What Are the Three Stages of Cushing’s Disease in Dogs?

Cushing’s disease in dogs does not have a formal, universally recognized three-stage classification in veterinary medicine. No major veterinary textbook or professional guideline breaks the condition into numbered stages the way cancer staging works. What pet owners typically encounter online as “three stages” is a practical way of describing how the disease tends to progress: early and easily missed signs, a middle phase where the classic Cushing’s appearance develops, and a late phase where serious complications set in. That framework is useful for understanding the trajectory of the illness, but it is informal, and the boundaries between phases are blurry rather than sharp.

Why the “Three Stages” Idea Exists

Cushing’s disease, formally called hyperadrenocorticism, is caused by chronic overproduction of cortisol, usually driven by a tiny tumor on the pituitary gland (about 80 to 85 percent of cases) or less commonly by a tumor on one of the adrenal glands. The disease develops slowly, over months to years, and cortisol’s effects accumulate gradually. Because the earliest signs overlap with normal aging, many owners look back after diagnosis and realize their dog had subtle symptoms long before they sought veterinary attention. This slow, cumulative progression is what makes it natural to describe Cushing’s in phases, even though the veterinary profession does not formally stage it.

Phase One: The Subtle Early Signs

The first changes owners tend to notice are increased thirst and more frequent urination. A dog that used to make it through the night may start needing to go outside at 3 a.m., or may begin having accidents indoors. Appetite often picks up around the same time, sometimes dramatically. These signs are driven by cortisol’s effects on the kidneys and metabolism. Chronic cortisol elevation causes increased thirst, excessive eating, and early weight gain.¹

The trouble is that these early signs are easy to dismiss. Increased thirst can be blamed on warm weather, a dietary change, or simply getting older. A bigger appetite might seem like a good thing in a dog that was previously a picky eater. Many owners report that they noticed these changes in hindsight but did not connect them to a medical problem at the time. Veterinarians often say the same thing: the dog may have had abnormal bloodwork at a routine check, with a mildly elevated liver enzyme called alkaline phosphatase, but without more obvious clinical signs, the finding was noted and monitored rather than pursued aggressively.

Phase Two: The Classic Cushing’s Appearance

As cortisol levels remain high over weeks and months, the visible changes become harder to ignore. Dogs develop a distinctive look that experienced veterinarians can spot from across an exam room. The hallmarks include a pot-bellied appearance caused by weakened abdominal muscles and fat redistribution, symmetrical hair loss (often on the trunk and flanks while sparing the head and legs), and thin, fragile skin that bruises easily or develops dark patches. Muscle wasting becomes apparent, especially in the hind legs, and the dog may pant excessively even at rest.

Excessive cortisol weakens muscle and redistributes fat to the abdomen, creating that characteristic barrel shape. Dogs with Cushing’s typically show weight gain combined with muscle weakness and hair loss.¹ Skin infections and urinary tract infections become more common because cortisol suppresses the immune system. Some dogs develop hard, mineralized plaques on the skin called calcinosis cutis, which look like rough, chalky patches. These skin changes are among the more specific signs that prompt veterinarians to test for Cushing’s rather than treating the infections one at a time.

This middle phase is where most dogs get diagnosed. The combination of a pot belly, hair loss, increased drinking, and recurrent infections forms a recognizable pattern. It is also when owners typically report the biggest change in their dog’s quality of life: the dog may be less playful, slow to climb stairs, and reluctant to go on walks.

Phase Three: Serious Complications

Left untreated or poorly controlled, Cushing’s disease sets the stage for complications that can become life-threatening. The most common and clinically significant ones are high blood pressure, blood clots, and diabetes.

High Blood Pressure

Systemic hypertension is strikingly common in dogs with Cushing’s. One study found that about 82 percent of dogs with spontaneous hyperadrenocorticism had blood pressure readings at or above 150 mmHg, and nearly half had severe hypertension above 180 mmHg.² In a separate cohort of dogs with adrenal-dependent Cushing’s, roughly four out of five were hypertensive at diagnosis.³ Sustained high blood pressure can damage the kidneys, eyes, heart, and brain, sometimes producing symptoms like sudden blindness from retinal detachment.

