Hyperadrenocorticism (Cushing's Syndrome) in Cats

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Hyperadrenocorticism or Cushing's syndrome is caused by an excessive production of glucocorticoids, namely cortisol, by the adrenal gland. Glucocorticoids are essential body hormones, but chronically elevated amounts may cause illness.

In about 80 percent of cats a small pituitary tumor at the base of the brain is the cause of the disease. This tumor secretes adrenocorticotropic hormone (ACTH or) that stimulates the adrenal gland to produce elevated cortisol levels. This type of Cushing's syndrome is also called pituitary dependent hyperadrenocorticism.

The remaining 20 percent of Cushing's disease is caused by a tumor of the adrenal cortex, which is the outer layer of adrenal gland. This is also called adrenal dependent hyperadrenocorticism.

Most cats with Cushing's syndrome are middle-aged or older (average 10 to 11 years) and approximately 70 percent are female. There is no breed predilection. Cushing's syndrome is a rare disease in cats.

Over 90 percent of cats diagnosed with Cushing's disease have concurrent diabetes mellitus, commonly known as "sugar diabetes."

What to Watch For

The most common clinical signs of feline Cushing's syndrome are associated with the concurrent diabetes. These signs include:

  • Increased thirst
  • Increased urination
  • Increased appetite

    Other symptoms include:

  • Fragile, easily bruised or torn skin
  • Symmetrical hair loss
  • Poor or ungroomed hair coat
  • Pot-bellied appearance
  • Generalized muscle wasting
  • Lethargy
  • Recurrent infections
  • Weight gain or loss

    Diagnosis

    Cushing's syndrome is not a diagnosis that should be made solely on the basis of laboratory testing. Both historical information and physical exam findings are equally important in establishing a diagnosis and directing appropriate laboratory testing. Since the majority of cats with Cushing's syndrome are insulin-resistant diabetics – which means they have a poor response to insulin – a poorly regulated diabetic may prompt a clinical suspicion of hyperadrenocorticism. Diagnostic tests include:

  • CBC (complete blood count)
  • Biochemical profile
  • Urinalysis with culture and sensitivity
  • Blood pressure evaluation
  • Radiographs of the chest and abdomen
  • Abdominal ultrasound
  • ACTH stimulation test
  • Dexamethasone suppression test
  • Combined dexamethasone suppression – ACTH stimulation test
  • ACTH Level
  • CT (computer tomography) or MRI (magnetic resonance imaging) of the abdomen

    Treatment

    Treatment options for feline Cushing's disease are much more limited than in the dog.

  • Medical therapy has proven to be of limited value in the control of the disease. Treatment with o, p-DDD (lysodren) and ketoconazole are generally ineffective. A third drug, metyrapone, has shown some occasional successful treatment.

  • Surgical treatment is the treatment of choice in feline Cushing's disease. Since pituitary dependent Cushing's disease causes bilateral adrenal enlargement, the most effective treatment option is the surgical removal of both adrenal glands. This is a difficult surgery that requires extensive postoperative care, usually at a referral institution or specialty hospital.

  • Adrenal tumors should also be treated surgically with a unilateral adrenalectomy, or removal of the affected adrenal gland. This surgery, as well, should be done at a referral institution with 24-hour care available.

    Home Care

    After the removal of both adrenal glands, cats continue on medication for the remainder of their lives. Follow your veterinarian's instructions very carefully when administrating medications.

    Diabetic cats almost always have changes in their insulin requirements. Monitor for changes in water consumption and amount of urine produced.

    In the immediate postoperative time, frequent blood tests are needed to monitor the cat's blood glucose and electrolytes. Insulin requirements and oral medications need to be adjusted on the basis of laboratory tests. Once stable, cats need to be evaluated at least several times a year.

    Observe for any weakness, disorientation, lethargy, vomiting or diarrhea or any changes in your cat's attitude.

    Preventative Care

    Nothing can be done to prevent feline Cushing's disease, but knowing if your cat might be at risk of Cushing's disease is important for successful treatment. Early diagnosis and treatment leads to a better prognosis.

    If your cat is a diabetic that is difficult to regulate, Cushing's syndrome (although rare) may be the cause.

    • Symptoms seen with Cushing's disease in cats are: increased thirst, urination, and appetite. If the skin is affected, it may be thin, easily bruised, with symmetrical hair loss and poor or ungroomed hair coat.

    • Most cats with Cushing’s syndrome are middle-aged or older (average 10 to 11 years) and approximately 70 percent are female.

