Cushing’s Disease in Dogs: Signs, Diagnosis, and Treatment

a.k.a. hyperadrenocorticism, HAC

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Updated on September 26, 2024
SUMMARY OF CONTENT
Persistently high levels of cortisol (a natural steroid hormone) due to overproduction by the adrenal glands. Similar symptoms can also be caused by long-term administration of steroid medications such as prednisone (iatrogenic Cushing’s disease).
SEVERITY:
Variable

  • Diagnosis Icon
    Requires a diagnosis by a veterinarian
  • Time to Cure
    This is a chronic problem that requires lifelong treatment in most cases. In cases where surgery is the recommended treatment, removal of the tumor may or may not be curative of the disease.
  • Treatment Icon
    Treatable by a veterinarian and by the pet parent
  • Prevention Icon
    Limiting the use of steroid medications may prevent iatrogenic Cushing’s disease, but there are no known preventative measures for “true” Cushings Disease.
  • Spread Icon
    Transmission is not possible between animals, or from animals to people.
  • Lab Icon
    Physical exam, blood work, ACTH stimulation test, low dose dexamethasone suppression test, urinalysis, +/- abdominal ultrasound

VERY COMMON IN
Middle-aged to older dogs. Dachshunds, Poodles, Beagles, and some terrier breeds have a higher predisposition to Cushing’s disease.

Symptoms & Signs

The most common symptoms of Cushing’s disease are drinking and urinating more than normal (polydipsia/polyuria, or PD/PU), excessive panting, thinning hair coat, and a pot-bellied appearance with loss of muscle mass along the backbone and a noticeably rounded abdomen. Many dogs also have an increased appetite (polyphagia), and may also show increased irritability or resource guarding over food. Skin problems are also seen in many dogs with Cushing’s disease, including patches of hair loss (often on both sides of the trunk); thin, fragile skin that tears easily, or recurrent skin or ear infections. In advanced cases, calcinosis cutis can also be seen. This term refers to firm patches or nodules on the trunk or abdomen, caused by calcium deposition in the skin. Urinary tract infections are very common in dogs with Cushing’s disease, so signs may include straining to urinate, blood in the urine, or urinary accidents in the house.

Diagnosis

Cushing’s disease may be suspected based on the dog’s clinical appearance and symptoms, but specialized laboratory testing is required to make a diagnosis. A basic CBC/chemistry panel may show something called a stress leukogram (increased neutrophil count, and decreased lymphocyte/eosinophil count), as well as mildly elevated levels of red blood cells and platelets. An increase in ALP (alkaline phosphatase) and sometimes ALT (alanine transferase) is seen in 85-90% of dogs with Cushing’s disease. These are all non-specific changes, but can support a diagnosis of Cushing’s disease along with other lab results. A urinalysis will usually show dilute urine (specific gravity of less than 1.020), and urine protein levels may also be elevated. Urinary tract infections are common in dogs with Cushing’s disease, so white blood cells, blood, or bacteria may also be seen in the urine. Imaging by radiographs or ultrasound may show an enlarged liver or tumor on the adrenal glands. A definitive diagnosis of Cushing’s disease generally requires one or more of the following tests: Low dose dexamethasone suppression test (LDDST) This is considered to be the preferred diagnostic test in most cases, although there may be valid reasons that your veterinarian could choose to use a different test. To perform the LDDST, a baseline cortisol level is measured first thing in the morning, then the dog is given a low dose of an injectable steroid called dexamethasone. After that, cortisol levels are measured in four hours, and again in eight hours to see if there is a normal response. In a normal dog, the doses of dexamethasone will cause the body to greatly decrease the production of cortisol for the rest of the day – this means that cortisol levels should be virtually undetectable at the 4-hour and 8-hour mark. A dog with Cushing’s disease will fail to suppress cortisol production as expected, and will show elevated cortisol levels throughout the day. Some partial suppression at four hours is often seen in dogs with PDH, but dogs with ADH generally do not show any suppression at all – this means that the LDDST can be used to differentiate between PDH and ADH in some cases, which can be very useful in guiding treatment. ACTH stimulation test This test is generally less accurate than the LDDST for diagnosis of Cushing’s disease, but may be used in some cases because it takes less time (only 1-2 hours vs. 8+ hours) and is less likely to be affected by other illnesses that the patient may have, as can sometimes be an issue with the LDDST. For this test, a baseline cortisol level is measured first. Then, a dose of Cortrosyn (a synthetic version of ACTH) is administered, and cortisol levels are rechecked in one hour. A normal dog will show a moderate cortisol elevation in response to the ACTH. A dog with Cushing’s disease will usually show a greatly exaggerated response, with dramatically elevated cortisol levels at the 1-hour mark. This is the preferred test for confirming iatrogenic Cushing’s disease in cases where this is suspected. These dogs have chronically suppressed adrenal activity as a result of long-term steroid administration, so they show little to no response to the ACTH injection. Urine cortisol: creatinine ratio (UCCR) This test is very easy to perform – it requires only a urine sample collected at home, by the owner, on a normal day when the dog is not unduly stressed. The urine is sent to a reference lab, and cortisol levels in the urine are measured. High levels are suspicious for possible Cushing’s disease, but can also be caused by other things such as stress, anxiety, or other illnesses that may be present. Normal cortisol levels, however, essentially rule out Cushing’s disease as a possibility – so the UCCR can be a good screening test in some cases. **Abdominal ultrasound ** An abdominal ultrasound is often used to help differentiate between PDH and ADH, once a preliminary diagnosis of Cushing’s disease has been made. Dogs with ADH will generally have one markedly enlarged and misshapen adrenal gland (due to a tumor in this gland), while the other will be very small. In contrast, both adrenal glands are equally enlarged in dogs with PDH.

