Pheochromocytoma with adrenergic biochemical phenotype shows decreased GLP-1 secretion and impaired glucose tolerance

Abstract

Context: Impaired glucose homeostasis is a common finding in pheochromocytoma (PHEO),especially with adrenergic phenotype. The possible contribution of incretin dysfunction todysglycemia in PHEO patients has not been studied.Objective: To compare changes in pancreatic endocrine function and gut hormones' productionduring a liquid meal test before and 1 year after adrenalectomy.Methods: In a prospective study, we included 18 patients with PHEO (13 females) withadrenergic biochemical phenotype. A liquid meal test with predefined isocaloric enteralnutrition was performed to evaluate dynamic changes in pancreatic hormones and incretins.Results: During the meal test, insulin levels were significantly lower before adrenalectomyonly in the early phase of insulin secretion, but changes in area under the curve (AUC) didnot reach statistical significance (AUC = 0.07). Plasma glucagon (AUC < 0.01) and pancreaticpolypeptide levels (AUC < 0.01) were suppressed in comparison with the postoperative state.Impaired response to the meal was found preoperatively for glucagon-like peptide-1 (GLP-1;AUC P < 0.05), but not glucose-dependent insulinotropic polypepide (GIP; AUC P = 0.21). Nosignificant changes in insulin resistance indices were found, except for the homeostatic model assessment-beta index, an indicator of the function of islet ß cells, which negatively correlatedwith plasma metanephrine (R =-0.66, P < 0.01).Conclusions: Our study shows suppression of pancreatic a and ß cell function and impairedGLP-1 secretion during a dynamic meal test in patients with PHEO, which is improved after itssurgical treatment. These data demonstrate a novel and potentially significant interconnectionbetween excessive catecholamine production and the secretion of glucoregulatory hormones.