Pituitary dysfunction after cranial radiotherapy for brain tumor

Abstract

Background: Cranial radiotherapy for extrapituitary brain tumor is a rare cause of acquired pituitary deficiency. The main objective of the present study was to evaluate the incidence and time onset of pituitary deficit and to investigate predictive factors.

Material and methods: This retrospective cohort study included 246 patients referred to our endocrinology department between 2005 and 2021 for hormone testing after radiotherapy for extrapituitary brain tumor. Incidence of pituitary deficit was reported with 95% confidence intervals [95% CI]. Deficit-free survival was estimated on the Kaplan Meier method.

Results: Mean (SD) age at inclusion was 32.2 years (20.3). One hundred and forty-one patients were male (57.3%). One hundred and seventy-five (71.1%) were irradiated after and 71 (28.9%) at or before the age of 15. Mean (SD) follow-up was 10 years (7). At the end of the study, 118 patients (48.0%) had ≥1 hormonal deficit: GH deficit in 88 patients (36.5%), TSH deficit in 61 (24.8%), LH/FSH deficit in 47 (19.5%); ACTH deficit was identified in 12 patients (4.9%), and was never isolated. The overall incidence of pituitary deficits was 10.3 per 100 person-years (95% CI [30.8; 65.3]) and did not differ according to age at irradiation. Pituitary deficits occurred within a mean (SD) 2.6 years (2.5), 4.9 years (3.3), 4.0 years (2.4) and 4.8 years (3.1) for ACTH, TSH, GH and LH/FSH, respectively. The only factor associated with deficit-free survival was pituitary gland D50 (maximum dose received by at least 50% of gland volume): D50 37-44Gy compared to 1-24Gy; HR: 2.51; 95% CI [1.09; 5.80]; P=0.031.

Conclusion: Half of the patients presented pituitary deficits 10 years after irradiation for extrapituitary brain tumor. However, ACTH deficit was rare, and never isolated, suggesting that it is not necessary to carry out a dynamic test for ACTH if no other deficits are diagnosed.

Keywords: Brain tumor; Cancer survivor; Hypothalamic-pituitary dysfunction; Late endocrine effect; Radiotherapy.