What Blood and Urine Test Results Suggest Cushing’s Disease in Dogs and Cats?

 

What Blood and Urine Test Results Suggest Cushing’s Disease in Dogs and Cats?

By Dr Duncan Houston

An elevated alkaline phosphatase result is one of the most common reasons an owner is told that their dog “might have Cushing’s disease”. It is also one of the most common reasons Cushing’s is suspected too quickly.

A high ALP result can occur with Cushing’s syndrome, but it can also be caused by medication, liver or gallbladder disease, diabetes and several other conditions. Routine laboratory results are clues, not a diagnosis.

What matters is the overall pattern. Suspicion becomes much stronger when compatible blood and urine changes occur alongside increased thirst, excessive urination, panting, increased appetite, a pot-bellied appearance, thin skin, hair loss or muscle weakness.

Quick Answer

Routine blood and urine tests cannot confirm Cushing’s syndrome, but they can reveal a suspicious pattern. In dogs, common clues include increased ALP, high cholesterol, mild hyperglycaemia, a stress leukogram, dilute urine, proteinuria and systemic hypertension.

Cats often show a different pattern. Feline Cushing’s is uncommon and is frequently associated with diabetes mellitus, hyperglycaemia, glucose in the urine, fragile skin and difficulty regulating blood glucose. Specific endocrine testing is still required before a diagnosis can be made.

What Is Cushing’s Syndrome?

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

In dogs, naturally occurring Cushing’s syndrome is usually caused by:

• A pituitary tumour producing excessive adrenocorticotropic hormone, known as pituitary-dependent hypercortisolism

• A cortisol-producing adrenal tumour, known as adrenal-dependent hypercortisolism

• Less commonly, another abnormal source of hormone stimulation

Approximately 85% of naturally occurring canine cases are ACTH-dependent, with the large majority caused by pituitary tumours. The remaining naturally occurring cases are usually caused by adrenal tumours.

Cushing’s syndrome can also be caused by prolonged exposure to glucocorticoid medication. This is called iatrogenic Cushing’s syndrome.

Potential sources include:

• Steroid tablets

• Steroid injections

• Ear medications

• Eye drops

• Skin creams or sprays

• Long-acting steroid preparations

In iatrogenic cases, the body’s own cortisol production may actually be suppressed. This means that simply measuring cortisol and finding a normal or low result does not rule out excessive glucocorticoid effects.

Can Routine Bloodwork Diagnose Cushing’s Syndrome?

No.

A complete blood count, serum biochemistry panel and urinalysis can raise suspicion, but none of these tests confirms Cushing’s syndrome.

The diagnosis should begin with the animal’s clinical signs and physical examination. Specific endocrine tests should generally only be performed when there are multiple compatible clinical or laboratory abnormalities.

Testing an animal simply because one liver enzyme is elevated creates a considerable risk of false-positive results and misdiagnosis. Stress, illness and uncontrolled diabetes can all interfere with Cushing’s testing.

Common Laboratory Clues in Dogs

The following findings can occur in dogs with naturally occurring Cushing’s syndrome:

Laboratory finding	Why it may occur	Important limitation
Increased ALP	Glucocorticoids induce a steroid-associated ALP isoenzyme in dogs and can cause hepatic vacuolar change	High ALP is common but highly nonspecific
Increased ALT	Cortisol can contribute to hepatocyte swelling, glycogen accumulation and liver cell injury	ALT also rises with many other liver conditions
Hypercholesterolaemia	Cortisol alters fat metabolism	Hypothyroidism, diabetes and hepatobiliary disease can also increase cholesterol
Mild hyperglycaemia	Cortisol opposes insulin activity and increases glucose production	Stress and diabetes are important alternatives
Stress leukogram	Cortisol changes the distribution of white blood cells	Illness, stress and steroid medication can produce the same pattern
Thrombocytosis	Glucocorticoids may increase platelet numbers	Not specific to Cushing’s
Erythrocytosis	An increased red blood cell concentration can occur	Not present in every affected dog
Dilute urine	Cortisol interferes with the kidney’s response to antidiuretic hormone and increases water intake	Kidney disease, diabetes and other disorders also cause dilute urine
Proteinuria	Hypertension and glomerular changes can allow protein to enter the urine	Kidney and urinary tract disease must also be considered
Systemic hypertension	Chronic cortisol excess can affect blood vessels and blood pressure regulation	Hypertension has many possible causes

Not every dog with Cushing’s has every abnormality. Conversely, a dog can have several of these abnormalities without having Cushing’s syndrome.

