Defective expression of prohormone convertase 4 and enhanced expression of insulin-like growth factor II by pleural solitary fibrous tumor causing hypoglycemia.
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A 75-year-old man was admitted to our hospital because of unconsciousness. His plasma glucose was very low, but his serum levels of insulin and IGF-I were also low. He was found to have a giant solitary pleural tumor, which was completely resected, after which his hypoglycemia ameliorated postoperatively. Histologically, the tumor was consistent with the pathological diagnosis of a solitary fibrous tumor derived from the pleura. Immunohistochemical study revealed positive immunostaining for IGF-II in tumor cells. The presence of high molecular weight (HMW) form of IGF-II in the tumor tissue and patient's serum was confirmed by Western blot analysis. Steady-state mRNA levels of IGF-II and prohormone convertases (PC) 4, a potential protease responsible for IGF-II processing, as determined by RT-PCR were about 14-fold greater and 5-fold less in the tumor tissue than those in normal placental tissue, respectively. Therefore, it is suggested that biologically active, unprocessed HMW form of IGF-II generated from the impaired processing of IGF-II precursor by the defective PC4 expression in the tumor was responsible for the non-islet cell tumor hypoglycemia (NICTH) in the present case.