Trilostane for Dogs with Cushing's Disease: Dosing, Monitoring, and Best Practices

Cushing's disease (hyperadrenocorticism or hypercortisolism) is one of the most frequently diagnosed endocrine disorders in middle-aged and senior dogs. Managing hypercortisolism requires careful monitoring, especially when trilostane is used as part of a dog's treatment.

As a veterinary professional, you must know that balancing cortisol suppression without triggering iatrogenic hypoadrenocorticism demands accurate initial dosing and strict follow-ups.

This guide covers recent updates on trilostane dosage for dogs, monitoring protocols, and side effects, along with what the published survival data actually says about how long a dog can live on trilostane.

What is Trilostane?

Trilostane is a competitive inhibitor of 3β-hydroxysteroid dehydrogenase. 3β-HSD is the enzyme responsible for converting pregnenolone to progesterone in the adrenal cortex. 

Trilostane is an oral medication used in veterinary medicine primarily to treat Cushing's disease (hypercortisolism) in dogs. It is also occasionally prescribed for cats and horses with similar endocrine disorders.

Primary Uses of Trilostane for Dogs

• Pituitary-Dependent Cushing's: The most common form of canine hypercortisolism. A pituitary tumor signals the adrenal glands to produce excess cortisol. Trilostane is commonly used to manage this condition.
• Adrenal-Dependent Cushing's: A tumor in one of the adrenal glands causes excess cortisol production. Trilostane is also used to manage this form of Cushing's disease.
• Alopecia X: Trilostane is sometimes prescribed off-label to manage hair loss in certain dog breeds, although evidence supporting its use is limited.

Common Brand Names of Trilostane

The most widely known FDA-approved brand name for veterinary trilostane is Vetoryl. It is also commonly compounded by veterinary pharmacies in custom strengths for small or specific doses.

How Trilostane Works: The Pharmacology Behind It

Trilostane temporarily blocks the enzyme 3β hydroxysteroid dehydrogenase (3β HSD) in the adrenal glands that the body uses to make cortisol. This blockage is reversible, so when the medication wears off, the enzyme will start working again.

Trilostane is proven safe and effective in dogs for the treatment of Cushing’s disease (hyperadrenocorticism) and is different from mitotane.

Mitotane, on the other hand, destroys cells in the adrenal gland, and the effect is permanent. Trilostane temporarily blocks an enzyme involved in the production of cortisol. This renders its effects more reversible. Nevertheless, trilostane may suppress cortisol production excessively, resulting in iatrogenic hypoadrenocorticism (Addisonian crisis). Due to this risk, dogs treated with trilostane require regular follow-up monitoring throughout treatment.

Trilostane Dosage for Dogs

The FDA-approved Vetoryl label recommends a starting dose of 2.2 to 6.7 mg/kg once daily, given with food. This wide range reflects the limited capsule sizes available rather than a free dosing choice; the lowest capsule combination that falls within the range for a given body weight should always be selected.

Most veterinarians favor beginning at a lower dose that is given twice a day, particularly for dogs who require more steady cortisol levels throughout the day. Once- or twice-daily administration is determined by clinical response, monitoring results, and by the owner's ability to administer medication twice a day. 

Monitoring Trilostane Therapy: Building a Defensible Protocol

There is no single monitoring protocol that all veterinary endocrinologists agree is superior. The ALIVE project (Aligning Language In Veterinary Endocrinology) frames the goal of treatment simply: improve quality of life, reduce or eliminate clinical signs, and reduce longer-term complications and mortality.

Regardless of the dosing strategy, the ALIVE project's core recommendation is to always interpret lab results alongside the clinical findings rather than chasing a number in isolation.

Routine monitoring helps confirm that the dog is responding well to trilostane and receiving the appropriate dose. It also helps identify excessive cortisol suppression early. Trilostane overdose can cause iatrogenic hypoadrenocorticism (Addisonian crisis) in dogs.

Reexamination During Trilostane Therapy

A widely used framework, summarized in AAHA's review of trilostane monitoring strategies, suggests reexamination at 10 to 14 days after starting or adjusting the dose, another at 30 days, and then reevaluate every 90 days once the patient is well controlled.

The purpose of the first recheck is mainly to rule out oversuppression rather than to increase the dose. At the 30-day recheck, the dose can be increased if clinical signs of hyperadrenocorticism persist, provided lab work confirms the adrenal glands are not already oversuppressed. 

ACTH Stimulation Test

The ACTH stimulation test has traditionally been the most common method of monitoring a dog on trilostane. It is usually carried out 2-5 hours after administering the medicine, depending on the protocol of the laboratory. It determines the ability of the adrenal glands to respond to the given synthetic ACTH and is especially helpful in suspected cases of hypoadrenocorticism (Addison's disease). 

Although it remains widely used, studies have found that ACTH stimulation test results do not always match the dog's clinical response. A dog may have cortisol values within the target range but still show signs of poor disease control, or vice versa. For this reason, test results should always be interpreted together with the dog's clinical signs. If a dog becomes unwell or excessive cortisol suppression is suspected, an ACTH stimulation test remains the preferred method for evaluating adrenal function.

