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

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

Peng Yu  1   2 , Haoyue Yuan  1 , Xiaomu Li  3 , Hong Chen  4
Affiliations

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

Peng Yu et al. Endocrine. 2025 Jan.

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.

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Conflict of interest statement

Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. Ethics approval: This study was conducted in accordance with the principles of the Declaration of Helsinki. Written, informed consent was obtained from all of the participants, and the study was approved by the ethics committee of Zhongshan Hospital, Fudan University, China.

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