Science and Technology Production
JVIM - Combined treatment of trilostane and retinoic acid in dogs with Pituitary-Dependent Hypercortisolism
Congreso
Date:
2021Publishing House and Editing Place:
Wiley-BlackwellSummary *
Pituitary-Dependent Hypercortisolism (PDH) is a severe metabolic disorder and represents 80-85% of cases of spontaneous hypercortisolism in dogs. Trilostane is a potent inhibitor of an early stage of adrenal steroidogenesis, but has no therapeutic effects on pituitary tumor. Retinoic acid (RA) inhibits proliferation, invasion and tumor growth, reducing ACTH production and tumor size. The aim of this study was to evaluate the combined effect of trilostane and RA to control hypercortisolism and tumor growth. In this prospective study, 8 dogs with PDH with ?partial response? to trilostane -persistence of clinical signs and biochemical abnormalities- were included. The diagnosis of PDH was made according to: clinical signs, urine cortisol creatinine ratio (UCCR), low-dose dexamethasone suppression test, plasma ACTH, abdominal ultrasound and MRI. Dogs received RA (2 mg/Kg/day) for 6 months, while continuing with trilostane (3-4 mg/Kg/12hrs). The concentrations of ACTH, cortisol, UCCR and routine laboratory were evaluated at the beginning of trilostane treatment, at the beginning of combined treatment of trilostane with RA, and at 3 and 6 months of combined treatment. MRI was performed at the beginning of the combined treatment and at 6 months. Statistical analysis performed by Wilcoxon test, expressed as median and ranges (p<0.05). ACTH concentrations showed significant increases after treatment with trilostane (p<0.01). With the addition of RA, ACTH concentrations were reduced at 3 months (p<0.01), and normalized in 6/8 cases. UCCR was reduced with trilostane (p<0.01), but were further reduced with the combined treatment (p<0.01). The concentrations of cholesterol, triglycerides, ALP and ALT were significantly reduced with trilostane (p<0.01), but were further reduced with the combined treatment (p<0.05). The combination of trilostane and RA achieved a complete clinical remission in 5/8 cases. In dogs that underwent MRI (4/8), a significant reduction in pituitary tumor size was observed at 6 months (p<0.05). No adverse effects were observed during the study. The combined treatment of trilostane with RA is effective to control clinical signs and biochemical abnormalities of PDH. This study suggests that this combination allows optimizing pharmacological treatment of PDH-affected dogs, since it controls not only hypercortisolism, but also the activity and proliferation of pituitary tumor. Information provided by the agent in SIGEVAKey Words
trilostanehyperadrenocorticismCushing´s Diseaseretinoid acid