Salvatori, Roberto

Abstract Context Biochemical test results are central to clinical decision-making for the diagnosis and management of Cushing syndrome (CS). With emerging research and increasing availability of different tests, updated consensus on the utility of these biomarkers is warranted. Objective To establish an updated consensus on the role of biomarkers in the diagnosis and monitoring of adrenocorticotropic hormone-dependent CS, address novel therapeutic approaches, and identify areas for future research. Design A modified 2-round Delphi panel was conducted. Consensus was defined as ≥70% agreement/disagreement for Likert-scale statements or ≥70% selection of the same option for single-choice questions. Setting Participants represented a range of international expertise. Participants Forty-one participants took part in the Delphi panel, with no attrition between rounds (one nonclinician was not required to complete the second round). An 8-member Steering Committee guided statement development. Results Of statements designed to reach consensus, 45% (14/31) and 44% (11/25) statements reached consensus in Rounds 1 and 2, respectively. Notably, most panelists reported the use of late-night salivary cortisol for diagnosis of mild CS and for monitoring following pituitary surgery or medical or radiation therapy. Most panelists responded that block-and-replace therapies can be considered in patients with cyclical or severe CS, and consensus was reached that restoration of circadian rhythm is a treatment goal for patients with CS. Conclusion Areas of alignment among experts on the diagnosis and monitoring of CS are presented. The findings from this study are intended to support clinicians in their clinical decision-making and highlight priority areas for future research.

Abstract Context There are limited head-to-head trials comparing pharmacological treatments for acromegaly. Objective Systematically review the efficacy and safety of pharmacological treatments for acromegaly and conduct a network meta-analysis (NMA) enabling indirect comparisons. Methods MEDLINE and Embase were searched to identify randomized controlled trials (RCTs) of acromegaly therapies. Screening and data extraction followed PRISMA guidelines. Feasibility assessment evaluated homogeneity and consistency assumptions required for NMA. Bayesian NMAs estimated relative treatment effects and ranking probabilities. Results Twenty-two records covering 18 RCTs were included. Biochemical control rates were comparable among long-acting injectable somatostatin receptor ligands (SRLs), including lanreotide autogel (LAN-ATG), octreotide long-acting release (OCT-LAR), pasireotide, the GH receptor antagonist pegvisomant, oral octreotide (O-OCT), octreotide subcutaneous depot (SC-OCT-D), and the once-daily oral SRL paltusotine. Paltusotine demonstrated significantly higher biochemical control vs O-OCT and SC-OCT-D (odds ratios [ORs], 95% credible intervals [CrIs]: 7.34 [1.48-36.07] and 7.85 [1.72, 36.25]). Pasireotide showed significantly higher biochemical control vs OCT-LAR (OR: 2.03 [1.29-3.23]). Paltusotine had significantly lower discontinuations due to adverse events (AEs) vs O-OCT and SC-OCT-D, (ORs: 0.022 [0.001-0.424] and 0.022 [0.001-0.343]), with similar rates to other treatments. Treatment-emergent AEs (TEAEs) and serious TEAEs were comparable across treatments. Rankings suggested paltusotine as the treatment with the highest probability of ranking as the most effective (or tolerable) treatment across all endpoints studied. Conclusion This systematic review and NMA consolidate recent high-quality RCT evidence for acromegaly treatments. Paltusotine emerges as a promising alternative to injectable SRLs, with favorable efficacy, safety, and AE-related discontinuation patterns. These findings may inform clinical decision-making and guideline development, if confirmed by clinical experience.

Objective This study presents a comparative analysis of cost efficacy between the microscopic and endoscopic transsphenoidal approaches, evaluating neurological outcome, extent of resection (EOR), and inpatient hospital costs. Design This study was a retrospective chart review. Setting This study was conducted at a tertiary care center. Participants The study group consisted of 68 patients with transsphenoidal surgeries between January 2007 and January 2014. Main Outcome Measures Two-sample t-tests and Pearson's chi-square test evaluated inpatient costs, quality-adjusted life years (QALYs), volumetric EOR, and neurological outcomes. Results Total inpatient costs per patient was $22,853 in the microscopic group and less ($19,736) in the endoscopic group (p = 0.049). Operating room costs were $5,974 in the microscopic group and lower in the endoscopic group ($5,045; p = 0.038). Operative time was 203.6 minutes in the microscopic group and 166.3 minutes in the endoscopic group (p = 0.032). The QALY score, length of hospital stay, and postoperative outcomes were found to be similar between the two cohorts. Multivariate linear regression modeling suggested that length of stay (p < 0.001) and operative time (p = 0.008) were important factors that influenced total inpatient costs following transsphenoidal surgery. Conclusion This study shows that transsphenoidal surgery is more cost effective with the endoscopic approach than with the microscopic approach and depends on efficiency in the operating room as well as reduction in the length of hospitalization.