    The adrenal glands are two small endocrine organs located near each kidney. The glands have two separate parts: the cortex (outer layer) and the medulla (inner layer). The adrenal cortex is the layer that is responsible for glucocorticoid or cortisol production. Normally, the adrenal gland's production of glucocorticoids is regulated by higher functions in the brain. The area of the brain called the hypothalamus secretes the hormone CRH (corticotrophin releasing hormone). CRH then stimulates the pituitary gland to produce ACTH (adrenocorticotropic hormone), which in turn stimulates the production of glucocorticoids by the adrenal cortex. Elevated glucocorticoid levels normally lead to suppression of ACTH production, thus maintaining homeostasis.

    In feline Cushing's disease, elevated cortisol levels are caused by either a pituitary tumor producing increased ACTH or by an adrenocortical tumor directly producing elevations in cortisol. Chronically elevated cortisol levels may predispose a cat to become a diabetic; cause muscle atrophy and weakness; cause skin to be more fragile – even to the extent of bruising or tearing with minor manipulation; cause suppression of the immune system; and changes in the body conformation.

    Other diseases that might cause similar clinical signs include:

  • Diabetes mellitus. The vast majority of cats that have Cushing's disease are diabetic. If a cat is not a diabetic, it is unlikely (but possible) that the disease is cushingoid.

  • Feline acromegaly. Acromegaly or an excess of growth hormone is caused by a growth hormone secreting tumor in the pituitary gland. Cats usually present as insulin resistant diabetics with body conformational changes. Typical changes include an increase in the cat's head and paw size. The lower jaw may also protrude.

  • Hyperthyroidism. Elevated levels of thyroid hormones may cause cats to eat and drink excessively, urinate more and lose weight. Hyperthyroid cats may also have poor hair coats and have generalized muscle atrophy.

  • Liver disease may cause an enlarged liver and a protruding abdomen. Many cats drink excessively and have a poor hair coat with liver disease.

  • Feline fragile skin syndrome. Fragile skin syndrome is a condition that causes the cat's skin becomes thinner and weaker. It may be associated with metabolic or neoplastic conditions. Its exact cause is unknown.

  • Diagnosis In-depth

    The diagnosis of feline Cushing's syndrome is very difficult to achieve accurately. The diagnosis should always be made on the basis of the clinical suspicion and then supported with the appropriate diagnostics. The most common reason to suspect feline Cushing's syndrome is insulin-resistant diabetes. Diagnostic tests that are important in evaluating a potential cat with Cushing's syndrome include:

  • CBC. The CBC evaluates the red blood count for anemia and the white blood count for any abnormalities. No consistent findings in the CBC are typical in the cushingoid cat; however, the CBC remains important in determining any problems that might be associated with disease. Anemia and evidence of chronic infections might be noted.

  • Biochemical profile. The most consistent lab abnormality in feline Cushing's disease is an elevated blood glucose associated with diabetes. The alkaline phosphatase enzyme, so often elevated in dogs, is elevated in about 1/3 of cats, but this may also be elevated from the concurrent diabetes. Cats lack the specific steroid-induced isoenzyme found in the dog that produces the increase in this enzyme. Other liver enzymes and cholesterol may also be elevated in the cushingoid, diabetic cat.

  • Urinalysis with culture and sensitivity. Most cats with Cushing's syndrome have glucose in their urine, due to the poorly regulated diabetes. This combined with the suppression of the immune system, caused by the elevated cortisol levels, makes the cat susceptible to urinary tract infections.

  • X-rays of the chest and abdomen evaluate for any evidence of metastatic cancer. It would be rare to visualize an adrenal tumor, but X-rays remain as an important diagnostic in getting an overall health assessment of the cat.

  • Blood pressure measurement. Chronic evaluations in cortisol levels may lead to elevations in blood pressure (hypertension).

  • Abdominal ultrasound. An abdominal ultrasound is a very useful diagnostic aid in evaluating the size and shape of the liver, and especially adrenal glands. A single enlarged adrenal gland would be indicative of a primary adrenal tumor. Bilateral enlargement would suggest adrenal hyperplasia or enlargement due to a pituitary tumor.

  • ACTH stimulation test. The pituitary hormone ACTH is injected into the cat and cortisol levels are measured pre- and post-injection. Ideally, the cushingoid cat would have an exaggerated response to ACTH, with the post-cortisol level being elevated above the normal. Unfortunately, there are significant false positive readings (cats without Cushing's that test positive) and false negatives (cats with Cushing's that test negative). The test needs to be evaluated with caution.

  • Dexamethasone suppression testing. Normally, dexamethasone causes a decrease of cortisol production by the adrenals. In cats with Cushing's syndrome, the normal suppression of the cortisol is usually not seen when low doses of dexamethasone are used. Low dose dexamethasone suppression testing in the cat requires a higher dosage of dexamethasone than commonly used in dogs, thus a high dose test is used in attempting to diagnose the disease.

