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A phase III study has demonstrated that 6-month pasireotide treatment induced disease control with good safety in 15–26% of patients with Cushing’s disease (CD). The aim of the current study was to evaluate the 6-month efficacy and safety of pasireotide treatment according to the real-world evidence. Thirty-two CD patients started pasireotide at the dose of 600 µg twice a day (bid) and with the chance of up-titration to 900 µg bid, or down-titration to 450 or 300 µg bid, on the basis of urinary cortisol (UC) levels or safety. Hormonal, clinical and metabolic parameters were measured at baseline and at 3-month and 6-month follow-up, whereas tumour size was evaluated at baseline and at 6-month follow-up. At baseline, 31 patients had very mild to moderate disease and 1 patient had very severe disease. Five (15.6%) patients discontinued treatment for adverse events; the remaining 27 patients (26 with very mild to moderate disease and 1 with very severe disease), reached 6-month follow-up. Considering the group of patients with very mild to moderate disease, responsiveness, defined by the normalization (1 and ≤1.1 ULN) of UC levels, was registered in 21 patients (full control in 19 and near control in 2), corresponding to 67.7% and 80.8% according to an “intention-to-treat” or “per-protocol” methodological approach, respectively. Weight, body mass index, waist circumference, as well as total and LDL-cholesterol significantly decreased, whereas fasting plasma glucose and glycated haemoglobin significantly increased. Hyperglycaemia was documented in 81.2%, whereas gastrointestinal disturbances in 40.6% of patients. In conclusion, in the real-life clinical practice, pasireotide treatment normalizes or nearly normalizes UC in at least 68% of patients with very mild to moderate disease, with consequent improvement in weight, visceral adiposity and lipid profile, despite the occurrence or deterioration of diabetes in the majority of cases, confirming the usefulness of this treatment in patients with milder disease and without uncontrolled diabetes.

Purpose: Patients with Cushing’s disease (CD) experience metabolic alterations leading to increased cardiovascular mortality. Recently, the visceral adiposity index (VAI) has been proposed as a marker of visceral adipose tissue dysfunction (ATD) and of the related cardiometabolic risk. We aimed to evaluate the impact of 12-month pasireotide treatment on cardiometabolic risk in CD patients. Methods: This is a multicentre, prospective, and observational study. Sixteen CD patients, referred to the Endocrine Units of the University Hospitals of Messina, Napoli, Padova, and Palermo (Italy), successfully treated with pasireotide for 12 month have been enrolled. In all patients, we assessed anthropometric, clinical, and biochemical parameters and calculated VAI, ATD severity, Framingham, and atherosclerotic cardiovascular disease (ASCVD) risk scores, before and after 6 and 12 months of treatment with pasireotide (1200–1800 mcg/daily). Results: Before starting pasireotide treatment, ATD was present in 7/16 patients (mild in 2/16, moderate in 3/16, and severe 2/16). After 12 months of treatment: (i) 24h-urinary free cortisol levels (p = 0.003), BMI (p < 0.001), waist circumference (p = 0.001), LDL-cholesterol (p = 0.033), total-cholesterol (p = 0.032), triglycerides (p = 0.030), VAI (p = 0.015), and ATD severity (p = 0.026) were significantly decreased as compared to baseline; (ii) ATD was present in only 1/16 patients; (iii) prevalence of diabetes mellitus (p = 0.015) and HbA1c levels (p = 0.001) were significantly increased as compared to baseline; (iv) Framingham and ASCVD risk scores were not significantly different from pre-treatment values. Conclusions: Twelve-month pasireotide treatment significantly reduces VAI and ATD in CD patients. These positive effects on cardiometabolic risk occur despite no change in Framingham and ASCVD risk scores and the increase in the prevalence of diabetes mellitus.