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Pharmaceuticals2026-05-27 · 10 min read

Canine Cushing's Disease: Testing, Trilostane, and What Monitoring Actually Requires

How Cushing's disease is diagnosed in dogs, what the ACTH stimulation test and LDDST actually measure, and why trilostane monitoring involves more than a single blood draw.

Ran Chen
Ran Chen
Founder, VetMedGuide. Life-sciences operator and 10× global market-access lead.
Published

Cushing's disease — hyperadrenocorticism — is one of the most common endocrine disorders in older dogs, and one of the most frustrating to confirm and manage well. The signs are unmistakable once you know them: excessive thirst and urination, a pot-bellied appearance, thinning skin, hair loss, and recurring skin or urinary infections. But getting from those signs to a confirmed diagnosis, and then keeping the disease controlled over months and years, requires specific testing, clear communication between veterinarian and owner, and disciplined recheck schedules.

This article covers how Cushing's is diagnosed, what role trilostane (Vetoryl) plays in treatment, and what the monitoring process actually looks like in practice.

What Cushing's disease is and why it matters

Canine hyperadrenocorticism occurs when a dog's body produces too much cortisol. Roughly 85% of cases are pituitary-dependent (PDH), where a small benign tumor on the pituitary gland signals the adrenal glands to overproduce cortisol. The remaining cases are adrenal-dependent (ADH), caused by a tumor on one or both adrenal glands directly.

Cushing's is not curable with medication alone, but it is manageable. Left untreated, it leads to progressive muscle wasting, thinning skin, high blood pressure, increased susceptibility to infections, and a significantly reduced quality of life. The goal of treatment is not to eliminate cortisol entirely — cortisol is essential for normal body function — but to bring it down to a range where clinical signs improve without causing the opposite problem: iatrogenic hypoadrenocorticism (Addisonian crisis), which is a medical emergency.

Which dogs are most likely affected

Cushing's overwhelmingly affects middle-aged and older dogs. Poodles, Dachshunds, Boxers, Boston Terriers, and Yorkshire Terriers are overrepresented, but any breed can develop it. Most dogs are diagnosed between 6 and 10 years of age.

The classic owner complaint is that the dog is drinking and urinating far more than usual — sometimes double or triple their normal water intake. Other signs include a distended abdomen, panting at rest, exercise intolerance, thinning coat, and recurrent skin infections that do not resolve as expected with antibiotics alone.

Many of these signs overlap with diabetes, kidney disease, and liver disease, which is why testing matters.

How Cushing's is diagnosed: the testing ladder

No single test definitively diagnoses Cushing's disease in every patient. The standard diagnostic approach is a stepwise process that starts with screening tests and moves to confirmatory and localizing tests.

Step 1: Screening tests

The urine cortisol-to-creatinine ratio (UCCR) is sometimes used as an initial screen. A normal result makes Cushing's unlikely, but an elevated result does not confirm it — stress, other illnesses, and even the time of day can raise urine cortisol.

The low-dose dexamethasone suppression test (LDDST) is the most commonly used screening test in general practice. It measures cortisol before and eight hours after a small dose of dexamethasone is given intravenously. In a normal dog, the dexamethasone suppresses cortisol production. In a dog with Cushing's, cortisol remains elevated. The LDDST is sensitive — meaning it catches most true Cushing's cases — but it has a significant false-positive rate, especially in sick or stressed dogs.

The ACTH stimulation test can also be used for screening, though it is more commonly used for monitoring treatment. It measures cortisol before and one hour after synthetic ACTH (cosyntropin) is administered. An exaggerated cortisol response supports a diagnosis of hyperadrenocorticism, but the test can miss up to 15–20% of dogs with Cushing's, particularly those with mild or early disease.

Step 2: Distinguishing pituitary from adrenal disease

Once hyperadrenocorticism is confirmed, the next step is determining whether the source is pituitary or adrenal:

  • The high-dose dexamethasone suppression test (HDDST) can help distinguish PDH from ADH. Dogs with PDH often show cortisol suppression at the high dose; dogs with ADH typically do not.
  • Endogenous ACTH concentration measured via blood draw can also differentiate: high or normal ACTH suggests PDH, while low or undetectable ACTH suggests ADH.
  • Abdominal ultrasound allows direct visualization of the adrenal glands. Symmetrically enlarged adrenals support PDH; a single large adrenal mass with atrophy of the opposite gland suggests ADH.

When testing is inconclusive

False positives, false negatives, and discordant results are common enough that the veterinary literature explicitly acknowledges the limitations of every test. A dog that is sick from a non-endocrine illness may have an abnormal LDDST simply from the stress of being hospitalized. Dogs on medications that affect cortisol metabolism or NSAIDs like meloxicam may also have results that do not reflect true Cushing's.

The clinical picture — the signs the owner is seeing at home — should always anchor interpretation. A dog with convincing clinical signs and one supportive test result is usually treated. A dog with weak clinical signs and a single borderline test result is usually monitored and retested later.

