Pituitary vs Adrenal Cushing’s in Dogs and Cats: How Vets Tell the Difference

Pituitary vs Adrenal Cushing’s in Dogs and Cats: How Vets Tell the Difference

By Dr Duncan Houston

Once Cushing’s syndrome has been confirmed, the next question is where the excess cortisol is coming from.

In most dogs, the problem begins with an ACTH-producing pituitary tumour. In others, an adrenal tumour produces cortisol independently. The distinction matters because an adrenal tumour may be surgically removable, while pituitary-dependent disease may be managed medically or treated directly with pituitary surgery or radiation in selected patients.

However, classification is not as simple as seeing whether cortisol suppresses during one test. Two mistakes cause particular confusion: failure to suppress does not prove an adrenal tumour, and finding an adrenal mass does not prove that the mass is causing the Cushing’s syndrome.

Quick Answer

Approximately 80% to 85% of naturally occurring canine Cushing’s cases are pituitary-dependent, while around 10% to 15% are caused by an adrenal tumour. Partial cortisol suppression during a low-dose dexamethasone suppression test supports pituitary-dependent disease, but failure to suppress cannot confirm an adrenal cause because up to 35% of dogs with pituitary disease also fail to suppress.

When the low-dose test does not classify the disease, the most useful next steps are usually endogenous ACTH measurement and adrenal imaging. CT or MRI may then be recommended when adrenal surgery, pituitary surgery or radiation treatment is being considered. Cats require a similar but more individualised approach because feline Cushing’s syndrome is rare and the available evidence is more limited.

What Are the Two Main Types of Cushing’s Syndrome?

Cushing’s syndrome describes the clinical effects of excessive glucocorticoid activity.

Naturally occurring disease is usually classified as one of two types.

Pituitary-dependent Cushing’s syndrome

Pituitary-dependent hypercortisolism occurs when a tumour within the pituitary gland releases excessive adrenocorticotropic hormone, usually shortened to ACTH.

ACTH circulates through the bloodstream and repeatedly stimulates both adrenal glands to produce cortisol.

This means that pituitary-dependent disease is usually associated with:

• Measurable, normal or elevated endogenous ACTH

• Stimulation of both adrenal glands

• Bilaterally normal-sized or enlarged adrenal glands

• A pituitary tumour that may be microscopic or visibly enlarged

• Possible neurological signs if the pituitary tumour becomes large

Strictly speaking, Cushing’s disease refers specifically to this pituitary-dependent form.

Adrenal-dependent Cushing’s syndrome

Adrenal-dependent hypercortisolism occurs when abnormal adrenal cortical tissue produces cortisol without waiting for stimulation from the pituitary gland.

The excessive cortisol suppresses normal pituitary ACTH secretion. The unaffected adrenal gland may then become smaller because it is no longer receiving normal ACTH stimulation.

Adrenal-dependent disease is therefore commonly associated with:

• Low or undetectable endogenous ACTH

• A mass or abnormal enlargement involving one adrenal gland

• A small or atrophied opposite adrenal gland

• No cortisol suppression during dexamethasone testing

• Potential local invasion or metastasis when the tumour is malignant

Adrenal tumours may be benign or malignant. Some dogs also have bilateral adrenal disease or more unusual forms of hypercortisolism, so the pattern is not always perfectly tidy.

What about medication-induced Cushing’s syndrome?

Iatrogenic Cushing’s syndrome is caused by prolonged exposure to glucocorticoid medication rather than a naturally occurring pituitary or adrenal tumour.

Potential sources include:

• Steroid tablets

• Steroid injections

• Ear medication

• Eye drops

• Inhaled medication

• Skin creams and sprays

Iatrogenic disease is not classified as pituitary-dependent or adrenal-dependent in the same way. The medication usually suppresses both pituitary ACTH secretion and the animal’s own adrenal cortisol production. An ACTH stimulation test is more useful than a dexamethasone suppression test when medication-induced disease is suspected.

