Endocrinopathy After Childhood Cancer Treatment

Abstract

Due to remarkable improvements in treatment and supportive care over the past several decades, survival rates for childhood cancer currently exceed 80%. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at particularly high risk for long-term morbidity, such as endocrine insufficiencies, metabolic complications, and cardiovascular morbidity. Research report that 40-50% of survivors will develop an endocrine disorder over their lifetime. Deficiencies of one or more anterior pituitary hormones have been described following therapeutic CRT for primary brain tumors, nasopharyngeal tumors, and following prophylactic CRT for childhood acute lymphoblastic leukemia (ALL). For at risk-survivors, new endocrinopathies can develop decades following cancer treatment, and lifelong surveillance is mandatory. Studies have consistently shown a strong correlation between the total radiation dose and the development of pituitary deficits. Further, age at treatment and also time since treatment has strong implications on pituitary hormone deficiencies. Risk factors for low BMD include high dose methotrexate, cumulative doses of glucocorticoids, male gender, and low physical activity. Any combination of these factors may result in osteopenia, not reaching optimal peak bone mass and osteoporosis later in life. Infertility is an important potential consequence of treatment for childhood cancer and identification of survivors for whom strategies to preserve fertility are required. Women treated with radiotherapy affecting ovarian and uterine function are at high risk of acute ovarian failure, premature menopause, complications including spontaneous abortion and preterm labor. Radiotherapy to the gonads, total body irradiation, and high dose chemotherapy may result in a number of effects on the male reproductive system in survivors. Detailed information about the past cancer treatment including surgery, the type and cumulative doses of chemotherapy, and radiotherapy volumes and doses are needed to estimate health risks associated with childhood cancer. A risk-based care approach, for all childhood cancer survivors, should include a systematic plan for lifelong screening, surveillance, and prevention that incorporates risk estimates.