cosyntropin and trilostane

Lowering the cosyntropin dose needed for ACTH stimulation would make the test more economical.. To compare the cortisol response to 1 and 5 μg/kg cosyntropin IV in dogs being screened for hyperadrenocorticism (HAC) and in dogs receiving trilostane or mitotane for pituitary-dependent HAC.. Healthy dogs (n = 10); client-owned dogs suspected of having HAC (n = 39) or being treated for pituitary-dependent HAC with mitotane (n = 12) or trilostane (n = 15).. In this prospective study, healthy dogs had consecutive ACTH stimulation tests to ensure 2 tests could be performed in sequence. For the first test, cosyntropin (1 μg/kg IV) was administered; the second test was initiated 4 hours after the start of the first (5 μg/kg cosyntropin IV). Dogs suspected of having HAC or being treated with mitotane were tested as the healthy dogs. Dogs receiving trilostane treatment were tested on consecutive days at the same time post pill using the low dose on day 1.. In dogs being treated with mitotane or trilostane, the 2 doses were pharmacodynamically equivalent (90% confidence interval, 85.1-108.2%; P = 0.014). However, in dogs suspected of having HAC, the doses were not pharmacodynamically equivalent (90% confidence interval, 73.2-92.8%; P = 0.37); furthermore, in 23% of the dogs, clinical interpretation of test results was different between the doses.. For dogs suspected of having HAC, 5 μg/kg cosyntropin IV is still recommended for ACTH stimulation testing. For dogs receiving mitotane or trilostane treatment, a dose of 1 μg/kg cosyntropin IV can be used.

Topics: Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Animals; Antineoplastic Agents; Case-Control Studies; Cosyntropin; Dihydrotestosterone; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Female; Hormones; Hydrocortisone; Male; Mitotane

The acute activation of adrenal glucocorticoid synthesis by ACTH has long been believed to be mediated by cAMP as the major second messenger, although increases in cellular cAMP concentration have not been observed at low concentrations of ACTH. We found that steroidogenesis in bovine adrenal fasciculata-reticularis cells was activated by the addition of arachidonic acid or its 15-lipoxygenase metabolite, 15-hydroperoxyeicosatetraenoic acid. The cellular 15-lipoxygenase pathway was significantly activated by 1 pM ACTH, at which concentration no increase in cellular cAMP synthesis was observed. The 1 pM ACTH-induced stimulation of steroidogenesis was completely suppressed by a lipoxygenase inhibitor, AA-861. The stimulation was independent of the increase in cellular cAMP. These results show that the action of 1 pM ACTH on steroidogenesis may be mediated by the 15-lipoxygenase metabolite(s) as a solo second messenger. The addition of ACTH at concentrations higher than 10 pM increased both the 15-lipoxygenase activity and cellular cAMP synthesis. Under these conditions, the 15-lipoxygenase metabolite(s) and cAMP were shown to mediate the activation of steroidogenesis synergistically. The presence of a dual second messenger system could explain the stimulation of steroidogenesis by ACTH at physiological concentrations.

Topics: Animals; Arachidonate 15-Lipoxygenase; Arachidonic Acids; Benzoquinones; Bucladesine; Cattle; Cells, Cultured; Cosyntropin; Cyclic AMP; Dihydrotestosterone; Enzyme Inhibitors; Indomethacin; Isoquinolines; Kinetics; Leukotrienes; Lipid Peroxides; Lipoxygenase Inhibitors; Masoprocol; Pregnenolone; Sulfonamides; Tetrahydronaphthalenes; Zona Fasciculata; Zona Reticularis