Hypothalamic‐pituitary axis irradiation dose thresholds for the development of hypopituitarism in adult‐onset gliomas

• Published in: Clinical endocrinology (Oxford) 2019-07, Vol.91 (1), p.131-140
• Main Authors: Kyriakakis, Nikolaos, Lynch, Julie, Orme, Steve M., Gerrard, Georgina, Hatfield, Paul, Short, Susan C., Loughrey, Carmel, Murray, Robert D.
• Format: Article
• Language: English
• Subjects: Adrenocorticotropic hormone; Adults; adult‐onset gliomas; Brain cancer; Brain tumors; Children; cranial radiotherapy; Follicle-stimulating hormone; Glioma; growth hormone deficiency; Growth hormones; Hormone replacement therapy; Hypopituitarism; Hypothalamus; Luteinizing hormone; Pituitary (anterior); Pituitary hormones; Radiation therapy; Skull; Surveillance; Well being
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/cen.13971

Summary Background Childhood brain tumour survivors who receive cranial radiotherapy undergo regular surveillance for the development ofhypothalamic‐pituitary (HP) axis dysfunction. Much less attention has been given to radiation‐induced hypopituitarism in patients with malignant brain tumours of adult onset. Design Retrospective cohort study. Patients/Measurements We assessed the effects of cranial radiotherapy (cXRT) on pituitary function in 58 adults (32 male) with gliomas distant to the HP axis. The XRT dose exposure at the HP axis was correlated with individual axis dysfunction to establish dose thresholds. Results Mean age at cXRT was 41.2 ± 10.9 years and duration of endocrine follow‐up 8.2 ± 5.2 years. Mean XRT dose to the HP axis was 35.9 ± 15.5 Gy. Overall prevalence of radiation‐induced hypopituitarism was 84.5%. GH, LH/FSH, ACTH and TSH deficiency were present in 82.8%, 20.7%, 19% and 6.9% of patients, respectively. Hyperprolactinaemia was noted in 10.3% (n = 6) and was persistent in one case. GH deficiency and “any degree of hypopituitarism” positively correlated with the radiotherapy dose to the hypothalamic‐pituitary axis. HP axis XRT dose thresholds for the development of GHD, LH/FSH, ACTH and TSH deficiency were established at 10, 30, 32 and 40.8 Gy, respectively. A gradual increase in the prevalence of all anterior pituitary hormone deficits was observed throughout the follow‐up period. Conclusions Hypopituitarism post‐cXRT in adults with gliomas is a frequent, progressive and dose‐dependent phenomenon. Dose thresholds suggest long‐term endocrine surveillance is important where the HP axis XRT dose is higher than 30 Gy. Identification of deficits to allow early and appropriate hormone replacement therapy is important to improve well‐being in these individuals with limited prognosis.