# Trilostane Vetoryl Dosing: Monitoring Cushings Dogs with ACTH Stim


## Key Takeaways

- Trilostane (Vetoryl) is a 3β-HSD inhibitor used to manage pituitary-dependent hyperadrenocorticism (PDH) by reducing cortisol synthesis.
- The ACTH stimulation test (ACTHst) is the gold standard for monitoring trilostane efficacy, assessing adrenal cortisol response post-ACTH administration.
- A therapeutic target post-ACTH cortisol concentration is typically 2.0-7.0 µg/dL (55-200 nmol/L), aiming to suppress cortisol without inducing iatrogenic hypocortisolism.
- Modern dosing protocols favor conservative, low-dose, twice-daily (BID) administration (0.5-2.5 mg/kg BID) for improved safety and efficacy compared to once-daily (SID) dosing.
- Regular monitoring, including ACTHst at 10-14 days, 1, 3, and 6 months, and then every 3-6 months thereafter, is critical for dose titration and early detection of adverse effects like iatrogenic hypoadrenocorticism.
- Compounded trilostane carries a significant risk of inaccurate dosing, with studies showing only 40.9% of packets having acceptable active ingredient strength, necessitating careful consideration and enhanced monitoring if used.

---

If your [dog](/knowledge/veterinary-medicine/clinical-methods/dog) has been diagnosed with pituitary-dependent hyperadrenocorticism (PDH), commonly called Cushing's disease, trilostane (Vetoryl) is likely the prescribed treatment. The cornerstone of safe and effective therapy is not just the dose itself, but the rigorous monitoring protocol that follows, with the ACTH stimulation test (ACTHst) as the primary tool for dose adjustment. This article provides a definitive, source-grounded guide to trilostane dosing and monitoring using the ACTHst.

**Owner-Facing Triage Summary:** Trilostane is a potent medication that lowers cortisol production. The goal of treatment is to control clinical signs without causing dangerous side effects. Monitoring with the ACTH stimulation test is essential because the correct dose varies significantly between dogs and can change over time. Never adjust your dog's trilostane dose without a veterinarian's guidance. If your dog shows signs of weakness, vomiting, diarrhea, or severe lethargy after starting or changing a dose, contact your veterinarian or an emergency clinic immediately, as these can be signs of dangerously low cortisol (hypoadrenocorticism).

## Understanding Trilostane (Vetoryl) and Its Role in Canine Cushing's Disease

Trilostane is a synthetic steroid analogue that acts as a competitive, reversible inhibitor of the 3-beta hydroxysteroid dehydrogenase (3β-HSD) enzyme system [<a href="#ref-1">1</a>]. This enzyme is crucial in the adrenal cortex for the synthesis of cortisol. By inhibiting this step, trilostane effectively reduces the production of cortisol, the primary glucocorticoid responsible for the clinical signs of Cushing's syndrome. It is widely recognized as the current treatment of choice for managing PDH in dogs [<a href="#ref-2">2</a>]. While it can be used for adrenal-dependent hypercortisolism (adrenal tumors), its use is most extensively documented and studied for PDH [<a href="#ref-3">3</a>][<a href="#ref-4">4</a>][<a href="#ref-5">5</a>].

The medication is available under the brand name Vetoryl, and its use has revolutionized the management of a disease that was once difficult to treat. The primary objective of therapy is to control the clinical signs of hypercortisolism (such as excessive thirst, urination, hunger, hair loss, and pot-bellied appearance) while avoiding the adverse effects of iatrogenic hypocortisolism (Addison's disease-like state) [<a href="#ref-2">2</a>][<a href="#ref-4">4</a>].

## The Critical Importance of the ACTH Stimulation Test

The ACTH stimulation test is the standard and most widely recognized method for monitoring trilostane therapy [<a href="#ref-2">2</a>][<a href="#ref-6">6</a>]. It assesses the functional capacity of the adrenal glands to produce cortisol in response to an exogenous challenge of synthetic ACTH (cosyntropin). This test provides a dynamic measurement of how well the trilostane is suppressing cortisol production at the time of testing.

