Trilostane (Vetoryl®) is an oral enzyme inhibiting drug that blocks the production of several adrenal steroids, including cortisol and aldosterone. In a recent study, 78 dogs with pituitary-dependent hyperadrenocorticism (PDH) were treated with trilostane for up to 3 years. The dose of trilostane was: Dogs < 5 kg, 30 mg q 24h; 5-20 kg, 60 mg q 24h; > 20 kg, 120 mg q 24h. The study's salient findings included:

• LDDS had a sensitivity of 82% in diagnosing PDH.
• ACTH stimulation had a sensitivity of 60% in diagnosing PDH.
• Steroids were not given concurrently.
• Dogs were re-evaluated at 10 days; and 4, 12 and 24 weeks after starting therapy. Clinical signs and ACTH stimulation tests taken 2-4 hours post-trilostane administration were monitored, and the trilostane dose adjusted if necessary.
• Response to treatment: 70% had improvement of polydipsia, polyuria and polyphagia within 4 weeks of starting therapy. There was marked improvement in skin disease within 3 months of treatment in 62% of the dogs. Clinical signs of hyperadrenocorticism were poorly controlled in 8 dogs. Pre- and post-ACTH concentrations decreased significantly 1-3 weeks after commencing treatment. By day 28, 81% of dogs had post-ACTH cortisol concentrations < 9 µg/dL. Dosage adjustment over the treatment period was made in 45% of dogs. In 2 dogs, medication was stopped due to development of hypocortisolemia, and neither dog needed to resume treatment during the 1.8 and 2.7 years followup, respectively. These results suggested self-cure of PDH, unless the original diagnosis was incorrect or a pituitary tumor became infarcted.
• Trilostane was well tolerated. After 3 years, 65% of dogs were still alive. Of those that died, median survival time was 18 months. Seventeen were euthanized and 9 died spontaneously. In comparison, the mean survival time for PDH dogs treated with mitotane (Lysodren®) was 26 months.
• Adverse effects included transient biochemical abnormalities in a few dogs, namely, mild hyperkalemia, azotemia, hyperbilirubinemia, and hypercalcemia. Two dogs died shortly after beginning trilostane therapy and 2 dogs developed iatrogenic Addison's disease.
  
  Trilostane is not licensed for use in the U. S., and can be obtained only from England with a prescription and new drug waiver permit from the FDA. This would enable importation of a 90-day supply of the drug (for more information, see www.arnolds.co.uk). To date, U.S. veterinarians using trilostane are pleased with results and report fewer adverse effects as compared with mitotane. However, the senior U. K. author for the published study still prefers mitotane as she believes it to be more efficacious. Trilostane may be useful for a treatment trial in cases where the diagnosis of Cushing's disease is uncertain. Monitor clinical signs and ACTH stimulation tests at 10 days and then again every 3-6 months.

In a second study, trilostane was given to 11 dogs with PDH at the mean starting dose of 6 mg/kg. The dogs were monitored clinically and by routine blood and urine tests, ACTH stimulation tests, and adrenal gland ultrasonography at 1, 3-4, 6-7, 12-16, and 24-28 weeks after starting therapy. All dogs became more active and had reduced polyuria, polydipsia, and panting. Nine of 10 dogs had reduced polyphagia, and 9 of 11 had improved skin condition. Post-ACTH concentrations decreased within the first week of treatment. Clinical signs resolved in 9 dogs and improved in the other 2 within 6 months of treatment. The adrenal glands increased in size on ultrasonography. One dog was transiently lethargic and one was anorexic. Hyperkalemia was also seen in some dogs and may reflect reduction in aldosterone synthesis. Thus, trilostane treatment was safe and efficacious, and resulted in less common and less severe adverse effects than those typically seen with mitotane treatment. Further evaluation of the safety of trilostane is needed.