Worse muscle mass loss in adrenal Cushing syndrome vs. Cushing’s disease: a comparative evaluation of chemiluminescence and LC-MS/MS cortisol assessment

Muscle mass loss is a serious complication of Cushing’s syndrome. This study aims to compare muscle mass loss between two subtypes of Cushing’s syndrome and to evaluate the clinical value of comprehensive LC-MS/MS steroid profiling alongside chemiluminescence (CL). In a retrospective cohort of 78 premenopausal women (37 Cushing’s disease [CD] and 41 adrenal Cushing syndrome [ACS]), clinical features, muscle mass, and 11 steroid hormones were compared. In addition, the independent associations between muscle mass index (appendicular skeletal muscle mass/height squared, ASM/height 2 ) and endocrine variables was analyzed. ROC curve analysis was applied to evaluate the predictive utility of CL and LC-MS/MS cortisol for muscle depletion. The serum and urinary cortisol, serum ACTH, testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulphate and cortisone concentrations with CD were higher than those with ACS, and the muscle mass with CD was also higher compared with ACS. In the fully adjusted multivariable linear regression model, serum cortisol maintained a negative trend with ASM/height 2 , while BMI and Cushing’s subtype served as primary independent determinants. In the CL group, the AUC was 0.717. In the LC-MS/MS group, the AUC was 0.728. In premenopausal women, the muscle mass with CD is significantly higher than that with ACS. This may indicate a higher severity of myopathy in ACS patients. Muscle wasting in Cushing’s syndrome represents a multifactorial process driven by mechanical load, subtype-specific androgen status, and cortisol exposure. Furthermore, CL cortisol offers a reliable, accessible first-line assessment tool, while LC-MS/MS provides added value through multi-steroid profiling.