Single-session radiosurgery for Cushing disease after failed resection: a retrospective single-center cohort study

Cushing disease (CD) from an adrenocorticotropic hormone-secreting pituitary adenoma causes substantial morbidity when hypercortisolism persists or recurs after transsphenoidal surgery (TSS).

To define endocrine control, radiographic response, toxicity, and predictors after single-session Gamma Knife radiosurgery for residual or recurrent CD.

Retrospective single-center cohort study, 1990-2026; median endocrine follow-up 54 months.

Single academic tertiary referral center.

186 adults with residual or recurrent CD after ≥1 TSS and ≥12 months of follow-up. Median age 40.8 years; 78.0% female.

Single-session frame-based SRS (median prescription dose 23.0 Gy; maximum dose 48.0 Gy).

Prespecified primary outcome was durable biochemical control off medications (sustained 24-hour urinary free cortisol [UFC] normalization without cortisol-lowering therapy), modeled with competing-risks methodology.

UFC normalized in 152 patients (81.7%), including 134 (72.0%) off all medications. Cumulative incidence of durable off-medication control was 51% (95% CI: 44-58%) at 12 months and 64% (95% CI: 56-71%) at 120 months. New endocrinopathy reached 42% (95% CI: 32-52%) at 120 months; new visual deficit occurred in 3.2%. A TSS-to-SRS interval <6 months independently predicted higher durable control (P < .001), while higher baseline AM cortisol (P < .001), whole-sella treatment (P = .013), and female gender (P = .027) predicted lower durable control. Higher maximum dose was the sole independent predictor of new endocrinopathy (P = .009).

Single-session SRS achieves durable medication-free control in approximately two-thirds of patients with residual or recurrent CD, with excellent tumor control and meaningful delayed endocrine toxicity warranting long-term surveillance.