Trilostane (Vetoryl): the first-line medical treatment

Trilostane is the only FDA-approved medical treatment for both pituitary-dependent and adrenal-dependent Cushing's syndrome in dogs. It is marketed as Vetoryl capsules (Dechra Veterinary Products) and is available in multiple capsule strengths that can be combined for individualized dosing.

How trilostane works

Trilostane competitively inhibits the enzyme 3β-hydroxysteroid dehydrogenase, which is required for the synthesis of cortisol. It does not destroy the adrenal gland — the effect is reversible. This means that if the drug is stopped, cortisol production resumes, which is both a safety feature and a reason why consistent daily administration matters.

Starting dose and administration

The FDA label recommends a dose range of 2.2 to 6.7 mg/kg/day. In practice, many veterinary endocrinologists start at lower doses — approximately 1 to 2 mg/kg once or twice daily — and adjust upward based on clinical response and monitoring tests. Trilostane should be given with food to improve absorption.

The dose is individualized. Two dogs of the same weight with the same diagnosis may require very different doses to achieve control. This is not a medication where a single starting dose works for every patient.

Why trilostane over mitotane (Lysodren)

Mitotane (Lysodren) was historically the primary treatment for Cushing's. It works by physically destroying the adrenal cortex — a cytotoxic effect that is not reversible. While effective, mitotane carries a higher risk of causing permanent hypoadrenocorticism and requires more intensive monitoring during the initial loading phase. Trilostane has largely replaced mitotane as the first-line therapy because its effects are reversible and its side-effect profile is generally considered more manageable.

What monitoring actually requires

This is where Cushing's management often breaks down. The medication is relatively straightforward to start. The discipline of ongoing monitoring is what determines whether the dog stays well or cycles between over- and under-treatment.

The monitoring schedule

The standard monitoring timeline after starting trilostane:

  • 10 to 14 days after starting: first ACTH stimulation test, performed 4 to 6 hours after the morning dose with food. Serum biochemistry including electrolytes should be run at the same time.
  • 30 days after starting: second ACTH stimulation test and clinical reassessment. This is the earliest point at which dose increases are typically considered.
  • 90 days after starting: third reassessment.
  • Every 3 months thereafter for the life of the dog.

What the ACTH stimulation test measures during treatment

The target post-ACTH cortisol range on trilostane is approximately 1.45 to 9.1 μg/dL, measured at 4 to 6 hours post-dose with food. Values below this range suggest over-suppression and may require dose reduction or temporary discontinuation. Values above this range, combined with ongoing clinical signs, suggest under-treatment.

It is important to understand that the ACTH stimulation test during treatment is measuring something different from the diagnostic ACTH test. During treatment, the test is checking whether the adrenal glands are adequately suppressed — not whether the dog has Cushing's.

The emerging role of pre-pill cortisol

Recent research has explored whether a single basal (pre-pill) cortisol measurement can replace the full ACTH stimulation test for routine monitoring. A pre-pill cortisol drawn just before the morning dose — at trough drug levels — can identify over-suppression reasonably well. However, it is less useful for detecting under-treatment.

A 2021 systematic review in Veterinary Evidence concluded that pre-pill cortisol is a good rule-out test for adrenal over-suppression but should not replace clinical assessment or periodic ACTH stimulation testing. The clinical signs the owner reports — water intake, appetite, energy level, skin condition — remain the most important single monitoring tool.

Signs of over-suppression to watch for

Owners should be explicitly told to watch for:

  • Lethargy or depression that is new or worsening
  • Decreased appetite or refusal to eat
  • Vomiting or diarrhea
  • Weakness, especially in the hind legs
  • Collapse

These may indicate iatrogenic hypoadrenocorticism — the adrenal glands have been suppressed too far. This is a medical emergency. If any of these signs occur, the owner should stop trilostane and contact their veterinarian immediately. This is not a "wait and see the next morning" situation.

When surgery or referral is appropriate

For dogs with adrenal-dependent Cushing's (ADH), surgical removal of the affected adrenal gland may be curative. This is a major abdominal surgery with significant risk, particularly in a dog that is already metabolically compromised from excess cortisol, but it offers the possibility of a permanent solution. Referral to a board-certified surgeon is standard.

For dogs with large pituitary macroadenomas that are causing neurologic signs, referral to a veterinary neurologist or internist for advanced imaging (MRI or CT) and potential radiation therapy should be discussed early, before neurologic deterioration progresses.

What owners should ask their veterinarian

The most productive conversations happen when owners know what to ask:

  • "Which form of Cushing's does my dog have — pituitary or adrenal?"
  • "Which diagnostic tests are you recommending, and what are the limitations of each?"
  • "What is the target cortisol range we are aiming for during treatment?"
  • "How often will my dog need monitoring bloodwork, and what does it cost?"
  • "What signs should I watch for that mean I should stop the medication and call you?"
  • "If my dog is not improving on the current dose, how long before we adjust?"

Cushing's disease management is a long-term partnership between owner and veterinarian. The dogs that do best are the ones whose owners understand that the disease requires ongoing adjustment — not a single prescription that stays the same forever.

Sources

Topics
Endocrinology
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