### How the ACTH Stim Test Works
The test involves measuring a baseline (pre-ACTH) cortisol level, followed by the administration of synthetic ACTH (cosyntropin). A second blood sample is taken 1 to 2 hours later to measure the post-ACTH cortisol level. The post-ACTH cortisol concentration is the key value used to determine if the trilostane dose is appropriate, too high, or too low [<a href="#ref-2">2</a>][<a href="#ref-4">4</a>][<a href="#ref-5">5</a>]. A common protocol uses 5 µg/kg of cosyntropin IV, though research has shown that a lower dose of 1 µg/kg may be pharmacodynamically equivalent in dogs being treated for PDH, offering a potential cost-saving alternative [<a href="#ref-7">7</a>].

### Interpreting Post-ACTH Cortisol Results
The goal is to achieve a post-ACTH cortisol concentration within a specific therapeutic target range. While the exact target can vary slightly based on clinician preference and the specific protocol, a widely accepted target range is between 2 and 7 µg/dL (approximately 55 to 200 nmol/L) [<a href="#ref-2">2</a>][<a href="#ref-4">4</a>]. Some protocols, especially those using lower initial doses, may aim for a slightly lower range of 1.5 to 5.4 µg/dL [<a href="#ref-4">4</a>]. The key is that the post-ACTH cortisol should be suppressed from the pre-treatment diagnostic values, indicating adequate adrenal blockade, but not so low as to risk iatrogenic hypocortisolism.

## Trilostane Dosing Protocols: Finding the Right Starting Point

Historically, trilostane was dosed based on bodyweight categories (e.g., <5 kg, 5-20 kg, >20 kg) with fixed doses [<a href="#ref-4">4</a>]. However, current best practice has shifted towards a more conservative, weight-based dosing strategy to minimize the risk of adverse effects.

### Initial Dose Recommendations
The modern approach favors starting with a lower dose. Recommended starting doses typically range from 0.5 to 2.5 mg/kg given twice daily (BID) [<a href="#ref-5">5</a>][<a href="#ref-8">8</a>]. Some protocols even begin with a dose as low as 0.2 to 1.1 mg/kg BID [<a href="#ref-8">8</a>]. This conservative approach is supported by evidence showing that it is effective and reduces the risk of iatrogenic hypocortisolism [<a href="#ref-5">5</a>][<a href="#ref-8">8</a>][<a href="#ref-9">9</a>]. For once-daily (SID) dosing, a starting dose of 2 to 5 mg/kg is often used, but twice-daily dosing is increasingly favored for more consistent control [<a href="#ref-3">3</a>][<a href="#ref-4">4</a>].

### Once Daily vs. Twice Daily Administration
The frequency of administration is a critical decision. Trilostane's duration of effect is relatively short, often less than 12 hours, and in some cases, its cortisol-suppressing effect may not last a full 24 hours [<a href="#ref-10">10</a>]. Studies comparing once-daily (SID) and twice-daily (BID) protocols have provided valuable insights:

- **Faster Control with BID:** Twice-daily administration has been shown to achieve post-ACTH cortisol concentrations within the therapeutic range sooner and in a higher proportion of dogs compared to once-daily dosing [<a href="#ref-3">3</a>][<a href="#ref-11">11</a>].
- **More Consistent Suppression:** BID dosing provides more consistent cortisol suppression throughout the day, avoiding the "escape" period where cortisol levels rise before the next dose [<a href="#ref-3">3</a>][<a href="#ref-10">10</a>].
- **Comparable Total Daily Dose:** Interestingly, the total daily dose of trilostane required to control PDH is often not statistically different between SID and BID protocols, but BID tends to be more effective at controlling clinical signs [<a href="#ref-3">3</a>].
- **Owner Compliance:** While BID may be more effective, it requires a greater commitment from the owner. The choice between SID and BID should be made on a case-by-case basis, considering the dog's response, the owner's schedule, and the specific clinical scenario [<a href="#ref-11">11</a>].

