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

Abstract

Background: Measurement of plasma-free metanephrines is the test of choice to identify pheochromocytoma in human patients.Objectives: To establish the sensitivity and specificity of plasma-free metanephrine (fMN) and free normetanephrine (fNMN) concentrations to diagnose pheochromocytoma in dogs.Animals: Forty-five client-owned dogs (8 dogs with pheochromocytoma, 11 dogs with adrenocortical tumors, 15 dogs with nonadrenal disease, and 11 healthy dogs.)Methods: 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).Results .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%.Conclusions and Clinical Importance: 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.

Clinical features, outcome and prognostic factors in dogs diagnosed with non‐cortisol‐secreting adrenal tumours without adrenalectomy: 20 cases (1994–2009)

“…When clinical signs are observed, they result from the excessive secretion of catecholamines; some of these clinical signs are depression, panting, weakness, tachycardia and polyuria/polydipsia (Quante and others 2010). These tumours can be diagnosed by measuring the urinary catecholamines and metanephrines to creatinine ratios, or measuring plasma-free normetanephrine, although some of these tests lack the adequate sensitivity and specificity, are not widely available for clinicians or validated for its use in dogs (Quante and others 2010, Gostelow and others 2013). …”

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of inoperable, metastatic, or recurrent canine pheochromocytomas: 5 dogs (2014–2017)

“…Only dogs with complete records regarding signalment, history, initial complaint, physical examination findings, abdominal and thoracic imaging, treatment with toceranib for at least 10 weeks, and with adequate follow-up including records of side effects, were included in the study. The diagnosis of a PC was based on histopathology of the surgically removed tumor, or suspicion of a PC based on elevated plasma or urine metanephrine or normetanephrine levels as previously described [3, 23–27]. …”

“…Pheochromocytomas overproduce catecholamines, specifically epinephrine and norepinephrine, in an episodic manner, leading to intermittent clinical signs, including weakness, collapse, hypertension, panting, polyuria and polydipsia, and decreased appetite [1, 2]. Pheochromocytomas are uncommon in the dog, but must be considered malignant as severe consequences including invasion into the caudal vena cava, retroperitoneal hemorrhage, and metastatic spread can occur [2, 3]. …”

“…However, anesthesia and surgical removal of an adrenal tumor is a high-risk procedure, carrying an overall 51% postoperative complication rate, which increases to 60% in dogs with PC [4]. These complications can include significant blood pressure variations, tachyarrhythmias, intraoperative hemorrhage, and intraoperative death [3, 4]. Vascular invasion into the caudal vena cava, reported in up to 82% of cases, [4, 5] complicates the surgical approach, but the impact on survival in these cases is unclear [4–6].…”

Pheochromocytoma and Multiple Endocrine Neoplasia

“…During the last few years, a small number of studies has investigated urinary and/or plasma catecholamines and metanephrines (Kook et al, 2007;Cameron et al, 2010;Quante et al, 2010;Salesov et al, 2012;Gostelow et al, 2013). Until recently, biochemical testing for pheochromocytoma had only infrequently been performed in dogs due to low medical awareness of pheochromocytoma, limited availability of techniques, lack of reference ranges, and problems with 24-hour urine collection with regard to the urine test.…”