How Common Is Each Type?

In dogs:

• Approximately 80% to 85% have pituitary-dependent disease

• Approximately 10% to 15% have adrenal-dependent disease

• A small minority have unusual causes or concurrent pituitary and adrenal abnormalities

A CT-based study of 201 dogs with spontaneous hypercortisolism classified 82% as pituitary-dependent, 13% as adrenal-dependent and 5% as having concurrent pituitary and adrenal lesions.

Feline Cushing’s syndrome is much less common. Most affected cats appear to have pituitary-dependent disease, but exact percentages are difficult to establish because reported feline case numbers are small. Many affected cats also have diabetes mellitus, fragile skin, muscle weakness or several concurrent illnesses that complicate diagnosis.

Why Does Classification Matter?

Classification helps answer three practical questions:

1. Is there a surgically removable adrenal tumour?

2. Is there a pituitary tumour that requires direct treatment?

3. Is medical cortisol control the most realistic option?

Feature	Pituitary-dependent disease	Adrenal-dependent disease
Primary abnormality	ACTH-producing pituitary tumour	Cortisol-producing adrenal cortical tumour
Endogenous ACTH	Usually measurable, normal or elevated	Usually low or undetectable
Typical adrenal pattern	Both glands normal-sized or enlarged	One mass with a smaller opposite gland
Medical treatment	Trilostane or mitotane may control cortisol	Trilostane or mitotane may control cortisol
Potential definitive treatment	Hypophysectomy in specialist centres	Adrenalectomy
Role of radiation	May treat an enlarging pituitary tumour	Usually not the main treatment for a resectable adrenal tumour
Advanced imaging	Brain CT or MRI when treatment planning or neurological signs justify it	Abdominal CT for surgical planning and staging

Adrenalectomy is the preferred treatment for a resectable cortisol-secreting adrenal tumour. Pituitary-dependent disease is commonly treated medically, although hypophysectomy or radiation may be considered when appropriate expertise is available or the pituitary mass itself is causing problems.

Does Every Pet With Cushing’s Need Classification?

No.

Classification is particularly important when:

• Adrenalectomy would be considered

• Pituitary surgery would be considered

• Radiation treatment is being considered

• A large pituitary mass may be causing neurological signs

• Adrenal imaging is abnormal

• The test results conflict

• Prognostic information will change the owner’s decisions

However, if a dog’s owner would not pursue adrenalectomy even if an adrenal tumour were found, the dog can often be treated with trilostane without fully determining whether the disease is pituitary-dependent or adrenal-dependent. Trilostane is used to control cortisol in both forms.

The decision should therefore be based on whether the result will change treatment, not simply on the fact that another test exists.

Classification Comes After Confirmation

The pituitary-versus-adrenal question should generally be addressed only after naturally occurring Cushing’s syndrome has been established.

A high ALP, dilute urine, pot-bellied appearance or adrenal nodule does not independently confirm Cushing’s syndrome.

All available cortisol tests can produce false-positive or false-negative results. Testing is most useful when the patient has multiple compatible clinical or laboratory abnormalities, and significant acute illness has been stabilised first.

A structured work-up usually begins with:

• Clinical history

• Physical examination

• Complete blood count

• Serum biochemistry

• Urinalysis

• Blood pressure

• Assessment for proteinuria or urinary infection where indicated

• A suitable endocrine test, usually an LDDST in a stable dog

Only after the diagnosis is supported should the source of the hypercortisolism be classified.

How Does the Low-Dose Dexamethasone Suppression Test Help?

The low-dose dexamethasone suppression test, or LDDST, is primarily used to diagnose naturally occurring Cushing’s syndrome. In some dogs, it can also identify a pituitary pattern.

