Endocrine disorders in childhood cancer survivors: More answers, more questions

Treatment of pediatric malignancies has advanced substantially over the past several decades, resulting in a rapidly growing group of long-term childhood cancer survivors (CCS). Improved survival leads to an increasing number of individuals who may be at increased risk of substantial morbidity and even mortality as a direct or indirect consequence of their prior cancer therapy. Moreover, many CCS face lifelong health-related challenges after curative treatment of a childhood malignancy. Around 73% of the survivors will experience at least one chronic health-condition within 30 years of their cancer diagnosis, with a 42% cumulative incidence rate for severe, disabling, or life-threatening conditions or death due to a chronic disease. Endocrine disorders are common in CCS, and may not only play a central role in long-term health and wellbeing, but can also significantly diminish short-term health, especially during childhood. In CCS, endocrine integrity is essential for adequate recovery, for development and growth and optimal daily (school) life participation. As in many late adverse effects in CCS, endocrine disturbances are most often related to cancer treatment. Particularly patients receiving radiation therapy and alkylating chemotherapy are at high risk of developing endocrinopathies. In addition to their anti-carcinogenic effects, these therapies may cause direct injury to the hypothalamic-pituitary axis, thyroid gland, and the gonads. The current thesis focuses primarily on the etiology, epidemiology, risk factors and optimal surveillance strategy of diverse endocrine disorders in survivors of a childhood malignancy.