Pituitary dysfunction after cranial radiotherapy for brain tumor.

in Annales d'endocrinologie by Julie Chapon, Julien Berthillier, Amna Klich, Ronan Tanguy, Nathalie Perreton, Pauline Drouin, Aude Brac-de-la-Perrière, Chantal Simonet, Helene Lasolle, Gerald Raverot, Fabien Subtil, Françoise Borson-Chazot

TLDR

  • The study found that radiotherapy for extrapituitary brain tumors can increase the risk of pituitary deficiency, with a higher radiation dose to the pituitary gland being associated with a higher risk,

Abstract

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. This retrospective cohort study included 246 patients referred to our endocrinology department between 2005 and 2021 for hormone testing after radiotherapy for extra-pituitary brain tumor. Incidence of pituitary deficit was reported with 95% confidence intervals [95% CI]. Deficit-free survival was estimated on the Kaplan Meier method. Mean (SD) age at inclusion was 32.2 years (20.3). 141 patients were male (57.3%). 175 (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 37-44 Gy compared to 1-24 Gy; HR: 2.51; 95% CI [1.09; 5.80]; p = 0.031. 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.

Overview

  • The study aimed to investigate the incidence and time of onset of pituitary deficiency in patients who received radiotherapy for extrapituitary brain tumors and to identify predictive factors,
  • The study included 246 patients referred to an endocrinology department between 2005 and 2021 for hormone testing after radiotherapy for extra-pituitary brain tumors,
  • The study evaluated the relationship between radiation dose to the pituitary gland and the development of pituitary deficits

Comparative Analysis & Findings

  • The incidence of pituitary deficits was 10.3 per 100 person-years, with a range of 30.8-65.3% and no difference according to age at irradiation
  • Pituitary deficits occurred within a mean of 2.6, 4.9, 4.0, and 4.8 years 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), with a hazard ratio of 2.51 and a 95% CI of 1.09-5.80

Implications and Future Directions

  • The study highlights the importance of long-term follow-up and monitoring of patients who have received radiotherapy for extrapituitary brain tumors
  • The findings suggest that a dynamic test for ACTH may not be necessary if no other deficits are diagnosed, given the rarity of ACTH deficit
  • Future studies could investigate the relationship between radiation dose to specific areas of the brain and the development of pituitary deficits
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