The canine LDDST protocol

The usual protocol is:

1. Collect a baseline cortisol sample.

2. Administer dexamethasone at 0.01 mg/kg intravenously.

3. Collect another cortisol sample at four hours.

4. Collect a final sample at eight hours.

The eight-hour result is used first to determine whether the test supports Cushing’s syndrome. The laboratory’s own assay-specific cut-offs should always be used.

What suppression suggests pituitary disease?

Once the eight-hour result supports Cushing’s syndrome, pituitary-dependent disease is supported when either:

• The four-hour cortisol falls below the laboratory’s suppression threshold

• The four-hour cortisol falls below 50% of baseline

• The eight-hour cortisol falls below 50% of baseline

This indicates that the abnormal pituitary tissue has retained at least some sensitivity to glucocorticoid feedback.

Does failure to suppress mean adrenal Cushing’s?

No.

This is the most important limitation of the LDDST as a classification test.

Up to approximately 35% of dogs with pituitary-dependent Cushing’s do not show a recognised suppression pattern. Their cortisol may remain high at both four and eight hours, making the result look similar to adrenal-dependent disease.

Therefore:

• Suppression supports pituitary-dependent disease

• Failure to suppress is inconclusive

• Failure to suppress does not prove an adrenal tumour

• Further differentiation requires endogenous ACTH and imaging

The mistake is treating a non-suppressing LDDST as though the test has located the lesion. It has not.

What Is the High-Dose Dexamethasone Suppression Test?

The high-dose dexamethasone suppression test, or HDDST, is a differentiation test rather than a preferred initial diagnostic test.

The commonly described dose is:

• Dogs: 0.1 mg/kg dexamethasone intravenously

• Cats: 1 mg/kg dexamethasone intravenously

Cortisol is measured at baseline and again after dexamethasone administration. Suppression below the laboratory reference threshold or below 50% of baseline supports pituitary-dependent disease.

What does a non-suppressing HDDST mean?

It remains inconclusive.

Some pituitary tumours, particularly larger or more autonomous tumours, do not suppress even after a high dexamethasone dose. Therefore:

• Suppression supports pituitary disease

• Failure to suppress does not prove adrenal disease

• A non-suppressing HDDST still needs endogenous ACTH and imaging

Because endogenous ACTH and modern imaging provide more direct information, the HDDST often has a secondary role in current classification strategies.

What Is Endogenous ACTH Testing?

Endogenous ACTH testing measures the ACTH naturally circulating in the animal’s blood.

It is a classification test. It is not a stand-alone test for diagnosing Cushing’s syndrome.

Expected pattern with pituitary-dependent disease

A pituitary ACTH-producing tumour continues releasing ACTH despite high cortisol.

Endogenous ACTH is therefore usually:

• Within the laboratory reference interval

• Elevated

• Clearly measurable rather than fully suppressed

Expected pattern with adrenal-dependent disease

A cortisol-producing adrenal tumour releases cortisol independently.

That cortisol suppresses the normal pituitary gland, so endogenous ACTH is usually:

• Low

• Very low

• Undetectable

This makes endogenous ACTH one of the most direct biochemical methods of distinguishing pituitary-dependent from adrenal-dependent Cushing’s.

Can endogenous ACTH be inconclusive?

Yes.

Possible problems include:

• Values falling within a diagnostic grey zone

• Intermittent or pulsatile ACTH secretion

• Laboratory-specific differences

• Poor sample handling

• Atypical or bilateral adrenal disease

• Concurrent pituitary and adrenal lesions

The result should therefore be interpreted alongside adrenal imaging, dexamethasone suppression and the clinical picture.

Why is sample handling so important?

ACTH is unstable in whole blood and can degrade after collection. Degradation produces an artificially low result, which can make pituitary-dependent disease appear adrenal-dependent.

Cornell’s veterinary diagnostic laboratory recommends:

1. Collecting blood into an EDTA tube.

2. Centrifuging it immediately.

3. Separating the plasma from the cells.

4. Transferring the plasma into a plastic tube.

5. Freezing the plasma promptly.

6. Shipping it frozen according to the laboratory’s instructions.

The exact collection and transport requirements should be confirmed with the receiving laboratory before the sample is taken.

