Trilostane for Cushing's Disease in Dogs: Treatment Guide for Owners
Complete guide to trilostane for Cushing's disease in dogs — dosing, costs, side effects, monitoring schedules, and what to expect from treatment.
What Is Cushing's Disease in Dogs?
Cushing's disease — medically known as hyperadrenocorticism (HAC) — occurs when a dog's body produces excessive cortisol, the stress hormone. In roughly 80-85% of cases, the root cause is a benign tumor on the pituitary gland (pituitary-dependent hyperadrenocorticism, or PDH). The remaining 15-20% stem from tumors on one or both adrenal glands (adrenal-dependent hyperadrenocorticism, or ADH). A third form, iatrogenic Cushing's, results from long-term steroid medication use.
According to the Merck Veterinary Manual, Cushing's disease affects approximately 1 to 2 per 1,000 dogs, making it one of the more common endocrine disorders in middle-aged and older dogs. Without treatment, elevated cortisol progressively damages organs — leading to diabetes, kidney disease, hypertension, and increased infection susceptibility.
Trilostane (brand name Vetoryl®) is the only FDA-approved medication for treating both pituitary-dependent and adrenal-dependent Cushing's disease in dogs. It works by inhibiting the enzyme 3-beta-hydroxysteroid dehydrogenase in the adrenal glands, effectively blocking cortisol production at its source.
FDA Approval: 2008 (first and only approved drug for canine HAC)
Drug Class: Competitive inhibitor of 3β-HSD enzyme
Form: Hard gelatin capsules (10 mg, 30 mg, 60 mg, 120 mg)
Prescription Required: Yes
Administration: Oral, once or twice daily with food
Always consult your veterinarian before starting, adjusting, or stopping any medication for your dog.
Symptoms of Cushing's Disease: Early Warning Signs vs. Advanced Stages
Cushing's disease develops gradually, often over months or even years. Many owners dismiss early symptoms as normal aging. Recognizing the progression pattern is critical for timely intervention.
| Category | Early Warning Signs (Months 1–6) | Advanced Symptoms (6+ Months Untreated) |
|---|---|---|
| Appetite & Thirst | Increased water consumption (polydipsia), slightly increased appetite | Extreme thirst — drinking 2-10x normal volume; ravenous, food-obsessed behavior; stealing food |
| Urination | More frequent potty breaks, occasional indoor accidents | House-training regression, large urine volumes, potential urinary tract infections |
| Coat & Skin | Slightly thinning hair along flanks and back | Bilateral symmetric alopecia (hair loss); thin, fragile skin; dark hyperpigmented patches; calcinosis cutis (calcium deposits under skin) |
| Body Shape | Mild weight gain around midsection | Pronounced "pot-bellied" appearance from muscle wasting and liver enlargement; visible spine/rib prominence with distended abdomen |
| Energy & Behavior | Slightly less active, sleeping more | Significant muscle weakness, difficulty climbing stairs or jumping, panting at rest, lethargy |
| Reproductive | Irregular heat cycles in intact females | Testicular atrophy in intact males; anestrus in intact females |
| Neurological (PDH) | Rare in early stages | Macrotumor signs (if pituitary tumor >1cm): head pressing, circling, disorientation, seizures — occurs in ~10-20% of PDH cases |
A useful home screening method: measure your dog's water intake over 24 hours. Normal intake is approximately 45-65 mL per kg of body weight per day (roughly 1 ounce per pound). If your 30-lb dog is consistently drinking more than 45 ounces (about 5.5 cups) daily, this warrants veterinary investigation.
Risk Factors: Which Dogs Are Most Vulnerable?
- Age: Most commonly diagnosed in dogs aged 7–12 years; rare under age 5
- Weight: Small to medium breeds more commonly affected by PDH; larger breeds slightly more prone to adrenal tumors
- Sex: Females are slightly overrepresented (~55-60% of cases)
- Genetics: Strong breed predispositions identified (see below)
- Iatrogenic risk: Dogs on chronic corticosteroid therapy (e.g., prednisone for allergies, autoimmune disease)
Breed Predisposition
According to the American Kennel Club, the following breeds show higher-than-average incidence of Cushing's disease:
- Highest risk: Poodles (all sizes), Dachshunds, Yorkshire Terriers, German Shepherds, Boston Terriers
- Elevated risk: Beagles, Cocker Spaniels, Miniature Schnauzers, Staffordshire Bull Terriers, Bichon Frises
- Adrenal tumors specifically: Larger breeds including Australian Shepherds and Labrador Retrievers show slightly higher ADH rates
If your dog falls into one of these breeds and is over age 6, annual senior bloodwork panels become especially important for early detection — even before clinical symptoms appear.
