by Dr. N.J.Hayes, DVM

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What is Addison's Disease?

Addison's disease is the common name for the insufficient production of the hormones cortisol (glucocorticoids) or aldosterone (mineralocorticoids) or both. The scientific name for this disease is hypoadrenocorticism, which refers to an insufficient production of certain essential hormones by the adrenal glands. Addison's Disease is another endocrine disorder, but at the opposite end of the spectrum from Cushing's. Addison's is caused by damage to the outer layer of the adrenal gland (adrenal cortex).

What are the adrenal glands?

The adrenal glands are two small glands which sit next to the kidneys,(located ahead of each kidney). Their size does not correlate with their importance. The adrenal glands are really two endocrine (ductless or hormone producing) glands in one. They are responsible for producing several important hormones including adrenaline, estrogen and testosterone, cortisone, and aldosterone. The center of the gland is called the medulla and the outer area is called the cortex.

Addison's disease concerns the hormones produced by the outer area, or cortex. The adrenal cortex makes two important steroid hormones, cortisol and aldosterone.

• Cortisol mobilizes nutrients, modifies the body's response to inflammation, stimulates the liver to raise the blood sugar, is essential for the breakdown of fats and protein, and also helps to control the amount of water in the body. Cortisone is responsible for a normal appetite and sense of well-being. Cortisol production is regulated by another hormone, adrenocorticotrophic hormone (ACTH), which is made in the pituitary gland which is located just below the brain.
  
  
• Aldosterone regulates the electrolyte and water balance of the body and is involved in the excretion of potassium and retention of sodium. This affects blood volume and blood pressure.

What causes the disease?

Types: There are three forms of Addison's disease:

1. Primary: atrophy (dying off) of the adrenal gland due to disease

   The causes of Primary Addison's disease are not completely understood. However, it is believed that the major cause of primary Addison's disease results from an auto-immune reaction in which the body's immune system erroneously makes antibodies against the cells of the adrenal cortex which causes decreased production of adrenocortical hormones. Other common causes of primary Addison's in dogs include:

   • infections
   • cancer (metastatic tumors)
   • granulomatous disease
   • trauma
   • drug side effects
   • various types of inflammation

   Certain parts of the cortisone-producing adrenal glands waste away to such an extent they are only minimally functional.

   • Secondary hypoadrenocorticism is from failure of the pituitary to stimulate the adrenals with adrenocorticotropic hormone (ACTH) This is usually due to problems with the pituitary gland which include:
     • inflammation
     • trauma
     • tumors
     • Secondary adrenocorticism probably occurs most often when prednisone or other cortisone that has been administered for medical reasons are suddenly withdrawn.
     • It can occur as a result of pituitary cancer or some other process that interferes with production of hormones that stimulate the adrenal glands.

Addison's disease is considered uncommon in dogs.The disease typically affects young or middle-aged female dogs between 4 and 7 years old. Studies have found that 70% to 85% of dogs with Canine Addison's Disease are female. Some breeds seem to be affected more commonly than others. Great Danes, rottweilers, Portuguese water dogs, Standard Poodles, West Highland White Terriers and Wheaten Terriers have an increased risk.

What are the symptoms of Addison's Disease?

Most dogs with Addison's disease initially have vague waxing and waning symptoms that take place over months or years, making diagnosis difficult. They may appear suddenly, or be intermittent. Because the symptoms are so vague, the biggest pitfall with Addison's disease is it's recognition. Because the symptoms are so vague, the pet owner often talks himself or herself out of a veterinary visit. Since other more common diseases have similar signs, veterinarians often may not initially suspect hypoadrenocorticism. To further complicate matters, if basic blood test abnormalities are mild, it may not appear warranted to run the ACTH test. Diagnosis is frequently a matter of eliminating other possibilities.

Once Addison's is correctly diagnosed, a properly treated dog can live a normal, active life.

Some of the most common signs a pet owner may observe in a dog with Canine Addison's Disease include:

• vomiting, anorexia (not eating), weight loss, diarrhea: Most dogs with Addison's disease initially have gastrointestinal disturbances like nausea, sometimes with vomiting and diarrhea. Bloody diarrhea is less common. Recurring bouts of appetite loss can occur. Unintentional weight loss and a thin body condition may occur.
• lethargy (tired), depression, irritability, listlessness, slow, sluggish, lethargic movement:The slowly progressive loss of cortisol and aldosterone secretion usually produces a chronic, steadily worsening fatigue. Many dogs are described as just seeming off, or losing the normal sparkle in their eye.
• weakness:There may be generalized muscle weakness, such as a dog that can't jump onto the bed or couch as they've always done in the past. Shivering, shaking, muscle tremors or spasms may be present.
• Increased thirst:There is occasionally increased thirst with excessive drinking (polydipsia) and increased urine production (polyuria). The urine is often dilute.
• Dehydration:Severe dehydration increases waste products in the blood that are normally eliminated by the kidneys. Sick dogs often show a pattern of changes in their white blood cells (WBCs) called a stress leukogram. This pattern of changes in the WBCs is caused by cortisol. The absence of a stress leukogram in a sick dog may be a clue to consider Addison's disease.
  BUN and creatinine levels, generally indicators of kidney function, are often elevated. At this point many animals are diagnosed with renal failure, as the kidneys are unable to function properly.
• Darkening of the skin - skin color, patchy, Unnaturally dark color in some locations, Paleness may also occur.
• Sodium and potassium level, blood pressure, hypothermia, slow heart rates, weak pulse, bradycardia: This disease occasionally can be picked up by changes in the ratio between sodium or potassium. When this happens it is still extremely important to treat for it.

