How Is Cushing’s Disease Diagnosed in Dogs and Cats?

By Dr Duncan Houston

Cushing’s disease is not diagnosed from one high cortisol result, one elevated liver enzyme or one abnormal-looking adrenal gland.

The diagnosis is built by matching the animal’s clinical signs with routine laboratory findings and then selecting the most appropriate hormone test. This matters because stress, diabetes, liver disease, steroid medication and other illnesses can all produce misleading results.

There is no perfect test that identifies every affected animal and excludes every unaffected one. Patient selection and careful interpretation are often more important than simply choosing whichever test is most readily available.

Quick Answer

For a stable dog with convincing signs of naturally occurring Cushing’s syndrome, the low-dose dexamethasone suppression test is usually the preferred initial diagnostic test. A urine cortisol-to-creatinine ratio is mainly useful for ruling the disease out, while the ACTH stimulation test is especially valuable when steroid-induced Cushing’s is suspected or when monitoring treatment.

Cats require a different approach. The low-dose dexamethasone suppression test remains the most reliable diagnostic test, but cats require a higher dexamethasone dose than dogs. The ACTH stimulation test has poor sensitivity in cats and is not recommended as the main diagnostic test.

What Is Cushing’s Syndrome?

Cushing’s syndrome, also called hypercortisolism or hyperadrenocorticism, describes the clinical effects of excessive glucocorticoid activity.

Naturally occurring Cushing’s syndrome usually develops because of:

• A pituitary tumour producing excessive ACTH

• A cortisol-producing adrenal tumour

• Less commonly, another abnormal source of hormonal stimulation

Cushing’s syndrome can also develop after prolonged exposure to glucocorticoid medication. This is called iatrogenic Cushing’s syndrome.

Potential medication sources include:

• Steroid tablets

• Steroid injections

• Ear drops

• Eye drops

• Skin creams

• Sprays

• Long-acting steroid preparations

Strictly speaking, Cushing’s disease refers to pituitary-dependent disease, while Cushing’s syndrome includes pituitary, adrenal and medication-induced causes. However, the term Cushing’s disease is commonly used more broadly by owners and veterinary teams.

When Should a Pet Be Tested for Cushing’s?

Cushing’s testing should be performed when the clinical picture makes the disease genuinely likely.

In dogs, suspicion is stronger when at least two compatible clinical or biochemical abnormalities are present, such as:

• Increased thirst

• Increased urination

• Increased appetite

• Excessive panting

• A pot-bellied appearance

• Muscle weakness

• Thin skin

• Symmetrical hair loss

• Recurrent skin infections

• Poor hair regrowth

• Increased alkaline phosphatase

• High cholesterol

• Dilute urine

• Proteinuria

• Systemic hypertension

Testing a dog solely because ALP is elevated creates a significant risk of a false-positive diagnosis. When no compatible clinical signs are present, other causes of the laboratory abnormality should usually be investigated first.

What matters most before testing?

The veterinary team should establish:

1. Whether the clinical signs genuinely fit Cushing’s syndrome

2. Whether another illness could explain the findings

3. Whether the patient is currently stable

4. Whether glucocorticoids or other interfering medications have been used

5. Whether the result would change treatment or further investigation

A positive result in a highly suspicious patient is more meaningful than the same result in an animal with no relevant clinical signs. This is known as pretest probability, and it is central to interpreting all Cushing’s tests.

Can a Random Cortisol Test Diagnose Cushing’s?

No.

A single resting or basal cortisol measurement cannot diagnose or exclude Cushing’s syndrome.

Cortisol is released in pulses and can rise in response to stress, pain, illness and handling. A healthy animal may have a high cortisol result, while an animal with Cushing’s can have a cortisol concentration within the laboratory reference interval at a particular moment.

Dynamic tests are used because they assess how the pituitary and adrenal glands respond to stimulation or suppression rather than measuring one isolated cortisol value.

Which Tests Are Used to Diagnose Cushing’s Syndrome?

