Radiation-induced hypopituitarism after cancer therapy: who, how and when to test

Abstract

Subtle to frank abnormalities in hypothalamic-pituitary axis function are frequently seen in cancer survivors who have received prophylactic or therapeutic cranial irradiation. The growth hormone (GH) axis is the most vulnerable to radiation damage, and isolated GH deficiency can occur after doses as low as 18 Gy. Furthermore, the frequency of GH deficiency can reach 50-100% within 3-5 years of cranial irradiation with doses of 30-50 Gy. TSH and adrenocorticotropic hormone deficiency occur in 3-6% of patients after conventional irradiation (30-50 Gy). Abnormalities in gonadotropin secretion are dose-dependent: gonadotropin deficiency is seen only after doses of 30 Gy or more, whereas lower doses usually lead to precocious puberty. Hyperprolactinemia predominantly occurs in young women after intensive irradiation and is usually subclinical. The frequencies of gonadotropin, adrenocorticotropic hormone and TSH deficiencies substantially increase with intensive irradiation (greater than 60 Gy) and after conventional irradiation for pituitary tumors, with a cumulative incidence of 30-60% after 10 years. The irreversible and progressive nature of radiation-induced anterior-pituitary hormone deficiencies and their adverse effect on body image, growth, sexual function, skeletal health and quality of life makes it essential that cancer survivors are tested regularly to ensure appropriate diagnosis and timely hormone replacement therapy.