Interplay between endocrine disorders and liver dysfunction: Mechanisms of damage and therapeutic approaches

Figure 3 The link between adrenal diseases and liver dysfunction. Molecular pathways connecting adrenal endocrine disorders with liver dysfunction and metabolic complications. In secondary hyperaldosteronism, excess aldosterone from the zona glomerulosa activates mineralocorticoid receptors, leading to sodium and water retention, ascites, and worsening portal hypertension. Aldosterone also increases insulin receptor degradation, contributing to insulin resistance and disrupting glucose homeostasis. In adrenal insufficiency, reduced cortisol from the zona fasciculata impairs anti-inflammatory responses, promoting autoimmune reactions and proinflammatory cytokines like interleukin-6 and tumor necrosis factor-α, which drive liver inflammation and fibrosis. Excess cortisol disrupts insulin signaling pathways in hypercortisolism, causing hyperglycemia, increased cholesterol and triglyceride synthesis, and ectopic hepatic fat accumulation, leading to steatotic liver disease. In pheochromocytoma, excessive catecholamines from the adrenal medulla increase adrenergic stimulation, resulting in lipolysis, oxidative stress, and reactive oxygen species production, causing vasoconstriction, hypoperfusion, and liver cell damage. These combined effects manifest as elevated liver enzymes, ascites formation, and fibrosis. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ATP: Adenosine triphosphate; ROS: Reactive oxygen species; ADP: Adenosine diphosphate; NAD: Nicotinamide adenine dinucleotide.