Prediction of remission and recurrence of Cushing's disease following transsphenoidal surgery (TSS): a single center, 20-year, retrospective series.

PURPOSE: Cushing's disease (CD) is a rare condition with variable surgical outcomes. This study aimed to assess remission and recurrence rates in CD patients undergoing transsphenoidal surgery (TSS) at a major Israeli referral center, and to identify predictive factors for these outcomes. We hypothesized that microadenomas would have higher remission rates than macroadenomas.

METHODS

This retrospective analysis included 97 CD patients who underwent TSS at Tel Aviv Sourasky Medical Center (2002-2022). Remission was defined by biochemical criteria and clinical improvement. Suspected recurrence was confirmed by pathological dexamethasone suppression and/or elevated urinary free cortisol. Univariate and multivariate analyses identified predictors of remission, while Kaplan-Meier survival analysis and Cox proportional hazard modeling determined factors associated with recurrence.

RESULTS

The overall remission rate was 63.9%, with no significant difference between microadenomas (58.7%) and macroadenomas (73.5%), a finding confirmed in a sensitivity analysis limited to cases with pathologically confirmed adenomas. Multivariate logistic regression showed predictors of remission were adenoma presence in pathology specimens (OR = 31.25, P < 0.001) and first-time surgery status (OR = 9.42, P = 0.002), while younger age was a contributory factor (OR = 0.963, P = 0.05). The relapse rate was 22.6% over a median follow-up of 63 [IQR 35-109.5] months. Glucocorticoid withdrawal syndrome emerged as a novel protective factor against recurrence (P = 0.045).

CONCLUSIONS

This largest analysis of TSS outcomes for CD in Israel challenges established notions about remission predictors, including our initial hypothesis about microadenomas. The identification of glucocorticoid withdrawal syndrome as a predictor of long-term remission provides a potential avenue for post-operative monitoring in the local healthcare context.