Can the ACTH Stimulation Test Classify Cushing’s?

No.

The ACTH stimulation test assesses adrenal cortisol production before and after synthetic ACTH is administered. It may help confirm Cushing’s in selected dogs, diagnose medication-induced adrenal suppression and monitor treatment.

It cannot reliably determine whether naturally occurring disease is pituitary-dependent or adrenal-dependent.

It is also relatively insensitive for cortisol-producing adrenal tumours. Up to approximately 41% of dogs with adrenal-dependent disease may have a false-negative ACTH stimulation test.

A strong ACTH stimulation response does not mean the disease is pituitary-dependent, and a weak response does not safely classify an adrenal tumour.

What Does Adrenal Ultrasound Show?

Abdominal ultrasound evaluates the size, shape and internal appearance of both adrenal glands.

Typical pituitary-dependent pattern

Both adrenal glands may be:

• Symmetrically enlarged

• Normal in shape

• Homogeneous

• Similar in size

• Maintaining a recognisable corticomedullary structure

This reflects ongoing stimulation of both glands by excessive pituitary ACTH.

Typical adrenal-dependent pattern

Ultrasound may show:

• A mass involving one adrenal gland

• Irregular or asymmetric enlargement

• Heterogeneous internal appearance

• Mineralisation

• Possible vascular invasion

• A small or difficult-to-identify opposite adrenal gland

The small contralateral gland is important because it supports chronic suppression of ACTH by an autonomously cortisol-producing tumour.

Can ultrasound confirm the type by itself?

Not always.

Ultrasound findings can be misleading because:

• Adrenal nodules may be incidental

• Both adrenal glands may contain lesions

• Pituitary and adrenal abnormalities may occur together

• A cortisol-producing adrenal tumour can be bilateral

• Normal adrenal size varies with body size

• The opposite gland may not be visualised clearly

• Operator experience affects interpretation

• Ultrasound cannot always determine tumour invasion accurately

A study using CT identified concurrent pituitary and adrenal lesions in 5% of dogs with spontaneous hypercortisolism and in 10% of dogs with non-suppressing dexamethasone results.

This is why an adrenal mass should not automatically be blamed for the cortisol excess.

Does an Adrenal Mass Prove Adrenal-Dependent Cushing’s?

No.

An adrenal mass may be:

• A cortisol-producing cortical tumour

• A non-functional cortical tumour

• A pheochromocytoma

• An aldosterone-producing lesion

• Metastatic disease

• An incidental age-related adrenal nodule

• A concurrent lesion in a dog whose Cushing’s is actually pituitary-dependent

The diagnosis becomes much stronger when several findings agree:

• Cushing’s syndrome has been confirmed

• Endogenous ACTH is suppressed

• One adrenal gland contains a mass

• The opposite adrenal gland is small

• No pituitary-dependent suppression pattern is present

A unilateral adrenal mass with normal or elevated endogenous ACTH and a normal or enlarged opposite gland raises the possibility that the adrenal lesion is incidental or concurrent rather than the source of cortisol.

Does Adrenal Tumour Size Predict Cancer?

Tumour size may influence concern, but no single measurement can reliably classify an adrenal tumour as benign or malignant.

Features that are generally more concerning include:

• Irregular margins

• Heterogeneous contrast enhancement

• Invasion into adjacent blood vessels

• Invasion into surrounding organs

• Enlarged regional lymph nodes

• Evidence of distant metastasis

• Rapid growth over time

CT studies show that tumour type and vascular invasion are better assessed using a combination of imaging features rather than one diameter cut-off. Recent data also show overlap in the size of different adrenal cortical tumour categories.

The claim that every adrenal tumour above a particular size is malignant is therefore too absolute.

