Cushing's Disease

TL;DR. Cushing's disease is a common hormonal disorder in older pets, primarily dogs, caused by the overproduction of cortisol. It leads to symptoms like excessive thirst, increased urination, hair loss, and a pot-bellied appearance, and requires careful diagnostic testing and lifelong management.

Cushing's disease is caused by a breakdown in communication between the pituitary gland in the brain and the adrenal glands near the kidneys.

What is it?

Cushing's disease, known scientifically as hyperadrenocorticism, is a common endocrine (hormonal) disorder that primarily affects middle-aged to older dogs, and occasionally cats. The disease is characterized by the chronic overproduction of cortisol, a vital hormone produced by the adrenal glands. Cortisol plays a crucial role in regulating blood sugar, managing stress, controlling weight, fighting infections, and keeping skin and muscles healthy. However, when the body is constantly flooded with too much cortisol, these normal processes break down, leading to a wide range of systemic symptoms.

To understand Cushing's disease, it helps to understand the communication loop between the brain and the abdomen. Under normal conditions, the pituitary gland—a tiny, pea-sized master gland located at the base of the brain—secretes a chemical messenger called adrenocorticotropic hormone (ACTH). This hormone travels through the bloodstream to the adrenal glands, which are located just ahead of the kidneys. In response to ACTH, the adrenal glands produce and release cortisol. In a healthy pet, when cortisol levels rise, the brain detects this and dials back its production of ACTH. In a pet with Cushing's disease, this feedback loop is broken, resulting in continuous, unregulated cortisol production.

There are two primary forms of spontaneous Cushing's disease:

• Pituitary-Dependent Hyperadrenocorticism (PDH): This is by far the most common form, accounting for the vast majority of cases. It is caused by a tumor on the pituitary gland. As noted in a leading veterinary internal medicine reference:

  "Pituitary-dependent hyperadrenocorticism (PDH) is the most common cause of spontaneous hyperadrenocorticism, accounting for approximately 80% to 85% of cases. A functional adrenocorticotropic hormone (ACTH)–secreting pituitary tumor is found at necropsy in approximately 85% of dogs with PDH."

• Adrenal-Dependent Hyperadrenocorticism (ATH): This form is caused by a tumor directly on one of the adrenal glands. The tumor autonomously secretes cortisol regardless of what the pituitary gland tells it to do. According to a standard veterinary dermatology reference:

  "The disease is caused by a hyperfunctioning adrenal tumor (15%–20% of cases) or pituitary tumor (80%–85% of cases). Pituitarydependent hyperadrenocorticism (PDH) is caused by excessive production of adrenocorticotropic hormone (ACTH), usually from a pituitary microadenoma or macroadenoma."

There is also a third form called iatrogenic hyperadrenocorticism, which is not caused by a tumor but rather by the external administration of steroid medications. This occurs when pets receive high doses or long-term courses of glucocorticoids (such as prednisone or dexamethasone) to treat allergies, skin conditions, or immune-mediated diseases. Even topical medications can cause this issue, particularly in smaller pets.

Causes & risk factors

The primary cause of spontaneous Cushing's disease is the development of a tumor. In pituitary-dependent cases (PDH), the tumor is typically a benign microadenoma (a very small tumor), though occasionally it can be a larger macroadenoma. In adrenal-dependent cases (ATH), the tumor can be either benign (an adenoma) or malignant (an adrenocortical carcinoma).

For iatrogenic Cushing's, the cause is purely environmental and treatment-related. A leading veterinary textbook explains the risk factors for this form:

"Iatrogenic hyperadrenocorticism typically results from excessive administration of glucocorticoids to control allergic or immune-mediated disorders. It can also develop as a result of the administration of eye, ear, or skin medications containing glucocorticoids, especially in small dogs (weight < 10 kg) receiving them long term."

While Cushing's disease can develop in any dog or cat, it is most frequently diagnosed in middle-aged to older animals. In dogs, several breeds are suspected to have a genetic predisposition to the disease. These include:

• Boxer
• Boston Terrier
• Dachshund
• Poodle
• Scottish Terrier
• German Shepherd Dog
• Beagle
• Labrador Retriever

In cats, Cushing's disease is rare. When it does occur, it is often associated with concurrent, severe insulin-resistant diabetes mellitus, making it a particularly challenging condition to manage in felines.

Signs to watch for

The signs of Cushing's disease develop gradually, often over several months or even years. Because many of these signs are associated with normal aging, owners sometimes overlook them in the early stages. However, as cortisol levels remain persistently high, the clinical signs become more pronounced.

