doi:10.1210/clinem/dgz329 J Clin Endocrinol Metab, May 2020, 105(5):e2039–e2049 https://academic.oup.com/jcem e2039 CLINICAL RESEARCH ARTICLE ISSN Print 0021-972X ISSN Online 1945-7197 Printed in USA © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals. permissions@oup.com Received 11 October 2019. Accepted 6 January 2020. First Published Online 8 January 2020. Corrected and Typeset 23 March 2020. Thigh Muscle Fat Infiltration Is Associated With Impaired Physical Performance Despite Remission in Cushing’s Syndrome Luciana Martel-Duguech, 1,2,3 Alicia Alonso-Jiménez, 3,4 Helena Bascuñana, 5 Jordi Díaz-Manera, 3,4 Jaume Llauger, 6 Claudia Nuñez-Peralta, 6 Betina Biagetti, 7 Paula Montesinos, 8 Susan M. Webb, 1,2,3 and Elena Valassi 1,2,3 1 IIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau, 08025 Barcelona, Spain; 2 Universitat Autónoma de Barcelona, Departament de Medicina, CP 08035, Barcelona, Spain; 3 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), 08025 Barcelona, Spain; 4 Neuromuscular Disorders Unit, Neurology Department, Hospital Sant Pau, 08025 Barcelona, Spain; 5 Rehabilitation Unit, Hospital Sant Pau, 08025 Barcelona, Spain; 6 Radiology Department, Hospital Sant Pau, 08025 Barcelona, Spain; 7 Endocrinology Department, Hospital Vall d’Hebron, 08035 Barcelona, Spain; and 8 Philips Healthcare, 28050 Madrid, Spain ORCiD number: 0000-0002-3864-0105 (E. Valassi). Context: Muscle weakness is common in patients with Cushing’s syndrome (CS) and may persist after the resolution of hypercortisolism. Intramuscular fatty infltration has been associated with the deterioration of muscle performance in several conditions. Objectives: To quantify the degree of fatty infltration in the thigh muscles of “cured” CS patients and evaluate the relationship between intramuscular fatty infltration and physical performance. Design: This was a cross-sectional study. Setting: Tertiary referral center. Patients: Thirty-six women with CS in remission, and 36 controls matched for age, BMI, menopausal status, and level of physical activity. Main Outcome Measures: We analyzed the percentage fat fraction (FF) of the thigh muscles in the anterior, posterior, and combined anterior and posterior compartments using MRI and 2-point Dixon sequence. We assessed muscle function and strength using the following tests: gait speed (GS), timed up and go (TUG), 30-second chair stand, and hand grip strength. Results: Fat fraction in all the compartments analyzed was increased in patients as compared with controls. The performance on TUG, 30-second chair stand, and GS was more impaired in CS patients versus controls. In patients, greater FF was negatively associated with performance on functional tests. Fat fraction in the combined anterior and posterior compartments predicted performance on TUG (ß 0.626, P < 0.000) and GS (ß -0.461, P = 0.007), after adjusting for age, BMI, menopausal status, and muscle mass. Conclusions: Thigh muscle fatty infltration is increased in “cured” CS patients and is associated with poorer muscle performance. Future studies are needed to establish therapeutic strategies to improve muscle weakness in these patients. (J Clin Endocrinol Metab 105: e2039–e2050, 2020) Key Words: Cushing’s syndrome, muscle, fatty infltration, muscle performance G lucocorticoid excess in Cushing’s syndrome (CS) is associated with proximal myopathy, which leads to muscle weakness that mainly affects the lower limbs (1). While up to 70% of patients with endogenous Downloaded from https://academic.oup.com/jcem/article/105/5/e2039/5698174 by guest on 13 April 2023