Thyroid dysfunction in MASLD: Results of a nationwide study

Area of Science:

• Hepatology and Endocrinology
• Metabolic Disorders
• Thyroid Function

Background:

• Thyroid hormones significantly influence hepatic metabolism.
• Targeting thyroid hormone receptors is a new treatment for metabolic-associated steatotic liver disease (MASLD).
• The precise link between thyroid disorders and biopsy-confirmed MASLD is not fully understood.

Purpose of the Study:

• To investigate the association between hypothyroidism and hyperthyroidism with MASLD.
• To explore the causal relationship and mediation by metabolic factors using observational and Mendelian randomization (MR) analyses.
• To assess the impact of thyroid dysfunction on MASLD risk.

Main Methods:

• Nationwide matched case-control study using the Swedish ESPRESSO cohort (1969-2017).
• Identified 12,172 MASLD patients and 56,831 general population controls, including sibling controls.
• Used conditional logistic regression, Mendelian randomization, and mediation analyses to assess associations and causal inference.

Main Results:

• Hypothyroidism was linked to a 1.68-fold increased odds of MASLD, consistent in sibling analyses.
• Metabolic disorders accounted for approximately 41% of the hypothyroidism-MASLD association.
• Hyperthyroidism showed a potential inverse association with MASLD, though not statistically significant in MR analysis.

Conclusions:

• Hypothyroidism is a significant risk factor for developing MASLD.
• Hyperthyroidism may have a protective effect against MASLD.
• Metabolic dysfunction plays a crucial role in mediating the link between hypothyroidism and MASLD.