When Is Abdominal CT Recommended?

Abdominal CT is usually recommended before adrenalectomy.

It can help assess:

• Exact tumour dimensions

• Relationship with the kidneys, liver and pancreas

• Phrenicoabdominal vein involvement

• Renal vein involvement

• Caudal vena cava invasion

• Presence and extent of a tumour thrombus

• Regional lymph nodes

• The opposite adrenal gland

• Possible metastatic disease

• Surgical approach and anticipated complexity

Vascular invasion is particularly important because it can substantially change surgical planning and perioperative risk.

CT is not simply a more expensive way of repeating an ultrasound. Its primary value is detailed staging and surgical planning once an adrenal tumour is considered clinically important.

When Is Pituitary CT or MRI Recommended?

Brain imaging is most useful when:

• Neurological signs are present

• An enlarging pituitary macroadenoma is suspected

• Radiation treatment is being considered

• Hypophysectomy is being considered

• Pituitary size would influence prognosis or treatment

• Differentiation remains unresolved after other testing

Possible neurological signs include:

• Behavioural change

• Reduced awareness

• Circling

• Pacing

• Seizures

• Visual abnormalities

• Loss of learned behaviour

• Reduced appetite

• Marked changes in sleep or interaction

AAHA guidance specifically recommends considering pituitary CT in dogs with signs compatible with a macroadenoma or when radiation therapy or hypophysectomy would be pursued.

Does a normal pituitary scan exclude pituitary disease?

No.

Many ACTH-producing pituitary tumours are small. A microscopic or very small tumour may not produce obvious enlargement on CT or MRI.

In one CT study, a substantial proportion of dogs with biochemically supported pituitary-dependent disease did not have an enlarged pituitary gland. Imaging should therefore be interpreted as part of the whole investigation rather than as an absolute yes-or-no test.

How Do Vets Put the Results Together?

No individual test should be expected to answer every question.

Pattern strongly supporting pituitary-dependent disease

• Confirmed Cushing’s syndrome

• Suppression during the LDDST or HDDST

• Endogenous ACTH that is normal, measurable or elevated

• Two relatively symmetrical adrenal glands

• A pituitary lesion on CT or MRI, when visible

Pattern strongly supporting adrenal-dependent disease

• Confirmed Cushing’s syndrome

• No suppression during dexamethasone testing

• Low or undetectable endogenous ACTH

• A unilateral adrenal mass

• A small contralateral adrenal gland

• CT findings compatible with a cortisol-producing adrenal tumour

Pattern requiring further investigation

• No suppression but endogenous ACTH is not suppressed

• A unilateral adrenal mass but the opposite gland is normal or enlarged

• A pituitary mass and an adrenal mass are both present

• Both adrenal glands contain nodules or masses

• Endogenous ACTH is within an equivocal range

• Ultrasound and hormone results disagree

• The clinical signs do not fit the diagnosis

Discordant cases should not be forced into the most statistically common category. They may require repeat testing, advanced imaging or internal medicine referral.

A Practical Classification Pathway for Dogs

Step 1: Confirm naturally occurring Cushing’s syndrome

Use the clinical presentation, routine laboratory results and an appropriate endocrine test.

Do not attempt to classify disease from an adrenal image or high ALP result alone.

Step 2: Review the LDDST pattern

If the test confirms Cushing’s and shows appropriate partial suppression, pituitary-dependent disease is supported.

If there is no suppression, treat the result as unclassified rather than labelling it adrenal-dependent.

Step 3: Measure endogenous ACTH

A measurable or elevated result supports pituitary-dependent disease.

A low or undetectable result supports adrenal-dependent disease.

Confirm that the sample was collected and handled according to the laboratory’s protocol.

Step 4: Image both adrenal glands

Assess:

• Symmetry

• Shape

• Internal structure

• Contralateral gland size

• Vascular invasion

• Other abdominal disease

Step 5: Choose advanced imaging according to the likely source

If adrenal-dependent disease is suspected and surgery is possible, perform abdominal CT.