### The Case for Low-Dose, Twice-Daily Therapy
A significant body of evidence supports the use of low-dose, twice-daily trilostane as an initial protocol. Studies have demonstrated that starting with a low dose (0.2 to 1.1 mg/kg BID) is effective in managing clinical signs and is associated with fewer adverse effects [<a href="#ref-5">5</a>][<a href="#ref-8">8</a>][<a href="#ref-9">9</a>]. A study by Feldman (2011) showed that a starting dose of 0.21 to 1.1 mg/kg BID was effective, with many dogs achieving good control without requiring a dose increase [<a href="#ref-9">9</a>]. Furthermore, a 2022 study found that low-dose BID treatment provides a median survival time of 998 days, which is slightly longer than previously reported for other protocols [<a href="#ref-8">8</a>].

## Monitoring Protocol: The Roadmap to the Optimal Dose

Monitoring is not a one-time event but an ongoing process. The goal is to titrate the dose to the lowest effective amount that controls clinical signs and achieves the target post-ACTH cortisol.

### Initial Recheck (10-14 Days)
The first recheck is typically scheduled 10 to 14 days after starting treatment. At this visit, the veterinarian will:
- Perform an ACTH stimulation test 3 to 6 hours after the morning trilostane dose.
- Evaluate clinical signs, particularly drinking, urination, and appetite.
- Assess for any adverse effects.
- Adjust the dose based on the post-ACTH cortisol result and clinical response.

### Subsequent Rechecks (1, 3, and 6 Months)
After the initial adjustment, rechecks are typically scheduled at 1 month, 3 months, and then every 3 to 6 months thereafter. Each recheck involves the same process: ACTHst, clinical assessment, and dose adjustment if needed. The dose may need to be increased or decreased at any of these points [<a href="#ref-4">4</a>][<a href="#ref-12">12</a>]. Some dogs may remain stable for long periods, while others require frequent adjustments.

### Predicting the Required Dose
Research has focused on identifying predictors of the final trilostane dose. A key finding is that the post-ACTH cortisol concentration at the time of diagnosis (cpACTH) is associated with the final dose required. A 2024 study found that dogs with a diagnostic cpACTH of ≥ 27 µg/dL are 96% more likely to need a higher trilostane dosage to achieve satisfactory control [<a href="#ref-2">2</a>]. This information can help veterinarians anticipate which dogs may need more aggressive dose escalation.

## Factors Influencing Trilostane Response and Dosing

Several factors can influence how a dog responds to trilostane, necessitating dose adjustments.

### Poor Responders and Non-Responders
Some dogs do not respond adequately to trilostane therapy. A 2026 study identified variables associated with a poor response [<a href="#ref-12">12</a>]. At diagnosis, dogs that later became non-responders had:
- Higher alanine aminotransferase (ALT) levels.
- Higher endogenous ACTH (eACTH) concentrations.
- Higher pre-ACTH cortisol concentrations.
- A higher frequency of bilateral adrenomegaly (enlargement of both adrenal glands).

These dogs required more rechecks and significantly higher trilostane doses (median 3.25 mg/kg q12h) compared to good responders (median 1.22 mg/kg q12h) [<a href="#ref-12">12</a>].

### Concurrent Diseases: Diabetes Mellitus
Dogs with concurrent Cushing's syndrome and diabetes mellitus (DM) present a unique challenge. The management of one condition directly impacts the other. A 2023 study found that dogs with both conditions required higher final median doses of insulin than dogs with DM alone [<a href="#ref-13">13</a>]. However, the median trilostane requirements in dogs with concurrent CS and DM did not differ from dogs with CS alone [<a href="#ref-13">13</a>]. This suggests that the primary challenge in these cases is managing the insulin resistance, not necessarily increasing the trilostane dose. Another study on diabetic dogs with HAC found that insulin requirements and fructosamine concentrations do not consistently reduce during trilostane treatment, highlighting the complexity of managing these patients [<a href="#ref-14">14</a>].

