Response to therapy
U.S. importation process of trilostane from the United Kingdom
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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
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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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