  • Dexamethasone suppression/ACTH stimulation test. A protocol for combining both of these tests has been described and may provide stronger evidence for a diagnosis of feline Cushing's syndrome.

  • ACTH levels. The direct blood measurement of ACTH requires proper sample handling and a specialized laboratory to run the sample. ACTH levels are not be used to diagnosis Cushing's syndrome; rather, they are useful in differentiating pituitary from adrenal hyperadrenocorticism. Normal to elevated levels suggests pituitary dependent disease. Very low levels of ACTH correlate with a primary adrenal tumor.

  • CT or MRI evaluation of the pituitary or adrenal glands is a useful tool in assessing for potential tumors but require referral to a specialized center.

    Therapy In-depth

    Feline hyperadrenocorticism is a very debilitating disease. Stabilizing any secondary complicating diseases should be attempted before treating the Cushing's disease. Concurrent urinary tract infections require antibiotics. Diabetes is often difficult to regulate appropriately, but attempts to stabilize and decrease blood sugar to the safest levels should be attempted. Since feline Cushing's syndrome is so uncommon, only a limited number of cats have been managed. Medical therapy with a variety of drugs has been shown to be of only limited value. The surgical option seems to provide the best long-term prognosis for these cats. Treatment options that have been tried include:

  • O, p'-DDD (Lysodren) is the most useful drug in treating canine Cushing's syndrome. Unfortunately, cats are fairly resistant to the drug, even at high dosages.

  • Ketoconazole is an enzyme blocker that blocks the synthesis of cortisol in people and in dogs. It is not effective in cats.

  • Metyrapone is also an enzyme blocker and might be the most effective medical therapy in cats. Unfortunately very few cats have been tried on this drug, and the drug is not readily available.

  • Surgical management is the most effective treatment option. Unfortunately, many cushingoid cats are fragile surgical candidates that require very close pre- and post-operative monitoring and requiring 24- hour care. Since the goal of surgery is to remove one or both of the adrenal glands, a rapid decrease occurs of both the elevated glucocorticoids and normal mineralocorticoids, which are other hormones, specifically aldosterone, that are produced in the adrenal gland that maintain electrolyte balance. This leads to most of the surgical and post surgical metabolic complications. In order to minimize this effect both glucocorticoid and mineralocorticoid replacement therapy are given pre-operatively and continued post-operatively. If an adrenal tumor is suspected, and confirmed at surgery, the single adrenal gland is removed.

    If pituitary dependent Cushing's disease is confirmed, then both adrenals are removed. Intravenous fluids are given aggressively, as well as intravenous nutrition. In the diabetic patient, the blood sugar needs to be carefully monitored, and fast acting regular insulin is given as needed. Postoperative antibiotics are commonly given, as sepsis (blood infection) is a common complication. Blood electrolytes (specifically potassium, sodium and chloride) need to be monitored closely and medication adjusted to stabilize their levels. Managing the postoperative cat is challenging and usually requires specialized care.

  • Optimal treatment for your pet requires a combination of home and professional care. Follow-up can be critical, especially if your pet does not rapidly improve. Administer all prescribed medications as directed. Alert your veterinarian if you are experiencing problems treating your pet.

    The surgical treatment of removing both adrenal glands in the cat with Cushing's disease creates another condition, Addison's disease (hypoadrenocorticism), which requires life long medications and very close monitoring.

    Glucocorticoid therapy with prednisone will be required since your cat is no longer producing cortisol. It is usually possible to decrease the dose of prednisone down eventually to very small maintenance dosages. When decreasing the dose it is important to monitor for increased lethargy, anorexia or weakness. Notifying your veterinarian and increasing the prednisone dose usually improves the symptoms if they are being caused by a cortisol deficiency.

    Additionally, life long replacement therapy with the mineralocorticoid, fludrocortisone acetate (Florinef) is required. This drug maintains the normal electrolyte balance of sodium, potassium and chloride. Frequent blood tests are needed, especially for the first few weeks postoperatively. Adjustments in medication are made on the basis of the electrolyte results. Florinef is increased if the blood potassium is elevated. If needed, salt may be added to the diet to elevate blood sodium and chloride levels.

    Injectable mineralocorticoids (desoxycorticosterone pivalate or DOCP) can be given as a monthly injection instead of the daily oral medications.

    Since most cats are diabetics, the blood sugar level will need to be closely followed. Once the Cushing's disease is controlled, it is common for insulin requirements to decrease dramatically. Watch for changes in drinking, urination and attitude. You will need to work closely with your veterinarian to decrease insulin dosages and to avoid a hypoglycemic (low blood sugar) event. Watch for weakness, disorientation or seizures, as they may indicate a low blood sugar.

    After the first several weeks postoperatively, the long-term prognosis is good.

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