Test	Main role	Strongest advantage	Main limitation
Low-dose dexamethasone suppression test	Preferred initial test for many stable dogs and the most reliable diagnostic test in cats	High sensitivity and may also suggest pituitary disease	False-positive results can occur with stress or non-adrenal illness
ACTH stimulation test	Iatrogenic Cushing’s, selected spontaneous cases and treatment monitoring	Shorter test and generally less affected by illness than the LDDST	Can miss spontaneous Cushing’s, particularly adrenal-dependent disease
Urine cortisol-to-creatinine ratio	Screening and ruling Cushing’s out	Non-invasive and highly sensitive when collected at home	A high result is nonspecific and does not confirm Cushing’s
High-dose dexamethasone suppression test	Differentiation after Cushing’s has already been demonstrated	May support pituitary-dependent disease	Failure to suppress does not prove an adrenal tumour
Endogenous ACTH	Distinguishing pituitary from adrenal disease	Useful biochemical differentiation test	Requires strict sample handling
Ultrasound, CT or MRI	Localisation, staging and treatment planning	Shows adrenal or pituitary anatomy	Imaging alone cannot prove that a lesion is producing cortisol

No result should be interpreted without considering the pet’s clinical signs, medication history and concurrent illness.

How Does the Low-Dose Dexamethasone Suppression Test Work?

The low-dose dexamethasone suppression test, usually shortened to LDDST, examines whether cortisol production can be suppressed by dexamethasone.

Dexamethasone acts like a powerful glucocorticoid signal. In a healthy animal, the pituitary gland recognises that enough glucocorticoid activity is present and reduces ACTH release. The adrenal glands then reduce cortisol production.

In an animal with naturally occurring Cushing’s syndrome, this normal feedback response is often impaired.

Low-Dose Dexamethasone Suppression Testing in Dogs

The usual canine protocol involves:

1. Collecting a baseline blood sample

2. Administering dexamethasone intravenously

3. Collecting another sample four hours later

4. Collecting a final sample eight hours later

The commonly used dexamethasone dose in dogs is 0.01 mg/kg intravenously, although the clinic must follow the protocol and interpretation ranges provided by its laboratory.

How is the result interpreted?

The eight-hour cortisol concentration is used primarily to decide whether the result supports Cushing’s syndrome.

If cortisol suppresses appropriately, Cushing’s becomes much less likely. If cortisol remains above the laboratory’s suppression threshold, the result supports Cushing’s in a dog with compatible signs.

The four-hour result and the degree of suppression relative to baseline may also provide evidence of pituitary-dependent disease.

For example, pituitary disease is supported when cortisol:

• Falls below the laboratory suppression threshold at four hours but rises again by eight hours

• Falls to less than half of the baseline concentration at either four or eight hours

However, these patterns are not present in every dog with pituitary-dependent disease. Up to approximately one-third of dogs with pituitary disease may fail to show a recognisable suppression pattern. Therefore, failure to suppress does not automatically mean the dog has an adrenal tumour.

Is the LDDST completely accurate?

No.

The LDDST is highly sensitive, meaning that it identifies most dogs with naturally occurring Cushing’s syndrome. Its specificity is lower, meaning some dogs without Cushing’s also produce abnormal results.

False-positive results are more likely when a dog has:

• Uncontrolled diabetes

• Significant pain

• Acute illness

• Chronic inflammatory disease

• Severe stress

• Another non-adrenal medical condition

This is why a positive LDDST in an otherwise healthy-looking dog with no characteristic signs should be questioned rather than accepted automatically.

What happens if the LDDST is negative?

A properly performed negative LDDST makes Cushing’s considerably less likely.

However, a negative result may occasionally occur with early, mild or fluctuating disease. When the clinical pattern remains strongly convincing, the vet may:

• Perform an ACTH stimulation test

• Repeat the LDDST after the signs have progressed

• Reassess for alternative diagnoses

• Seek advice from an internal medicine specialist

Repeatedly testing an animal with weak or nonspecific signs can eventually produce a false-positive result. The clinical suspicion should be reviewed before ordering additional endocrine tests.

What Is the ACTH Stimulation Test?

The ACTH stimulation test measures how strongly the adrenal glands respond when synthetic ACTH is administered.

The usual protocol involves:

1. Collecting a baseline cortisol sample

2. Administering synthetic ACTH

3. Collecting a second cortisol sample approximately one hour later

The test assesses the adrenal glands’ ability to produce cortisol when stimulated.

When Is the ACTH Stimulation Test Most Useful?

The ACTH stimulation test is particularly useful for:

• Diagnosing iatrogenic Cushing’s syndrome

• Assessing adrenal suppression caused by steroid medication

• Monitoring some dogs receiving trilostane or mitotane

• Investigating a dog when the LDDST is negative but clinical suspicion remains high

• Selected patients in which concurrent disease makes an LDDST difficult to interpret

It is generally less affected by non-adrenal illness than the LDDST, although false-positive results can still occur.