Pre-Trilostane Cortisol Test

Pre-trilostane cortisol measurement is an alternative monitoring method in which a single blood sample is collected immediately before the next scheduled trilostane dose. Research suggests that this approach correlates well with clinical control and may provide a better indication of treatment response than the traditional ACTH stimulation test in clinically stable dogs.

This method is less expensive because it requires only one cortisol measurement and does not require synthetic ACTH. The target pre-trilostane cortisol concentration is generally 40 to 140 nmol/L (1.5 to 5 µg/dL) when the dog is clinically well. If cortisol values fall below the target range or the dog develops signs of cortisol deficiency, additional testing, including an ACTH stimulation test, is recommended. Regardless of the monitoring method used, dose adjustments should always be guided by both cortisol results and the dog's clinical response.

Side Effects of Trilostane for Dogs

The most commonly reported trilostane side effects in dogs are mild and include:

• Decreased appetite
• Vomiting
• Diarrhea
• Lethargy

Mild hyperkalemia may occur because trilostane can reduce aldosterone production, although many dogs maintain normal potassium concentrations. Electrolytes should be monitored during treatment. 

Iatrogenic Hypoadrenocorticism (Addisonian Crisis)

Iatrogenic hypoadrenocorticism (Addisonian crisis) is a condition in which trilostane suppresses cortisol production too much, leaving the body without enough cortisol to function normally. The term "iatrogenic" means the condition is caused by medical treatment rather than occurring naturally.

In dogs receiving trilostane, this can happen if the dose is too high or, less commonly, if the adrenal glands become damaged. Without enough cortisol, the dog may develop the following:

• Profound lethargy
• Vomiting
• Diarrhea
• Collapse

Iatrogenic hypoadrenocorticism should be treated as an emergency requiring immediate discontinuation of trilostane, intravenous fluids, and glucocorticoid supplementation.

Dogs with a suspected Addisonian crisis should receive immediate veterinary care. Treatment generally includes discontinuing trilostane, intravenous fluids, and glucocorticoid therapy as directed by the attending veterinarian. 

Trilostane should be used cautiously in dogs with hepatic or renal dysfunction, following the product labeling and the veterinarian's clinical judgment. 

Reversible Cortisol Suppression vs. Adrenal Necrosis

Most cases of excessive cortisol suppression caused by trilostane are reversible. Since trilostane temporarily blocks cortisol production rather than damaging the adrenal glands, cortisol levels usually return to normal after medication is stopped or the dose is reduced.

A much more rare complication is a necrosis of the adrenal glands (adrenal necrosis), which is “permanent damage” of the adrenal glands. It is rare but can cause chronic adrenal insufficiency. Rare cases of adrenal necrosis have been reported during trilostane treatment, but the mechanisms are unclear. Some authors have suggested the prolonged ACTH stimulation as one possible factor, but this is not confirmed. 

Compounded Trilostane 

Vetoryl is the only FDA-approved trilostane product for dogs. However, compounded trilostane is sometimes prescribed for patients that need doses not available in the commercial capsule strengths, such as very small or very large dogs, or when treatment cost is a concern.

While many compounding pharmacies produce high-quality formulations, the potency and absorption of compounded trilostane can vary between pharmacies. Whenever a compounded product is used, it should be obtained from a reputable pharmacy, and the dog's clinical response and cortisol levels should be monitored just as closely as they would be with the FDA-approved product.

How Long Can a Dog Live on Trilostane?

Published median survival times for dogs with pituitary-dependent hyperadrenocorticism treated with trilostane range from about 549 to 998 days across different studies, roughly 18 months to nearly three years, with an overall figure of 2 to 3 years after diagnosis commonly cited in review literature.

A frequently referenced comparison found that dogs treated with trilostane lived significantly longer than untreated dogs, with median survival not yet reached in the treated group at the two-year mark, compared with a median of 506 days in the untreated group.

Prognostic factors associated with shorter survival include older age at diagnosis, the presence of calcinosis cutis, and a low body condition score, which is a helpful reminder that survival depends on more than the medication alone.

Best Practices for Long-Term Trilostane Management

• Start with the lowest dose appropriate for the patient's weight and the available capsule combination, and titrate from there based on monitoring.
• Maintain a consistent recheck schedule: 10 to 14 days, then 30 days, then every 90 days once the patient is controlled.
• Use the same monitoring test type for a given patient over time so results can be compared meaningfully.
• Educate every owner on the signs of an Addisonian crisis and consider dispensing an emergency glucocorticoid for home use.
• Screen for and manage concurrent disease, including diabetes, renal disease, and hepatic disease, before and during treatment.
• Record body weight at every visit, since dosing is weight-based and weight often shifts as clinical signs resolve.

Conclusion

Ultimately, trilostane (Vetoryl) is a highly effective, FDA-approved medication that safely manages both types of Cushing's disease in dogs by controlling cortisol production.

Although once-daily dosing remains the labeled recommendation, some dogs achieve better clinical control with divided twice-daily dosing after reassessment by the veterinarian. 

The key to success lies in strict follow-up testing at 14 days, 30 days, and every few months to catch any issues before they become dangerous. Always keep a close eye out for side effects like vomiting or extreme weakness, which could signal a serious emergency. With proper veterinary care and regular monitoring, most dogs do incredibly well, living comfortably for another 2 to 3 years after their diagnosis.