Hyperadrenocorticism (Cushing’s Disease)

What Is It?

Hyperadrenocorticism, or Cushing’s disease, is an endocrine disorder in which there is an excess amount of cortisol (a glucocorticoid) in the body. There are three main forms of the disease: pituitary-dependent hyperadrenocorticism, adrenocortical tumor, and iatrogenic hyperadrenocorticism.

Pituitary-dependent hyperadrenocorticism is the most common form of spontaneous disease and accounts for 80-85% of cases in dogs. In this form of the disease, the dog has a functional tumor in the pituitary gland that secretes a compound called adrenocorticotropic hormone or ACTH. This hormone, in turn, acts on both adrenal glands to stimulate the production of cortisol. Normal feedback controls are missing and the excessive secretion of ACTH persists despite having increased levels of cortisol circulating in the body.

The remaining 15-20% of cases of spontaneous hyperadrenocorticism are caused by an adrenocortical tumor, either an adenoma (benign) or adenocarcinoma (malignant). These tumors produce cortisol independently of the pituitary gland or the hypothalamus. The cortisol produced by these tumors suppresses the production of ACTH from the pituitary gland, and without this hormone, the opposite adrenal gland atrophies (becomes smaller).

Animals that have been receiving glucocorticoids orally, topically, or via injection may begin showing signs of hyperadrenocorticism. This is called iatrogenic hyperadrenocorticism. A thorough history and diagnostic testing will determine if this is the cause of your pet’s clinical signs.

Symptoms

Cushing’s disease most often affects dogs 6 years of age or older. Poodles, Dachshunds, Terriers, Schnauzers, German Shepherds, Beagles, Labrador Retrievers, and Boxers are the most commonly affected breeds, although all breeds are capable of developing the disease. The most common symptoms in dogs with Cushing’s disease include increased water consumption, increased urination, increased appetite, panting, abdominal enlargement (“pot belly”), bilateral hair loss, muscle weakness, and lethargy.

Patients with Cushing’s disease may present with secondary complications of the disease. Concurrent diabetes mellitus, pancreatitis (inflammation of the pancreas), urinary tract infections, poor wound healing, bladder stones, high blood pressure, and kidney disease may be present. A more severe complication, pulmonary thromboembolism or the deposition of blood clots within the lungs, causes severe respiratory distress. Some dogs with pituitary-dependent hyperadrenocorticism may begin to a variety of neurological signs if their pituitary tumor grows large enough to compress surrounding brain tissue. The presence of these secondary complications may make management of the disease more challenging.

Diagnosis

A thorough evaluation is necessary whenever hyperadrenocorticism is suspected. This will include a thorough medical history, a complete physical examination, a complete blood count (CBC), a serum chemistry profile, and a urinalysis (UA). A urine culture may be necessary if a urinary tract infection is suspected and a thyroid test should be performed to rule out hypothyroidism.

Diagnostic imaging can be useful in the diagnosis of hyperadrenocorticism. Abdominal radiographs and abdominal ultrasonography are used to assess the size of the adrenal glands and ascertain whether there is any involvement of other abdominal organs in the case of a malignant adenocarcinoma. A CT scan is most useful if a pituitary tumor (macroadenoma) is suspected.

Confirmation of the diagnosis of hyperadrenocorticism depends on specific testing. An ACTH stimulation test or a low-dose dexamethasone suppression test are the most common screening tests performed. For an ACTH stimulation test, a baseline blood cortisol level is measured, an injection of synthetic ACTH is given, and the blood cortisol level is measured 1-2 hours later. If cortisol levels are dramatically elevated, a diagnosis of Cushing’s disease may be made. If cortisol levels remain low and unchanged, a diagnosis of iatrogenic hyperadrenocorticism is likely. However, this test only identifies hyperadrenocorticism in 60% of dogs with adrenocortical tumors and in 80-85% of dogs with pituitary-dependent Cushing’s disease, so normal results do not necessarily rule out the disease. For a low-dose dexamethasone suppression test, a baseline blood cortisol level is measured, an injection of a steroid medication (dexamethasone) is given, and blood cortisol levels are measured 4 and 8 hours later. A normal patient will have a decrease in blood cortisol levels in response to the steroid injection. A patient with Cushing’s disease will either not have a decrease in blood cortisol levels, or will have a decrease 4 hours post-injection but return to their baseline level 8 hours post-injection. This test has the advantage of sometimes being able to differentiate between pituitary-dependent versus adrenal-dependent Cushing’s disease.

Another good screening test for this disease is a urine cortisol : urine creatinine ratio. If this test is normal, your pet is most likely not affected by Cushing’s disease. However, if this test is abnormal, further testing should be performed. An abdominal ultrasound may be able to identify an adrenal tumor or bilaterally enlarged adrenal glands, which can further help diagnose Cushing’s disease.

The results of clinical signs, physical examination findings, routine blood work, and various diagnostic tests must be evaluated together in order to make an appropriate diagnosis.

Treatment

Not all dogs diagnosed with Cushing’s need to be treated. Treatment of this disease is expensive, requires careful monitoring, and can lead to serious side effects. The general rule of thumb is that this disease should be treated if it is causing problems for the pet (lethargy, panting), for the owner (urinating in the house), or for your veterinarian (frequent urinary tract infections, diabetes). Your veterinarian will discuss the pros and cons of treating your particular pet.

The treatment of choice for Cushing’s disease is a medication called trilostane (Vetoryl). Trilostane is an active steroid analogue that inhibits the synthesis of steroids including cortisol and aldosterone. Side effects are infrequent with this medication, but careful monitoring is still essential. Some patients exhibit lethargy and decreased appetite. Less commonly (in 2-3% of cases), adrenal necrosis and development of hypoadrenocorticism (abnormally low cortisol and aldosterone levels) can occur. 10-14 days after starting medication, an ACTH stimulation test is performed to evaluate the success of therapy and the dosage of medication is adjusted if needed. Once the correct dose is established, an ACTH stimulation test should generally be performed at 30 days, 90 days, and every 6 months thereafter. More frequent monitoring will be necessary if your pet is exhibiting any adverse effects. 

Other medications, including mitotane, ketoconazole and L-deprenyl (selegiline), have been used for the treatment of Cushing’s disease, but are used infrequently since the introduction of trilostane. Radiation therapy may be an option for treatment of pituitary macroadenomas. Surgical adrenalectomy is an option for adrenocortical tumors, but is risky. Following adrenalectomy, patients must be treated with oral glucocorticoids and possibly mineralocorticoids. 

Any secondary complications of hyperadrenocorticism must also be addressed. Concurrent diabetes mellitus, urinary tract infections, glomerulonephropathies, high blood pressure, pancreatitis, bladder stones, and blood clots must be treated appropriately.

Prognosis

Prognosis depends, in part, on the age and overall health of the patient and the development of secondary complications. Treatment of Cushing’s disease usually significantly improves their quality of life (and the quality of their owner’s life, too!). Most pets respond well to treatment. Treatment and monitoring can be costly over time, especially for larger-breed dogs. Pets with pituitary tumors are at greater risk of major complications due to the potential for neurologic abnormalities. If you have concerns about how to navigate the diagnosis and treatment of Cushing’s disease, please reach out to your veterinarian for guidance.

Content prepared by St. Francis Animal Hospital, 1227 Larpenteur Ave. West, Roseville MN. 55113