What Is a Stress Leukogram?

A stress leukogram is a characteristic pattern of white blood cell changes.

It usually includes:

• Increased mature neutrophils

• Reduced lymphocytes

• Reduced eosinophils

• Increased monocytes in dogs

This pattern can be caused by endogenous cortisol, steroid medication or the animal’s physiological response to illness and stress.

A stress leukogram does not mean that an animal is necessarily anxious or visibly distressed. A calm-looking dog can have this pattern. However, it is still nonspecific and cannot distinguish Cushing’s syndrome from pain, inflammation, hospital stress or glucocorticoid treatment.

How Significant Is a High ALP Result?

ALP is often the most striking abnormality on the bloodwork of a dog with Cushing’s syndrome.

Dogs produce a corticosteroid-associated ALP isoenzyme in response to glucocorticoids. Cortisol can also cause glycogen accumulation and vacuolar changes within the liver, which may contribute to enzyme elevations.

This steroid-induced ALP response is particularly important in dogs. Cats do not produce the same glucocorticoid-induced isoenzyme.

A very high ALP does not automatically mean Cushing’s

ALP can also increase because of:

• Steroid medication

• Phenobarbital and some other anticonvulsants

• Gallbladder or bile duct disease

• Other forms of hepatopathy

• Diabetes mellitus

• Bone growth in young animals

• Some bone diseases

• Certain cancers

The size of the ALP increase does not tell you the cause. A dog can have markedly elevated ALP without Cushing’s, while another dog with Cushing’s may have a much less dramatic increase.

When a dog has no clinical signs of Cushing’s and the only abnormality is high ALP, the sensible next step is usually to investigate other causes, review medications and confirm whether the change persists. Specific endocrine testing is not automatically indicated in an otherwise asymptomatic dog.

Why Can Cholesterol Be Elevated?

Cortisol changes how the body mobilises and processes fat. This can lead to increased cholesterol and, in some patients, other lipid abnormalities.

High cholesterol supports suspicion when it occurs alongside classic signs and other laboratory changes, but it is not specific.

Alternative causes include:

• Hypothyroidism

• Diabetes mellitus

• Cholestasis

• Some kidney diseases

• A non-fasted blood sample

• Certain inherited lipid disorders

Cholesterol should therefore be interpreted as part of the complete clinical picture rather than treated as a stand-alone Cushing’s marker.

Why Can Blood Glucose Be Elevated?

Cortisol increases glucose production and reduces the effectiveness of insulin.

Some dogs with Cushing’s have mild hyperglycaemia without being diabetic. Others develop concurrent diabetes mellitus.

Persistent hyperglycaemia becomes more concerning when it is accompanied by:

• Glucose in the urine

• Weight loss

• Increased thirst

• Increased urination

• Increased appetite

• An elevated fructosamine result

A single mildly increased glucose result can also be caused by recent food intake, illness or stress. Persistent abnormalities require further investigation rather than being automatically attributed to Cushing’s syndrome.

What Urine Changes Occur With Cushing’s Syndrome?

Dilute urine

Dogs with Cushing’s frequently drink and urinate more than normal. Their urine is therefore often poorly concentrated.

A urine specific gravity below approximately 1.020 is considered a compatible laboratory clue in dogs, but it is not diagnostic. Some affected dogs can still produce more concentrated urine, particularly if they are dehydrated at the time of testing.

