Hyperinsulinemia Tends to Induce Growth Without Growth Hormone in Children with Brain Tumors After Neurosurgery
Hypothalamo-pituitary dysfunction is commonly seen in children with brain tumors after neurosurgery, resulting in endocrine disorders, including growth hormone deficiency (GHD). GHD causes growth failure, and thus the majority of the patients need GH replacement therapy. Despite GHD, some patients grow normally or excessively, which has been recognized as growth without GH (GWGH). Since hyperinsulinemia is highly associated with the patients with GWGH, it has been considered to play an important role for promoting linear growth. However, the causes of hyperinsulinemia associated with GWGH and the mechanisms of GWGH remain elusive. The data to date collectively suggest that the location of brain tumors and/or the mode of surgery, insulin resistance associated with obesity, insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-1 and −3, leptin and prolactin (PRL) may contribute to the regulation of insulin secretion in patients with GWGH. Besides its metabolic effects, insulin exerts the diverse effects as a growth factor, including proliferation and differentiation of osteoblasts, leading to acceleration of linear growth. Interaction between insulin- and IGF-I-induced signaling pathways and of insulin with other hormonal factors such as leptin or PRL may play a crucial role for promoting linear growth in patients with GWGH. Despite normal or excessive linear growth, patients with GWGH still have metabolic abnormalities and retarded bone maturation. It remains elusive whether GH replacement therapy solves these problems and enables the patients to reach normal height in adulthood. Better understanding for the mechanisms of GWGH is essential to improve the quality of life of patients with GWGH. Because of a lack of accumulating data, further studies would be necessary to clarify the clinical characteristics and the mechanisms of GWGH in more detail in the future.
KeywordsInsulin Secretion Linear Growth Growth Hormone Deficiency Precocious Puberty Growth Spurt
The authors are grateful to Drs. T. Kamijo and H. Mizuno for their helpful suggestions.
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