Blood Clots

Cushing’s dogs are prone to a hypercoagulable state, meaning their blood clots too readily. Research has shown that the vast majority of dogs with Cushing’s show signs of this tendency, and the risk does not appear to depend on how long the dog has been symptomatic.⁴ Blood clots can lodge in the lungs (pulmonary thromboembolism), the large vessels of the abdomen, or other critical sites. A case report documented thrombi in both the abdominal aorta and the pulmonary artery in a Cushing’s dog, underscoring how dangerous this complication can be.⁵ Pulmonary thromboembolism is one of the leading causes of sudden death in dogs with uncontrolled Cushing’s.

Diabetes

Cortisol directly opposes insulin’s action, making the body’s cells resistant to the signal that tells them to absorb glucose. Over time, this insulin resistance can push a dog into full-blown diabetes mellitus. Cushing’s syndrome is one of the most common causes of insulin resistance in diabetic dogs, and the cortisol-driven effects include erratic blood sugar swings and a perceived short duration of insulin action.⁶ Managing a dog with both Cushing’s and diabetes simultaneously is a challenge because the conditions amplify each other: uncontrolled cortisol makes diabetes harder to stabilize, and the metabolic stress of diabetes complicates Cushing’s management.⁷

Getting a Diagnosis

Diagnosing Cushing’s is not as straightforward as running a single test. Veterinarians typically start with bloodwork and a urinalysis, looking for patterns like elevated liver enzymes, high cholesterol, dilute urine, and sometimes a mildly elevated blood glucose. These findings raise suspicion but are not diagnostic on their own. From there, specific hormone tests are used.

The two most common screening tests are the ACTH stimulation test and the low-dose dexamethasone suppression test (LDDST). The ACTH stimulation test measures how aggressively the adrenal glands respond to a synthetic hormone injection. It is reasonably specific when clinical suspicion is high, meaning a positive result in a dog that looks like a Cushing’s case is fairly reliable, but it is not very sensitive: a negative result does not rule the disease out.⁸ The LDDST catches more true cases but is also more likely to give false positives, especially in dogs that are stressed or have other illnesses.

Once Cushing’s is confirmed, the next step is figuring out whether the problem originates in the pituitary or the adrenal gland, because treatment decisions depend on the answer. The high-dose dexamethasone suppression test, measurement of blood ACTH levels, and imaging with CT or ultrasound all help distinguish between the two forms.⁹ Adrenal ultrasound can reveal whether both glands are enlarged (suggesting pituitary-driven disease) or whether one gland has a mass while the other has shrunk (suggesting an adrenal tumor).¹⁰

Treatment Options

For most dogs, Cushing’s is managed medically rather than surgically. Trilostane is the first-line drug in most countries. It works by reversibly blocking an enzyme the adrenal glands need to produce cortisol, which lowers cortisol levels without permanently damaging the gland tissue. This reversibility is a practical advantage: if the dose turns out to be too high, cortisol production can recover once the drug is adjusted.¹¹

Mitotane, the older alternative, works by a completely different mechanism: it actually destroys portions of the adrenal cortex. It can be effective, but carries a higher risk of causing the opposite problem, an adrenal crisis where the dog’s cortisol drops dangerously low. For this reason, mitotane is generally reserved for cases where trilostane does not achieve adequate control.¹¹ Studies comparing the two drugs for pituitary-dependent Cushing’s have found that dogs treated with twice-daily trilostane had a median survival of about 900 days compared to 720 days with mitotane.¹² For adrenal-dependent cases treated with either drug, survival times were similar at around 14 to 16 months.¹³

Surgery is an option in some situations. For adrenal tumors that have not spread, surgical removal of the affected gland (adrenalectomy) can be curative, though the perioperative risks are meaningful. Transsphenoidal hypophysectomy, which removes the pituitary tumor through an approach under the base of the skull, has been performed successfully in specialized centers and compares favorably to medical management, though recurrence rates increase over time and the procedure requires significant postoperative hormone supplementation.¹⁴ Very few veterinary hospitals offer this surgery, so for most owners it is not a practical option.

What Ongoing Monitoring Looks Like

Cushing’s management is not a “set it and forget it” situation. Dogs on trilostane need regular rechecks to make sure the dose is controlling cortisol without over-suppressing it. Over-suppression can cause an Addisonian crisis, the dangerous flip side of Cushing’s, where cortisol drops so low that the dog becomes weak, vomits, collapses, or refuses to eat.