### Compounded Trilostane: A Cautionary Note
The use of compounded trilostane is a common practice in some regions, but it carries significant risks. A 2021 study analyzed compounded trilostane packets and found that only 40.9% had an acceptable strength of the active ingredient [<a href="#ref-15">15</a>]. This inconsistency can lead to poor clinical control or unexpected toxicity, making monitoring even more critical. If compounding is necessary, a liquid suspension in cod liver oil has been shown to be stable for 60 days in amber glass bottles, but not in plastic [<a href="#ref-16">16</a>]. Clinicians should be aware of these potential issues and consider using the brand-name product (Vetoryl) when possible.

## Adverse Effects and Emergency Management

Trilostane is generally well-tolerated, but adverse effects can occur, particularly if the dose is too high or the dog is sensitive to the drug.

### Recognizing Iatrogenic Hypoadrenocorticism
The most significant adverse effect is iatrogenic hypocortisolism, an Addisonian crisis induced by excessive cortisol suppression. Clinical signs can include:
- Lethargy and weakness.
- Vomiting and diarrhea (or diarrhoea).
- Decreased appetite.
- Collapse or shaking.

These signs can occur at any time but are most common after a dose increase or if the dog is sensitive to the drug [<a href="#ref-17">17</a>][<a href="#ref-4">4</a>]. In a study of dogs that ingested an unintended single dose of trilostane, the most common clinical signs were vomiting (41.5%), lethargy (36.6%), and diarrhea (17.0%) [<a href="#ref-17">17</a>]. The median onset of signs was 2.5 hours after exposure [<a href="#ref-17">17</a>].

### Management of Trilostane Toxicosis
If a dog shows signs of trilostane toxicity, treatment is primarily supportive. In cases of accidental ingestion of another dog's medication, which is the most common cause of trilostane exposure (61.5% of cases), prompt veterinary attention is recommended [<a href="#ref-17">17</a>]. Treatment may include inducing vomiting if ingestion was recent, administering activated charcoal, and providing supportive care such as IV fluids and corticosteroids if clinical signs are severe. Fortunately, severe toxicity requiring veterinary treatment is relatively rare, occurring in only about 1% of exposure cases [<a href="#ref-17">17</a>].

## At a Glance: Trilostane Monitoring Decision Table

| Parameter | Target / Goal | Action |
| :--- | :--- | :--- |
| **Post-ACTH Cortisol** | 2.0 - 7.0 µg/dL (55 - 200 nmol/L) | **Within range:** Continue current dose. <br> **Above range:** Increase dose (typically 10-25%). <br> **Below range:** Decrease dose or temporarily stop, then restart at a lower dose. |
| **Clinical Signs** | Resolution of polyuria, polydipsia, polyphagia, and skin/hair changes. | **Controlled:** Maintain dose. <br> **Uncontrolled:** Re-evaluate with ACTHst; consider dose increase or change in dosing frequency. |
| **Adverse Effects** | None. | **Vomiting, lethargy, diarrhea:** Stop trilostane, contact veterinarian immediately. May require supportive care. |
| **Recheck Schedule** | Initial: 10-14 days. <br> Then: 1, 3, and 6 months, then every 3-6 months. | Adhere to the schedule for consistent monitoring and dose titration. |

## The Importance of Consistent Monitoring and Client Communication

Successful management of Cushing's disease with trilostane is a partnership between the veterinarian and the pet owner. Owners play a vital role in observing their dog's clinical signs and reporting any changes. The veterinarian relies on this information, combined with ACTHst results, to make informed dosing decisions.

The frequency of monitoring can be demanding, but it is essential for preventing both under-treatment (persistent clinical signs) and over-treatment (iatrogenic hypocortisolism). Long-term studies have shown that some dogs treated for more than two years may require a reduction or temporary cessation of the drug due to the development of iatrogenic hypoadrenocorticism [<a href="#ref-18">18</a>]. This underscores the need for lifelong, periodic monitoring.

## Limitations and When to Contact a Veterinarian

This article provides a comprehensive overview of trilostane dosing and monitoring, but it cannot replace individualized veterinary care. The information presented here is educational and is not a substitute for veterinary diagnosis or treatment.