Common Signs

• Polydipsia (excessive thirst): Your pet may drink significantly more water than usual, empty their water bowl frequently, or seek out unusual water sources.
• Polyuria (increased urination): Due to increased water intake, your pet will urinate more frequently and in larger volumes. House-trained pets may begin having accidents indoors or need to go out in the middle of the night.
• Polyphagia (excessive appetite): Pets often develop an insatiable appetite. They may beg constantly, steal food, or rummage through garbage.
• Abdominal enlargement: Often described as a "pot-bellied" appearance. This occurs because cortisol causes fat to redistribute to the abdomen while simultaneously weakening and wasting the abdominal muscles.
• Endocrine alopecia (hair loss): Symmetrical hair loss that typically affects the trunk, sides, and neck, while sparing the head and legs. The remaining coat may become dry, dull, and slow to regrow.
• Thin skin: The skin loses its elasticity and becomes fragile, sometimes tearing easily. Blood vessels may become visible through the skin.
• Panting: Excessive, heavy panting even when the pet is resting, in a cool environment, or inactive.
• Muscle weakness: Your pet may have difficulty climbing stairs, jumping onto furniture, or rising from a lying position due to muscle wasting.

Occasional Signs

• Calcinosis cutis: The development of hard, gritty, yellowish-white calcium deposits within the skin, which can become itchy, inflamed, and secondary infected.
• Neurologic signs: If a pituitary tumor grows large (a macrotumor), it can press on surrounding brain tissue, causing signs such as stupor, head pressing, circling, behavior changes, or blindness.
• Pulmonary thromboembolism: High cortisol levels make the blood more prone to clotting. A blood clot in the lungs is a life-threatening emergency characterized by sudden, severe difficulty breathing and collapse.

A pot-bellied abdomen and symmetrical hair loss are classic physical signs of Cushing's disease in dogs.

How vets diagnose it

Diagnosing Cushing's disease is rarely straightforward. Because the symptoms overlap with several other senior pet conditions, your vet will need to perform a combination of routine blood work, urinalysis, specific hormone tests, and imaging studies. No single test is 100% accurate, and a step-by-step diagnostic approach is required.

Your vet will start with baseline testing, including a complete blood count, chemistry panel, and urinalysis. Pets with Cushing's often show elevated liver enzymes (specifically alkaline phosphatase, or ALP), elevated cholesterol, and dilute urine. They may also have silent urinary tract infections due to cortisol's immunosuppressive effects.

If these baseline tests suggest Cushing's, your vet will recommend specific endocrine tests to confirm the diagnosis and determine whether the disease is pituitary- or adrenal-dependent:

• Urine Cortisol/Creatinine Ratio (UCCR): This is a highly sensitive screening test performed on a urine sample collected at home (to minimize stress). A normal result strongly suggests your pet does not have Cushing's. However, an elevated result does not confirm the disease, as stress or other illnesses can also raise cortisol levels. It is used primarily to rule out the condition.
• Low-Dose Dexamethasone Suppression (LDDS) Test: This is considered the gold standard diagnostic test. Your vet will take a baseline blood sample, inject a tiny dose of a synthetic steroid (dexamethasone), and take subsequent blood samples 4 and 8 hours later. In a healthy pet, the body detects the synthetic steroid and suppresses its own cortisol production. In a pet with Cushing's, this suppression fails to occur or occurs only temporarily.
• ACTH Stimulation Test: This test measures how the adrenal glands respond to a synthetic version of the brain hormone ACTH. Blood is drawn before and one hour after the injection. Pets with Cushing's typically show an exaggerated, highly elevated cortisol response. This test is also the primary tool used to monitor treatment.
• High-Dose Dexamethasone Suppression (HDDS) Test: If Cushing's is confirmed but the vet needs to determine the underlying cause (PDH vs. ATH), a higher dose of dexamethasone can be used. Pituitary tumors will often suppress cortisol in response to a high dose, whereas adrenal tumors will not.
• Abdominal Ultrasound: This imaging tool allows your vet to physically evaluate the adrenal glands. Symmetrical enlargement of both glands suggests PDH, while a single large, irregular mass on one gland with a shrunken opposite gland suggests ATH.
• Endogenous ACTH Concentration: This blood test measures the actual level of ACTH in circulation. It is highly useful for differentiating PDH from ATH, particularly in cats. As a leading reference notes:

  "Plasma ACTH concentrations below the reference range, especially undetectable results, are consistent with ATH, and plasma ACTH concentrations in the upper half of the reference range or increased are consistent with PDH in cats."

• CT or MRI: Advanced imaging of the brain may be recommended if a pituitary macrotumor is suspected, especially if the pet is showing neurologic signs.

To summarize the diagnostic strategy, a leading internal medicine textbook outlines:

"Tests that I commonly use to establish the diagnosis of hyperadrenocorticism are UCCR in conjunction with the LDDS test, and tests that I commonly use to identify the cause (i. e. , PDH versus ATH) include the LDDS test and abdominal ultrasound. The HDDS test can be used if abdominal ultrasound is not available. An endogenous ACTH concentration is evaluated when abdominal ultrasound suggests an ad..."

An abdominal ultrasound is a vital diagnostic tool used to evaluate the size and shape of your pet's adrenal glands.

Treatment options

Treatment for Cushing's disease depends on the underlying cause (pituitary vs. adrenal) and the severity of the clinical signs. The goal of therapy is not necessarily to cure the disease, but to control the overproduction of cortisol and restore a good quality of life.