Other causes of dilute urine include:

• Chronic kidney disease

• Diabetes mellitus

• Liver disease

• Hypercalcaemia

• Pyometra

• Certain medications

• Diabetes insipidus

• Excessive behavioural water consumption

Proteinuria

Protein may be present in the urine because of systemic hypertension or changes affecting the renal glomeruli.

When protein is detected, the result may need to be quantified with a urine protein-to-creatinine ratio. Urine sediment, bacterial infection and blood pressure should also be considered before assuming the proteinuria is directly related to Cushing’s syndrome.

Bacteriuria and urinary tract infection

Dogs with hypercortisolism can develop bacteriuria without showing obvious signs such as straining, frequent small urinations or blood in the urine.

Recent studies have reported bacteriuria in approximately 12% to 18% of dogs with spontaneous hypercortisolism. Most positive cultures in these studies were subclinical, meaning that the dogs did not have recognisable lower urinary tract signs.

A urine sediment examination can sometimes appear relatively quiet despite a positive bacterial culture. For this reason, a urine culture may be considered when Cushing’s is strongly suspected or when there are other risk factors for urinary infection.

A positive culture does not automatically mean that antibiotics are required. The decision depends on whether the animal has clinical bacterial cystitis, the organism identified and the wider medical context. Unnecessary antibiotic treatment can promote resistance.

Should Blood Pressure Be Checked?

Yes.

Systemic hypertension can occur in dogs and cats with Cushing’s syndrome. Blood pressure should be considered as part of the broader assessment, particularly when there is:

• Proteinuria

• Kidney disease

• Sudden visual change

• Neurological abnormalities

• Evidence of cardiovascular disease

High blood pressure supports the need for further investigation, but it does not confirm Cushing’s syndrome because renal disease, hyperthyroidism, primary hyperaldosteronism and other conditions can also cause hypertension.

Why Is Cushing’s Syndrome Different in Cats?

Feline hyperadrenocorticism is uncommon, and cats do not reliably develop the classic canine laboratory pattern.

The majority of affected cats have concurrent diabetes mellitus. However, most cats with difficult-to-regulate diabetes do not have Cushing’s syndrome, so more common explanations should be investigated first.

Important clinical clues in cats include:

• Fragile or easily torn skin

• Failure of clipped hair to regrow

• Symmetrical hair loss

• Bruising

• A pot-bellied appearance

• Muscle weakness

• Poor body condition

• Persistent diabetes mellitus

• Excessive thirst and urination associated with hyperglycaemia

Common feline laboratory findings include:

• Hyperglycaemia

• Glucose in the urine

• Hypercholesterolaemia in some cats

• A stress leukogram in only about half of cases

ALP is often normal because cats lack the glucocorticoid-induced ALP isoenzyme found in dogs. A normal ALP therefore does not meaningfully exclude feline Cushing’s syndrome.

Urine concentration can also be misleading. Glucose increases the refractive index of urine, so a diabetic cat may have a urine specific gravity above 1.020 despite substantial thirst and urination.

Does Difficult-to-Regulate Diabetes Mean a Cat Has Cushing’s?

Not usually.

Cushing’s should be considered when poor diabetic regulation occurs alongside fragile skin, abnormal hair regrowth, abdominal distension, muscle weakness or other compatible findings.

Before testing for Cushing’s, the veterinary team should also assess for more common causes of poor diabetic control, including:

• Incorrect insulin administration

• Insulin storage problems

• Inconsistent dosing or feeding

• Rebound hyperglycaemia following low glucose

• Obesity

• Urinary tract infection

• Dental disease

• Pancreatitis

• Kidney disease

• Hyperthyroidism

• Hypersomatotropism or acromegaly

• Glucocorticoid or progestogen exposure

There is no single insulin dose that confirms Cushing’s syndrome. Some affected cats require high doses, while others do not appear dramatically insulin resistant.

How Strongly Do the Results Point to Cushing’s?

