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Trilostane is a competitive inhibitor of the enzyme
3-beta hydroxysteroid dehydrogenase. It works at the level of the adrenal
gland to block the normal steroidogenisis pathway of pregnenolone to progesterone
to cortisol, aldosterone, and androstenedione.
Pituitary dependant hyperadrenocorticism (PDH) is the most common cause of Cushing's disease seen in dogs. It is a disease of middle aged dogs with some breeds having a higher predilection (poodles, dachshunds, Boston terriers, and boxers. Both genders are affected.
Historically mitotane has been the treatment of choice for PDH. Mitotane causes selective necrosis of the zona fasiculata and the zona reticularis of the adrenal cortex. An induction period and a maintenance protocol are required with the use of mitotane and there is a relatively high incidence of side effects. Trilostane appears to have fewer and less severe side effects.
The use of Trilostane for the treatment of PDH has been studied and reported on in the last five years. The results of these studies have been uniformly very positive. Clinical results include a reduction in clinical signs such as polydypsia, polyuria, polyphagia, panting, increased activity level, improved coat quality and skin condition. Treatment with Trilostane resulted in reduction of both cortisol and aldosterone; although the reduction in cortisol was more marked than the reduction in aldosterone.
The dosage of Trilostane may need to be adjusted during the treatment period. Some dogs appear to be quite sensitive to the drug initially and then require a higher maintenance dose. The time required for response to therapy is about a month which is similar to the time required for response to Mitotane. The management and treatment of PDH requires regular monitoring of adreno-cortical hormone levels regardless of the drug used for treatment.
Other conditions where Trilostane has been used successfully
in dogs includes hyperadrenocorticism due to neoplasia and Alopecia X
in Pomeranians and Miniature Poodles.
Pituitary dependant hyperadrenocorticism is rare in
cats. Cats with PDH frequently also have concurrent diabetes mellitus.
Trilostane has been used for the treatment of PDH in cats although the
numbers of animals in the clinical reports are very small and the response
to treatment does not appear to be as successful as in the dog. It should
be noted that insulin requirements do not change in those cats that are
diabetic.
There is one favorable report from Australia on the
use of Trilostane in horses with Equine Cushing's syndrome. The report
was quite favorable regarding clinical improvement, decline in cortisol
levels, and lack of side effects. This is just one study and the work
has not been done comparing Trilostane to the more commonly used Pergolide.
• Trilostane is well tolerated in most dogs. Transient
biochemical abnormalities include mild hyperkalemia, azotemia, hyperbilirubinemia,
and hypercalemia. Clinical side effects are relatively rare but may include
lethargy, vomiting, and initial transient worsening of skin lesions.
• As with any treatment for Cushing's disease,
it is possible to create iatrogenic hypoadrenocorticism, or Addison's
disease. In these cases, Trilostane therapy should be discontinued.
• Concurrent use of potassium sparing diuretics should be avoided
because of potential hyperkalemia.
• No information regarding overdose was found.
Dr.
Barbara Forney is a veterinary practitioner in Chester County, Pennsylvania.
She has a master's degree in animal science from the University of Delaware
and graduated from the University of Pennsylvania School of Veterinary Medicine
in 1982.
She began to develop her interest in client education and medical writing 1997. Recent publications include portions of The Pill Book Guide to Medication for Your Dog and Cat, and most recently Understanding Equine Medications published by the Bloodhorse.
Dr. Forney is an FEI veterinarian and an active member of the AAEP, AVMA, and AMWA.
You can purchase books by Dr. Forney at www.exclusivelyequine.com
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