A Novel Evaluation of 24-hour 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 control subjects.Hormonal evaluation included serum cortisol, plasma ACTH, urinary free cortisol, and 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 = .02) and trunk fat mass (+ 27% ± 21%, P < .001), as well as reduced lean soft tissue (-7% ± 11%, P = .02) and appendicular lean soft tissue (-14% ± 14%, P < .001). 24hEE was lower by -154 ± 275 kcal/day (P = .04). Post-DST cortisol was positively correlated with protein oxidation rate (r = 0.5, P = .04) and with 24hEE (β = + 15.1 kcal/day per 1 μg/dL of post-DST cortisol, P = .04) independently of lean soft tissue. Conclusion: Using a whole-room indirect calorimetry, we have demonstrated that chronic active hypercortisolism in patients with CS is associated with a reduction in 24hEE, likely driven by the progressive loss of lean soft tissue due to sustained increase in protein oxidation.