Causation

In the majority of cases (80-85%), Cushing’s disease is caused by a microscopic tumor on the pituitary gland, a tiny gland in the brain that controls the secretion of a number of different hormones in the body. The tumor overproduces a substance called ACTH (adrenocorticotropic hormone), which in turn stimulates the production of cortisol by the adrenal glands in the abdomen. This is called pituitary-dependent hyperadrenocorticism, or PDH.

In 15-20% of affected dogs, the disease is caused by a tumor on one of the adrenal glands. The tumor overproduces cortisol in spite of normal biological mechanisms to limit production of this hormone, which results in the symptoms seen with Cushing’s disease. This is called adrenal-dependent hyperadrenocorticism, or ADH. Large-breed dogs are more likely to have this form of the disease than smaller dogs.

The syndrome known as iatrogenic Cushing’s disease is caused by long-term administration of a steroid medication, resulting in the same constellation of symptoms seen with “true” Cushing’s disease. This could be caused by daily administration of an oral medication like prednisone, or repeated dosing of a long-acting injectable steroid such as methylprednisolone or triamcinolone. This problem is most common in dogs who have chronic medical conditions such as allergies or immune-mediated diseases that require treatment with high doses of steroids for months or even years at a time.

Treatments

icon AT-HOME CARE
Most dogs with Cushing’s disease can be treated with daily medication. No particular diet changes or other treatment measures are needed, unless the dog develops complications or concurrent problems such as a UTI, high blood pressure, diabetes, or pancreatitis, and in these cases dietary changes or other measures may be required to treat some of these conditions.
icon SUPPORTIVE CARE
None
icon MEDICATIONS
Trilostane is the most common medication used to treat Cushing’s disease in dogs. This drug inhibits the synthesis of cortisol by the adrenal glands, and is typically given either once or twice daily, depending on your veterinarian’s instructions. Most dogs tolerate it very well with minimal side effects. Mitotane is another medication that is sometimes used, but its use is less common due to more severe side effects (including vomiting, diarrhea, and loss of appetite) and higher risks of causing permanent damage to the adrenal glands. Rarely, other medications such as ketoconazole, selegiline, or cabergoline may be used, but the use of these drugs for the treatment of Cushing’s disease in dogs is controversial, and they are only used in a very small percentage of cases. While many medications are often administered for ‘off-label’ or 'extra-label' use in veterinary medicine, it is important to know that off- or extra- label use of a medication can only be done by a veterinarian when there are no other more appropriate medications for a particular pet's circumstances. Your veterinarian must also know all vitamins, supplements, medications etc. your pet is taking to help avoid complications. You must also be sure to follow all instructions provided by your vet carefully and consult your veterinarian with any questions or concerns if they arise.
icon DEVICES
None
icon SURGERY
For dogs with ADH, adrenalectomy (surgery to remove the affected adrenal gland) is the recommended treatment of choice. If all goes well, this surgery is curative and the dog will not need to be on any long-term medication as long as the other adrenal gland is still functioning normally, so it’s well worth discussing this with your veterinarian if your dog has been diagnosed with ADH. However, adrenalectomy is a complex surgical procedure that generally must be performed by a specialist, and carries a significant risk of serious complications including pancreatitis, pulmonary thromboembolism (a blood clot in the lungs), pneumonia, sepsis, renal failure, and hypoadrenocorticism (Addison’s disease) in some cases. Advanced imaging including a CT scan or MRI may also be needed prior to surgery to check for additional tumor sites, since some adrenal tumors are malignant. Surgery can also be performed to remove the pituitary tumor in dogs with PDH. This procedure is called a transsphenoidal hypophysectomy, and is performed fairly commonly in humans with this disease. In dogs, however, it’s a highly specialized procedure that is performed in only a handful of referral hospitals, and is not commonly utilized as a treatment option.
