One of the most common endocrine disorders of middle-aged and older dogs, hyperadrenocorticism, is primarily pituitary-dependent (PDH). Currently, the most common therapy for PDH is mitotane. Although mitotane has fairly good efficacy, side effects and other disadvantages are possible. A promising new drug is trilostane, a competitive inhibitor of b-hydroxysteroid dehydrogenase that processes the conversion of pregnenolone to progesterone in the adrenal gland. This study was designed to determine the efficacy and toxicity of twice-daily dosing of trilostane in dogs with PDH and to evaluate the long-term effects. Initially, dogs were dosed as follows: dogs weighing less than 5 kg were given 15 mg PO Q 12 H, dogs weighing 5 to 20 kg were give 30 mg PO Q 12 H, dogs weighing 20 to 40 kg received 60 mg PO in the morning and 30 mg PO in the evening, and dogs weighing more than 40 kg received 60 mg PO Q 12 hours. The dogs were reevaluated at 7 days and at 1, 3, and 6 months after initiation of treatment and every 6 months thereafter. At the first evaluation, an adrenocorticotropin hormone stimulation test was performed 4 to 6 hours after administration of trilostane. Overall, the dogs did well and had a mean survival time of 930 days; however, because some dogs are still alive, final survival days cannot be calculated. In previous studies, dogs treated with trilostane once a day had a mean survival of 540 days and dogs treated with mitotane survived 803 days.
COMMENTARY: Although twice-daily dosing may not be as convenient for the owner, the lower overall doses and longer survival were certainly a benefit. Since about 25% of the treated dogs had at least one episode of hypoadrenocorticism, it is advisable to examine patients every 3 to 6 months, even when they appear clinically normal.
Long-term efficacy of trilostane administered twice daily in dogs with pituitary-dependent hyperadrenocorticism. Alenza DP, Arenas C, Lopez ML, Melian C. JAAHA 42:269-276, 2006.