Hypopituitarism following radiotherapy

Abstract

Deficiencies in anterior pituitary hormones secretion ranging from subtle to complete occur following radiation damage to the hypothalamic-pituitary (h-p) axis, the severity and frequency of which correlate with the total radiation dose delivered to the h-p axis and the length of follow up. Selective radiosensitivity of the neuroendocrine axes, with the GH axis being the most vulnerable, 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%. Compensatory hyperstimulation of a partially damaged h-p axis may restore normality of spontaneous GH secretion in the context of reduced but normal stimulated responses; at its extreme, endogenous hyperstimulation may limit further stimulation by insulin-induced hypoglycaemia resulting in subnormal GH responses despite normality of spontaneous GH secretion in adults. In children, failure of the hyperstimulated partially damaged h-p axis to meet the increased demands for GH during growth and puberty may explain what has previously been described as radiation-induced GH neurosecretory dysfunction and, unlike in adults, the ITT remains the gold standard for assessing h-p functional reserve. Thyroid-stimulating hormone (TSH) and ACTH deficiency occur after intensive irradiation only (>50 Gy) 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 (>60 Gy) used for nasopharyngeal carcinomas and tumors of the skull base, and following conventional irradiation (30-50 Gy) for pituitary tumors. The frequency of hypopituitarism following stereotactic radiotherapy for pituitary tumors is mostly seen after long-term follow up and is similar to that following conventional irradiation. Radiation-induced anterior pituitary hormone deficiencies are irreversible and progressive. Regular testing is mandatory to ensure timely diagnosis and early hormone replacement therapy.