Dehydroepiandrosterone sulfate as a potential biomarker for assessing the etiology of canine naturally occurring Cushing’s syndrome

Canine naturally occurring Cushing's syndrome (CS) is usually caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a functional adrenocortical tumor (adrenal-dependent hypercortisolism; ADH). Although endogenous adrenocorticotropic hormone (eACTH) measurement combined with imaging tests is one of the most reliable methods for differentiating PDH from ADH, it has some limitations. In humans, dehydroepiandrosterone sulfate (DHEAS) levels may help determine CS etiology. This study aimed to assess the role of DHEAS concentrations in differentiating PDH from ADH in dogs and correlate DHEAS and eACTH concentrations. A multicenter, retrospective, cross-sectional study was conducted, including dogs diagnosed with CS. They were divided into groups according to suspected CS etiology, sex and neutered status. A total of 38 dogs were included; 33/38 (87 %) were classified as having PDH and 5/38 (13 %) ADH. There were 19 females and 19 males, of which 16 and 9 were neutered, respectively. Median DHEAS concentrations were significantly higher in intact males (2.45 ng/mL; interquartile range 1.02-7.80 ng/mL) than in neutered males (0.68 ng/mL; interquartile range 0.42-2.03 ng/mL; p = 0.017). Females showed a positive correlation between DHEAS and eACTH levels (r = 0.588; p = 0.008). There were no significant differences in DHEAS concentrations between PDH and ADH (p = 0.645). Moreover, ROC curve analysis demonstrated poor ability of DHEAS to differentiate PDH from ADH (AUC 0.430). In conclusion, DHEAS does not appear to be a relevant biomarker for determining CS etiology in dogs and ACTH may not be a major driver for its synthesis.