A Novel Evaluation of 24-h Energy Metabolism in Cushing’s Syndrome: The Metabolic Cost of Hypercortisolism

Context Hypercortisolism leads to metabolic alterations (glucose dysregulation, increased protein catabolism, and increased lipolysis and lipogenesis) that contribute to weight gain, increased fat mass, and muscle loss in patients with Cushing’s syndrome (CS). Objective We examined the relationship between body composition and 24-hour energy metabolism in patients with active disease. Methods This cross-sectional case-control study included 16 patients with active CS and 16 sex, weight and height-matched controls subjects. Hormonal evaluation included serum cortisol, plasma ACTH, urinary free cortisol, 1-mg dexamethasone suppression test (DST) cortisol. Body composition was assessed by dual-energy X-ray absorptiometry. 24-hour energy expenditure (24hEE) and macronutrient oxidation rates were measured by 24-hour whole-room indirect calorimetry. Results Compared to control subjects, patients with CS exhibited higher total fat mass (+ 9 ± 14%, p=0.02) and trunk fat mass (+ 27% ± 21%, p<0.001), as well as reduced lean soft tissue (−7% ± 11%, p=0.02) and appendicular lean soft tissue (−14 % ± 14%, p<0.001). 24hEE was lower by −154 ± 275 kcal/d (p=0.04). Post-DST cortisol was positively correlated with protein oxidation rate (r=0.5, p=0.04) and with 24hEE (β = + 15.1 kcal/d per 1 μg/dL of post-DST cortisol, p=0.04) independently of lean soft tissue. Conclusion Using a whole-room indirect calorimetry, we have demonstrated that chronic active hypercortisolism in patients with Cushing’s syndrome is associated with a reduction in 24hEE, likely driven by the progressive loss of lean soft tissue, due to sustained increase in protein oxidation.