Predicting Long-Term Outcomes in Cushing Disease: So Close and Yet So Far

Le résumé fourni par la source

Cushing disease is a debilitating condition with increased morbidity and mortality (1). Patient management relies on surgical removal of the corticotroph tumor, but long-term follow-up studies report recurrence rates of 18% and higher (2, 3). Accordingly, patients with Cushing disease in remission require lifelong monitoring for recurrence (1). Somatic variants in the USP8 gene are established as driver genetic events in corticotroph tumorigenesis (reviewed in (4)). In the decade that followed, several studies used uni- and multivariable analyses to address the association between USP8 status and time to recurrence, but with variable outcomes (listed in (5)). Two studies utilizing survival analyses and multivariate Cox proportional hazard models identified USP8 variant association with recurrence in one study but not in the other study that included a larger cohort with longer follow-up (92 patients with 75 achieving remission, up to 15 years follow-up) (6, 7). Against the backdrop of these investigations, Zhou and colleagues utilized a single-center cohort of 107 patients with Cushing disease (103 achieved remission) and found that USP8 variant tumors are associated with a higher risk of recurrence compared to tumors with USP8 reference sequence (8). Thirteen patients (13%) experienced recurrence, with a mean follow-up period of 65 months after surgery. The recurrence rate was significantly higher in USP8 variant compared to tumors carrying the reference allele (27% vs 6%; P = .009). Their data support the association of USP8 variants with shorter recurrence-free survival, with similar hazard ratios adjusted for other variables to what was previously reported (6).

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.