Pheochromocytoma With Adrenergic Biochemical Phenotype Shows Decreased GLP-1 Secretion and Impaired Glucose Tolerance

J Clin Endocrinol Metab. 2020 Jun 1;105(6):dgaa154. doi: 10.1210/clinem/dgaa154.


Context: Impaired glucose homeostasis is a common finding in pheochromocytoma (PHEO), especially with adrenergic phenotype. The possible contribution of incretin dysfunction to dysglycemia in PHEO patients has not been studied.

Objective: To compare changes in pancreatic endocrine function and gut hormones' production during a liquid meal test before and 1 year after adrenalectomy.

Methods: In a prospective study, we included 18 patients with PHEO (13 females) with adrenergic biochemical phenotype. A liquid meal test with predefined isocaloric enteral nutrition was performed to evaluate dynamic changes in pancreatic hormones and incretins.

Results: During the meal test, insulin levels were significantly lower before adrenalectomy only in the early phase of insulin secretion, but changes in area under the curve (AUC) did not reach statistical significance (AUC = 0.07). Plasma glucagon (AUC < 0.01) and pancreatic polypeptide 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). No significant changes in insulin resistance indices were found, except for the homeostatic model assessment-beta index, an indicator of the function of islet β cells, which negatively correlated with plasma metanephrine (R = -0.66, P < 0.01).

Conclusions: Our study shows suppression of pancreatic α and β cell function and impaired GLP-1 secretion during a dynamic meal test in patients with PHEO, which is improved after its surgical treatment. These data demonstrate a novel and potentially significant interconnection between excessive catecholamine production and the secretion of glucoregulatory hormones.

Keywords: glucagon; incretins; insulin; meal test; pheochromocytoma; secondary diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms / complications*
  • Adrenergic Agents / adverse effects*
  • Adult
  • Aged
  • Biomarkers / metabolism*
  • Blood Glucose / analysis
  • Female
  • Follow-Up Studies
  • Gastrointestinal Hormones / metabolism
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucose Intolerance / etiology*
  • Glucose Intolerance / metabolism
  • Glucose Intolerance / pathology
  • Humans
  • Incretins / adverse effects
  • Male
  • Meals
  • Middle Aged
  • Pancreatic Hormones / metabolism
  • Phenotype
  • Pheochromocytoma / complications*
  • Prognosis
  • Prospective Studies


  • Adrenergic Agents
  • Biomarkers
  • Blood Glucose
  • Gastrointestinal Hormones
  • Incretins
  • Pancreatic Hormones
  • Glucagon-Like Peptide 1