If pituitary-dependent disease is suspected and neurological signs, radiation or hypophysectomy are relevant, perform brain CT or MRI.

Step 6: Reassess conflicting findings

Do not select a treatment based on whichever single result appears most dramatic.

The best classification comes from agreement between endocrine physiology and imaging anatomy.

How Is Cushing’s Syndrome Classified in Cats?

Feline hypercortisolism is uncommon and often more difficult to investigate.

Most affected cats have:

• Concurrent diabetes mellitus

• Difficult diabetic regulation

• Muscle weakness

• Abdominal distension

• Poor hair regrowth

• Thin or fragile skin

• Skin that tears easily

Most difficult-to-regulate diabetic cats do not have Cushing’s syndrome, so insulin technique, hypersomatotropism, infection, pancreatitis and other more common causes should be considered first.

The feline LDDST

Cats require a higher dexamethasone dose than dogs:

• 0.1 mg/kg intravenously

• Baseline cortisol

• Four-hour cortisol

• Eight-hour cortisol

Failure to suppress at four or eight hours supports feline Cushing’s syndrome. The same broad suppression principles may help classification, but feline results should be interpreted cautiously because the disease is rare and published case numbers are limited.

Endogenous ACTH in cats

The physiological interpretation is similar:

• Measurable or elevated ACTH supports pituitary-dependent disease

• Suppressed ACTH supports an autonomous adrenal source

However, endogenous ACTH should be combined with adrenal imaging rather than treated as an isolated answer.

Adrenal imaging in cats

A unilateral adrenal mass with a small opposite gland and suppressed ACTH supports adrenal-dependent disease.

Two relatively symmetrical adrenal glands with measurable ACTH support pituitary-dependent disease.

CT or MRI of the pituitary may be recommended when hypophysectomy, radiation or a pituitary mass is being considered.

What about the feline HDDST?

Suppression during a high-dose dexamethasone test supports pituitary-dependent disease.

Failure to suppress remains inconclusive because some cats with pituitary-dependent disease also fail to suppress. Imaging and endogenous ACTH are still needed when classification will change treatment.

Can the ACTH stimulation test classify feline disease?

No.

The ACTH stimulation test has poor sensitivity for diagnosing feline Cushing’s syndrome and should not be relied upon as the main diagnostic or classification test.

How Does Classification Change Treatment?

Pituitary-dependent Cushing’s in dogs

Common treatment options include:

• Trilostane

• Mitotane

• Transsphenoidal hypophysectomy in specialist centres

• Radiation therapy for selected pituitary tumours

Trilostane controls adrenal cortisol production but does not remove the pituitary tumour. Dogs with an enlarging pituitary mass may therefore need separate treatment directed at the tumour itself.

Adrenal-dependent Cushing’s in dogs

Adrenalectomy is the preferred definitive treatment when the tumour is resectable and the dog is an appropriate surgical candidate.

Medical treatment with trilostane or mitotane may be used when:

• Surgery is declined

• The tumour cannot be safely removed

• Metastatic disease is present

• The patient is not a suitable anaesthetic candidate

• Medical stabilisation is needed before surgery

Classification therefore determines whether the abnormal tumour itself can potentially be removed rather than merely controlling cortisol production.

Pituitary-dependent Cushing’s in cats

Trilostane is the most commonly used medical treatment. Radiation therapy may help selected cats with pituitary-dependent disease, and hypophysectomy is available through a small number of specialist centres.

Adrenal-dependent Cushing’s in cats

Adrenalectomy may be curative for a cat with a unilateral functional adrenal tumour.

Because feline Cushing’s is uncommon and many cats have significant diabetes or fragile skin, surgical planning and postoperative care require considerable experience.

Can Treatment Begin Before the Type Is Known?

Yes, in some cases.

