NIAGARA-ON-THE-LAKE, Canada—Long-term survivors of childhood cancer are at increased risk of several late effects, including premature cardiovascular disease and insulin resistance as young adults. New research suggests that one cause of these conditions may be growth hormone deficiency (GHD) causedby cancer therapy.
GHD was the focus of two presentations at the 2008 International Conference on the Long-Term Complications of Treatment of Children and Adolescents for Cancer. The meeting was sponsored by Roswell Park Cancer Institute and the National Cancer Institute.
All of the research was done at the University of Minnesota’s division of pediatric hematology/oncology/blood and marrow transplantation. The investigators examined whether GHD could be linked to the increased frequency of obesity and heart disease in childhood cancer survivors.
Increase GHD awareness
In one study (abstract 14), the group examined 116 patients who survived childhood cancer for a range of 5 to 17 years after diagnosis. At the time of the study, the mean age of the subjects was 16; all but 3 had started puberty.
GHD was determined by standardized growth hormone stimulation tests and dual-energy x-ray absorptiometry (DEXA) was performed to determine body composition. GHD was defined as a peak GH level < 10 ng/mL in patients < 18 years and less than < 4.1 ng/mL in adults after stimulation test.
After screening, 33 patients were diagnosed as having GHD. Compared to patients without GHD, this group had increased insulin resistance, greater body mass index (BMI), elevated triglycerides, larger waist circumference, and more abdominal subcutaneous fat.
“We believe we can use these data to increase awareness of GHD in our patients, their families, and future care providers,” said Pauline Mitby, MPH. “We suggest that screening for GHD as part of follow-up to cancer therapy may help identify at-risk patients and potentially allow them to begin therapy to minimize these late effects,” she said.
The second study (abstract 15), included 56 patients who received hematopoietic cell transplantation (HCT) for acute leukemia (67%) or lymphoma at age 18 years or younger. The control group was made up of 41 siblings.
GHD was diagnosed in 21% of survivors. Metabolic syndrome (see Sidebar) was present in 45% of survivors with GHD and 7% of those without GHD vs 5% in the control group (P = .005 and 0.75, respectively). GHD survivors were more likely to be insulin resistant than siblings (P = .002).
After adjusting for gender and age, survivors with GHD were 11.9 times more likely (95% CI: 2.4-79.4) to have high triglycerides and 9.6 times more likely (95% CI: 1.83-64.1) to have high fasting glucose, compared with siblings. There was no significant difference in BMI, total fat mass, waist circumference, HDL-cholesterol, or blood pressure in GHD survivors vs siblings.
“Our analyses suggest that survivors of childhood cancer are at an increased risk of metabolic syndrome, but that the risk is higher in children who received HCT as part of their therapy,” K. Scott Baker, MD, commented.
The data showed an increased risk of GHD and metabolic syndrome, even when the patient’s weight was within a healthy BMI range. “This suggests that as adults this population will need to be vigilant because their weight will not be an indicator to their primary care physician about these potential cardiovascular health risks,” Dr. Baker said.
Future analyses will further examine survivors who received total body irradiation with or without cranial radiation to determine if they are at an even greater risk of GHD and subsequently cardiovascular disease.
‘A real problem’
Metabolic syndrome is a real problem, commented Daniel Green, MD, from the Department of Epidemiology and Cancer Control at St. Jude Children’s Research Hospital.
“One point that stands out is that obesity is not necessarily a feature of metabolic syndrome,” Dr. Green said. “Thus, being able to identify the at-risk patients will become important in order to determine appropriate interventions.”