Why can the ACTH stimulation test miss Cushing’s?

Some animals with Cushing’s do not produce an exaggerated response to ACTH.

The test is particularly likely to miss adrenal-dependent Cushing’s syndrome. Published estimates show substantially lower sensitivity in dogs with functional adrenal tumours than in dogs with pituitary-dependent disease.

A normal ACTH stimulation result therefore does not reliably rule out spontaneous Cushing’s syndrome, especially when an adrenal tumour remains possible.

Can the ACTH stimulation test distinguish pituitary from adrenal Cushing’s?

No.

An exaggerated response may support hypercortisolism, but it does not reliably reveal whether the abnormal cortisol production originates from the pituitary gland or an adrenal tumour.

Further differentiation requires results from the LDDST pattern, endogenous ACTH measurement, adrenal imaging or advanced pituitary imaging.

How Does the ACTH Stimulation Test Diagnose Iatrogenic Cushing’s?

Iatrogenic Cushing’s develops when glucocorticoid medication suppresses the animal’s normal pituitary and adrenal activity.

In these cases, the animal may show physical signs of excessive glucocorticoid exposure while producing very little of its own cortisol.

The ACTH stimulation test may show:

• A low baseline cortisol

• Little or no increase after synthetic ACTH

This pattern supports adrenal suppression associated with exogenous glucocorticoid exposure.

Medication-induced Cushing’s should always prompt a careful review of tablets, injections, ear preparations, eye drops, skin products and medications used by other pets in the household.

What Is the Urine Cortisol-to-Creatinine Ratio?

The urine cortisol-to-creatinine ratio, or UCCR, compares urinary cortisol with creatinine.

Because urine accumulates over several hours, the result reflects cortisol production over a longer period than one blood sample.

The UCCR is highly sensitive but poorly specific.

That means:

• A low result makes Cushing’s very unlikely

• A high result does not prove that Cushing’s is present

Stress, illness and many other conditions can increase urinary cortisol.

Why should the urine be collected at home?

Transport, hospital admission, handling and urine collection at a clinic can increase cortisol production.

A free-catch urine sample collected at home reduces this stress effect. In dogs, morning urine is often preferred because it reflects several hours of cortisol production, but home collection is more important than an exact clock time.

The ACVIM consensus recommends collecting urine at home at least two days after a veterinary visit when practical.

What does a high UCCR mean?

A high UCCR means that further assessment may be justified. It does not confirm Cushing’s syndrome.

The next step may involve:

• An LDDST

• An ACTH stimulation test in selected dogs

• Reassessment for concurrent illness

• Review of the strength of the original clinical suspicion

A high UCCR in a sick, stressed or hospitalised animal is particularly difficult to interpret.

What does a normal UCCR mean?

A normal or low result makes Cushing’s syndrome unlikely.

The UCCR is therefore most useful when the level of suspicion is low and the aim is to exclude the disease without immediately performing a full dynamic blood test.

What Is the High-Dose Dexamethasone Suppression Test?

The high-dose dexamethasone suppression test, or HDDST, uses a larger dose of dexamethasone than the LDDST.

Its main purpose is differentiation, not initial confirmation.

Some pituitary tumours retain partial sensitivity to glucocorticoid feedback and will suppress after a higher dexamethasone dose. Cortisol-producing adrenal tumours generally do not suppress because their hormone production is independent of pituitary control.

However, a significant proportion of pituitary-dependent cases also fail to suppress at the higher dose.

This means:

• Suppression supports pituitary-dependent disease

• Failure to suppress does not prove adrenal-dependent disease

• Additional testing may still be required

The HDDST should not be used as the first or only test to decide whether an animal has Cushing’s syndrome.

What Is Endogenous ACTH Testing?

Endogenous ACTH testing measures the animal’s naturally produced ACTH concentration.

In pituitary-dependent Cushing’s:

• ACTH is usually measurable, normal or increased

• Both adrenal glands may be stimulated

In adrenal-dependent Cushing’s:

• Excess cortisol from the adrenal tumour suppresses pituitary ACTH production

• Endogenous ACTH is usually very low

Endogenous ACTH is a differentiation test. It should be performed after hypercortisolism has already been demonstrated.

