Endocrine complications in long-term survivors of childhood cancers

Abstract

Endocrine disturbances are among the most frequently reported complications in childhood cancer survivors, affecting between 20 and 50% of individuals who survive into adulthood. Most endocrine complications are the result of prior cancer treatments, especially radiotherapy. The objective of the present review is to discuss the main endocrine complications observed in this population, including disorders of the hypothalamic-pituitary axis, disorders of pubertal development, thyroid dysfunction, gonadal dysfunction, decreased bone mineral density, obesity, and alterations in glucose metabolism with a special focus on recent findings reported from the Childhood Cancer Survivor Study.

Self-reported endocrine late effects in adults treated for brain tumours, Hodgkin and non-Hodgkin lymphoma: a registry based study in Northern Germany

“…Moreover, the length of clinical follow-up needs to be considered in this context as the majority of irradiation induced thyroid malignancies arise O10 years after local radiotherapy. It appears possible that the median time of clinical follow-up was too short in our current study and therefore no significantly elevated incidence of secondary malignancies was observed in any location as exemplarily depicted for thyroid neoplasia (14,38). Almost half of all male participants in our study reported on reduced libido and/or erectile dysfunction.…”

“…International studies including a systematic clinical follow-up on extended cohorts revealed that the risk of relapse decreases with an increasing time interval to the initial diagnosis; in contrast, the incidence particularly of endocrine late effects remains significantly elevated for many years even in the absence of any signs of relapse from the initial malignant disease. These data are almost exclusively derived from paediatric cancer survivors with a prevalence of at least one chronic disease in up to 70% of cases 30 years after initial diagnosis and about 50% related to an endocrine disorder (13,14). These effects are frequently associated with unspecific symptoms such as fatigue and impaired capability of physical performance.…”

Late thyroid complications in survivors of childhood acute leukemia. An L.E.A. study

“…This cumulative incidence is much higher than that reported by Chow et al (15-year cumulative incidence of hypothyroidism: 1.6%), probably because their study also included patients treated with chemotherapy alone, and because the methodology used may have undervalued the incidence of hypothyroidism (retrospective study, self-reported thyroid dysfunction). 4 Primary hypothyroidism has been linked to exposure to thyroid radiation, 25 primarily in solid tumors such as Hodgkin lymphoma 15,16 and brain tumors, 10,14 although it was also found to be associated with cranial or craniospinal irradiation in patients with childhood acute leukemia. 4 Cranial irradiation in patients with acute lymphoblastic leukemia has long been suggested to play a role in hypothyroidism, 3,4,26 although a few authors have argued that the impact of prophylactic cranial radiation is controversial.…”

“…17 According to the literature, the risk of primary hypothyroidism seems to be strongly associated with the total irradiation dose received by the thyroid gland. 25 It has been suggested that the risk of hypothyroidism is higher in patients exposed to craniospinal irradiation than in those who undergo cranial irradiation. 4 We, however, did not find similar results, which may be due to the small number of patients who received craniospinal irradiation.…”

“…This is consistent with the reports of most studies in the field, which describe peripheral hypothyroidism as the most common thyroid disorder following treatment in leukemia survivors. 5,25,29,35 However, Sanders et al reported 74 cases of central hypothyroidism among 791 patients, 17 which may be due to a high number of single doses of total body irradiation. It was previously shown that single-dose total body irradiation is associated with increased toxicity and notably greater thyroid toxicity.…”