Glucose Intolerance in the Carcinoid Syndrome

Abstract

We assayed glucose tolerance and insulin secretion in ten patients with metastatic carcinoid tumors and the carcinoid syndrome ("active tumors") and in seven patients with metastatic carcinoid tumors without the carcinoid syndrome ("inactive tumors"). The patients with "active tumors" had elevated serum serotonin levels while the patients with "inactive tumors" had normal serum serotonin levels. Of the ten patients with "active tumors," five had diabetic and three had borderline intravenous glucose disposal rate constants (KG = 0.88 +/- 0.07, M. +/- S.E.M.). Their KG was significantly lower (p less than 0.01) than a group of age-matched normals. All of the patients with "inactive tumors" had normal KG values (KG = 1.67 +/- 0.24). Their KG did not differ from that of age-matched normal subjects. Both groups of carcinoid patients had a comparable decrease in their insulinogenic index. Two days' administration of the serotonin antagonist cyproheptadine (Cypro) to eight of the patients with "active tumors" resulted in a significant increase in the "insulinogenic index" (50%) but a nonsignificant increase in the KG (12%). Administration of p-chlorophenylalanine, a compound that blocks serotonin synthesis, resulted in an increase in both the KG (60%) and the "insulinogenic index" (55%). The insulin half-life (t1/2) of patients with "active tumors" (6.1 +/- 0.4 min.) did not differ from the t1/2 of normal subjects (6.6 +/- 0.4 min.), suggesting that the decreased plasma insulin levels following intravenous glucose were due to impaired insulin secretion rather than accelerated insulin destruction. Seven of the patients received treatment with the antitumor agent streptozotocin (Strepto). The patients received cumulative doses of from 70 to 300 mg. of Strepto per kilogram body weight with no impairment in glucose tolerance or insulin secretion. We conclude that there is high incidence of glucose intolerance (80%) and impaired insulin secretion in patients with the carcinoid syndrome and that serotonin plays a role in producing these alterations.

Risk factors associated with neuroendocrine tumors: A U.S.‐based case–control study

“…Another important finding of this study was the first evidence of a significant association between preexisting diabetes mellitus and gastric carcinoids, particularly among women. The relationship between diabetes and active carcinoid tumors was reported in a study by Feldman et al ,25 who assayed glucose tolerance and insulin secretion in 17 patients with “active” or “inactive” metastatic carcinoid tumors, depending on whether or not carcinoid syndrome was present. The study showed a high incidence of glucose intolerance (80%), elevated serum serotonin and impaired insulin secretion in patients with carcinoid syndrome, suggesting that serotonin plays a role in producing these alterations.…”

Visceral Obesity and Metabolic Syndrome Are Associated with Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors

“…In women with pre-existing T2DM, gastric endocrine tumors (especially T1-GET) and small bowel NETs were found to be increased seven-fold and two-fold, respectively [ 24 ]. Increased prevalence of impaired glucose tolerance in patients with serotonin secreting metastatic NETs when compared to non-secreting tumors was initially reported in 1975 [ 30 ]. Moreover, a recent publication from Valente et al concluded that non-recent diabetes was associated with an increased occurrence of pNETs especially in metastatic disease and an advanced grade [ 31 ].…”

Risk Factors for Pancreatic Neuroendocrine Tumors

“…[11] Other investigators have reported an association between diabetes and the carcinoid syndrome. [11, 18] An association between recent-onset diabetes and pancreatic adenocarcinoma has been observed, which may represent the effect of proteins secreted by the tumor on beta-cell function and insulin resistance. [19] There are several potential explanations for this association.…”