Addisons

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Canine hypoadrenocorticism
Addison's Disease

Affected Animals
Female dogs are more likely to develop Addison's disease. Younger dogs of an average age of four to five years are more commonly affected than older dogs. Any breed of dog can develop Addison's disease, although in some studies, the majority of affected dogs were of mixed breeding. Veterinarians have observed that Labrador retrievers, Rottweilers, and West Highland white terriers seem to be diagnosed with Addison's disease at a higher frequency than other breeds.

Overview
Clinically known as canine hypoadrenocorticism, Addison's disease results from the decreased production of steroid hormones by the adrenal glands. The common symptoms of Addison's disease are not very specific, and can include lethargy, weakness, gastrointestinal upset, and poor appetite. Often these symptoms appear intermittently during an extended period of time.

Although some dogs may be diagnosed while in a relatively stable condition, most are diagnosed when an Addisonian crisis develops -- a severe stage of the disease in which shock and collapse can occur. If a dog is treated successfully for an Addisonian crisis, however, the long-term outlook is excellent, as most dogs can be controlled with oral or injectable medications to replace the deficient hormones.

Clinical Signs
Clinical signs include anorexia, or an absent appetite, a thin body condition, depression, vomiting, diarrhea, weakness, collapse, polyuria, or increased thirst, signs that come and go over time, trembling or shaking, and abdominal pain.

Symptoms
See Clinical Signs

Description
Addison's disease refers to the syndrome that results from failure of the adrenal glands to produce the hormones that they normally make. The adrenal glands are two small structures located alongside each kidney. The main hormones produced by the adrenal gland are steroids. There are two major classes of these steroids: mineralocorticoids and glucocorticoids. Aldosterone, the main hormone in the mineralocorticoids class, plays a major role in regulating sodium, potassium, and water balance. Cortisol, the main hormone in the glucocorticoids class, acts on almost every major tissue in the body, helping to regulate glucose production and metabolism, influencing fat and protein breakdown, stimulating red blood cell formation, helping to regulate blood pressure, counteracting stress, and suppressing inflammation.

Despite their different control mechanisms, both classes of steroids usually are affected by primary adrenal gland failure in Addison's disease. However, some animals will have symptoms primarily related to mineralocorticoid deficiency, while others will experience problems primarily from glucocorticoid deficiency. Although sex hormones such as estrogens and androgens also are produced by the adrenal glands, signs due to deficiencies of these hormones do not occur in dogs with Addison's disease.

Destruction of 85 to 90 percent of the steroid-producing cells in the adrenal gland appears necessary for signs to develop secondary to deficiencies of mineralocorticoids and glucocorticoids. This destruction is most commonly due to immune system-mediated destruction of the adrenal glands. Less frequently, infections, inflammation, cancer, drug therapy, or abnormalities in blood supply to the adrenal gland can contribute to the development of Addison's disease. Secondary adrenal gland failure due to problems that affect the hypothalamus or pituitary gland may also occur, resulting in the signs seen with Addison's disease.

Symptoms of Addison's disease may follow an intermittent course, often coming and going over a long period of time before the illness is suspected. Occasionally, Addison's disease can be diagnosed in dogs with relatively mild symptoms. However, it is common for dogs not to be diagnosed until a life-threatening crisis due to Addison's disease develops. Severe signs of illness including shock and collapse characterize these crises. Usually, the animal can be stabilized successfully if it receives immediate treatment with fluid resuscitation and medications to improve electrolyte and acid-base system abnormalities and to replace deficient glucocorticoids. Once the initial crisis passes, maintenance treatment with either oral or injectable mineralocorticoids, and for many dogs, oral glucocorticoids will be necessary for life. Despite the serious nature of Addison's disease, the vast majority of dogs can be well controlled with medication. However, supplementing some dogs with glucocorticoid insufficiency will be necessary during any stressful period.

Atypical Addison's disease refers to primary or secondary adrenal gland failure in dogs that do not exhibit the classic symptoms or electrolyte abnormalities usually seen in Addison's disease. Animals diagnosed with this condition may have more subtle changes on blood tests and other diagnostic procedures. Although these dogs will not have the classic findings with Addison's disease, they will exhibit abnormally low responses to ACTH on the ACTH stimulation test, and generally they will respond to treatment with glucocorticoids alone, since the sodium and potassium regulation will remain normal.

Diagnosis
In many cases, changes on routine screening tests, including the complete blood count, biochemistry profile, and urinalysis, will trigger the suspicion of Addison's disease. Chest x-rays may reveal a reduced heart size and esophageal enlargement. An electrocardiogram may show changes if the potassium concentration is elevated.