How Is Cushing's Disease Diagnosed?
Diagnosis is a multi-step process. No single test is definitive — your veterinarian will build a case through screening tests, confirmatory tests, and differentiation tests to determine whether the cause is pituitary or adrenal. Here is the typical diagnostic flow:
- Clinical Suspicion → Vet observes symptoms + reviews history → If Cushing's suspected, proceed to screening
- Baseline Bloodwork & Urinalysis → CBC, chemistry panel, urinalysis → Look for elevated ALP (alkaline phosphatase), elevated cholesterol, dilute urine, stress leukogram
- Screening Test #1: Low-Dose Dexamethasone Suppression Test (LDDST) → Blood drawn at 0, 4, and 8 hours after dexamethasone injection → If cortisol fails to suppress below 1.4 µg/dL at 8 hours, Cushing's is likely (sensitivity ~95% for PDH)
- Screening Test #2: ACTH Stimulation Test → Blood drawn before and 1 hour after synthetic ACTH injection → If post-ACTH cortisol exceeds 20-22 µg/dL, supports diagnosis (specificity ~93%, but sensitivity only ~80% for PDH)
- Differentiation: High-Dose Dexamethasone Suppression Test (HDDST) → Determines pituitary vs. adrenal origin → ~70% of PDH dogs suppress; ADH dogs do not
- Imaging: Abdominal Ultrasound → Evaluates adrenal gland size/symmetry → Bilateral enlargement suggests PDH; unilateral mass suggests ADH
- Advanced Imaging (if indicated): CT or MRI of brain → Recommended if neurological signs present or if pituitary macrotumor suspected → Assesses tumor size for treatment planning
Diagnostic Cost Breakdown
| Test / Procedure | Low Range | Average | High Range | Notes |
|---|---|---|---|---|
| Initial exam + bloodwork panel | $200 | $350 | $500 | CBC, chemistry, urinalysis |
| LDDST (screening) | $150 | $250 | $400 | Requires 3 blood draws over 8 hours |
| ACTH stimulation test | $150 | $225 | $350 | Includes synthetic ACTH (Cortrosyn®) cost |
| Abdominal ultrasound | $300 | $450 | $600 | Specialist referral may increase cost |
| High-dose dexamethasone test | $150 | $250 | $350 | Optional — used for differentiation |
| CT scan (brain/abdomen) | $1,200 | $1,800 | $2,500 | Requires general anesthesia |
| MRI (brain) | $1,500 | $2,200 | $3,500 | For suspected pituitary macrotumor |
| Total diagnostic workup | $800 | $1,500 | $3,000+ | Varies based on tests needed |
Most dogs require the LDDST plus abdominal ultrasound at minimum, placing typical diagnostic costs in the $800-$1,500 range. If your vet recommends referral to a veterinary internal medicine specialist (DACVIM), expect the higher end of these ranges.
Trilostane Treatment: How It Works, Dosing, and Monitoring
Trilostane is the cornerstone of medical management for Cushing's disease in dogs. Unlike the older drug mitotane (Lysodren®), which chemically destroys adrenal tissue, trilostane reversibly inhibits cortisol production — making it safer and easier to adjust.
How Trilostane Works
Trilostane blocks the enzyme 3-beta-hydroxysteroid dehydrogenase, which converts pregnenolone to progesterone — a critical step in the cortisol synthesis pathway. This reduces cortisol output without permanently damaging the adrenal glands. If you stop the medication, cortisol production resumes, which is why trilostane is a lifelong treatment commitment.