Level of suspicion	Typical situation	What to do
Low suspicion	One isolated abnormality, such as high ALP, without increased thirst, urination, appetite, panting or skin changes	Review medication history, investigate other causes and repeat laboratory testing when recommended
Moderate suspicion	Persistent laboratory abnormalities with one or two compatible clinical signs	Arrange a veterinary review within the next one to two weeks and discuss whether further endocrine testing is justified
High suspicion	Multiple classic signs combined with increased ALP, hypercholesterolaemia, stress leukogram, dilute urine, proteinuria or hypertension	Perform a structured Cushing’s investigation once the patient is clinically stable
Urgent or critical	Collapse, breathing difficulty, neurological signs, repeated vomiting, inability to eat, severe weakness, jaundice or suspected diabetic ketoacidosis	Seek same-day or emergency care and investigate the acute illness before testing for Cushing’s

The greater the number of compatible clinical and laboratory findings, the stronger the justification for endocrine testing. One abnormal number is rarely enough.

What Else Can Look Like Cushing’s Syndrome?

Many of the classic clinical signs and laboratory abnormalities overlap with other diseases.

Increased thirst and urination

Important alternatives include:

• Diabetes mellitus

• Chronic kidney disease

• Liver disease

• Pyometra

• Hypercalcaemia

• Urinary tract disease

• Diabetes insipidus

• Medication effects

Increased appetite

Other causes include:

• Diabetes mellitus

• Malabsorption or maldigestion

• Intestinal disease

• Certain medications

• Behavioural food-seeking

• Inadequate calorie intake

Hair loss and thin skin

Differentials include:

• Hypothyroidism

• Chronic skin infection

• Demodicosis

• Sex hormone disorders

• Medication effects

• Poor nutrition

• Other endocrine or systemic disease

Pot-bellied appearance

This may also be caused by:

• Obesity

• Liver enlargement

• Abdominal fluid

• An abdominal mass

• Pregnancy

• Severe muscle weakness

• Chronic intestinal or organ disease

The mistake is assuming that one recognisable feature has only one explanation. Cushing’s becomes more likely when several findings fit together and the major alternatives have been considered.

How Do Vets Confirm Cushing’s Syndrome?

Step 1: Select the right patient for testing

All available Cushing’s tests can produce false-positive or false-negative results.

Testing is most accurate when the animal:

• Has multiple compatible clinical signs

• Has supporting routine laboratory abnormalities

• Is not experiencing major uncontrolled illness

• Has had interfering medications identified

• Has been assessed for important alternative diagnoses

AAHA guidance recommends testing when clinical suspicion is high, generally meaning that at least two compatible clinical or biochemical abnormalities are present.

Step 2: Perform an appropriate endocrine test

Low-dose dexamethasone suppression test

The low-dose dexamethasone suppression test is the preferred initial diagnostic test for many stable dogs with suspected naturally occurring Cushing’s syndrome.

A baseline cortisol sample is collected, dexamethasone is administered, and additional cortisol samples are measured at four and eight hours.

A healthy hypothalamic-pituitary-adrenal axis should suppress cortisol production after dexamethasone. In Cushing’s syndrome, suppression may be inadequate or may occur temporarily before cortisol escapes suppression.

The test can sometimes provide evidence that the disease is pituitary-dependent, but failure to suppress does not automatically prove that an adrenal tumour is present.

ACTH stimulation test

The ACTH stimulation test measures adrenal response before and after synthetic ACTH is administered.

It may be particularly useful:

• When iatrogenic Cushing’s is suspected

• When a dog has important concurrent disease

• When an LDDST is negative but clinical suspicion remains high

• For some treatment-monitoring protocols

Its sensitivity is lower than the LDDST for naturally occurring Cushing’s, particularly in dogs with adrenal tumours. A negative ACTH stimulation test therefore does not always exclude the disease.

The ACTH stimulation test is not recommended as the primary diagnostic test for feline Cushing’s because of poor sensitivity.

