How I Treat Cushing's Disease

_Catherine Scott-Moncrieff, VetMB, MS, MA, Diplomate ACVIM & EVCIM

Saturday, January 17 • 2:45-3:35, Gaylord_In the United States, canine pituitary hyperadrenocorticism is most commonly treated medically with mitotane or trilostane. Hypophysectomy, uncommon in the United States, is used in Europe with promising results. Mitotane, a derivative of DDT, is a potent adrenocorticolytic drug administered for 7 to 10 days until water consumption decreases or there is decreased appetite, depression, diarrhea, or vomiting. The initial loading dose is 50 mg/kg per day divided Q 12 H. Repeated adrenocorticotropic-hormone (ACTH)-stimulation tests are performed to monitor therapy, the goal of which is to keep pre- and postcortisol concentrations between 2 and 6 µg/mL. Maintenance therapy (50 mg/kg Q 7-10 days) is begun after this goal is achieved. ACTH tests are monitored 1 month after initial treatment and then every 3 to 4 months. The drug can cause some significant side effects. Oral prednisolone should be available to the owner in cases of medical crisis. Mean survival of dogs in 1 study was 2.2 years. Trilostane is a synthetic, hormonally inactive steroid analog that blocks production of several adrenal steroids, including cortisol and aldosterone. The mean starting dose is 3 mg/kg Q 12 H, which is then decreased or increased on the basis of ACTH-stimulation tests done 4 to 6 hours after drug administration. ACTH-stimulation tests should be done 10, 30, and 90 days after the start of treatment and then 30 days after any dose adjustment. The drug is well tolerated. Median survival comparing mitotane with trilostane was 708 days and 662 days, respectively. Other drugs used to treat hyperadrenocorticism include ketoconazole and L-deprenyl. Ketoconazole does not result in good long-term control, and L-deprenyl has been reported to be effective in fewer than 20% of dogs. Bilateral adrenalectomy is an option in dogs that do not respond to medical therapy.**COMMENTARY:** This presentation highlights the use of trilostane in the medical management of Cushing's syndrome in dogs. Trilostane is a new adrenal enzyme inhibitor that has been shown to be safe and effective in both dogs and cats with either pituitary- or adrenal-dependent hyperadrenocorticism. It is anticipated that trilostane will be available soon in the United States. As many practitioners have not yet had the opportunity to use trilostane, this review nicely summarizes its mechanism of action, dosing, and monitoring guidelines. Trilostane will probably become first-line therapy for most dogs diagnosed with this common endocrine disorder.