Trilostane: A therapeutic consideration for canine hyperadrenocorticism - Veterinary Medicine
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Trilostane: A therapeutic consideration for canine hyperadrenocorticism
Choices in medical therapy for dogs with hyperadrenocorticism can be limited. Studies have shown that trilostane provides another option for treating this disease—as well as alopecia X.


Response to therapy

U.S. importation process of trilostane from the United Kingdom
More than 85% of dogs have shown both clinical and biochemical improvement (decreased alkaline phosphatase activity and cholesterol concentration) after a month of trilostane therapy, with substantial improvements in post-ACTH stimulation cortisol concentrations.7,11,13 Survival times for patients treated with trilostane (662 to 930 days14,15 ) compare favorably with those receiving mitotane (708 days).15

Adverse effects

Reports indicate that trilostane is generally safe and effective, but complications can occur.11 The most common is transient hypocortisolemia, which manifests as anorexia and lethargy. Clients must be instructed to discontinue trilostane if such signs occur, and an ACTH stimulation test and serum electrolyte panel should be performed. The drug should be restarted with a 50% dose reduction when the patient is again eating and active.

A case example of trilostane treatment for canine PDH
Although trilostane seems to preferentially inhibit cortisol synthesis, aldosterone production can also be compromised.7 If this occurs, serum electrolyte abnormalities are evident (hyponatremia, hyperkalemia), and the patient may appear dehydrated and weak. Once again, discontinuing therapy should be curative, but any patient showing substantial compromise may need fluid support.

Rarely, trilostane has been associated with acute adrenal gland necrosis.16,17 The mechanism for this is not understood, as the drug is not expected to be cytotoxic. It is possible that complete shutdown of steroid hormone synthesis is somehow injurious to cell metabolism. This rare event does not appear to be dose-dependent because it may occur when therapy is first started or after several months.16,17 It is essential to promptly identify this syndrome and start appropriate treatment (fluid therapy, glucocorticoids, and mineralocorticoids). This complication is permanent and irreversible, and lifelong supplementation of both mineralocorticoids and glucocorticoids will be necessary.

Switching from another therapy

If a patient receiving mitotane, ketoconazole, or selegiline is poorly controlled or adverse effects are noted, a switch to trilostane is appropriate. To minimize complications, I recommend stopping the previous medication for two weeks, so that clinical signs of hyperadrenocorticism are evident before starting trilostane. In addition, an ACTH stimulation test should be done to confirm exaggerated adrenal gland function.

Treating adrenocortical tumors

Historically, functional adrenal tumors are resistant to medical therapy.18 High doses of mitotane may be required to reduce hypercortisolemia, and some patients show no response at all.18 It should be noted, however, that mitotane may have a direct cytotoxic effect on neoplastic adrenal tissue, independent of its ability to effectively control cortisol production.19 Ketoconazole may control clinical signs in up to 30% of dogs, but side effects are commonly reported.20

In contrast, trilostane has been demonstrated to control the clinical signs of hyperadrenocorticism in dogs with adrenocortical tumors, even in dogs with distant metastases.21,22 The drug will not slow tumor growth, but it can control clinical signs and improve patient well-being.21,22

In dogs with operable adrenal tumors, surgical morbidity from infection and thromboembolism may be mitigated by pretreatment with trilostane, although this has not been evaluated systematically.10 I recommend a two-week course at the standard dose, with an ACTH stimulation test performed at day 10. I also recommend that trilostane be discontinued 24 hours before surgery, at which time the usual perioperative management for anticipated hypocortisolemia becomes necessary.


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