Effect of trilostane on hormone and serum electrolyte concentrations in dogs with pituitary-dependent hyperadrenocorticism

Abstract

Background: The effects of trilostane on key hormones and electrolytes over 24 hours in dogs with pituitary-dependent hyperadrenocorticism (PDH) are unknown.

Objectives: To determine the plasma concentration of cortisol, endogenous adrenocorticotropic hormone (ACTH), aldosterone, sodium, potassium, and ionized calcium concentrations, and plasma renin activity over a 24-hour period after administration of trilostane to dogs with well-controlled PDH.

Animals: Nine dogs (mean age 9.3 ± 0.67 years, mean weight 31.9 ± 6.4 kg) with confirmed PDH.

Methods: Prospective study. Thirty days after the first administration of trilostane, blood samples were taken at -30, 0 (baseline), 15, 30, 60, and 90 minutes, and 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours after administration of trilostane and plasma concentration of cortisol, endogenous ACTH, aldosterone, sodium, potassium, ionized calcium, and renin activity were determined.

Results: Cortisol concentrations decreased significantly (P < .001) 2-4 hours after trilostane administration. From baseline, there was a significant (P < .001) increase in endogenous ACTH concentrations between hours 3-12, a significant increase (P < .001) in aldosterone concentration between hours 16-20, and a significant (P < .001) increase in renin activity between hours 6-20. Potassium concentration decreased significantly (P < .05) between hours 0.5-2.

Conclusion and clinical importance: Treatment with trilostane did not cause clinically relevant alterations in plasma aldosterone and potassium concentration. Results suggest that in dogs with PDH, the optimal time point for an ACTH-stimulation test to be performed is 2-4 hours after trilostane dosing. Future studies are necessary to establish interpretation criteria for a 2- to 4-hour postpill ACTH-stimulation test.

Keywords: Adrenal gland; Hypercortisolism; Treatment.

Figure 1

Cortisol concentrations in 9 dogs with pituitary‐dependent hypercortisolism on day 30 of treatment with trilostane. The not normally distributed data were initially logarithmized and mean and standard deviation of these values were calculated. For graphical representation, these results were retransformed yielding the geometric mean and dispersion factor (=geometric SD). Positive whiskers indicate geometric mean times dispersion factor, whereas negative whiskers show geometric mean divided by dispersion factor. Asterisks show significant changes from baseline concentrations.

Figure 2

Concentrations of endogenous ACTH in 9 dogs with pituitary‐dependent hypercortisolism on day 30 of treatment with trilostane. For explanation of graphical presentation, see Figure 1.

Figure 3

Aldosterone concentrations in 9 dogs with pituitary‐dependent hypercortisolism on day 30 of treatment with trilostane. For explanation of graphical presentation, see Figure 1.

Figure 4

Plasma renin activity in 9 dogs with pituitary‐dependent hypercortisolism on day 30 of treatment with trilostane. For explanation of graphical presentation, see Figure 1.

Figure 5

Potassium concentrations in 9 dogs with pituitary‐dependent hypercortisolism on day 30 of treatment with trilostane. As data were approximately normal distributed, graphical presentation shows mean results ± SD.