Trilostane is a synthetic steroid enzyme inhibitor developed to address endocrine imbalances in animals. It works by inhibiting the enzyme 3β-hydroxysteroid dehydrogenase, which plays a role in the production of various steroid hormones, including cortisol. This action makes trilostane a treatment for hyperadrenocorticism, commonly known as Cushing’s disease, a condition characterized by excessive cortisol production primarily in dogs.
Initial Approval and Early Use
Trilostane initially saw use in human medicine for conditions such as Cushing’s syndrome and certain types of breast cancer. Its effectiveness in inhibiting steroid production then led to its introduction into veterinary medicine. During this early period, trilostane was viewed as a promising advancement for managing canine hyperadrenocorticism, offering a new method to control the overproduction of cortisol in dogs.
This medication gained recognition as the first drug approved to treat both pituitary-dependent and adrenal-dependent forms of Cushing’s disease in dogs. Veterinarians and pet owners observed improvements in clinical signs, such as reduced thirst and urination, and a decrease in elevated cortisol levels. The initial positive outcomes fostered optimism for its widespread application in veterinary practices.
The Reasons for Its Withdrawal
Despite its early promise, trilostane faced significant challenges that led to its withdrawal from the U.S. human market in April 1994. The primary reasons for this removal stemmed from inconsistencies in its efficacy and concerns regarding its safety profile. Manufacturing issues contributed to variable potency between different batches of the drug.
Reports indicated that compounded versions of trilostane, prepared by pharmacies, showed considerable variations in the actual drug content, sometimes ranging from 39% to over 150% of the stated amount. This inconsistency made it difficult to administer a reliable and predictable dose, leading to unpredictable patient responses. Furthermore, widespread use revealed adverse side effects, including gastrointestinal upset like vomiting, diarrhea, and decreased appetite, along with lethargy.
More concerning were instances of over-suppression of cortisol production, which could result in hypoadrenocorticism, sometimes referred to as an Addisonian crisis. This condition, where cortisol levels become too low, can be life-threatening if not addressed promptly. The cumulative impact of these issues prompted the FDA to re-evaluate its safety and effectiveness, leading to its market withdrawal.
The Reintroduction and Evolution of Treatment
After its initial withdrawal, trilostane was eventually reintroduced for veterinary use, specifically in dogs. The product, known as Vetoryl, received approval from the U.S. Food and Drug Administration (FDA) in December 2008. This reintroduction was made possible by improvements in manufacturing processes and the implementation of stricter quality control measures, ensuring a more consistent and dependable formulation of the drug.
The approved veterinary product became available in various capsule sizes, including 5, 10, 30, 60, and 120 milligrams, allowing for more precise and individualized dosing. This addressed previous concerns about inconsistent potency and the challenges of accurate administration. Along with the reintroduction came updated guidelines for its use, emphasizing the importance of careful monitoring through regular clinical assessments and blood tests, such as ACTH stimulation tests, to prevent over-suppression of cortisol.
Modern Management of Adrenal Conditions
In current veterinary practice, trilostane (Vetoryl) is widely recognized as the primary medical treatment for canine hyperadrenocorticism. It remains the only FDA-approved medication for both pituitary-dependent and adrenal-dependent forms of Cushing’s disease in dogs. The goal of treatment is to reduce excessive cortisol levels, which helps alleviate clinical signs such as increased thirst, urination, and appetite, ultimately enhancing the dog’s comfort and overall well-being.
Effective management involves accurate diagnosis, individualized dosing, and consistent, ongoing monitoring, often every three to six months. This monitoring includes observing clinical signs and performing blood tests, such as ACTH stimulation tests or pre-pill cortisol levels, to ensure appropriate cortisol suppression without causing a deficiency. While trilostane is the most common approach, other treatment options exist for specific cases, such as surgical removal of adrenal tumors or the use of other medical therapies like mitotane.