The MAR is the largest and first non-European registry of the disease. Our findings highlight important within-country differences in treatment choice due to variations in the availability of resources.

BackgroundTreating hypercortisolism in patients with Cushing’s disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles.MethodsIn a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing’s disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein.ResultsSixteen patients received 5 years of pasireotide treatment. Among these, median (95% confidence interval) percentage change from baseline in mean urinary free cortisol was −82.6% (−89.0, −41.9) and −81.8% (−89.8, −67.4) at months 12 and 60. Eleven patients had mean urinary free cortisol ≤ upper limit of normal at month 60. Improvements in clinical signs were sustained during long-term treatment. The safety profile of pasireotide at 5 years was similar to that reported after 12 months. Fifteen of 16 patients experienced a hyperglycaemia-related adverse event; glycated haemoglobin levels were stable between months 6 and 60. Adverse events related to hyperglycaemia, bradycardia, gallbladder/biliary tract, and liver safety were most likely to first occur by month 6; adverse event severity did not tend to worsen over time.ConclusionsThis represents the longest prospective trial of a medical therapy for Cushing’s disease to date. A subset of patients treated with pasireotide maintained biochemical and clinical improvements for 5 years, with no new safety signals emerging. These data support the use of pasireotide as an effective long-term therapy for some patients with Cushing’s disease.

A half dose of dynamic resonance imaging contrast material increases the sensitivity of MRI detection of ACTH-secreting pituitary tumors.

Objective: Cushing's disease (CD) can significantly impair patients' health-related quality of life (HRQOL). This study investigated the treatment effectiveness of pasireotide on HRQOL of CD patients, and assessed the relationships between HRQOL and urinary free cortisol (UFC) and CD-related signs and symptoms. Design: In this phase III, randomized, double-blind study, patients with UFC R1.5!upper limit of normal (ULN) received s.c. pasireotide 600 or 900 mg twice daily. The trial primary endpoint was UFC at or below ULN at month 6 without dose titration. Open-label treatment continued through month 12. HRQOL was measured using the Cushing's Quality of Life Questionnaire (CushingQoL) instrument at baseline and follow-up visits until month 12 during which clinical signs and features of CD, and the Beck Depression Inventory II (BDI-II), were also collected. Methods: Pearson's/Spearman's correlations between changes in CushingQoL and changes in clinical signs and symptoms were assessed. Changes in CushingQoL and the proportion of patients achieving a clinically meaningful improvement in CushingQoL were also compared among patients stratified by mean UFC (mUFC) control status (controlled, partially controlled, and uncontrolled) at month 6. Analyses were also conducted at month 12, with multivariable adjustment for baseline characteristics and CushingQoL. Results: Change in CushingQoL was significantly correlated with changes in mUFC (rZK0.40), BMI (rZK0.39), weight (rZK0.41), and BDI-II (rZK0.54) at month 12 but not at month 6. The percentage of CushingQoL responders at month 12 based on month 6 mUFC control status were as follows: 63, 58.8, and 37.9% in the controlled, partially controlled, and uncontrolled groups respectively. Adjusted CushingQoL scores at month 12 were 58.3 for controlled patients (DZ11.5 vs uncontrolled, PZ0.012) and 54.5 for partially controlled patients (DZ7.7 vs uncontrolled, PZ0.170). Conclusions: Pasireotide treatment can result in a meaningful HRQOL improvement among those who complete a 12-month treatment period, most often among patients achieving biochemical control.

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