RADIOIMMUNOASSAY OF INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II IN THE CEREBROSPINAL-FLUID OF PATIENTS WITH PITUITARY AND OTHER CENTRAL-NERVOUS-SYSTEM TUMORS

TUMOR CELLS ARE characterized by abnormalities in growth and metabolism, including the autocrine secretion of certain growth factors. On the basis of our previous demonstration of the production of insulin-like growth factors (IGFs) and their binding proteins by central nervous system (CNS) tumors, we asked whether the levels of IGFs in the CSF may be altered in patients with pituitary and other CNS tumors and may reflect autocrine secretion. We used specific radioimmunoassays for ICF-I and -II and measured these growth factors in the cerebrospinal fluid (CSF) from 26 patients with tumors located adjacent to the ventricular system. The tumors included were eight pituitary tumors (five nonsecreting, three growth hormone secreting), five gliomas, two meningiomas, five medulloblastomas, three metastases, and three other tumors. CSF from patients without tumors served as controls. For radioimmunoassay, CSF was treated with acetic acid overnight and ICE-binding proteins were separated from IGFs by C-2 solid phase cartridge extraction. The pituitary tumors were characterized by significantly elevated levels of IGFs in the CSF. In nonsecreting pituitary tumors, the levels of ICF-I in the CSF were similar to normal levels, whereas ICE-II levels were significantly elevated. In acromegalic patients, levels of both IGF-I and -II in the CSF were significantly elevated compared with normal levels and compared with levels in patients with nonsecreting tumors. In contrast, the levels of IGFs in the CSF from most of the primary and metastatic CNS tumors did not significantly differ from normal values. In summary, although IGFs may contribute to the regulation of cell growth in primary CNS tumors, CSF levels are not elevated. In contrast, levels of IGFs in the CSF are significantly elevated in pituitary tumors, suggesting that IGFs may play a role in the pathogenesis of pituitary tumors and may be important markers for pituitary tumors.