Severe insulin-requiring diabetes in a noradrenergic giant pheochromocytoma: a secretory-metabolic phenotype paradox

Pheochromocytoma is a rare catecholamine-secreting neuroendocrine tumor associated with hypertension and dysglycemia in 20% to 40% of cases. Insulin-requiring diabetes has been reported in tumors with an adrenergic profile, owing to epinephrine-mediated inhibition of β-cell secretion. A 37-year-old man with a normal body mass index and an 18-year history of insulin-requiring diabetes and hypertension was found to have a right adrenal mass measuring 10.1 × 8.0 × 6.7 cm. Biochemical evaluation showed a noradrenergic profile, with urinary normetanephrine greater than 5000 μg/24 hours (SI: >26 400 nmol/day; reference range, 70-538 μg/24 hours [SI: 370-2841 nmol/day]) and normal urinary metanephrine. Right adrenalectomy and histopathology confirmed an intra-adrenal pheochromocytoma. After surgery, insulin was discontinued, and glycated hemoglobin remained below 6.1% (SI: 41-43 mmol/mol) without therapy. A preoperative insulin requirement of 0.83 units/kg/day, normal C-peptide, and negative glutamic acid decarboxylase antibodies supported a mixed and reversible mechanism involving catecholamine-induced insulin resistance and β-cell suppression. Severe postoperative hypoglycemia was attributed to reversal of catecholamine excess. This case challenges the association of severe diabetes with adrenergic pheochromocytomas and suggests that catecholamine burden and exposure duration may be more important determinants of metabolic severity than secretory profile alone, after prolonged exposure to high catecholamine concentrations.