A dog with confirmed Cushing’s may begin trilostane before full classification when:

• The owner would not pursue adrenalectomy

• Advanced imaging is unavailable

• Medical control is the chosen treatment regardless of type

• The patient needs cortisol control while further investigation is planned

However, classification should not be skipped when an adrenal tumour might be surgically removed or a pituitary mass may require direct treatment.

The important distinction is between not knowing because the answer would not change management and not knowing because the investigation stopped too early.

How Urgent Is Cushing’s Classification?

Classification is usually not an emergency in an otherwise stable patient.

Situation	What it means	Recommended action
Stable	Confirmed Cushing’s, eating normally, comfortable and awaiting differentiation	Arrange classification testing on a planned basis
Needs prompt review	Worsening thirst, urination, panting, weakness or poor diabetic regulation	Contact the veterinary clinic within the next few days
Urgent	Reduced appetite, vomiting, diarrhoea, marked lethargy, rapid deterioration or new neurological signs	Seek same-day veterinary assessment
Emergency	Collapse, seizures, severe breathing difficulty, inability to stand or reduced consciousness	Go to an emergency veterinary hospital immediately

Anorexia, vomiting and diarrhoea are not typical signs of uncomplicated canine hypercortisolism. They may indicate diabetic ketoacidosis, pancreatitis, gallbladder disease, pulmonary thromboembolism, infection, medication-associated hypocortisolism or another acute illness.

When Is It an Emergency?

Seek immediate veterinary care if a dog or cat with known or suspected Cushing’s develops:

• Collapse

• Seizures

• Severe weakness

• Inability to stand

• Reduced consciousness

• Sudden major behavioural change

• Circling or other neurological abnormalities

• Rapid or laboured breathing

• Repeated vomiting

• Complete refusal of food

• Severe dehydration

• Signs of diabetic ketoacidosis

• Rapid deterioration over several hours

In a patient with a known pituitary tumour, new neurological signs may indicate enlargement of the pituitary mass rather than simply worsening cortisol excess. The acute problem should be stabilised before elective classification testing is continued.

What Should You Do Next?

1. Confirm whether Cushing’s has actually been established

Ask which test confirmed the disease and whether the result fits the pet’s clinical signs.

2. Obtain the complete dexamethasone results

Do not rely only on being told that the test was “positive”.

Ask for:

• Baseline cortisol

• Four-hour cortisol

• Eight-hour cortisol

• Laboratory suppression threshold

• Percentage suppression from baseline

The pattern may already support pituitary-dependent disease.

3. Decide whether classification will change treatment

Discuss whether the owner would consider:

• Adrenalectomy

• Pituitary surgery

• Radiation

• Advanced imaging

• Medical treatment regardless of type

4. Measure endogenous ACTH correctly

Confirm the laboratory’s collection, storage and shipping requirements before obtaining the sample.

5. Image both adrenal glands

Do not assess only the obvious mass. The size and appearance of the opposite gland provide important physiological information.

6. Use CT or MRI when it will answer a treatment question

Abdominal CT is most useful for adrenal surgical planning.

Pituitary CT or MRI is most useful when neurological disease or pituitary-directed treatment is relevant.

7. Refer conflicting cases

Internal medicine referral is appropriate when:

• Hormone and imaging results disagree

• Both pituitary and adrenal lesions are present

• Bilateral adrenal masses are found

• The endogenous ACTH result is equivocal

• The diagnosis remains uncertain

• Surgery or radiation is being considered

Common Classification Mistakes

Assuming no dexamethasone suppression means an adrenal tumour

A significant proportion of dogs with pituitary-dependent disease do not suppress.

Calling an adrenal nodule the cause without endocrine evidence

An adrenal mass can be incidental or concurrent with pituitary-dependent disease.

Using the ACTH stimulation test to determine the type

The ACTH stimulation test does not reliably distinguish pituitary-dependent from adrenal-dependent disease.