Urine cortisol-to-creatinine ratio

The urine cortisol-to-creatinine ratio is highly sensitive but poorly specific.

This means:

• A low result makes Cushing’s unlikely

• A high result does not confirm Cushing’s

• Stress and other illnesses can cause false-positive results

It is best used as a rule-out test rather than a stand-alone confirmation test. Urine should be collected at home to reduce the effects of veterinary-visit stress.

For cats, at least two morning urine samples collected at home may be used for initial screening. A positive feline UCCR should be followed by an LDDST.

Step 3: Determine the underlying cause

Once Cushing’s syndrome has been confirmed, further testing may include:

• Abdominal ultrasound

• Endogenous ACTH measurement

• CT of the adrenal glands

• CT or MRI of the pituitary gland

These tests help determine whether the disease is pituitary-dependent or adrenal-dependent.

Imaging should not replace endocrine testing. An adrenal mass can be incidental and does not prove that the mass is producing cortisol. Similarly, normal-looking adrenal glands do not completely exclude Cushing’s syndrome.

Does Blood Need to Be Collected Before 10 am?

No general “before 10 am” rule applies to the diagnosis of canine Cushing’s syndrome.

Dogs do not have a clinically useful circadian cortisol pattern for this purpose. The LDDST can be started at different times of day as long as the baseline, four-hour and eight-hour samples are collected according to the protocol.

A single random cortisol concentration has no diagnostic value for confirming canine Cushing’s syndrome because cortisol secretion is pulsatile and overlaps considerably between healthy, stressed and affected dogs.

Morning urine may be preferred for UCCR testing because it often represents several hours of urine production, but reducing stress by collecting the sample at home is more important than chasing an exact clock time.

Does the Animal Need to Fast?

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

Once the test has started, food may be withheld until sampling is complete depending on the laboratory and veterinary protocol. Owners should follow the clinic’s specific instructions rather than applying a universal fasting rule.

Can Medication Affect the Results?

Yes.

Glucocorticoids can alter cortisol testing and suppress the hypothalamic-pituitary-adrenal axis. This includes steroid-containing oral, injectable, ear, eye and skin medications.

AAHA guidance recommends allowing approximately:

• Two weeks after short-acting glucocorticoids

• Up to four weeks after longer-acting glucocorticoids

The correct withdrawal period depends on the exact drug, dose, duration and patient. Never stop long-term steroid medication abruptly without veterinary instructions because withdrawal can be dangerous.

When Is Suspected Cushing’s an Emergency?

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

However, affected animals can develop serious complications or unrelated illnesses that require urgent treatment.

Seek emergency veterinary care for:

• Collapse

• Sudden or severe breathing difficulty

• Blue, grey or very pale gums

• Seizures

• Circling, marked confusion or other sudden neurological changes

• Sudden blindness

• Severe weakness or inability to stand

• Repeated vomiting or diarrhoea

• Refusal to eat with marked lethargy

• A painful or suddenly enlarged 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 diabetic ketoacidosis, pancreatitis, gallbladder disease, pulmonary thromboembolism, an enlarging pituitary mass or another acute illness.

The acute problem should be stabilised before performing elective Cushing’s testing. When possible, AAHA recommends waiting approximately two to four weeks after improvement of a significant acute illness because stress can produce false-positive endocrine results.

What Should You Do Next?

1. Do not focus on one abnormal number

Review the entire CBC, biochemistry panel and urinalysis alongside the animal’s clinical signs.

2. Record the clinical pattern

Monitor:

• Water intake

• Urination frequency

• Overnight accidents

• Appetite

• Panting

• Abdominal shape

• Coat and skin changes

• Muscle strength

• Body weight

• Activity and behaviour

3. Review every medication and supplement

Include tablets, injections, creams, ear drops and eye drops. Also mention medications belonging to another pet or household member if skin contact or accidental exposure is possible.