A definitive diagnosis depends on the results of a test of adrenal gland function called the ACTH stimulation test. Serum concentrations of cortisol, one of the main hormones produced by the adrenal gland, are measured before and after the administration of either synthetic or natural ACTH. Measurements of another hormone called aldosterone, which helps regulate the sodium and potassium balance, also can be checked, although this procedure is fairly uncommon. Measurement of aldosterone may be helpful in distinguishing primary failure of the adrenal glands from secondary adrenal gland failure due to abnormalities in the hypothalamus or the pituitary gland. Similarly, measurement of yet another hormone, called adrenocorticotropic hormone, also may be used to distinguish between primary and secondary adrenal failure.

Prognosis
With appropriate medical treatment, the long-term outlook for dogs with Addison's disease is excellent. Effective communication between the owner and veterinarian is vital in managing dogs with Addison's disease, and owners should always have prednisone on hand in case it is needed in a crisis situation.

Transmission or Cause
Addison's disease most commonly is caused by primary failure of the adrenal gland to secrete adequate amounts of mineralocorticoids, glucocorticoids, or both. It is thought that immune system-mediated destruction of the adrenal gland is the most common cause of primary adrenal gland failure. Other causes can include infection or inflammation in the adrenal gland; abnormalities in blood supply to the adrenal gland or bleeding within the gland; infiltration of cancer cells within the adrenal gland; the deposition of abnormal proteins within the adrenal gland; and physical trauma to the glands. Rapid withdrawal of drugs such as prednisone after chronic administration and overdoses of drugs used to treat Cushing's disease can result in adrenal gland failure. Secondary adrenal gland failure can occur due to primary problems in either the hypothalamus or the pituitary gland.

Treatment
The treatment of dogs with Addison's disease depends on the severity of the presenting signs. Many dogs diagnosed with Addison's disease are severely ill at the time of presentation, often with potentially life-threatening fluid deficits and abnormal serum electrolyte concentrations. These animals must receive immediate medical attention, since rapid treatment is extremely important to stabilize dogs experiencing an Addisonian crisis. The main goals of treatment are to correct fluid volume deficits, to improve blood vessel integrity, to provide a source of glucocorticoids, to correct electrolyte and acid base abnormalities, and to confirm the diagnosis. Fluid volume deficits are addressed most appropriately with intravenous fluid administration; usually, saline is used. If low blood sugar concentrations are known or suspected, then the fluids should be supplemented with dextrose. Glucocorticoids usually are given via injection. Glucocorticoids that will not affect ACTH stimulation test results are better used than those that might make it difficult to confirm a diagnosis of Addison's disease if they are given prior to the ACTH stimulation test.

Electrolyte imbalances are corrected with the intravenous fluids and with administration of mineralocorticoid replacement drugs. These drugs generally are not used until the diagnosis is confirmed, since the other measures used to treat a dog in crisis are usually successful in stabilizing a dog in an Addisonian crisis. Sometimes it will be necessary to take specific measures to lower dangerously high serum potassium concentrations, such as the administration of glucose and insulin, calcium, and sodium bicarbonate. Bicarbonate also can be used to treat animals with extreme acid-base system disturbances. Most dogs in crisis will improve within one to two hours with appropriate treatment. Intravenous fluids often are maintained for 24 to 48 hours, until the dog is eating and drinking on its own without vomiting. Injectable medications can then be switched to oral medications.

Once the crisis period has passed, dogs are given either oral or injectable mineralocorticoids. The oral medications need to be given on a daily basis, usually twice a day, and sometimes very high doses are needed to control the disease. The injectable mineralocorticoid used most commonly is called DOCP. It is given via injection approximately every 25 days, and is almost always effective. For many dogs, especially large breed dogs, the injectable drug is much less expensive than the oral form. Most dogs with Addison's disease do well clinically with mineralocorticoid replacement alone, but others will require glucocorticoid supplementation with prednisone as well. As many as 50 percent of dogs on injectable DOCP also will require prednisone administration. For any dog with Addison's disease that may be undergoing stress, surgery, or that develops a non-adrenal gland dependent disease, prednisone should be considered on a short-term basis. Dogs that are used as working dogs also should take prednisone on a short-term basis.

Prevention
There is no known way to prevent the development of Addison's disease, except for cases in which it is caused by rapid withdrawal of prednisone or other steroids that have been used for long periods of time. Slowly tapering the doses of such drugs before discontinuing them is almost always effective in preventing the development of Addison's disease in these patients.