Pheochromocytomas may be difficult to differentiate from adrenocortical tumors in dogs until diagnosis with histopathology is obtained. Fine-needle aspiration biopsy of adrenal masses is an invasive technique, with risk for complications. Measurement of urine catecholamine metabolites necessitates acidification of the urine with hydrochloric acid and associated handling risks. Ideally, a blood marker that reliably can differentiate between catecholamine-producing tumors and adrenocortical tumors, would be preferable. However, direct measurement of plasma catecholamines and their metabolites are less reliable than measurement of urine catecholamine metabolites in dogs. Measurement of serum inhibin concentrations is useful in gonadoectomized dogs only. In human medicine, chromogranin A (CgA) is an established marker for neuroendocrine tumors (NETs). Chromogranin A is stored in secretory granules of neuroendocrine tissues and co-secreted with epinephrine and norepinephrine at sympathetic stimuli. The metabolites of CgA are more stable in plasma than are the catecholamines. The aim of the present study was to measure and compare serum concentrations of the CgA epitopes vasostatin and catestatin in serum collected before surgery from dogs with histologically confirmed catecholamine-producing tumors and dogs with adrenocortical tumors.

Serum samples were collected before surgery from 23 dogs with adrenal tumors and in one dog with an extra-adrenal neuroendocrine tumor. All tumors and their tissue origin were confirmed by histopathology. There were 12 catecholamine-producing tumors (11 pheochromocytomas, 1 extra-adrenal tumor), and 12 adrenocortical tumors. Serum concentrations of vasostatin and catestatin were analyzed by a radioimmunoassay (RIA) that has previously been validated for the use in dogs. Statistical analysis was performed with a non-parametric test using the software R version 3.0.2.

In the dogs with catecholamine-producing tumors, the median serum vasostatin concentration was 0.82 nmol/l (IQ range, 0.52 to 1.60 nmol/l). In the dogs with adrenocortical tumors, the median serum vasostatin concentration was 0.50 nmol/l (IQ range, 0.34 to 0.59 nmol/l). Serum vasostatin concentrations were significantly higher in dogs with catecholamine-producing tumors, than in dogs with adrenocortical tumors (Wilcoxon signed rank test, independent groups, p<0.05). There was no statistically significant difference in serum catestatin concentrations between the two groups.

Based on the results from this study, it can be concluded that the serum CgA epitope vasostatin may be a valuable serum biomarker to differentiate catecholamine-producing tumors from adrenocortical tumors.

Disclosures

Disclosures to report:

The research was financed by a grant from Ture F and Karin Forsbergs Foundation. Dr. Stridsberg developed the method in the department´s laboratory at Uppsala University for research purposes only. For other research purposes Dr. Hanson has received the European Society Endocrinology/Dechra Veterinary Products, travel grant for researchers in veterinary endocrinology, and financial support from the Foundation for Research, Agria Insurance Company, the Swedish Research Council.