4. Complete the minimum diagnostic database

This commonly includes:

• Complete blood count

• Serum biochemistry

• Urinalysis

• Blood pressure

• Urine protein-to-creatinine ratio when indicated

• Urine culture when appropriate

5. Address concurrent illness first

Uncontrolled diabetes, acute gastrointestinal illness, infection and other major diseases can interfere with Cushing’s testing.

6. Select the endocrine test according to the patient

The correct test differs depending on whether the patient is a dog or cat, whether medication exposure is possible and whether concurrent disease is present.

7. Confirm the diagnosis before beginning treatment

Do not treat Cushing’s solely because ALP is high, an adrenal gland looks enlarged or a UCCR is positive.

Common Mistakes Owners and Clinicians Should Avoid

Diagnosing Cushing’s from ALP alone

High ALP raises a question. It does not answer it.

Testing an acutely sick or severely stressed patient

Acute disease can create false-positive results, particularly with an LDDST.

Forgetting about steroid ear or eye medication

Topical preparations can have systemic effects and can interfere with endocrine testing.

Requesting a random cortisol test

A single cortisol measurement cannot confirm or exclude Cushing’s syndrome.

Treating a high UCCR as definitive

A positive UCCR requires further testing because many nonadrenal illnesses increase urinary cortisol.

Assuming hard-to-regulate feline diabetes must be Cushing’s

Cushing’s is uncommon in cats. Insulin technique, infection, pancreatitis, obesity, acromegaly and other causes should be assessed.

Stopping steroid medication suddenly

Long-term glucocorticoid exposure can suppress natural adrenal function. Medication changes must be supervised by a veterinarian.

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 clinically justified

• Using the lowest effective dose

• Reviewing long-term steroid requirements regularly

• Monitoring for increased thirst, urination, appetite, panting and skin changes

• Avoiding unsupervised dose changes

• Tapering medication when medically appropriate

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

Senior dogs receiving routine veterinary care should have changes in drinking, urination, appetite, skin, coat, body shape and muscle condition investigated rather than dismissed as ageing.

Frequently Asked Questions

Does a high ALP result mean my dog has Cushing’s disease?

No. High ALP is common in dogs with Cushing’s, but it is also caused by medications, liver and gallbladder disease, diabetes and other conditions. Clinical signs and specific endocrine testing are required.

What urine specific gravity suggests Cushing’s in a dog?

A urine specific gravity below approximately 1.020 is a compatible clue, particularly in a dog that drinks and urinates excessively. It is not diagnostic and must be interpreted alongside kidney function, glucose and other findings.

Can a dog have Cushing’s with normal routine bloodwork?

Yes, particularly in early or mild disease, but the absence of typical abnormalities reduces the level of suspicion. Endocrine testing should still be based primarily on compatible clinical signs.

Can a urine cortisol-to-creatinine ratio confirm Cushing’s?

No. A low UCCR makes Cushing’s unlikely, but a high result can occur with stress and other illnesses. A positive result requires confirmation with another endocrine test.

Does difficult-to-control diabetes mean my cat has Cushing’s?

Not necessarily. Most difficult diabetic cats do not have Cushing’s syndrome. Insulin handling, injection technique, infection, pancreatitis, obesity, acromegaly, thyroid disease and other causes should be investigated first.

Final Takeaway

Routine laboratory tests can point towards Cushing’s syndrome, but they cannot diagnose it.

In dogs, the most suggestive pattern includes compatible clinical signs alongside increased ALP, high cholesterol, a stress leukogram, dilute urine, proteinuria or hypertension.

In cats, Cushing’s is much less common and often presents through diabetes mellitus, fragile skin, poor hair regrowth and abdominal or muscular changes. The classic canine ALP pattern may be absent.

The real question is not whether one value is abnormal. It is whether the animal’s history, physical examination and laboratory results form a consistent clinical pattern that justifies endocrine testing.

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If you are unsure whether your pet’s laboratory results are consistent with Cushing’s syndrome or require urgent investigation, ASK A VET™ can help you organise the findings and understand what questions to discuss with your veterinarian next.