Why is sample handling important?

ACTH degrades rapidly after blood collection.

The sample generally needs to be:

• Collected into an appropriate EDTA tube

• Separated promptly

• Transferred into a suitable plastic tube

• Frozen

• Transported according to the laboratory’s instructions

Poor handling can produce an artificially low result, potentially making pituitary disease look like adrenal disease.

Does an Adrenal Mass Confirm Cushing’s Syndrome?

No.

An adrenal mass may be:

• Producing cortisol

• Producing another hormone

• Non-functional

• Benign

• Malignant

• An incidental finding unrelated to the clinical signs

Endocrine evidence of hypercortisolism should generally be established before an adrenal lesion is assumed to be the cause of Cushing’s syndrome.

Imaging becomes particularly useful after diagnosis because it can assess:

• The size and shape of both adrenal glands

• Whether one gland is enlarged and the other is small

• Local invasion into surrounding tissues or blood vessels

• Possible metastatic disease

• Surgical suitability

Abdominal ultrasound is useful but operator-dependent. CT generally provides more detailed information for adrenal surgical planning.

Pituitary CT or MRI may be recommended when neurological signs are present, radiation therapy is being considered or pituitary size would influence treatment planning.

How Is Cushing’s Syndrome Diagnosed in Cats?

Feline Cushing’s syndrome is uncommon and can be more difficult to diagnose than canine disease.

Most affected cats are middle-aged or older, and many have concurrent diabetes mellitus. However, most cats with difficult-to-regulate diabetes do not have Cushing’s syndrome.

Stronger feline clues include:

• Fragile or easily torn skin

• Failure of clipped hair to regrow

• Symmetrical hair loss

• Muscle weakness

• A pot-bellied appearance

• Bruising

• Persistent hyperglycaemia

• Glucose in the urine

• Poor diabetic regulation despite appropriate treatment

Routine canine clues are less reliable in cats. ALP may remain normal because cats lack the steroid-induced ALP isoenzyme found in dogs.

Low-Dose Dexamethasone Suppression Testing in Cats

The feline LDDST follows a similar sampling schedule to the canine test:

1. Baseline cortisol sample

2. Dexamethasone administration

3. Four-hour cortisol sample

4. Eight-hour cortisol sample

However, cats require a higher dexamethasone dose. The recommended feline dose is 0.1 mg/kg intravenously, compared with 0.01 mg/kg in dogs.

Failure to suppress at four or eight hours in a cat with compatible clinical signs supports feline hyperadrenocorticism.

Is UCCR Useful in Cats?

Yes, primarily as a screening and rule-out test.

At least two morning urine samples should be collected at home. A negative result makes feline Cushing’s unlikely, while a positive result should be followed by an LDDST.

A positive UCCR alone is not enough to diagnose a cat with Cushing’s syndrome.

Is the ACTH Stimulation Test Useful in Cats?

It is not recommended as the primary diagnostic test for naturally occurring feline Cushing’s syndrome because its sensitivity is poor.

A cat can have Cushing’s syndrome and still produce an ACTH stimulation result that does not appear diagnostic.

The test may have roles in treatment monitoring or assessment of adrenal suppression, but it should not be relied upon to exclude naturally occurring feline hypercortisolism.

How Is Pituitary Disease Distinguished From an Adrenal Tumour?

Once Cushing’s syndrome has been demonstrated, differentiation may involve:

• Suppression patterns during the LDDST

• Endogenous ACTH measurement

• Abdominal ultrasound

• Adrenal CT

• Pituitary CT or MRI

• An HDDST in selected cases

Differentiation matters because treatment options and prognosis differ.

An adrenal tumour may be treated surgically in an appropriate patient. Pituitary-dependent disease may be managed medically, with hypophysectomy or with radiation therapy in selected cases.

Not every animal requires every differentiation test. The appropriate work-up depends on whether surgery or advanced treatment is being considered and whether the result will alter management.

What Can Cause a False-Positive Cushing’s Test?

False-positive results can occur because cortisol is part of the normal stress response.

Important causes include:

• Acute illness

• Uncontrolled diabetes mellitus

• Pain

• Hospitalisation

• Chronic inflammation

• Severe infection

• Significant liver or gallbladder disease

• Cancer

• Physiological stress

• Inappropriate patient selection

The LDDST is particularly vulnerable to false-positive results in animals with significant non-adrenal illness.

