Abstract Disclosure: E. Valassi: None. L. Martel-Duguech: None. H. Bascuñana: None. V. Priego-Corredor: None. J. Viñals-Ribé: None. O. González-Viñuela: None. T. Caparrós-Pons: None. S.M. Webb: None. Background: Patients with Cushing’s disease (CD) in remission and controlled acromegaly (ACRO) present with residual metabolic derangements, muscle dysfunction, and poor quality of life (QoL). Although exercise is known to exert positive effects on psychophysical health in several conditions, evidence demonstrating its potential benefits in pituitary diseases is scanty. Main hypothesis: A personalized program of combined (aerobic and resistance training) exercise lasting 12 weeks improves cardiometabolic parameters, body composition, physical performance and QoL in patients with CD in remission and controlled ACRO. Methodology: Ten female patients with CD in remission [mean (±SD) age, 59±4 years, mean (±SD) BMI, 35±2 Kg/m2, median (IQR) duration of remission, 5(4) years] and 10 male patients with controlled ACRO [mean (±SD) age, 53±9 years, mean (±SD) BMI, 27±4 Kg/m2, median (IQR) duration of control, 6(3) years] underwent a 12-week, structured, personalized program of combined aerobic and resistance exercise, under the supervision of professional trainers. We evaluated the following parameters at baseline and within 72 hours after the completion of the exercise program: blood pressure (BP), BMI, waist and neck circumferences; physical performance (gait speed, hand grip strength, 30-Second Chair Stand; Timed “Up and Go”); lumbar and femoral bone mineral density (BMD) and body composition, using dual x-ray absorptiometry (DXA); muscle thickness (cm) at the middle and distal third of rectus femoris (RF) and vastus intermedius (VI) on both sides, using muscle ultrasound scans in the transverse plane (Philips Affiniti 70; The Netherlands); quality of life (QoL), using the questionnaires CushingQoL in CD patients and AcroQoL in ACRO patients. Major results: After completion of the exercise program, CD patients had lower diastolic BP and waist circumference as compared with baseline (p<0.05). Physical performance globally improved (p<0.01 for all function tests). Femoral BMD was higher, percentage of lean mass increased while trunk fat decreased (p<0.01). RF and VI muscle thickness was greater at both the middle and distal third on the right side (p<0.01), and at the distal third on the left as compared with baseline (p<0.05). ACRO patients had a lower systolic BP as compared with baseline. Gait speed and hand grip strength increased while performance on the 30-Second Chair Stand improved (p<0.05). Muscle thickness at the middle third of the right RF was greater as compared with baseline (p<0.05). QoL was unchanged in both CS and ACRO patients at the end of the program. Conclusions: A customized exercise program promotes beneficial cardiometabolic and muscle changes in patients with CD and ACRO and, therefore, should be offered in a specialized pituitary clinic, within an integrated multidisciplinary team approach. Study financed by ISCIII research project number FIS PI21/01223 Presentation: 6/1/2024