Dosing Guidelines
Your veterinarian will determine the exact dose based on your dog's weight, baseline cortisol levels, and clinical response. The following table reflects commonly used starting doses — but never adjust your dog's dose without veterinary guidance.
| Dog Weight | Typical Starting Dose (Once Daily) | Capsule Size | Twice-Daily Dosing (if needed) |
|---|---|---|---|
| Under 11 lb (5 kg) | 10 mg | 10 mg capsule | 10 mg every 12 hours |
| 11–22 lb (5–10 kg) | 30 mg | 30 mg capsule | 10-30 mg every 12 hours |
| 22–44 lb (10–20 kg) | 60 mg | 60 mg capsule | 30-60 mg every 12 hours |
| 44–88 lb (20–40 kg) | 120 mg | 120 mg capsule | 60-120 mg every 12 hours |
| Over 88 lb (40+ kg) | 120 mg | 120 mg capsule | 120 mg every 12 hours |
Administration tip: Trilostane should always be given with food — ideally a meal containing some fat — to improve absorption and reduce gastrointestinal side effects. Many veterinarians now recommend twice-daily dosing because it provides more consistent cortisol suppression throughout the 24-hour period, reducing "end-of-dose" symptom breakthrough.
The Critical Monitoring Schedule
Monitoring is not optional — it is essential to prevent both undertreatment (ongoing organ damage) and overtreatment (potentially fatal Addisonian crisis). The standard monitoring protocol after starting trilostane:
- 10-14 days: First ACTH stimulation test + clinical assessment — check for over-suppression
- 30 days: Second ACTH stimulation test + electrolyte panel (sodium/potassium ratio)
- 90 days: Full recheck with ACTH stim, bloodwork, and owner symptom report
- Every 3-6 months thereafter: Ongoing monitoring for life — ACTH stim test + chemistry panel
During each monitoring visit, the ACTH stimulation test should be performed 4-6 hours after the morning trilostane dose. The target post-ACTH cortisol level is typically between 1.4 and 9.1 µg/dL, though your vet may adjust this range based on your dog's clinical response.
If trilostane suppresses cortisol too aggressively, your dog can develop iatrogenic Addison's disease (hypoadrenocorticism). This is a medical emergency. Signs include:
- Severe lethargy or collapse
- Vomiting and diarrhea (possibly bloody)
- Loss of appetite
- Weakness, trembling, or inability to stand
Treatment Options Compared: Trilostane vs. Alternatives
While trilostane is the first-line treatment, it is not the only option. Your veterinarian may recommend alternatives based on tumor type, your dog's overall health, and your budget.
| Treatment | Best For | Success Rate | Ongoing Cost/Year | Key Considerations |
|---|---|---|---|---|
| Trilostane (Vetoryl®) | PDH and ADH — first-line medical management | ~80-85% clinical improvement within 4-8 weeks | $600–$2,400 | Lifelong daily medication; requires regular monitoring; well-tolerated by most dogs |
| Mitotane (Lysodren®) | PDH when trilostane unavailable or ineffective | ~75-80% response rate | $300–$800 | Permanently destroys adrenal cortex; higher risk of Addisonian crisis; loading phase requires close monitoring |
| Adrenalectomy (surgery) | ADH — unilateral adrenal tumor | ~70-85% cure rate for benign adenomas | $3,000–$7,000 (one-time) | Potentially curative for ADH; requires experienced surgeon; perioperative mortality ~2-5%; risk of thromboembolism |
| Radiation therapy | PDH with pituitary macrotumor causing neurological signs | ~50-70% improvement in neurological signs | $4,000–$8,000 (course) | Does not cure HAC — still need trilostane; multiple sessions over 3-4 weeks; availability limited to specialty centers |
| Supportive care only | Dogs too frail for treatment or owner financial constraints | N/A — manages symptoms | $200–$600 | Does not slow disease progression; focuses on quality of life; shorter survival expected |
For the vast majority of dogs with pituitary-dependent Cushing's (the most common form), trilostane remains the standard of care. The American College of Veterinary Internal Medicine (ACVIM) consensus statement recommends trilostane as the first-line medical treatment for PDH.
Trilostane Costs in Detail
The ongoing expense of trilostane treatment is a significant consideration for dog owners. Here is a realistic breakdown:
- Medication cost per month: $50-$200 depending on dose and pharmacy (compounded trilostane may be 20-40% cheaper than brand-name Vetoryl®)
- Monitoring visits per year: 2-4 visits after the first year, each costing $150-$400 (exam + ACTH stim test + bloodwork)
- Annual total (medication + monitoring): $1,000-$3,600
- First-year total (diagnosis + medication + intensive monitoring): $2,000-$6,000
Pet insurance can offset a meaningful portion of these costs if your policy covers chronic conditions and your dog was enrolled before diagnosis. Typical reimbursements for Cushing's management range from $1,500 to $5,000 annually depending on your plan's annual limit and reimbursement percentage.
