Contribution to the pathogenesis of tumour hypoglycaemia.

Abstract

Abstract In a patient with severe hypoglycaemia associated with an intrahepatic fibrosarcoma, hyperinsulinism could be excluded, since normal serum insulin and insulinlike activity (ILA) levels were measured in the fasting state and during glucose, glucagon, and tolbutamide tolerance tests. Treatment with methylprednisolone led to an improvement of the clinical condition of the patient. Diazoxide treatment was ineffective. Blood glucose levels were higher during corticoid therapy, but total glucose assimilation remained unchanged. Studies of the metabolism of [1‐14C] glucose before and during treatment with prednisolone showed that an inhibition of hepatic glycogenolysis was not significant for the pathogenesis of the hypoglycaemia. The differences of glucose and blood lactate after glucose i. v. before and during prednisolone suggested, however, that gluconeogenesis was increased as a result of corticoid therapy. Measurements of hepatic enzyme activities also favoured this hypothesis: activities of FDP'ase and G‐6‐P'ase were low before treatment and increased by a factor of 1.5 and 5 respectively during treatment, indicating a stimulation of the gluconeogenetic processes in the liver. It is concluded that the combination of tumoral glucose overutilization with hepatic glucose underproduction due to impaired gluconeogenesis was the pathogenetic mechanism responsible for the hypoglycaemia of this patient. Electron microscopic studies of the tumour cells revealed abundant mitochondria and a highly active ergastoplasm. In addition, secretory granules were found in the cytoplasm and some even in the mitochondria.