How to Identify MASLD Forms Secondary to Endocrine Derangements in Clinical Practice

Secondary forms of metabolic dysfunction-associated steatotic liver disease (MASLD) have different pathogeneses, outcomes, and specific treatment approaches. The aim of this narrative review is to discuss the principal forms of MASLD secondary to endocrine disorders. MASLD is associated with hypothyroidism both in adults and in children. Impaired intrahepatic thyroid hormonce receptor β signalling contributes to the progression of metabolic dysfunction-associated steatohepatitis and explains why resmetirom, a liver-specific thyromimetic, improves lipid profile and liver histology in this condition. Thyroid-stimulating hormone testing should be performed in all patients with MASLD. Women with the classic hyperandrogenic polycystic ovary syndrome (PCOS) phenotype are strongly at risk of MASLD, suggesting that hyperandrogenism determines visceral adiposity, metabolic dysfunction, and progressive MASLD in this patient population. All women with PCOS should therefore undergo MASLD screening. The risk of MASLD is significantly increased among growth hormone deficiency (GHD) subjects versus matched controls without GHD. This is due to the roles of growth hormone (GH) and insulin-like growth factor 1, which act on various hepatic cell types to mitigate the progression of steatosis and liver fibrosis. In adults, GHD presents with central obesity, sarcopenia, and osteopenia. MASLD rapidly develops among subjects with hypothalamic-pituitary diseases and ‘hypothalamic obesity’ owing to impaired GH/ insulin-like growth factor axis, hypogonadotropic hypogonadism, and hypothyroidism. Medical history of any conditions predisposing to panhypopituitarism may offer clues to identify panhypopituitarism-related MASLD, which may also be suspected in subjects with ‘cryptogenic’ cirrhosis and hypernatremic hyperosmolality. These MASLD forms secondary to endocrine disorders carry important implications for further research and clinical practice. Endocrine aspects of MASLD may disclose novel therapeutic pathways. A high index of suspicion is requested in clinical practice to triage subjects with MASLD secondary to endocrine disorders.