Urinary Catecholamine and Metanephrine to Creatinine Ratios in Dogs with Pheochromocytoma
Pheochromocytomas (PHEO) are neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia. In people diagnosis crucially depends on biochemical evidence of production of the secretory product of the tumor. Widely used biochemical tests include measurements of urinary catecholamines and its metabolites. In veterinary medicine biochemical testing is difficult to perform due to limited availability of techniques and lack of established reference ranges, and PHEO is most commonly identified as an incidental finding at necropsy. Measurement of urine catecholamine concentrations has been documented only in one dog with PHEO, however results were inconclusive. Recently, we reported on catecholamine- and metanephrine:creatinine (crea) ratios of spot urine samples in healthy dogs. The purpose of this study is to evaluate the biochemical diagnosis of PHEO in 6 dogs with histologically confirmed disease.
Between October 2004 and July 2007, all dogs with ultrasonographic evidence of adrenal gland enlargement and clinical suspicion of PHEO were enrolled into the study. The final criterion for inclusion was histopathological confirmation. 10 healthy client-owned dogs served as controls. During the study period 11 client-owned dogs were evaluated and histopathology confirming PHEO was available in 6/11 dog. Urine sampling procedures varied in dogs with PHEO. In one dog, urine was collected by the owner on day 7 (d7) after discharge from the hospital. In five dogs urine was collected during the initial work-up. Additional urine specimens were sampled in two dogs on day 2 (d2), resp. on days 6 (d6) and 7 (d7) after discharge by their owners. Results were compared to timely corresponding values from 10 healthy dogs collected in a veterinary hospital (t0), and 1 resp. 7 days later at home (t1, t7). Urinary free catecholamines comprising epinephrine, norepinephrine, and dopamine and urinary fractionated metanephrines comprising free and conjugated metanephrine and normetanephrine were separated and quantitatively determined by high pressure liquid chromatography with electrochemical detection using commercial reagents (BIO-RAD,Munich, Germany). Values were expressed as ratios to crea (nM:mM).
Normetanephrine:crea ratios were consistently increased compared to controls, ranging from 103 to 6430 (t0: 14-91; median 59.5, t1: 32-100; median 57.5, and t7: 21-79; median 55).
Four dogs had increases well above (414; resp. 243 on d2, 476, 925, and 6430 (d7)) even the highest results of healthy dogs at t0, whereas 2 dogs showed only smaller increases: (161) and (157 resp. 103 on d6, and 131 on d7). Highest normetanephrine : crea ratios were found in bilateral PHEO (2/6). All other ratios showed more overlap.
In conclusion, urinary normetanephrine:crea ratios are useful in diagnosing canine PHEO. In view of our first results these patients should ideally have their urine samples collected in their home environment. Results in one dog suggest that documentation of smaller but persistently increased normetanephrine:crea ratios on repeated measurements can further substantiate the diagnosis.