Improvement of insulin sensitivity after adrenalectomy in patients with pheochromocytoma

Objective: Decreased insulin secretion is considered to be the main cause for pheochromocytoma-associated diabetes mellitus. Data from animal and evidence from clinical studies suggest that catecholamines can induce insulin resistance. However, there is no study investigating the effect of catecholamine excess on insulin resistance in patients with pheochromocytopma by the euglycemic hyperinsulinaemic clamp technique. Research Design and Methods: We characterized the effect of high catecholamine plasma concentrations on glucose metabolism and insulin resistance. Euglycemic hyperinsulinemic clamps were performed in 10 patients with pheochromocytoma with and without diabetes mellitus before and 5 wk after adrenalectomy. Results: In five patients with diabetes mellitus, glucose infusion rate required to maintain euglycemia during the clamp (mean+/-SEM) significantly improved from 27.5+/-6.5 mumol/kg.min before surgery to 44.6+/-12.3 mumol/kg.min 5 wk after adrenalectomy (P<0.05). In five individuals without diabetes, total glucose disposal improved from 105 +/- 13.6 to 130 +/- 11.2 (P<0.05). Improved insulin sensitivity after surgery was confirmed by a decrease of fasting hyperinsulinemia from 210+/-74 pmol/liter (diabetes mellitus) and 69+/-9 pmol/liter (no diabetes) before to 134+/-56 pmol/liter and 54+/-8 after surgery respectively (P<0.01). In three patients, diabetes and hyperinsulinemia were reversed by the surgical removal of the pheochromocytoma. Conclusion: Our data provide evidence that endogenous catecholamine excess in patients with pheochromocytoma can induce or aggravate insulin resistance both in patients with type 2 diabetes and patients with normal glucose tolerance.