24 hour hormone and serum electrolyte levels of dogs with pituitary-dependent hyperadrenocorticism treated with trilostane

摘要

Ten dogs with PDH took part in this study. After confirming the diagnosis, treatment with once daily trilostane was started. On their 10th and 30th day of therapy, the dogs were controlled clinically and an ACTH stimulation test was performed 3 to 4 hours after trilostane dosing. On the 30th day of therapy, the dogs were hospitalized and over 24 hours, blood samples were taken for the measurement of trilostane, ketotrilostane, endogenous ACTH, cortisol, aldosterone, renin and serum electrolytes.On the 10th and 30th day of therapy, clinical improvement was good in all but one dog. Laboratory findings including the ACTH stimulation test results had generally improved on the 30th day of therapy, although some of the parameters still were not within the reference range. None of the patients showed any adverse effects. Nevertheless, on the 30th day of therapy, one of the dogs collapsed suddenly and, although regenerating quickly, was removed from further blood sampling.Trilostane absorption was quick and ketotrilostane was formed immediately. For both substances, peak concentrations were reached 1.5 to 3 (4) hours after trilostane administration. Accordingly, lowest serum cortisol and aldosterone levels were found at nearly the same time points. Although cortisol and aldosterone levels were very low in all dogs, none showed any adverse effects. Because the negative feedback mechanism caused by high cortisol levels was removed, all dogs showed highest endogenous ACTH levels 4 to 8 hours after trilostane dosing. At all time points, all dogs had endogenous ACTH levels well above the reference range. Because there was quite marked inter-individual variation over the 24 hours and in some dogs changes in endogenous ACTH levels were only minimal, its measurement is most likely not useful for the evaluation of therapeutical success of trilostane.Serum renin activity remained rather unchanged during the day. While changes in serum sodium and calcium were insignificant, serum potassium showed some astonishing development: At times when aldosterone was at its lowest concentration and high potassium levels would be expected, potassium levels were low, but nevertheless well inside the reference range. An aldosterone-like effect of trilostane or of accumulating steroid precursors seems possible, although further studies are necessary to verify these hypotheses. This may be one of the reasons why trilostane is more secure in the treatment of PDH than lysodren.