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Purpose Clinical trials have demonstrated the favorable efficacy/safety profile of pasireotide in patients with Cushing’s disease (CD). We report interim long-term results of an ongoing real-world evidence study of subcutaneous pasireotide in patients with CD. Methods Adults with CD receiving pasireotide, initiated before (prior-use) or at study entry (new-use), were monitored for ≤ 3 years during a multicenter observational study (http://clinicaltrials.gov identifier NCT02310269). Primary objective was to assess long-term safety of pasireotide alone or with other CD therapies. Results At the time of this interim analysis, 127 patients had received pasireotide (new-use, n = 31; prior-use, n = 96). Eight patients had completed the 3-year observation period, 53 were ongoing, and 66 had discontinued. Among 31 new-use and 92 prior-use patients with ≥ 1 safety assessment, respectively: 24 (77%) and 37 (40%) had drug-related adverse events (AEs); 7 (23%) and 10 (11%) had serious drug-related AEs. Most common drug-related AEs were nausea (14%), hyperglycemia (11%) and diarrhea (11%); these were more frequently reported in new users and mostly of mild-to-moderate severity. 14 (45%) new-use and 15 (16%) prior-use patients experienced hyperglycemia-related AEs. Mean urinary free cortisol (mUFC) was within normal range at baseline and months 1, 12 and 24, respectively, in: 1/16 (6%), 9/18 (50%), 1/3 (33%) and 0/0 new users; 28/43 (65%), 15/27 (56%), 27/33 (82%) and 12/19 (63%) prior users. Conclusions Pasireotide is well tolerated and provides sustained reductions in mUFC during real-world treatment of CD. The lower rate of hyperglycemia-related AEs in prior users suggests that hyperglycemia tends not to deteriorate if effectively managed soon after onset. Clinical Trial Registration Number: NCT02310269.

Context Unilateral adrenalectomy has been proposed in selected patients with primary bilateral macronodular adrenocortical hyperplasia (PBMAH), but its long-term outcome is unclear. Objective The aim of this study was to analyze long-term clinical and biochemical outcomes of unilateral adrenalectomy vs bilateral adrenalectomy in patients with PBMAH in comparison with the outcome of cortisol-producing adenoma (CPA) treated with unilateral adrenalectomy. Design Retrospective observational study in three German and one Italian academic tertiary care center. Patients and methods Twenty-five patients with PBMAH after unilateral adrenalectomy (unilat-ADX-PBMAH), nine patients with PBMAH and bilateral adrenalectomy (bilat-ADX-PBMAH), and 39 patients with CPA and unilateral adrenalectomy (unilat-ADX-CPA) were included. Results Baseline clinical and biochemical parameters were comparable in patients with unilat-ADX-PBMAH, bilat-ADX-PBMAH, and unilat-ADX-CPA. Directly after surgery, 84% of the patients with unilat-ADX-PBMAH experienced initial remission of Cushing syndrome (CS). In contrast, at last follow-up (median, 50 months), 32% of the patients with unilat-ADX-PBMAH were biochemically controlled compared with nearly all patients in the other two groups (P = 0.000). Adrenalectomy of the contralateral side had to be performed in 12% of the initial patients with unilat-ADX-PBMAH. Three of 20 patients with unilat-ADX-PBMAH (15%) died during follow-up, presumably of CS-related causes; no deaths occurred in the other two groups (P = 0.008). Deaths occurred exclusively in patients who were not biochemically controlled after unilateral ADX. Conclusions Our data suggest that unilateral adrenalectomy of patients with PBMAH leads to clinical remission and a lower incidence of adrenal crisis but in less sufficient biochemical control of hypercortisolism, potentially leading to higher mortality.