Endocrine meets hepatic: the thyroid–liver axis in health and disease—an overview

Abstract

The thyroid and the liver share a complex and bidirectional relationship, where thyroid hormones significantly influence hepatic metabolism and vice versa. Through the hypothalamic–pituitary–thyroid (HPT) axis, thyroid hormones regulate lipid, glucose, and protein metabolism, while the liver plays a pivotal role in thyroid hormone metabolism, transport, and conversion. Disturbances of the thyroid–liver metabolic axis can have significant clinical consequences. Examples include the association between hypothyroidism and metabolic dysfunction-associated steatotic liver disease (MASLD), as well as the development of non-thyroidal illness syndrome (NTIS) in patients with chronic liver disease. In addition, autoimmune thyroid and liver diseases may coexist due to shared immunological mechanisms. Recent advances, including the approval of resmetirom by the U.S. Food and Drug Administration (FDA) in 2024 and its subsequent approval by the European Medicines Agency (EMA) in 2025, highlight the therapeutic potential of thyromimetics for treatment of metabolic-associated steatohepatitis (MASH) and support further exploration of thyroid hormone signaling as a therapeutic target in liver disease. Additionally, emerging research explores the utility of thyroid biomarkers as prognostic tools, offering new prospects to enhance screening and optimize treatment strategies. This review synthesizes insights from over 40 research articles, focusing on the molecular mechanisms underpinning the thyroid–liver axis and evaluating its clinical and therapeutic implications. These findings underscore the vital role of thyroid hormones in liver health and suggest innovative approaches for managing thyroid-related liver disorders.