Carcinoid syndrome, acromegaly, and hypoglycemia due to an insulin-secreting neuroendocrine tumor of the liver

We report a patient with a hepatic neuroendocrine tumor showing an extraord inary change of the tumor's humoral manifestations from a clinically docume nted extrapituitary acromegaly and a typical carcinoid syndrome toward a hy perinsulinemic hypoglycemia syndrome. At the primary manifestation of the t umor, an increased serum level of insulin-like growth factor I due to overp roduction of GHRH and an increased urinary excretion of 5-hydroxyindoleacet ic acid were found. The clinical manifestation of the GHRH excess was an ar thralgia, which resolved completely after operative tumor debulking and nor malization of insulin-like growth factor I and GHRH serum levels. The secre tion of serotonin from the tumor resulted in a typical carcinoid syndrome i ncluding right-sided valvular heart disease. On the later course of the dis ease, the humoral manifestations of the tumor were supplemented by the secr etion of insulin, leading to recurrent severe hyperinsulinemic hypoglycemia . The hepatic origin of hyperinsulinism was demonstrated by selective arter ial calcium stimulation. Moreover, tumor cells revealed insulin and C-pepti de immunoreactivity in the immunohistochemical analysis. The patient died 8 yr after the initial diagnosis of the tumor, and a carefully performed aut opsy procedure confirmed the absence of any extrahepatic tumor manifestatio n.