Endocrine health conditions in adult survivors of childhood cancer: the need for specialized adult-focused follow-up clinics

Abstract

Background: Survival rates among childhood cancer survivors (CCS) have enormously increased in the last 40 years. However, this improvement has been achieved at the expense of serious late effects that frequently involve the endocrine system. Aim: To evaluate the cumulative incidence of endocrine diseases in a cohort of long-term CCS. Materials and methods: We analyzed the clinical data of 310 adults, followed for a median time of 16.0 years after the first cancer diagnosis. The monitoring protocols applied to each patient were personalized on the basis of cancer diagnosis and previous treatments, according to the Children's Oncology Group guidelines. Results: The cumulative incidence of endocrine late effects steadily increased over time. At the last follow-up visit available, 48.46% of females and 62.78% of males were affected by at least one endocrine disease. The most common disorders were gonadal dysfunction, primary hypothyroidism, and GH deficiency (GHD). The main risk factors for endocrine disease were male sex (hazard ratio (HR)Z1.45, 95% confidence interval (95% CI) 1.05-1.99), radiotherapy (HRZ1.91, 95% CI 1.28-2.84), hematopoietic stem cells transplantation (HRZ3.11, 95% CI 2.23-4.34), and older age at cancer diagnosis (HRZ1.89, 95% CI 1.25-2.85). Male sex was associated with a higher risk of gonadal disorders, whereas radiotherapy specifically increased the risk of GHD and thyroid dysfunction. Conclusions: Endocrine disorders among CCS have a high prevalence and increase over time. Thus, endocrinologists need to cope with an increasing demand for health care in a field that is still little developed and that, in perspective, could also be extended to some selected types of adult cancer survivors.

DIAGNOSIS OF ENDOCRINE DISEASE: Endocrine late-effects of childhood cancer and its treatments

“…Thyroid complications are among the most common endocrine sequelae in the overall population of CCS (3,16). The risk of developing primary thyroid disease was significantly higher in survivors than that in sibling controls regardless of exposure to highrisk treatments, such as neck radiotherapy, in a recent report from the CCSS (16).…”

“…Primary hypothyroidism is one of the most common endocrine late-effects reported in CCS (3,16,88). Its overall prevalence among adult CCS has been reported at 13.8-20.8% (3,89).…”

“…Its overall prevalence among adult CCS has been reported at 13.8-20.8% (3,89). One of the highest rates is in survivors of pediatric Hodgkin lymphoma, where up to 50% experienced hypothyroidism at 20 years from diagnosis after thyroid exposure to radiation doses ≥45 Gy (88).…”

“…The prevalence of Leydig cell failure among patients exposed to high-risk therapies (alkylating agents or radiation potentially affecting the male reproductive system) has been reported at 11.5-13.3% in adult CCS followed long term (3,89). The prevalence of Leydig cell failure among CCS treated with alkylating agents was reported at 10-57%, but it was subclinical in the vast majority of cases (normal testosterone values with elevated LH) and rarely required treatment (114,115,116).…”

“…Endocrine complications are among the most common late-effects in CCS and they frequently occur because of exposures to radiotherapy and/or alkylating agent chemotherapy. It is estimated that 50% of CCS will experience at least one endocrine or reproductive complication during the course of his/her lifetime (3). The present manuscript offers a summary of the main endocrine late-effects in CCS including hypothalamic/pituitary (HP) axis dysfunction and complications affecting the thyroid and gonads, as well as decreased bone mineral density (BMD) and metabolic derangements leading to obesity and/or diabetes mellitus.…”