Ignoring the opposite adrenal gland

A small contralateral gland supports an autonomous cortisol-producing adrenal tumour. A normal or enlarged contralateral gland may suggest continued pituitary ACTH stimulation.

Trusting one tumour-size threshold

Size contributes to assessment but cannot independently classify an adrenal tumour as benign or malignant.

Mishandling the endogenous ACTH sample

ACTH degradation can produce a falsely low result and an incorrect adrenal classification.

Ordering advanced imaging without deciding how the result will be used

CT and MRI are most valuable when they guide surgery, radiation, prognosis or another meaningful treatment decision.

Assuming the statistically common type must be correct

Pituitary disease is more common, but probability should not replace proper classification when the result changes treatment.

Performing endocrine tests during acute illness

Stress and non-adrenal illness can produce misleading cortisol results. Stabilise the acute problem first whenever possible.

How Can Misleading Results Be Reduced?

The risk of incorrect classification can be reduced by:

• Testing only when the clinical suspicion of Cushing’s is strong

• Stabilising important concurrent disease first

• Waiting approximately two to four weeks after recovery from a significant acute illness when practical

• Reviewing all glucocorticoid exposure

• Allowing appropriate withdrawal periods after steroid medication

• Using the receiving laboratory’s sample protocol

• Interpreting laboratory-specific cortisol cut-offs

• Combining endocrine and imaging findings

• Imaging both adrenal glands

• Obtaining specialist review when findings conflict

AAHA advises avoiding endocrine testing within approximately two weeks of short-acting glucocorticoid exposure and up to four weeks after some longer-acting glucocorticoids. Medication should never be stopped abruptly without veterinary instructions.

Frequently Asked Questions

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

Sometimes. Partial suppression supports pituitary-dependent disease. Failure to suppress is inconclusive and does not prove adrenal-dependent disease.

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

No. The mass may be non-functional, incidental or concurrent with pituitary disease. Endogenous ACTH, the opposite adrenal gland and the complete endocrine pattern must also be assessed.

What is the most useful blood test for distinguishing pituitary from adrenal Cushing’s?

Endogenous ACTH is one of the most direct biochemical classification tests. Normal or elevated ACTH supports pituitary disease, while suppressed ACTH supports an autonomous adrenal source. Correct sample handling is essential.

Does every dog with Cushing’s need a CT scan?

No. Abdominal CT is most useful before adrenal surgery, while brain CT or MRI is most useful when neurological signs, radiation or pituitary surgery are relevant. Dogs being managed medically may not require advanced imaging when the result would not change treatment.

Can Cushing’s be treated before the source is classified?

Yes. Trilostane can control cortisol production in both pituitary-dependent and adrenal-dependent disease. Classification becomes particularly important when definitive surgery or pituitary-directed treatment is being considered.

Final Takeaway

Classifying Cushing’s syndrome is not about choosing whichever test result looks most dramatic.

A suppression pattern during the LDDST supports pituitary-dependent disease, but failure to suppress does not diagnose an adrenal tumour. Endogenous ACTH provides direct information about whether the pituitary is still stimulating the adrenal glands, while ultrasound and CT show what the glands physically look like.

The strongest classification occurs when the physiology and anatomy agree:

• Suppression, measurable ACTH and two stimulated adrenal glands support pituitary-dependent disease.

• Suppressed ACTH, a unilateral adrenal mass and a small opposite gland support adrenal-dependent disease.

When the findings conflict, do not force the patient into the most common category. Concurrent pituitary and adrenal lesions occur, small pituitary tumours may be invisible and adrenal nodules may be incidental.

Most importantly, classification should answer a treatment question. It matters most when adrenalectomy, pituitary surgery, radiation or prognosis will be influenced by the result.

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If you are unsure what your pet’s dexamethasone results, endogenous ACTH level or adrenal imaging means, ASK A VET™ can help you organise the findings and understand what questions to discuss with your veterinarian next.