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. 2025 Jul 24.
doi: 10.1007/s40618-025-02658-6. Online ahead of print.

Characteristic volume, texture, and functional connectivity alterations in hypothalamic subunits of adult primary hypothyroidism: a multiparametric MRI analysis

Liting Wang #  1 , Jiancang Cao #  2 , Jinghe Tian  1 , Huiyan Zhang  3 , Chen Yang  1 , Wenwen Zhang  2 , Gang Huang  2 , Lianping Zhao  4
Affiliations

Characteristic volume, texture, and functional connectivity alterations in hypothalamic subunits of adult primary hypothyroidism: a multiparametric MRI analysis

Liting Wang et al. J Endocrinol Invest. .

Abstract

Purpose: Primary hypothyroidism arises from insufficient production of thyroid hormone (TH), characterized by serum thyroid stimulating hormone levels above the reference range (0.35-4.94 mIU/L) and serum-free thyroxine (FT4) levels normal/reduced the reference value (9.01-19.05 pmol/L). TH secretion is regulated via the hypothalamus-pituitary-thyroid axis. Although hypothyroidism is known to affect the brain, its impact on hypothalamic subunits remain incompletely understood.

Methods: In this cross-sectional study, we recruited 145 adults, including 43 with overt hypothyroidism (OH), 50 with subclinical hypothyroidism (SCH), and 52 healthy controls (HCs). All participants underwent demographic, clinical, neuropsychological, and cranial magnetic resonance imaging (MRI) evaluations. Hypothalamic subunit volumes were quantified, texture features extracted, and seed-based functional connectivity (FC) analyses of resting-state functional MRI data were conducted. Correlations between aberrant MRI indices and clinical or neuropsychological parameters were evaluated.

Results: Both OH and SCH participants exhibited impaired cognitive function and increased anxiety/depression scores. In OH, the volume of the right anterior inferior subunit was significantly increased, whereas the texture metric IMC1 (Informational Measure of Correlation 1) was decreased in both the left and right hypothalamus. FC from left anterior inferior, left posterior, and right posterior subunits to multiple cortical regions was elevated in OH compared to HCs. These alterations showed correlations with TH levels and neuropsychological measures. In SCH, no significant hypothalamic abnormalities were observed; although the volume of right anterior inferior subunit was positively correlated with free thyroxine (FT4) and total T4 levels.

Conclusion: These findings indicate that hypothalamic subunits in OH undergo both morphological and functional alterations, likely reflecting compensatory mechanisms associated with disturbed TH regulation. SCH, exhibits negligible hypothalamic changes. These findings underscore a severity-dependent progression of neuropathophysiological changes in hypothyroidism, enhance our understanding of hypothyroidism-related brain damage, and highlight potential targets for future therapeutic interventions.

Keywords: Functional connectivity; Hypothalamic subunits; Hypothyroidism; Magnetic resonance imaging; Texture analysis.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethics approval and consent to participate: This study was performed in line with the principles of the Declaration of Helsinki. Approved by the Ethics Committee of Gansu Provincial Hospital (Approval No.2019-96, 2023-500). All participants in this study signed informed consent to participate. Consent for publication: All participants included in this study provided written informed consent for the publication of their anonymized data. The consent forms are retained by the authors and are available for review by the editor if requested.

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