Prognosis and Life Expectancy with Cushing's Disease
This is the question every owner asks: how long will my dog live with Cushing's disease? The answer depends heavily on the type, stage at diagnosis, and how well the disease responds to treatment.
| Scenario | Median Survival Time | 2-Year Survival Rate | Key Factors |
|---|---|---|---|
| PDH — well-controlled with trilostane | 2.0–2.5 years from diagnosis | ~55-65% | Most common scenario; many dogs die of unrelated age-related conditions |
| PDH — poorly controlled or non-compliant monitoring | 1.0–1.5 years | ~30-40% | Higher risk of diabetes, kidney failure, infections |
| PDH with pituitary macrotumor (>1cm) | 0.5–1.5 years | ~25-40% | Neurological complications drive prognosis; radiation may improve outcomes |
| ADH — benign adenoma, surgical removal | 2.5–4.0+ years | ~65-80% | Potentially curative; best prognosis of all scenarios |
| ADH — malignant carcinoma | 0.5–1.0 year | ~15-25% | High metastasis rate; surgery + trilostane may extend survival |
| Iatrogenic Cushing's (steroid-induced) | Variable — often reversible | High if steroids can be tapered | Gradual steroid withdrawal under vet supervision; adrenal function typically recovers |
An important perspective: many dogs with well-managed PDH live full, comfortable lives for years after diagnosis. The median survival of 2-2.5 years is heavily influenced by the fact that most dogs are already 8-12 years old at diagnosis — meaning they are competing with other age-related causes of mortality. In practice, well-managed Cushing's dogs often die from unrelated causes (cancer, heart disease, kidney failure) rather than from Cushing's itself.
Home Care and Daily Management
Managing a dog on trilostane requires daily attention and some lifestyle adjustments. Here is a practical framework:
Daily Routine
- Consistent feeding schedule: Feed at the same times daily — trilostane must be given with food
- Medication timing: Set a phone alarm for dosing times; missing doses causes cortisol rebound
- Water access: Never restrict water — even if your dog drinks excessively, this is the disease, not a behavioral issue. Provide fresh water at all times and consider additional water bowls
- Potty schedule: Increase outdoor breaks — your dog physically cannot hold it as long. This is not a training issue; punishing accidents will only increase stress (and cortisol)
- Exercise: Moderate, regular walks are beneficial. Avoid intense exertion, especially in hot weather, as muscle weakness is common
Skin and Coat Care
Coat regrowth is one of the most visible signs that trilostane is working — but it takes time. Expect noticeable hair regrowth within 3-6 months of adequate cortisol control. In the meantime:
- Avoid shaving or aggressive grooming of thin-coated areas — the skin is fragile
- Use gentle, moisturizing shampoos (oatmeal-based or veterinary-recommended)
- Monitor for skin infections — Cushing's dogs are immunosuppressed and prone to bacterial and yeast skin infections
- Report any new dark patches, crusty lesions, or hard calcium deposits (calcinosis cutis) to your vet
Monitoring at Home
Keep a simple daily log tracking:
- Water intake (measure with a marked bowl or bottle)
- Appetite level (1-5 scale)
- Energy level (1-5 scale)
- Any vomiting, diarrhea, or unusual behavior
Share this log at every monitoring appointment. Trends in these metrics often signal the need for dose adjustment before bloodwork does.
When to Call the Vet: Red Flags That Can't Wait
- Collapse or inability to stand — possible Addisonian crisis or thromboembolic event
- Severe vomiting or diarrhea (especially bloody) — may indicate adrenal insufficiency
- Seizures, head pressing, or disorientation — possible pituitary macrotumor expansion
- Acute difficulty breathing or rapid breathing at rest — possible pulmonary thromboembolism (PTE), a known and often fatal complication of Cushing's
- Complete refusal to eat for 24+ hours while on trilostane
- Extreme lethargy — won't get up, unresponsive
For suspected medication overdose or toxic ingestion: ASPCA Animal Poison Control — (888) 426-4435 (24/7, consultation fee applies) or Pet Poison Helpline — (855) 764-7661.
