Addition of Cabergoline to Trilostane Treatment for Dogs with Pituitary-Dependent Hypercortisolism

Addition of cabergoline to trilostane treatment for dogs with pituitary-dependent hypercortisolism Stefania Golinelli1, Federico Fracassi 1, Álan Gomes Pöppl2, Viviani De Marco3, Diego Daniel Miceli4, Kyoung won Seo5, Edward C. Feldman6 1Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell’Emilia, Italy; 2Department of Animal Medicine, School of Veterinary Medicine, Federal University of Rio Grande do Sul, Rio Grande do Sul, Brazil 3Naya Especialidades, Sao Paulo, Brasil 4Endocrinology Unit, School of Veterinary Medicine, University of Buenos Aires, Faculty of Veterinary Sciences, Buenos Aires, Argentina 5Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 6Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, California Trilostane (T) is usually effective in controlling the hypercortisolemic state in canine pituitary-dependent hypercortisolism (PDH), however, its effect on pituitary tumor (PT) function and growth has not been reported. Cabergoline (C), a dopamine agonist, is a potential “pituitary-targeting” drug. This study aimed to evaluate the addition of cabergoline to trilostane in controlling PDH’s clinical signs and/or blocking growth or even reducing the size of PTs. This prospective, controlled, multicenter study included 25 dogs with PDH (PT height [PTh] 12 mm). Thirteen dogs (TC group; TCg) were treated with T median 0.5 mg/Kg (minimum 0.3-maximum 3.2) and C (23 mcg/Kg q48h) (TC group, TCg) and 12 dogs with only T (T group, Tg) for at least 6 months. Each dog underwent a pituitary CT scan at the beginning (T0) and the end of the study (T180-T365); pituitary/brain ratio (PBr) was calculated from each scan. Each dog was monitored at T30 (days), T60, T120, T180, and T365 with a clinical evaluation (standardized questionnaire, higher scores were associated with worst PDH clinical control), urine specific gravity, cortisol (prepill or ACTH stimulation test) and endogenous ACTH (eACTH) measurement. Results of the questionnaire, USG, eACTH, and PBr were not significantly different between TCg and Tg at any time point. At T0 PTh was significantly higher (P=0.0290) in the TCg versus the Tg. Questionnaire scores were significantly higher (P=0.0101) at T30 versus T365 in the Tg. In the Tg the PTh and the PBr were significantly higher (P=0.0469 and P=0.0445, respectively) at T365 versus T0. In the TCg, PTh was smaller in 4/12  1.2 mm (0.7-4.7); PTh did not show any change in 2/12; PTh increased in 6/12 dogs 1.7 mm (1-4.2); and one dog died before the end of the study. In the Tg, PTh was smaller in 5/12 0.17 mm (0.03-0.3), was not visualized at either T0 or T365 in one, and it increased in 6/12 dogs 2 mm (1-5.7). In TCg the PBr reduced in 4/12 dogs 0.07 (0.01-0.13) and increased in 8/12 dogs 0.08 (0.06-0.43). In the Tg, the PBr reduced in 3/12 0.02 (0.01-0.03), did not show any change in 3/12, and increased in 6/12 dogs 0.15 (0.06-0.35). In conclusion, the combination of trilostane and cabergoline treatment does not improve the control of PDH’s clinical signs in comparison with trilostane treatment alone. However, cabergoline, potentially, plays a role in controlling the PT growth in PDH dogs.