Children who have been treated for brain tumors often experience significant weight gain, and new findings suggest that this could be a sign of hypothalamic-pituitary (HP) dysfunction.
“We believe that endocrine surveillance should be initiated early, as delay in treating endocrine deficiencies could have serious effects on the metabolic health in childhood brain tumor survivors (CBTS),” commented lead investigator Jiska van Schaik, MSc, a PhD-student in pediatric endocrinology and oncology at Wilhelmina Children’s Hospital and Princess Máxima Center, Utrecht, the Netherlands.
In addition, “support regarding weight control should also always be initiated early to prevent the development of serious obesity with increased the risk for morbidities and premature mortality at a later age,” she added.
The Dutch study of 661 children who survived a brain tumor found that one third become overweight, obese, or had gained a significant amount of weight during the follow-up period.
Among 578 survivors who were between 4 and 20 years of age at follow-up, 20.3% were classified as overweight and 8.5% as obese, as compared with 10.5% and 2.7%, respectively, in the general Dutch population within the same age group.
Similarly, among 78 CBTS between 20 and 30 years of age, 21.8% were overweight and 7.7% obese, vs 20.8% and 5.9%, respectively, in the general population.
The study was published in the Journal of Clinical Oncology.
“It has already been reported in the literature that there is a high prevalence of obesity in childhood brain tumor survivors, but these previous papers included survivors of craniopharyngioma, which greatly influences the overall prevalence,” said van Schaik.
“We know that the rate of obesity in craniopharyngioma survivors is very high,” she continued. This study specifically excluded children with craniopharyngioma or pituitary tumors.
“Additional data, including the prevalence of also overweight and significant weight gain in CBTS, has not been reported before,” she told Medscape Medical News. “Therefore, we believe this data provided new and interesting information on significant weight gain during follow-up.”
Overweight/obesity and significant weight gain could be associated with endocrine deficiencies, such as diabetes insipidus and central precocious puberty, van Schaik explained, which may be indicative of HP dysfunction.
“Therefore, we believe that physicians should be more aware of the development of overweight/obesity or the development of significant weight gain in their patients, as it could be a reflection of HP dysfunction, and thus more endocrine surveillance is needed,” she said.
Weight Gain Linked to HP Dysfunction
There was a significant difference in prevalence of HP disorders between survivors who were normal weight vs those who were overweight or obese, and this was seen for all pituitary disorders except for growth hormone deficiency.
Of survivors with a normal body mass index (BMI), 14.7% were diagnosed with an anterior pituitary disorder, compared with 24.6% who were overweight and 23.2% who were obese.
A diagnosis of diabetes insipidus was made in 1.5% of normal-weight CBTS, 5.2% of those who were overweight, and in 10.7% of obese CBTS. Central precocious puberty was observed in 4.6%, 18.7%, and 10.7%, respectively.
There was also a small percentage (n = 14, 2.1%) of children who were underweight at follow-up, of whom 6 developed growth hormone deficiency. The CBTS in this underweight subset had received chemotherapy and/or radiotherapy more frequently as compared with the rest of the cohort. The proportion of children who had received chemotherapy was 71.4% among underweight survivors, compared with 33.9% for normal weight, 40.3% overweight, and 41.4% for obese (P = .019); for radiotherapy, these were 92.9% for the underweight subset vs 35.9%, 38.1%, and 46.4%, respectively (P < .001).
Surveillance and Early Intervention
Commenting on these results, Karen Moody, MD, associate professor, Department of Pediatrics Patient Care, University of Texas MD Anderson Cancer Center, Houston, emphasized that physicians should be aware of the fact that CBTS are at risk for weight gain resulting in obesity.
“The increased rate of overweight and obesity in survivors of childhood brain tumor survivors is well known and largely — but probably not completely — driven by tumor- and/or treatment-related hypothalamic-pituitary dysfunction,” said Moody, who was not involved with the study. “The current paper advances our understanding of this phenomenon by excluding children with craniopharyngioma and pituitary lesions in their analysis and then measuring the risk for the remaining group of children with brain tumors.”
This exclusion has allowed for more direct quantification of the risk for obesity and overweight in children with brain tumors as well as the risk for hypothalamic-pituitary dysfunction. “Current pediatric oncology guidelines include screening children after diagnosis of a brain tumor to classify their risk for hypothalamic-pituitary dysfunction, taking into consideration tumor location and treatment,” Moody said. “It is currently best practice to screen children diagnosed with a brain tumor for their risk for hypothalamic-pituitary dysfunction and order laboratory testing depending on screening evaluation.”
The goal is to identify children with HP dysfunction as early as possible so that appropriate treatment including medications and patient education can be initiated. “More research is needed to understand if and how diet and exercise could be leveraged in this population, in the context of hypothalamic-pituitary dysfunction, to normalize weight and optimize health outcomes in the short and long term,” she added.
The study was supported by Stichting Kinderen Kankervrij (KiKa). Van Schaik has disclosed no relevant financial relationships.
J Clin Oncol. Published online February 23, 2021. Abstract
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