What Can Cause a False-Negative Result?

Potential reasons include:

• Early or mild Cushing’s syndrome

• Fluctuating cortisol secretion

• An ACTH stimulation test in an adrenal-dependent case

• Recent glucocorticoid or progestogen use

• Incorrect test dosing

• Incorrect blood sampling times

• Laboratory or sample-handling problems

• Use of an inappropriate assay or reference interval

When a result does not match the patient, the first step should be to review the clinical picture and test quality rather than immediately assuming either the test or the diagnosis is correct.

Can Medication Interfere With Cushing’s Testing?

Yes.

Glucocorticoids and progestogens can suppress the hypothalamic-pituitary-adrenal axis and alter test results.

Relevant glucocorticoids may be present in:

• Tablets

• Injectable medication

• Ear preparations

• Eye drops

• Inhalers

• Skin creams

• Sprays

• Medications applied to another animal

Current AAHA guidance suggests allowing approximately two weeks after short-acting glucocorticoids and up to four weeks after some longer-acting preparations before testing, although the correct interval depends on the drug, dose and duration of use.

Long-term steroid medication must never be stopped abruptly without veterinary instructions. Sudden withdrawal can cause dangerous adrenal insufficiency.

What about phenobarbital?

Phenobarbital can produce clinical and biochemical changes that resemble Cushing’s syndrome, including increased liver enzymes.

Available evidence does not show a consistent major effect on every adrenal test, but interpretation can still be difficult. Phenobarbital should not be stopped suddenly merely to perform Cushing’s testing because abrupt anticonvulsant withdrawal can trigger seizures.

Does Testing Need to Begin Before 10 am?

There is no universal rule that canine Cushing’s testing must begin before 10 am.

Dogs have pulsatile cortisol secretion, but there is no clearly established time-of-day requirement that meaningfully improves diagnostic discrimination. The important factors are correct dosing, accurate sample timing and use of the laboratory’s protocol.

Morning urine is often preferred for UCCR testing because it represents several hours of urine production. However, collection in a calm home environment matters more than a precise clock time.

Individual laboratories may still have their own scheduling and processing requirements, which the clinic should follow.

Does a Pet Need to Fast Before Cushing’s Testing?

Fasting is generally not required before an LDDST, although excessive lipaemia can interfere with some cortisol assays.

A clinic may still request fasting because:

• Other blood tests are being performed

• The laboratory has specific requirements

• Food may contribute to lipaemia

• Sedation or imaging is planned

Owners should follow the instructions given by the veterinary clinic rather than applying a universal fasting rule.

How Strongly Do the Results Point to Cushing’s?

Level of suspicion	Typical situation	Recommended next step
Low	One isolated laboratory abnormality, such as increased ALP, with no characteristic signs	Investigate other causes, review medications and monitor for progression
Moderate	One or two compatible signs with mixed or nonspecific laboratory findings	Complete the minimum database, rule out common alternatives and consider a UCCR or targeted endocrine test
High	Multiple characteristic signs with supporting blood and urine abnormalities in a stable patient	Perform an appropriate dynamic test, usually an LDDST in dogs without significant comorbidity
Unreliable testing situation	Acute illness, uncontrolled diabetes, severe pain or hospital stress	Stabilise the patient before elective Cushing’s testing when possible
Critical	Collapse, breathing difficulty, severe neurological signs, diabetic ketoacidosis or marked acute deterioration	Treat the emergency immediately and postpone routine Cushing’s testing

Patient selection has a major effect on diagnostic accuracy. A weak clinical suspicion should not be converted into a diagnosis by repeatedly ordering endocrine tests until one returns abnormal.

What Else Can Look Like Cushing’s Syndrome?

Diabetes mellitus

Diabetes can cause increased thirst, urination, appetite and recurrent infection. Uncontrolled diabetes can also produce false-positive Cushing’s test results.

Chronic kidney disease

Kidney disease can cause increased drinking, increased urination, muscle loss and dilute urine.

Liver or gallbladder disease

These conditions may cause marked ALP elevation, liver enlargement, abdominal distension and changes in appetite.

Hypothyroidism

Hypothyroidism can contribute to lethargy, weight gain, skin changes, hair loss and high cholesterol in dogs.

Chronic glucocorticoid exposure

Steroid medication may produce almost identical clinical signs to naturally occurring Cushing’s syndrome.

