Endocrine Abstracts

Background: Improved survival rates from brain tumours have resulted in patients living longer with the effects of radiotherapy. Advances in conventional fractionated radiotherapy, such as intensity-modulated radiotherapy (IMRT), enable radiation to be delivered more precisely while partially sparing surrounding structures including the hypothalamic-pituitary axis. Despite these advances, the precise risk of hypopituitarism associated with IMRT in survivors of adult-onset non-pituitary primary brain tumours remains poorly understood.

Methods: A retrospective cohort study was conducted among patients referred to the endocrinology service in Beaumont Hospital, Ireland’s National Centre for the Management of Brain Tumours. Patients with adult-onset primary brain tumours treated with IMRT between 2011 and 2022 were included. Endocrine surveillance typically consisted of annual baseline pituitary assessments and either a synacthen (SST) or insulin tolerance/glucagon stimulation test based on whether patients were candidates for growth hormone (GH) replacement.

Results: The study included 69 patients (26 women) with a median age of 38.0 (IQR 30.0-46.2) years at radiotherapy completion. Gliomas were the most common neoplasm (n=38), followed by meningiomas (n=17), pinealomas (n=6), medulloblastomas (n=5) and ‘other’ brain tumours (n=3). Median total delivered radiotherapy dose was 54 (IQR 54-60) Gray. The prevalence of hypopituitarism was 26/69 (38%) after a median of 50 (IQR 29-76) months follow up. Thirty-nine patients had baseline pituitary function testing and an SST while 30 patients had baseline pituitary function testing and dynamic GH assessment. Nineteen of the thirty patients (63.3%) who underwent dynamic GH assessments had GH deficiency. All these patients had normal IGF-1 levels at the time of diagnosis. The risk of adrenocorticotrophic hormone (ACTH), gonadotropin, and thyroid stimulating hormone (TSH) deficiency was 17/69 (24.6%), 10/69 (14.5%) and 6/69 (8.7%), respectively. Five patients out of 69 (7.2%) developed panhypopituitarism. Fifty-two percent (36/69) of patients exhibited hyperprolactinaemia at their most recent assessment. Spearman’s rank identified significant positive correlations between time interval following radiotherapy and the risk of developing any hormone deficiency (r_s=0.27, P=0.03), gonadotropin (r_s=0.37, P=0.002), TSH (r_s=0.26, P=0.03) but not GH or ACTH deficiency.

Conclusion: This study demonstrated a high prevalence of hypopituitarism in adult-onset non-pituitary brain tumour survivors treated with IMRT. Almost two-fifths developed hypopituitarism at a median of 50 months follow up. The evolution of hypopituitarism occurred in a time-dependent fashion. Long-term systematic endocrine surveillance is crucial to enable timely diagnosis and treatment of hormone deficits, with the aim of optimising quality of life and preventing hypopituitarism-related complications in this patient cohort.