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Late Effects of Treatment for Childhood Cancer (PDQ®): Treatment - Health Professional Information [NCI] - Late Effects of the Endocrine System

Table 9. Pituitary Gland Late Effects continued...

Testis and Ovary

Testicular and ovarian hormonal function are discussed in the Late Effects of the Reproductive System section of this summary.

Metabolic Syndrome

The metabolic syndrome is highly associated with cardiovascular events and mortality. Definitions of the metabolic syndrome are evolving, but generally include a combination of central (abdominal) obesity with at least two or more of the following features:

  • Hypertension.
  • Atherogenic dyslipidemia (elevated triglycerides, reduced high-density lipoprotein [HDL] cholesterol).
  • Abnormal glucose metabolism (fasting hyperglycemia, hyperinsulinism, insulin resistance, diabetes mellitus type 2).[57]

An increased risk of metabolic syndrome or its components has been observed among cancer survivors. Long-term survivors of ALL, especially those treated with cranial radiation, may have a higher prevalence of some, potentially modifiable, risk factors for cardiovascular disease such as impaired glucose tolerance or overt diabetes, dyslipidemia, hypertension, and obesity.[58,59,60] In a cross-sectional study comparing cardiovascular risk factors and insulin resistance among 319 childhood cancer survivors (median age, 14.5 years; median time from diagnosis, 10.1 years) and 208 sibling controls, no difference was observed in weight and body mass index (BMI), although survivors had greater adiposity, percent fat, and lower lean body mass than siblings. Childhood cancer survivors also had higher total and low-density lipoprotein (LDL) cholesterol and triglycerides and lower insulin sensitivity compared with siblings.[61] In a young adult cohort of ALL survivors (mean age 30 years), 62% had at least one cardiovascular risk factor and 30% had two or more.[62] Another study observed no difference in prevalence of metabolic syndrome in 75 ALL survivors compared with a population-based control group.[63] However, survivors with metabolic syndrome were more likely to have GH insufficiency or GHD. Those treated with cranial radiation therapy also had an association with GH abnormalities and were more likely to have two or more components of the metabolic syndrome compared with survivors who were not treated with cranial radiation therapy.

A high frequency of cardiovascular risk factors has also been observed among hematopoietic cell transplant recipients.[64,65] French investigators reported an overall 9.2% (95% CI, 5.5–14.4) prevalence of metabolic syndrome in a cohort of 184 ALL survivors (median age 21.2 years).[66] Gender, age at diagnosis, corticosteroid therapy, or cranial radiation were not significant predictors of metabolic syndrome. However, hematopoietic cell transplantation with TBI was a major risk factor for metabolic syndrome (OR = 3.9, P = .03). Other investigators have reported a significantly increased risk of hyperinsulinemia, impaired glucose tolerance, or diabetes mellitus associated with exposure to TBI.[59,67] The association between TBI and excess risk for diabetes has also been observed by other investigators.[68] These data suggest that survivors might benefit from targeted screening and lifestyle counseling regarding risk reduction measures.

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