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Medical Treatment for Intractable Obesity in Pediatric Cancer Patients

Medical Treatment for Intractable Obesity in Pediatric Cancer Patients

A potential treatment for hypothalamic obesity that often afflicts children who receive treatment for brain tumors or leukemia has been discovered by researchers at St. Jude Children’s Research Hospital. Many of these childhood cancer survivors die in adulthood as a result of obesity and its associated diseases. Dieting and exercise have no effect on this type of obesity, and until recently, investigators have been unable to determine the cause of hypothalamic obesity or find an effective treatment.

However, at the recent Pediatric Academic Society meeting, a new study presented by clinicians from St. Jude shed light on the origins of and medical treatment for this condition. It indicates that the patient’s obesity is caused by the body’s inability to adequately release insulin. It also indicates that this condition can be treated with octreotide acetate (Sandostatin), a medication that inhibits the release of excess insulin.

Obesity Linked to Damaged Hypothalmus

According to the study, when a child is treated for a brain tumor or leukemia, either the tumor itself, surgery, chemotherapy, or radiation injures the hypothalamus, causing the body to produce excessive insulin.

"In early studies with rats, damage to a certain area of the hypothalamus caused obesity, hyperphagia, and hyperinsulinism. But we weren’t sure if the damage to the hypothalamus was having the same effect in humans," said Robert H. Lustig, MD, associate professor, University of Tennessee, consulting physician at St. Jude Children’s Research Hospital, and author of the study. "We also wanted to discover which came first: the obesity or the excess insulin, and whether these problems could be treated."

Dr. Lustig and his team assessed eight patients (four male and four female) 10 to 18 years of age with marked and worsening obesity that began after therapy for leukemia or brain tumors. In each patient, previous dietary restriction had not produced any weight loss, only continued weight gain. Oral glucose tolerance testing showed normal fasting glucose levels but mild glucose intolerance in five of the eight patients. Fasting insulin levels were minimally elevated, but peak insulin responses to glucose were markedly exaggerated in six patients.

Obesity--A Phenotype of Many Diseases

"Based on the data we collected in our initial research, we administered increasing doses of octreotide, an insulin inhibitor, for 6 months without dietary restriction," said Dr. Lustig. The children in the study were given three injections of octreotide per day for 6 months to a year. They responded with an average weight loss of 11 pounds or with weight maintenance. Dr. Lustig says that because damage sustained to the hypothalamus from the tumor or treatment is permanent, these children will likely need to continue this medication throughout their lives.

"This study increases our understanding of obesityin general, said Dr. Lustig. "Our research gives more credence to the idea that obesity is not one disease, but a ‘phenotype’ of many diseases, with different causes. This is significant because we have developed a specific treatment for a specific type of obesity. If other types of obesity can be discovered, other specific treatments can also be developed."

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