Long-term outcomes of pituitary radiotherapy and their predictive factors in childhood and adolescent-onset Cushing disease.

Abstract

Objective: Radiotherapy (RT) is an established second-line treatment in adult Cushing disease (CD). Data on pituitary RT in childhood and adolescent-onset CD is scarce. This study aims to demonstrate the effectiveness and long-term safety of fractionated conformal-RT (CRT) in childhood and adolescent-onset CD patients.

Methods: This single-center retrospective study included 34 out of 108 CD patients (<20 years at presentation) who underwent first-line, second-line (post-first transsphenoidal-surgery), or third-line (post-second transsphenoidal-surgery) CRT between 1994 and 2024, with a minimum 1-year follow-up post-CRT.

Results: Data from 34 patients (21 males, 7 prepubertal, and 24 microadenomas) with post-CRT median follow-up of 74.5 (34.5-127.3) months were analyzed. Post-CRT, 25/34 (73.5%) patients (overall cohort) achieved remission at 16.5 (8.75-39.25) months, with remission rates of 60%, 93.8%, and 53.8% in first, second, and third-line CRT, respectively. Younger age at CD diagnosis was an independent predictor of remission (HR: 0.805, P = .02). Relapse occurred in 6/25 (24%) at 19.0 (18.3-30.3) months. Ketoconazole use predicted relapse post-CRT (P = .006). Growth hormone deficiency occurred in 17/20 (85%), and 29/34 (41.4%) patients had low insulin-like growth factor-1 levels. New-onset hypogonadotropic hypogonadism (HH) and central hypothyroidism (CHT) occurred in 3/24 (12.5%) and 4/24 (16.7%) patients, respectively. Older age at CD diagnosis (17.5 vs. 13.0 years; P = .02) and at CRT administration (23 vs. 14 years; P = .04) predicted new-onset HH and/or CHT post-CRT.

Conclusion: Our study illustrates the favorable remission rates post-CRT in childhood and adolescent CD, with lower rates of new-onset HH/CHT. Ongoing monitoring is required, as relapse can occur in one-fourth of cases.