Endocrine aspects of metabolic dysfunction-associated steatotic liver disease (MASLD): Beyond insulin resistance

While the links between metabolic dysfunction associated steatotic liver disease liver disease (MASLD) and obesity, insulin resistance are widely appreciated, there are a host of complex interactions between the liver and other endocrine axes. While it can be difficult to definitively distinguish direct causal relationships and those attributable to increased adipocyte mass, there is substantial evidence of direct and indirect specific endocrine dysregulation and severity of MASLD. Strong evidence of direct and indirect effects exists for low levels of growth hormone, sex hormones, and thyroid hormone with development and severity of disease. The impact of steroid hormones, e.g. cortisol and dehydropepiandrosterone, and adipokines is much more divergent. Thoughtful assessment, based on individual risk factors and findings, and also of management of non-insulin endocrine axes should be performed in the evaluation and management of MASLD. Multiple therapeutic pharmaceutical targets have emerged that leverage various endocrine axes to reduce the fibroinflammatory cascade in metabolic dysfunction associated steatohepatitis (MASH).