The traditional monitoring approach uses the ACTH stimulation test, but research suggests that measuring cortisol before the daily trilostane dose and again three hours after may correlate better with how the dog is actually doing clinically.¹⁵ Baseline cortisol measurements have also shown promise as a simpler screening tool: values in a certain range can reliably predict whether adrenal suppression is adequate without needing a full stimulation test every time.¹⁶

What matters just as much as lab numbers is how the dog looks and feels at home. Owners are asked to track water intake, appetite, energy level, and any return of excessive panting or skin problems. A dog whose cortisol numbers look good on paper but is still drinking excessively and losing hair may need a dose adjustment. Conversely, a dog whose cortisol is slightly above the ideal range but is clinically comfortable and active may not need a higher dose. This is why monitoring is a partnership between lab results and the owner’s daily observations.

Breeds at Higher Risk

Cushing’s can occur in any breed, but certain breeds are significantly overrepresented. A large UK primary-care study found that Bichon Frises had about six times the odds of developing Cushing’s compared to crossbreeds, Border Terriers had about five times the odds, and Miniature Schnauzers about three times the odds. On the other end, Golden Retrievers and Labrador Retrievers had notably lower risk.¹⁷ Other breeds commonly associated with Cushing’s include Poodles, Dachshunds, and Yorkshire Terriers. The disease is overwhelmingly a condition of middle-aged to older dogs, with most diagnoses occurring after age eight.

The breed predisposition suggests a genetic component, though the specific genes involved have not been clearly identified. For owners of high-risk breeds, awareness of the early signs is particularly worthwhile. A Bichon Frise that starts drinking noticeably more water and developing thinning hair at age ten deserves a closer look than a dog where these changes would be more unusual.

Atypical Cushing’s and Diagnostic Puzzles

Not every dog with Cushing’s follows the textbook pattern. A subset of dogs show many of the clinical signs, including hair loss, skin changes, and recurrent infections, but test negative on the standard ACTH stimulation and dexamethasone suppression tests. This presentation has been called “atypical” or “occult” hyperadrenocorticism. One proposed explanation is that these dogs overproduce adrenal sex hormones rather than cortisol, though this theory remains debated and has not been definitively proven.¹⁸

Research comparing dogs with atypical hyperadrenocorticism to those with the classic pituitary-dependent form found that the atypical dogs did have higher cortisol than healthy controls, just not as high as dogs with full-blown pituitary-dependent disease. Their adrenal glands were enlarged to a similar degree, suggesting that cortisol excess may still play a role even when standard tests do not flag it.¹⁹ For owners, the practical takeaway is that a negative Cushing’s test does not always mean the disease is absent, especially if the clinical picture is otherwise convincing. A veterinary internist may pursue additional testing, including adrenal sex hormone panels, to investigate further.

Iatrogenic Cushing’s Syndrome

There is a form of Cushing’s that has nothing to do with tumors. Dogs that receive corticosteroid medications (prednisone, dexamethasone, and similar drugs) for long periods or at high doses can develop the same constellation of signs: excessive thirst, pot belly, hair loss, and skin fragility. This is called iatrogenic hyperadrenocorticism, and it is worth knowing about because it is both preventable and reversible.

A study of 28 dogs with iatrogenic Cushing’s found that skin problems were nearly universal, and most also showed increased drinking and urination. Their baseline cortisol levels were low and their adrenal glands barely responded to stimulation, the opposite of what you see in the naturally occurring disease. After the corticosteroid was tapered and withdrawn, initial improvement appeared in a mean of about six weeks, with complete resolution taking roughly another 12 weeks.²⁰ In one reported case, clinical signs resolved and blood values normalized once the corticosteroid therapy was discontinued.²¹

The important distinction for owners is that iatrogenic Cushing’s does not require trilostane or mitotane. The fix is to carefully taper the steroid under veterinary supervision. Abrupt withdrawal is dangerous because the dog’s adrenal glands have been suppressed and need time to wake back up. If your dog has been on long-term steroids for allergies, autoimmune disease, or another condition and starts looking like a Cushing’s patient, bring it up with your vet rather than assuming it is a coincidence.