First-Line Medical Therapy

• Trilostane (Adrenal Steroid Synthesis Inhibitor): This is the most common and widely preferred medication for both PDH and ATH in dogs. Trilostane works by selectively blocking the enzyme (3-beta-hydroxysteroid dehydrogenase) required to produce cortisol. It is given daily with food. Because its effects are reversible, your vet will need to perform regular monitoring tests (usually ACTH stimulation tests or pre-pill cortisol checks) to ensure the dose is safe and effective.

Second-Line Medical Therapy

• Mitotane (Adrenal Cytotoxic Agent / Antineoplastic): Mitotane is an older, highly effective medication that works by chemically destroying the cortisol-producing layers of the adrenal cortex. Treatment is divided into an "induction" phase (given daily to quickly wear down the adrenal gland) followed by a "maintenance" phase (given once or twice weekly). Mitotane requires extremely close monitoring, as overdosage can destroy too much of the gland, causing a permanent life-threatening deficiency in adrenal hormones (Addison's disease).

Alternative Medical Therapies

• Ketoconazole (Azole Antifungal): While primarily an antifungal medication, ketoconazole has a side effect of inhibiting cortisol synthesis. It is sometimes used in dogs that cannot tolerate trilostane or mitotane, though it is generally less effective.
• Metyrapone (Adrenal Steroid Inhibitor): This drug blocks a specific step in cortisol synthesis. It is rarely used in dogs but is occasionally utilized in cats to stabilize cortisol levels before surgery.

Surgical Therapy

• Adrenalectomy: For dogs with adrenal-dependent Cushing's (ATH), surgical removal of the affected adrenal gland can be curative if the tumor is benign and has not spread. However, this is a highly complex, high-risk surgery that is typically performed by a board-certified veterinary surgeon.

Prognosis

The prognosis for pets with Cushing's disease is highly variable and depends on several factors, including the type of Cushing's (PDH vs. ATH), the size of the tumor, the pet's age, and the presence of secondary medical complications.

For dogs with pituitary-dependent Cushing's (PDH) that are managed successfully with medication, the prognosis is generally good. Many dogs live comfortably for two to four years or more after diagnosis, often dying of unrelated age-related conditions rather than Cushing's itself. The treatment significantly improves their quality of life, reversing symptoms like excessive thirst, panting, and hair loss.

However, the prognosis is more guarded if the pet develops secondary complications. These include severe infections, insulin-resistant diabetes, or a life-threatening pulmonary thromboembolism. Additionally, if a pituitary tumor grows large enough to cause neurologic signs (macrotumor syndrome), the prognosis becomes poor unless radiation therapy or specialized brain surgery is performed.

For cats, the prognosis is generally guarded. Felines with Cushing's are often extremely fragile, have severe skin tearing issues, and are highly susceptible to secondary infections and difficult-to-control diabetes.

Prevention

Spontaneous Cushing's disease (PDH and ATH) is caused by naturally occurring tumors and cannot be prevented. There are no lifestyle changes, diets, or vaccines that can prevent these tumors from forming.

However, iatrogenic Cushing's is entirely preventable. If your pet requires steroid therapy for a chronic condition, your vet will work to find the lowest effective dose and taper the medication as quickly as possible. As an owner, you can help prevent this form of the disease by strictly following your vet's dosing instructions for any oral, topical, ear, or eye medications containing glucocorticoids, and by never administering leftover steroid medications without veterinary supervision.

When to call your vet

If your pet is currently being treated for Cushing's disease, or if you suspect they may be developing the condition, close observation is key.

You should schedule a non-emergency appointment if you notice:

• A gradual increase in water consumption or urination frequency.
• Symmetrical hair loss or changes in skin quality.
• A progressive loss of muscle mass or a sagging, pot-bellied abdomen.
• Persistent, heavy panting.

Seek immediate emergency veterinary care if your pet exhibits any of the following red-flag signs:

• Sudden, severe difficulty breathing or rapid, shallow breathing (a primary sign of a blood clot in the lungs).
• Extreme lethargy, weakness, or collapse.
• Vomiting, diarrhea, or a complete refusal to eat, especially if your pet is currently taking Trilostane or Mitotane (this can indicate a dangerous drop in cortisol levels, known as an Addisonian crisis).
• Neurologic signs such as seizures, constant circling, head pressing against walls, or sudden blindness.

For specific breeds

If you own a Boxer, Boston Terrier, Dachshund, Poodle, Scottish Terrier, German Shepherd Dog, Beagle, or Labrador Retriever, you should be particularly vigilant for the early signs of Cushing's disease. Because these breeds are suspected to have a genetic predisposition, routine senior wellness blood work and urinalysis are highly recommended starting around seven years of age. Catching the disease early, before severe muscle wasting or skin changes occur, allows for much smoother management and a better long-term quality of life for your pet.

Sources

• Small Animal Internal Medicine, 5th Edition, pp. 858, 859, 866, 882.
• Small Animal Dermatology: A Color Atlas and Therapeutic Guide, p. 301.

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