Urinary vanillylmandelic acid:creatinine ratio in dogs with pheochromocytoma E.A. Soler Arias a, c, * , R.H. Trigo b , D.D. Miceli a , P.N. Vidal a , M.F. Hernandez Blanco a , V.A. Castillo a a Universidad de Buenos Aires, Facultad de Ciencias Veterinarias, Cátedra de Clínica Médica de Pequeños Animales, Hospital Escuela de Medicina Veterinaria-U. Endocrinología, Av. Chorroarín 280 (1427), Ciudad Autónoma de Buenos Aires, Argentina b Universidad de Buenos Aires, Facultad de Ciencias Veterinarias, Cátedra de patología, Av. San Martín 5285 (1427), Ciudad Autónoma de Buenos Aires, Argentina c Endovett, Endocrinología Veterinaria, 3 de febrero 975 9B (1426), Ciudad Autónoma de Buenos Aires, Argentina article info Article history: Received 29 June 2020 Received in revised form 6 August 2020 Accepted 31 August 2020 Keywords: Adrenal tumor Hypercortisolism Neuroendocrine tumor Paraganglioma Pheochromocytoma Vanillylmandelic acid abstract Pheochromocytoma diagnosis in dogs is challenging because biochemical tests are not always available. In humans, urinary vanillylmandelic acid (VMA) is part of a pheochro- mocytoma biochemical diagnostic profile, whereas its diagnostic accuracy is currently unknown in dogs with pheochromocytoma. Prospectively, VMA was determined by HPLC and expressed as the ratio with respect to urinary creatinine (VMA:C). The diagnostic accuracy of the VMA:C ratio was evaluated by analyzing the receiver operating charac- teristic (ROC) curve in 10 healthy dogs, 8 dogs with pituitary-dependent hypercortisolism, 8 dogs with adrenal-dependent hypercortisolism, and 7 dogs with pheochromocytoma. The pheochromocytoma diagnosis was confirmed by histology and immunohistochemistry in all tumors. The VMA:C ratio was significantly higher in dogs with pheochromocytoma (158 [53.4 to 230.8]  10 3 ) than in dogs with adrenal-dependent hypercortisolism (48.1 [24.3 to 144.9]  10 3 ; P < 0.05), dogs with pituitary-dependent hypercortisolism (37.5 [32 to 47.1]  10 3 ; P < 0.001), and healthy dogs (33.8 [13.3 to 87.9]  10 3 ; P < 0.001). When using a VMA:C ratio >58.2  10 3 for pheochromocytoma diagnosis, a sensitivity of 85.7% and a specificity of 88.4% were obtained. Nevertheless, when using a cut-off ratio of 4 times the median VMA:C ratio determined in healthy dogs, there was no overlap (100% speci- ficity). The area under the ROC curve indicated that the VMA:C ratio test could be used to discriminate between dogs with and without pheochromocytoma, what leads to the conclusion that it is useful for pheochromocytoma diagnosis in dogs. Ó 2020 Elsevier Inc. All rights reserved. 1. Introduction Pheochromocytoma (PCC) is a catecholamine-producing neuroendocrine tumor originated in the chromaffin cells of the adrenal medulla [1]. Its excessive production of cate- cholamines, such as epinephrine or norepinephrine, is, in general, released episodically, causing unspecific but poten- tially fatal clinical signs [2]. Unfortunately, complete blood count, routine serum biochemistry, urinalysis, and imaging studies (eg, magnetic resonance imaging [MRI], computed tomography, and ultrasound) do not provide specific data in diagnosing this entity [3–6]. Currently, plasma and urinary catecholamines (norepinephrine and epinephrine) and metanephrines (normetanephrinednorepinephrine metab- olitedand metanephrinedepinephrine metabolite) are used in PCC diagnosis in dogs [6–9]. Of these tests, the urinary normetanephrine to creatinine ratio has shown superiority in differentiating between PCC, hypercortisolism (HC), and nonadrenal disease [6]. However, because of the limited availability of these biochemical tests, it is not possible to reach a PCC diagnosis in dogs. The cortisol-secreting adrenal * Corresponding author. Tel.: þ54 1138231967; fax: þ54947745104. E-mail address: mveterinario@yahoo.es (E.A. Soler Arias). Contents lists available at ScienceDirect Domestic Animal Endocrinology journal homepage: www.journals.elsevier.com/ domestic-animal-endocrinology 0739-7240/$ – see front matter Ó 2020 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.domaniend.2020.106559 Domestic Animal Endocrinology 74 (2021) 106559