The prevalence and predictors of Cushing disease recurrence: a 10-year experience of a pituitary tumor center of excellence

Abstract

Purpose Identifying predictors of recurrence in Cushing disease (CD) guides monitoring strategies. We aimed at analyzing the frequency and predictive factors of recurrence in CD. Methods Patients with CD operated between August/2013-December/2023 were included. Retrospective data on biochemical, radiological, histopathological and genetic data were collected. Remission was defined as post-operative cortisol concentrations below 2 mcg/dL within the first week of surgery or normalized cortisol values post-operatively. Recurrence was defined as new onset of hypercortisolism confirmed biochemically. Results Surgical remission was achieved in 81% of patients, but recurrence occurred in 27.4% of cases after a median follow up period of 38 months (range 16-101). Lower cortisol concentrations on the first and second post-operative days, and longer duration of glucocorticoid replacement (2.5 months vs 8-10 months, p = 0.045) were identified as protective factors for recurrence. Nadir cortisol concentrations ≤3 mcg/dL during the first post-operative week predicted long-term remission with 74% sensitivity, 85% specificity, 94% positive predictive value, and 50% negative predictive value (area under the curve 0.808, p = 0.001). Recurrence rates were lower in patients with microadenomas/no visible lesion compared to those with macroadenomas (19% vs 45%; p = 0.03). Age, gender, tumor diameter, USP8 and USP48 mutational status, cortisol on the 7th post-operative day and, ACTH immuno-positivity in histology were not associated with recurrence. Conclusion Recurrence in CD was seen in 27.4% of cases. Immediate post-operative cortisol concentrations and the duration of glucocorticoid use were predictors of recurrence. Recurrence was more frequent in patients with macroadenomas compared to those with microadenomas/no visible adenomas.