icon SPECIALISTS
If surgery is being considered as a treatment option, this will likely require referral to a specialist as discussed above. These surgical procedures are complex and difficult to perform in a general practice setting. For medical management, most cases of Cushing’s disease can easily be managed by your family veterinarian. However, referral to an internal medicine specialist may be recommended if there is difficulty getting your dog’s symptoms under control with medication. Referral to a specialty hospital for 24-hour intensive care may also be needed if serious complications or concurrent illnesses develop, such as pancreatitis or diabetes mellitus with DKA.

Cost Of Treatment

The cost of veterinary treatment can vary widely for various reasons, however, treating Cushing's Disease in dogs is usually expensive, and can range anywhere between $300 and $5,000.

Recovery

For patients with ADH who have an adrenalectomy performed, expected recovery time is generally 10-14 days. Patients with either PDH or ADH who are being managed on medication without surgery do not generally “recover” from their disease, as it is a chronic illness that will need to be managed with life-long medication. Symptoms of iatrogenic Cushing’s disease should resolve within a few days to a few weeks once steroid medications are discontinued.

Monitoring

For patients on trilostane, an ACTH stimulation test will need to be performed 14 days after starting medication to ensure that the starting dose is not too high. From there, most veterinarians recommend repeating this test in one month, then every 3-4 months thereafter as long as things are going well and the medication dose is unchanged. Any time a dosage change is required, an ACTH stimulation test is generally needed 2-4 weeks later to evaluate response. Monitoring for patients on mitotane is very similar, with ACTH stimulation testing needed at 7-10 days after starting medication, then every 3-6 months thereafter as long as things are going well. Patients who have undergone an adrenalectomy will typically be hospitalized for several days after surgery, and will need to be rechecked at 10-14 days for suture removal. Lab work may be recommended at this time to evaluate cortisol levels and check for possible complications. All patients who are undergoing treatment for Cushing’s disease need to be closely monitored for signs of low cortisol (hypoadrenocorticism, or Addison’s disease) since this is an occasional side effect of drugs like trilostane or mitotane, and can be a life-threatening problem. Symptoms of low cortisol levels include vomiting and diarrhea, not wanting to eat, or acting lethargic. If these symptoms are seen, you should contact your veterinarian right away for instructions. Dogs with Cushing’s disease are prone to a number of other illnesses, including diabetes mellitus, hypertension (high blood pressure) and urinary tract infections. For this reason, a urine culture and blood pressure check are needed at the time of diagnosis, and should be repeated along with a CBC/profile and urinalysis every 6 months thereafter. Cushing’s disease also increases the risk for pancreatitis, so owners should monitor for signs of this as well – including vomiting, not eating, abdominal pain, and acting lethargic.

Prevention

Limiting the use of steroid medications (both dose and duration of treatment) should prevent the occurrence of iatrogenic Cushing’s disease in dogs. There are no known preventative measures for “true” Cushing’s disease.

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Disclaimer

The information contained on this page is for educational purposes only. This medication should only be given under the advice of a veterinarian who has examined your pet under the laws applicable to your state of residence.