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Trilostane for Veterinary Use
by Barbara Forney, VMD
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. About 85% of dogs with Cushing's Disease have PDH. It is a disease of middle-aged dogs. Some breeds have a higher predilection (Poodles, Dachshunds, Boston Terriers and Boxers). Both genders are affected. The remaining 15% of dogs with hyperadrenocorticism have an adrenocortical neoplasia, adenoma or carcinoma.
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 is a newer, very promising drug to treat both PDH and to treat adrenocortical tumors. It appears to have fewer and less severe side effects than mitotane. Initially, trilostane was thought of as a once a day drug but recent research indicates that a lower dose and increased frequency of dosing may substantially decrease the incidence of side effects. Treatment with trilostane results in reduction of both cortisol and aldosterone; although the reduction in cortisol usually is more marked than the reduction in aldosterone. Clinical response includes a reduction in clinical signs such as polydypsia, polyuria, polyphagia, panting, increased activity level, improved coat quality and skin condition.
The dosage and frequency of administration may need to be adjusted during the treatment period. 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 adrenocortical hormone levels. Urine cortisol to urine creatinine ratio and urine specific gravity may be used to evaluate the treatment response.
Other conditions under which trilostane has been used successfully in dogs includes Alopecia X in Pomeranians and miniature poodles.
Pituitary dependant hyperadrenocorticism is rare in cats. Cats with PDH also frequently have concurrent diabetes mellitus. Trilostane has been used to treat 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 Side Effects
- Trilostane is well tolerated in most dogs. Transient biochemical abnormalities include mild hyperkalemia, azotemia, hyperbilirubinemia and hypercalemia.
- There may be a subset of dogs in which trilostane blocks the synthesis of mineralocorticoids more effectively than gluccocorticoids. This group of dogs is at increased risk for adverse reactions including dehydration, weakness, hyponatremia and hypokalemia.
- Side effects include lethargy, weakness, vomiting, anorexia and diarrhea. Rare fatalities have been reported. The incidence of side effects is higher with once a day dosing.
As with any treatment for Cushing's Disease, it is possible to create iatrogenic Addison's Disease. A case of adrenal necrosis subsequent to trilostane therapy has been reported in the literature.
Concurrent use of potassium sparing diuretics should be avoided because of potential hyperkalemia.
Different animals appear to have different sensitivities to trilostane. Information regarding overdose was not found in the literature but one may expect signs associated with hypoadrenocorticism in an overdose situation. Supportive care with IV fluids, electrolyte balancing and possibly exogenous corticosteroids may be useful in the short term.
About the Author
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 in 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.
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