Diabetes insipidus or behavioural water consumption

Both can cause profound thirst and urination without cortisol excess.

Chronic skin disease

Demodicosis, bacterial infection, fungal disease and other dermatological conditions can cause hair loss and recurrent infections.

Abdominal masses or fluid

An enlarged abdomen does not automatically mean Cushing’s. Liver enlargement, tumours, abdominal fluid, obesity and organ disease can create a similar appearance.

Other causes of feline insulin resistance

In a diabetic cat, difficult regulation is more commonly caused by factors such as insulin administration problems, infection, pancreatitis, obesity, dental disease or hypersomatotropism than by Cushing’s syndrome.

When Is Suspected Cushing’s an Emergency?

Uncomplicated Cushing’s syndrome usually develops gradually and is not an immediate emergency.

Seek urgent or emergency veterinary care if your pet develops:

• Collapse

• Severe weakness

• Inability to stand

• Sudden breathing difficulty

• Blue, grey or very pale gums

• Sudden blindness

• Seizures

• Circling or severe disorientation

• Repeated vomiting

• Severe diarrhoea

• Refusal to eat with marked lethargy

• A painful or rapidly enlarging abdomen

• Jaundice

• Signs of diabetic ketoacidosis

• Rapid deterioration over several hours

Anorexia, vomiting and diarrhoea are not typical signs of uncomplicated hypercortisolism. They may indicate a concurrent emergency such as diabetic ketoacidosis, pancreatitis, gallbladder disease, pulmonary thromboembolism, severe infection or treatment-related hypoadrenocorticism.

The acute problem should be treated first. When possible, elective endocrine testing should be delayed until the patient has recovered because illness-related stress can produce misleading results. AAHA guidance suggests waiting approximately two to four weeks after improvement of a significant acute illness when clinically practical.

What Should You Do Next?

1. Record the clinical signs

Monitor:

• Water intake

• Urination frequency

• Overnight accidents

• Appetite

• Panting

• Body weight

• Abdominal shape

• Hair loss

• Skin infections

• Muscle strength

• Activity

• Changes in diabetes control

Patterns over several weeks are more useful than one unusual day.

2. Provide a complete medication history

Include prescription medication, supplements, injections, ear drops, eye drops, creams, inhalers and products used on other animals.

3. Complete the minimum diagnostic database

This commonly includes:

• Complete blood count

• Serum biochemistry

• Urinalysis

• Urine culture when indicated

• Urine protein-to-creatinine ratio when indicated

• Blood pressure

• Assessment for concurrent diabetes or kidney disease

4. Stabilise significant concurrent illness

Acute gastrointestinal disease, uncontrolled diabetes, infection and other serious conditions should be addressed before elective Cushing’s testing whenever possible.

5. Choose the test according to the patient

For many stable dogs with strong clinical suspicion, this will be an LDDST.

For suspected medication-induced disease, an ACTH stimulation test is usually more appropriate.

For a low-suspicion patient in whom the aim is to rule out Cushing’s, a home-collected UCCR may be useful.

For cats, an appropriately performed feline LDDST is generally the most reliable diagnostic test.

6. Interpret the result with the clinical findings

A laboratory result should strengthen or weaken an existing clinical diagnosis. It should not create a diagnosis that otherwise makes little sense.

7. Differentiate the cause after Cushing’s is demonstrated

Once hypercortisolism has been established, determine whether differentiation between pituitary and adrenal disease would change treatment, prognosis or surgical planning.

Common Mistakes Owners and Veterinary Teams Should Avoid

Diagnosing Cushing’s from high ALP alone

ALP is an important clue in dogs, but it is not a Cushing’s test.

Ordering a random cortisol concentration

A single resting cortisol value cannot diagnose or exclude Cushing’s syndrome.

Treating a high UCCR as confirmation

A positive UCCR requires further assessment because stress and other illnesses commonly increase the result.

Assuming a normal ACTH stimulation test rules Cushing’s out

The ACTH stimulation test can miss spontaneous disease, particularly adrenal-dependent cases.

Assuming complete failure to suppress means an adrenal tumour

Some dogs with pituitary-dependent Cushing’s fail to suppress during both low-dose and high-dose dexamethasone tests.

Diagnosing Cushing’s from an adrenal mass alone

Imaging identifies anatomy. It does not prove that the lesion is producing cortisol.

