48","author":"Gutchess","year":"2010","journal-title":"Neuropsychologia"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2013.12.005","article-title":"Limbic systems for emotion and for memory, but no single limbic system","volume":"62","author":"Rolls","year":"2015","journal-title":"Cortex"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2018.12.012","article-title":"Experimentally induced subclinical hypothyroidism causes decreased functional connectivity of the cuneus: A resting state fMRI study","volume":"102","author":"Gobel","year":"2019","journal-title":"Psychoneuroendocrinology"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.582519\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T06:27:35Z","timestamp":1614148055000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.582519\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,24]]},"references-count":37,"alternative-id":["10.3389\/fendo.2021.582519"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2021.582519","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,24]]},"article-number":"582519"}}