- Return of excessive drinking/urination after initial improvement (dose may be too low)
- New skin infections or worsening hair loss despite treatment
- Mild vomiting or diarrhea (1-2 episodes) after starting trilostane
- Decreased appetite lasting more than one meal
- Noticeable increase in panting or restlessness
Prevention and Early Detection Strategies
Pituitary-dependent Cushing's disease cannot be prevented — the pituitary microadenomas that cause PDH arise spontaneously, and there is no known way to prevent their development. Adrenal tumors similarly cannot be prevented through lifestyle measures.
However, you can take meaningful steps to catch the disease early and prevent the iatrogenic form:
- Annual senior bloodwork: For dogs over age 7, annual chemistry panels often reveal elevated ALP (alkaline phosphatase) before clinical symptoms appear. This is your earliest laboratory clue.
- Steroid stewardship: Iatrogenic Cushing's is entirely preventable. If your dog requires long-term corticosteroid therapy (for allergies, autoimmune disease, etc.), work with your vet to use the lowest effective dose for the shortest duration. Ask about steroid-sparing alternatives like oclacitinib (Apoquel®), lokivetmab (Cytopoint®), or immunosuppressive protocols that reduce steroid dependence.
- Breed-aware screening: If you own a predisposed breed (Poodle, Dachshund, Yorkie, German Shepherd, Boston Terrier), discuss baseline cortisol screening with your veterinarian starting at age 6-7.
- Weight management: While obesity does not cause Cushing's, it compounds many of the same health risks (diabetes, joint disease, cardiovascular strain). Keeping your dog at an ideal body condition score (BCS 4-5/9) reduces the overall burden on their system.
Frequently Asked Questions
Can Cushing's disease in dogs be cured?
In most cases, no. Pituitary-dependent Cushing's (80-85% of cases) is managed, not cured — trilostane controls cortisol levels but does not eliminate the underlying pituitary tumor. The exception is adrenal-dependent Cushing's caused by a benign adenoma: surgical removal of the affected adrenal gland can be curative in approximately 70-85% of cases. Malignant adrenal carcinomas carry a much poorer prognosis even with surgery.
How quickly does trilostane start working?
Most owners notice reduced thirst and urination within 1-2 weeks of starting trilostane at an effective dose. Appetite normalization may take 2-4 weeks. Coat and skin changes take the longest — visible hair regrowth typically begins at 3-6 months and may continue improving for up to a year. If symptoms haven't improved after 4 weeks, your vet will likely adjust the dose.
Are there natural or alternative treatments for Cushing's disease?
There is no scientifically validated natural cure for Cushing's disease. Some supplements (melatonin, lignans from flaxseed) have been studied for mild adrenal imbalances, but they do not adequately control cortisol in clinically significant HAC. Using unproven alternatives instead of trilostane allows ongoing organ damage. Always discuss any supplements with your veterinarian — some can interfere with trilostane metabolism or liver function.
Can I give trilostane every other day to save money?
No. Trilostane has a short half-life (approximately 1.5 hours in dogs, though its biological effect lasts longer). Skipping doses allows cortisol to rebound, causing symptom flare-ups and inconsistent control. Inconsistent dosing also makes monitoring bloodwork unreliable, making it impossible for your vet to properly manage the disease. If cost is a concern, ask your vet about compounded trilostane (which can be 20-40% less expensive) or discuss whether a different dosing strategy might be appropriate.
What happens if I stop giving trilostane?
If trilostane is discontinued, cortisol production will resume to pre-treatment levels within days to weeks. Cushing's symptoms will return and progressive organ damage will continue. Unlike mitotane, trilostane does not permanently alter the adrenal glands — so the disease is never "treated" by past use. Any decision to stop trilostane should be made with your veterinarian, typically only in cases where the dog's quality of life is declining from other conditions and the owner is transitioning to hospice care.
Is trilostane safe long-term?
Yes — trilostane has been used in veterinary medicine since its FDA approval in 2008, with extensive long-term safety data. The most serious risk is iatrogenic Addison's disease from over-suppression, which is why the monitoring schedule is critical. Most dogs tolerate trilostane well for years. Mild side effects (occasional vomiting, decreased appetite) can often be managed by adjusting timing or splitting the dose. Regular monitoring of liver enzymes, electrolytes, and cortisol levels ensures long-term safety.
Jonas Cole
All our authors care for dogs every day — read more of their work on the authors page.
