Impact of cortisol on liver fat and metabolic health in adrenal incidentalomas and Cushing's syndrome

Endocrine. 2025 Jan;87(1):334-343. doi: 10.1007/s12020-024-04043-4. Epub 2024 Sep 25.

Abstract

Objective: To evaluate liver fat content in patients with non-functional adrenal incidentalomas (NFAI), mild autonomous cortisol secretion (MACS), and Cushing's syndrome (CS), and assess its relationship with cortisol levels.

Methods: This cross-sectional study used retrospective data from 103 NFAI patients, 100 MACS (serum cortisol after a 1-mg dexamethasone test >50 nmol/L), and 59 with CS. Abdominal CT scans measured hepatic and splenic CT values to calculate the liver-to-spleen (L/S) ratio. Metabolic indicators including fasting plasma glucose (FPG), LDL-c, HDL-c, HbA1c, etc were measured. Mediation analysis was used to explore the indirect effects of metabolic traits on the cortisol-liver fat relationship.

Results: Patients included 103 NFAI, 100 MACS, and 59 CS. MACS patients had higher NAFLD prevalence (57%) than NFAI (26.2%, p < 0.001) but lower than CS (66.1%, p < 0.001). MACS and CS were associated with NAFLD (OR 3.83 and OR 5.73, p < 0.01), adjusted for age, body mass index (BMI), and covariates. Midnight serum cortisol correlated with L/S ratio (p < 0.001). HbA1c and Triglyceride-glucose index (TyG) mediated 24.5% and 49.5% of the cortisol and L/S ratio association, respectively. FPG, HbA1c, HDL-c, and TyG mediated the association between MACS or CS and the L/S ratio. Homeostasis model assessment of insulin resistance (HOMA-IR), fructosamine, and triglycerides mediated for MACS, while alkaline phosphatase did so for CS. Total cholesterol, LDL-c, ALT, AST, γ-GT, insulin, and uric acid did not mediate the association.

Conclusion: MACS and CS are linked to significant metabolic disturbances, including increased liver fat and impaired glucose and lipid metabolism, contributing to fatty liver.

Keywords: Adrenal incidentalomas; Cortisol; Liver fat; MACS; Metabolic health.

MeSH terms

  • Adrenal Gland Neoplasms* / complications
  • Adrenal Gland Neoplasms* / metabolism
  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Cross-Sectional Studies
  • Cushing Syndrome* / blood
  • Cushing Syndrome* / metabolism
  • Female
  • Humans
  • Hydrocortisone* / blood
  • Liver* / diagnostic imaging
  • Liver* / metabolism
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / epidemiology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Retrospective Studies

Substances

  • Hydrocortisone
  • Blood Glucose

Supplementary concepts

  • Adrenal incidentaloma