**When to contact a veterinarian immediately:**
- If your dog exhibits any signs of weakness, collapse, severe lethargy, vomiting, or diarrhea after starting trilostane or after a dose change.
- If you accidentally give a double dose of trilostane.
- If your dog ingests another pet's trilostane.
- If you are concerned about any change in your dog's behavior (or behaviour) or condition.

**Breed-Level Limitations:** While certain breeds may be predisposed to Cushing's disease, the response to trilostane and the required dose cannot be predicted based on breed alone. Each dog must be treated and monitored as an individual. The dose is determined by clinical response and ACTHst results, not by breed-specific formulas. Furthermore, the cited studies often have small sample sizes, and their findings may not be directly applicable to every dog. Always discuss the specific risks and benefits of treatment with your veterinarian.

## Frequently Asked Questions

### 1. How often does my dog need an ACTH stimulation test while on trilostane?
The ACTH stimulation test is typically performed 10 to 14 days after starting treatment or changing a dose, then again at 1, 3, and 6 months, and subsequently every 3 to 6 months for long-term monitoring [<a href="#ref-4">4</a>][<a href="#ref-12">12</a>].

### 2. What is the target post-ACTH cortisol level for a dog on trilostane?
The widely accepted target post-ACTH cortisol concentration is between 2 and 7 µg/dL (55 to 200 nmol/L), although some protocols may aim for a slightly lower range [<a href="#ref-2">2</a>][<a href="#ref-4">4</a>].

### 3. Can I give my dog trilostane once a day instead of twice a day?
Yes, once-daily (SID) dosing is an option, but twice-daily (BID) dosing has been shown to achieve faster and more consistent control of clinical signs and post-ACTH cortisol levels [<a href="#ref-3">3</a>][<a href="#ref-11">11</a>]. The choice depends on your dog's individual response and your veterinarian's recommendation.

### 4. What are the signs of a trilostane overdose in dogs?
Signs of trilostane overdose (iatrogenic hypocortisolism) include vomiting, lethargy, diarrhea, decreased appetite, weakness, and in severe cases, collapse [<a href="#ref-17">17</a>][<a href="#ref-4">4</a>]. If you observe these signs, stop the medication and contact your veterinarian immediately.

### 5. My dog is also diabetic. How does trilostane affect insulin requirements?
Dogs with concurrent Cushing's disease and diabetes mellitus often require higher doses of insulin [<a href="#ref-13">13</a>]. However, trilostane requirements are typically similar to dogs with Cushing's disease alone [<a href="#ref-13">13</a>]. Insulin needs can fluctuate, so close monitoring of blood glucose and fructosamine is essential [<a href="#ref-14">14</a>].

### 6. Why does my dog's trilostane dose keep changing?
Dose adjustments are a normal part of trilostane therapy. The dose is titrated based on ACTHst results and clinical response. Some dogs may need increases over time, while others may need decreases due to changing sensitivity to the drug [<a href="#ref-2">2</a>][<a href="#ref-4">4</a>][<a href="#ref-18">18</a>].

### 7. Is it safe to use compounded trilostane instead of Vetoryl?
Compounded trilostane carries a risk of inaccurate dosing. A study found that only 40.9% of compounded packets had an acceptable strength of the drug [<a href="#ref-15">15</a>]. If compounding is necessary, it should be done by a reputable pharmacy, and the dog should be monitored even more closely.

### 8. What should I do if I accidentally miss giving my dog a trilostane dose?
If you miss a dose, give the next scheduled dose at the normal time. Do not give a double dose to make up for the missed one. If you have any concerns, contact your veterinarian for advice.


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<a id="ref-14"></a>[<a href="#ref-14">14</a>] [Retrospective evaluation of the effect of trilostane on insulin requirement and fructosamine concentration in eight diabetic dogs with hyperadrenocorticism.](https://pubmed.ncbi.nlm.nih.gov/21121919/)

<a id="ref-15"></a>[<a href="#ref-15">15</a>] [Evaluation of compounded trilostane packets for dogs with naturally occurring hyperadrenocorticism.](https://pubmed.ncbi.nlm.nih.gov/34114230/)

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