The Addisonian Crisis

Dogs with Addison's disease cannot cope with stress. When a normal pet is stressed, their adrenal glands produce more cortisol, which helps them deal with the stress. Because dogs with Addison's disease cannot make enough cortisol, they cannot deal with stress, so the signs may occur or worsen when stressed. What a dog finds stressful depends upon his/her temperament. For many dogs, any change in their day-to-day routine, such as being boarded, thunderstorms, or having house guests, is stressful and may precipitate or worsen signs of Addison's disease.

Potassium levels can elevate and disrupt normal function of the heart. When potassium levels get high, weak pulses, a slow heart rate, and heart arrhythmias can occur or the heart may stop. Dogs with this problem will sometimes suffer severe shock symptoms when stressed, which can lead to a rapid death. Blood pressure can drop to dangerously low levels. In the most extreme cases, the patient may present to the veterinarian in a state of circulatory collapse and shock (Addisonian crisis), due to its inability to adapt to the caloric and circulatory requirements in stress. Blood sugar may have dropped dangerously low. Potassium levels soar and disrupt the heart rhythm because there is not enough conserved sodium to exchange for potassium. The heart rate slows and arrhythmias result.

In addition to vomiting and diarrhea, a dog in hypoadrenal (Addisonian) crisis is extremely weak, may be in acute kidney failure and has a low body temperature. There is usually no history of trauma or toxic exposure so general treatment for shock is initiated. The animal must receive immediate veterinary care to save its life. This includes the administration of large volumes of intravenous fluids (sodium and chloride) and corticosteroids.The patient may not survive this episode.

X-rays may be done which may reveal a smaller than normal heart due to the reduction in volume of circulating fluid in the body as part of Addison's disease.

How is Addison's confirmed?

Addison's is confirmed by an ACTH response test. At times this disease can be hard to differentiate from renal failure because the symptoms and even the bloodwork can be similar. In cases in which the electrolyte levels are normal this is the only test for the problem and it will be missed unless it is looked for specifically. The patient receives a dose of ACTH, the pituitary hormone responsible for the release of corticosteroids in times of stress. A normal animal will show an elevation in cortisol in response to ACTH while an Addisonian has no corticosteroids to respond with. As this test takes several hours to complete, your dog will have to be admitted for the day.It sometimes takes days for results, therefore, treatment for Addison's Disease can usually be instituted on other laboratory results.Confirming the diagnosis of Addison's disease involves minimal testing and is relatively inexpensive to diagnose.

How is Addisonian's treated?

Once the diagnosis has been positively established, your veterinarian will decide what course of action is to follow according to each individual case. Careful monitoring of electrolytes is important throughout the early stages of Addison's disease management. Your Veterinarian is likely to give you a list of dates when further blood tests will be needed. When levels seem stable, these blood tests are repeated 2 to 4 times per year.

Once the animal has recovered to a normal state we can go onto Maintenance Therapy. Treatment for Addison's disease involves life-long replacement therapy.

Treatment for this disease is usually done by oral administration of fludrocortisone acetate (Florinef), salting the food, and administration of corticosteroids like prednisone. The disease can be managed with the administration of corticosteroid hormones even if the cause of the deficiency is unknown. With atypical and secondary Addison's the glucocorticoid is the only medication given.

An injectable preparation known as desoxycorticosterone pivalate (DOCP) is also available. There is some feeling among experts that DOCP produces better regulation of electrolytes than does oral Florinef. Some dogs however, do require glucocorticoid supplementation (such as a low dose of prednisone). It has a low incidence of side effects and is given as a single injection to the dog approximately once every 25 days.

Expected Long-Term Prognosis

The good thing about Addison's disease is: If the diagnosis is made early enough; with proper administration of medication and careful monitoring, the prognosis is excellent and there is no anticipated decrease in the patient's life expectancy.
Although, not curable this disorder is wonderfully treatable. Recognition of the disease and cost of the medication seem to be the biggest obstacles to a successful outcome.

While your dog with Addison's disease will need medications and monitoring for the rest of his life, most dogs with Addison's can return to their favorite activities. There is no need to alter his/her normal activities or diet. You will learn to read your dog, understand what his stress triggers are and to follow your instincts about his care. You can help your dog lead a normal, active and happy life.

Please do not hesitate to contact us at 309-685-4707 if you have any questions or concerns.

References:

• Tilley, LP, Smith, FWK, The 5 Minute Veterinary Consult, Canine and Feline. 1997, Williams & Wilkins.
• Mordecai Siegal (Ed.) The UC Davis Book of Dogs. 1995, HarperCollins Publishers.
• Bonagura, JD (ed.) Kirk's Current Veterinary Therapy XIII Small Animal Practice. 2000,W. B Saunders Company.
• Encyclopedia of Canine Veterinary Medical Information

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