Testing during severe acute illness

Stress and non-adrenal illness can make endocrine testing unreliable.

Stopping steroid medication suddenly

Long-term glucocorticoid therapy may have suppressed natural adrenal function. Withdrawal must be planned and supervised.

Are the Same Tests Used to Monitor Treatment?

Not necessarily.

Diagnosis and treatment monitoring are different questions.

The LDDST is primarily a diagnostic test. Dogs receiving trilostane are generally monitored through a combination of:

• Clinical signs reported by the owner

• Physical examination

• Serum biochemistry

• Electrolytes

• Cortisol testing selected by the veterinarian

The ACTH stimulation test has traditionally been used for trilostane monitoring, but it does not always correlate closely with clinical control. Pre-trilostane cortisol measurement is another monitoring strategy used by some clinicians.

There is no universally superior monitoring protocol. The animal’s appetite, thirst, urination, energy, gastrointestinal signs and overall wellbeing remain essential when assessing treatment safety.

In general, dogs are rechecked approximately:

• 10 to 14 days after starting trilostane or changing the dose

• At around 30 days

• About every three months once stable

The first recheck is focused on ensuring that cortisol has not been suppressed too far. Dose increases are generally not made at this early visit solely because Cushing’s signs have not completely resolved.

Cats treated with trilostane are commonly reassessed with a CBC, biochemistry and urinalysis after approximately 7 to 14 days and every three to four months thereafter. Clinical improvement and avoidance of hypocortisolism are central to feline monitoring.

Can Cushing’s Syndrome Be Prevented?

Naturally occurring pituitary and adrenal Cushing’s syndrome cannot currently be reliably prevented.

The risk of iatrogenic Cushing’s can be reduced by:

• Using glucocorticoids only when medically appropriate

• Using the lowest effective dose

• Reviewing long-term steroid treatment regularly

• Monitoring changes in thirst, urination, appetite, skin and muscle condition

• Avoiding unsupervised dose changes

• Tapering medication when medically appropriate

• Informing every treating veterinarian about all steroid-containing products

Early recognition is the most realistic protective strategy for naturally occurring disease.

Frequently Asked Questions

What is the best test for Cushing’s disease in dogs?

The LDDST is usually the preferred initial test for a stable dog with convincing signs and no major uncontrolled illness. The best test still depends on the clinical situation, medication exposure and likelihood of concurrent disease.

Can a urine test confirm Cushing’s disease?

A UCCR cannot usually confirm Cushing’s by itself. A low result makes the disease unlikely, while a high result normally requires a more specific endocrine test.

Can a dog have Cushing’s with a normal ACTH stimulation test?

Yes. The ACTH stimulation test can miss spontaneous Cushing’s, particularly when an adrenal tumour is responsible. A normal result should not be used alone to rule out the disease in a highly suspicious case.

Can the LDDST tell whether Cushing’s is pituitary or adrenal?

Sometimes. Certain suppression patterns support pituitary-dependent disease. However, failure to suppress does not prove adrenal-dependent disease, so endogenous ACTH or imaging may still be needed.

Does an adrenal mass mean my pet has Cushing’s disease?

No. An adrenal mass may be functional or non-functional and may be unrelated to the animal’s signs. Hormone testing and appropriate imaging interpretation are required before linking the mass to Cushing’s syndrome.

Final Takeaway

Cushing’s syndrome is not confirmed by one abnormal number.

The strongest diagnosis comes from:

• A compatible clinical history

• Supporting routine blood and urine findings

• Careful exclusion of important alternative diseases

• The correct dynamic endocrine test

• Interpretation based on the patient’s overall likelihood of disease

For most stable dogs, the LDDST is the preferred initial diagnostic test. The UCCR is most useful for ruling Cushing’s out, while the ACTH stimulation test is particularly important for iatrogenic disease and treatment monitoring.

Cats require species-specific interpretation and a higher dexamethasone dose during the LDDST. The ACTH stimulation test should not be relied upon as the primary feline diagnostic test.

The real clinical skill is not simply ordering cortisol tests. It is knowing which patient should be tested, which test answers the right question and whether the result genuinely fits the animal in front of you.

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If you are unsure what your pet’s cortisol test, urine result or adrenal imaging means, ASK A VET™ can help you organise the findings and understand what questions to discuss with your veterinarian next.