Long-term endocrine effects of chemotherapy in cancer childhood survivors and possible nutrition management

Advances in new therapies for childhood cancer have resulted in high cure rates. But there is greater risk for developing late adverse effects after treatment, including obesity, high blood pressure, cardiovascular diseases, and impaired glucose metabolism. Endocrinopathies are among the most frequently encountered late effects in cancer childhood survivors (CCS) (1). Alkylating agent basedchemotherapy, Mitogen-activated kinase inhibitors, immune system modulators and radiotherapy have been indicated to be associated with endocrinopathies. Endocrine disorders associated with thetreatment of pediatric cancer including disorders of the hypothalamus and pituitary, thyroid dysfunction, disorders of the gonads, bone complications, overweight, obesity, and glucose homeostasis (2). In the case of hypothalamus and pituitary disorders, growth failure and short stature is important in pediatric patients which are prevalent among CCS (3). Growth hormone deficiency, spinal and cranial irradiation, glucocorticoids, suboptimal nutrition and renal diseases are possible etiologies which could be contributed to growth failure in CCS. Growth hormone deficiency (GHD) could be masked by hyperinsulinemia in the context of rapid weight gain with normal linear growth (2). Central precocious puberty (CPP) is defined by the early activation of the hypothalamic–pituitary–gonadal which may lead to decreased adult height prospects. CPP also make fundamental psychosocial challenges in CCS(4). Radiotherapy and tumors near the hypothalamus may cause CPP. Hydrocephalus, female sex and elevated BMI are other additional risk factors (2). LH/FSH deficiency because of tumor related damage or radiotherapy to the hypothalamic–pituitary area, may cause delayed pubertal development in CCS. Tumors and radiotherapy also can induce Corticotropin (ACTH) deficiency with fatigue, weakness, nausea, vomiting, anorexia, and abdominal cramping(1). ACTHD also may develop life threatening complication like hypoglycemia related seizure and hypotensive shock. Anti-diuretic hormone (ADH) deficiency leads to central diabetes insipidus (DI). DI cannot concentrate urine with ensuing polyuria and dehydration. Tumors near the sellar region are the main etiology (5). Disorders of thyroids and gonads are actually because of their radiosensitive nature. Hyperthyroidism, hypothyroidism, autoimmune induced thyroid disease, thyroid neoplasms, germ cell and Leydig cell dysfunction and ovarian dysfunction are among most prevalent (1, 2). Obesity and metabolic syndrome (MetS) are well-known public health challenges. Survivors of Acute lymphoblastic Leukemia and brain tumors have higher risk of overweight and obesity (6). Radiotherapy over 20 Gy, and/or surgery especially near the sellar region and GHD are possible risk factors(7, 8). In fact Sellar region radiotherapy predisposes children for hypothalamic obesity characterized by hyperphagia and rapid weight gain with hyperinsulinemia(8). Obesity leads to inflammation and hormonal changes such as disturbed adipokines. Glucose metabolism also can be disturbed in CCS. Depletion of osteoblasts and estrogenic precursors cause osteocalcin reduction in the blood. On the other hand glucocorticoids impair skeletal glucose uptake and transport. Higher risk of diabetes mellitus has been reported. Risk factors including total body irradiation, abdominal radiotherapy and alkylating agents. Cancer therapies activate definite pathways that cause hormone disturbance, insulin resistance and inflammatory mediators. Systemic inflammation because of cancer and treatments results in adypocyte dysfunction and altered adipokines secretion(9). Undoubtedly nutrition has remarkable effect for management of these disorders. Based on child characteristics, type of cancer, type of therapy and present disorder, different management needs to be planned. Some of nutritional intervention aim to increase insulin sensitivity and some of them to prevent or treat obesity. Healthy Eating Index (HEI) has been proposed exactly because survivors reported to consume fewer whole grains and dietary fiber, and higher percentage of calories from fat, saturated fat, and refined carbohydrates and also higher calories than estimated energy in comparison with the suggested intake(10). The association between nutritional intake and its chronic health conditions are still inadequately elucidated in CCS. So we wish we can explain these endocrinopathies and also nutrition management.

کلیدواژه ها:

Cancer Risks ، Nutrition and Cancer ، Multidisciplinary Cancer Research ، Cancer Treatment and Management ، Chemotherapy