Adrenal steroid profiles measured by liquid chromatography-mass spectrometry in dogs with primary hypoadrenocorticism and healthy controls

Background Primary hypoadrenocorticism (pHA) in dogs typically results from immune-mediated destruction of the adrenal cortex, causing glucocorticoid and mineralocorticoid deficiencies. Whether broader alterations in adrenal steroidogenesis, particularly within the androgen axis, also occur has not been systematically investigated. The aim of this study was to describe adrenal steroid profiles in dogs with pHA using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and to compare them with those of healthy control dogs, stratified by sex and reproductive status. Serum samples from 43 dogs with hyponatremic, hyperkalemic pHA (either newly diagnosed and untreated, or receiving prednisolone and desoxycorticosterone pivalate [DOCP]) and 35 healthy control dogs were analyzed. Fourteen steroids, including common precursors, mineralocorticoids, glucocorticoids, and androgens, were quantified by LC-MS/MS. Gonadectomized dogs formed the primary study population; intact dogs were evaluated separately. Results Cortisol, 11-deoxycortisol, corticosterone, and cortisone concentrations were significantly lower in dogs with pHA than in healthy controls, consistent with primary adrenocortical failure. Beyond these expected findings, several unanticipated alterations were identified. Progesterone and 21-deoxycortisol concentrations were higher, and 17α-hydroxyprogesterone and androstenedione concentrations were lower in dogs with pHA than in healthy controls. Dihydrotestosterone concentrations showed a divergent pattern, being lower in newly diagnosed dogs and higher in treated dogs compared with healthy controls. 11-deoxycorticosterone concentrations were markedly increased in DOCP-treated dogs and correlated positively with DOCP dosage, consistent with a treatment-related effect. Dehydroepiandrosterone and dehydroepiandrosterone sulfate were below the limit of quantification in most dogs, precluding firm conclusions. Several steroids differed according to sex or gonadal status, underlining the importance of these factors in the interpretation of canine steroid profiles. Conclusions Dogs with pHA show not only reduced glucocorticoid- and mineralocorticoid-related steroids, but also distinct alterations in steroid intermediates and androgens. The alterations within the androgen axis are complex and do not support a simple uniform androgen deficiency pattern. These findings support the concept of a global disruption of adrenal steroidogenesis in canine pHA and suggest a possible application of LC-MS/MS-based multisteroid profiling for characterizing physiological and pathophysiological aspects of adrenal steroidogenesis in this disease.