10 Abstract Cushing's syndrome (CS) is a rare endocrine 11 disease, due to cortisol hypersecretion. CS patients have 12 comorbidities, often still present after biochemical cure. 13 Specific nursing healthcare programs to address this dis-14 ease and achieve improved health related quality of life 15 (HRQoL) are lacking. Thus, an educational nursing inter-16 vention, through the development and promotion of 17 specific educational tools, appears to be justified. The 18 objective of this study is to assess the effectiveness of an 19 educational nursing program in CS patients on HRQoL, 20 clinical parameters, level of pain and physical activity, 21 patterns of rest, and use of health resources. A prospective, 22 randomized study was conducted in two reference hospitals 23 for CS. Sixty-one patients (mean age 47 ± 12.7 years, 24 83.6 % females) were enrolled and divided into 2 groups: 25 an ''intervention'' group where educational sessions were 26 performed over 9 months and a ''control'' group, without 27 these sessions. Specific questionnaires were used at the 28 beginning and end of the study. After educational sessions, 29 the intervention group had a better score in the Cush-30 ingQoL questionnaire (p \ 0.01), reduced level of pain 31 (p \ 0.05), improved physical activity (p \ 0.01) and 32 healthy lifestyle (p \ 0.001) compared to the control 33 group. A correlation between the CushingQoL score and 34 reduced pain (r = 0.46, p \ 0.05), improved physical 35 activity (r = 0.89, p \ 0.01), and sleep (r = 0.53, 36 p = 0.01) was observed. This educational nursing program 37 improved physical activity, healthy lifestyle, better sleep 38 patterns, and reduced pain in CS patients, influencing 39 HRQoL and reducing consumption of health resources. 40 Moreover, the brief nature of the program suggests it as a 41 good candidate to be used in CS patients. Patients with cushing's syndrome (CS) suffer from multi-47 ple comorbidities, mainly cardiovascular (hypertension, 48 atherosclerosis, changes in heart functionality), and meta-49 bolic (dyslipidemia, central obesity, diabetes), as well as 50 thrombotic disorders, bone disorders, cognitive and neu-51 ropsychological impairment, and impaired sexual function 52 due to glucocorticoid (GC) excess [1][2][3][4][5][6].53 The assumption that resolution of hypercortisolism 54 normalized comorbidities is currently questioned, since R E V I S E D P R O O F55 there is evidence that cured CS patients still have increased 56 morbidity and mortality despite endocrine control [7][8][9]. 57 Most patients with CS develop metabolic syndrome, which 58 may persist after remission of hypercortisolism, con-59 tributing to increased cardiovascular risk and deserve to be 60 treated according to common standard practice [7]. 61 Awareness of this persistent increase in cardiovascular risk 62 in CS patients after endocrine cure leads to strict control of 63 improvable factors, including blood pressure, dyslipemia, 64 hyperglycemia, smoking, obesity, and prothrombotic state 65 [10]. 66 There is am...

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