Hypopituitarism as a consequence of brain tumours and radiotherapy

Abstract

Radiation-induced damage to the hypothalamic-pituitary (h-p) axis is associated with a wide spectrum of subtle and frank abnormalities in anterior pituitary hormones secretion. The frequency, rapidity of onset and the severity of these abnormalities correlate with the total radiation dose delivered to the h-p axis, as well as the fraction size, younger age at irradiation, prior pituitary compromise by tumour and/or surgery and the length of follow up. Whilst, the hypothalamus is the primary site of radiation-induced damage, secondary pituitary atrophy evolves with time due to impaired secretion of hypothalamic trophic factors and/or time-dependent direct radiation-induced damage. Selective radiosensitivity in the neuroendocrine axes with the GH axis being the most vulnerable to radiation damage accounts for the high frequency of GH deficiency, which usually occurs in isolation following irradiation of the h-p axis with doses less than 30 Gy. With higher radiation doses (30-50 Gy), however, the frequency of GH insufficiency substantially increases and can be as high as 50-100%, and TSH and ACTH deficiency start to occur with a long-term cumulative frequency of 3-6%. Abnormalities in gonadotrophin secretion are dose-dependent; precocious puberty can occur after radiation dose less than 30 Gy in girls only, and in both sexes equally with a radiation dose of 30-50 Gy. Gonadotrophin deficiency occurs infrequently and is usually a long-term complication following a minimum radiation dose of 30 Gy. Hyperprolactinemia, due to hypothalamic damage leading to reduced dopamine release, has been described in both sexes and all ages but is mostly seen in young women after intensive irradiation and is usually subclinical. A much higher incidence of gonadotrophin, ACTH and TSH deficiencies (30-60% after 10 years) occur after more intensive irradiation (>70 Gy) used for nasopharyngeal carcinomas and tumours of the skull base and following conventional irradiation (30-50 Gy) for pituitary tumours. Radiation-induced anterior pituitary hormone deficiencies are irreversible and progressive. Regular testing is mandatory to ensure timely diagnosis and early hormone replacement therapy to improve linear growth and prevent short stature in children cured from cancer, and in adults preserve sexual function, prevent ill health and osteoporosis and improve the quality of life.