Plasma‐Free Metanephrine and Free Normetanephrine Measurement for the Diagnosis of Pheochromocytoma in Dogs

Abstract

Measurement of plasma-free metanephrines is the test of choice to identify pheochromocytoma in human patients. To establish the sensitivity and specificity of plasma-free metanephrine (fMN) and free normetanephrine (fNMN) concentrations to diagnose pheochromocytoma in dogs. Forty-five client-owned dogs (8 dogs with pheochromocytoma, 11 dogs with adrenocortical tumors, 15 dogs with nonadrenal disease, and 11 healthy dogs.) A prospective study. EDTA plasma was collected from diseased and healthy dogs and submitted for fMN and fNMN measurement by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Free MN concentration (median [range]) was significantly higher in dogs with pheochromocytoma (8.15 [1.73-175.23] nmol/L) than in healthy dogs (0.95 [0.68-3.08] nmol/L; P < .01) and dogs with adrenocortical tumors (0.92 [0.25-2.51] nmol/L; P < .001), but was not different from dogs with nonadrenal disease (1.91 [0.41-6.57] nmol/L; P ≥ .05). Free NMN concentration was significantly higher in dogs with pheochromocytoma (63.89 [10.19-190.31] nmol/L) than in healthy dogs (2.54 [1.59-4.17] nmol/L; P < .001), dogs with nonadrenal disease (3.30 [1.30-10.10] nmol/L; P < .001), and dogs with adrenocortical tumors (2.96 [1.92-5.01] nmol/L); P < 0.01). When used to diagnose pheochromocytoma, a fMN concentration of 4.18 nmol/L had a sensitivity of 62.5% and specificity of 97.3%, and a fNMN concentration of 5.52 nmol/L had a sensitivity of 100% and specificity of 97.6%. Plasma fNMN concentration has excellent sensitivity and specificity for the diagnosis of pheochromocytoma in dogs, whereas fMN concentration has moderate sensitivity and excellent specificity. Measurement of plasma-free metanephrines provides an effective, noninvasive, means of identifying dogs with pheochromocytoma.