Saturday, April 30, 2011

Hypoadrenocorticism (Addison’s Disease) in Cats

Hypoadrenocorticism, also called adrenal insufficiency or Addison’s disease, is a disorder in which the adrenal gland does not produce sufficient adrenal hormones that are essential for life.  When the adrenal glands fail, the consequences are very severe. Untreated, hypoadrenocorticism may lead to death.

Fortunately, naturally occurring hypoadrenocorticism is extremely rare in cats, with less than 25 cases reported. However, the disease is generally missed because veterinarians rarely consider this problem as a differential diagnosis in cats.

A much more common reason that cats develop hypoadrenocorticism is long-term treatment with steroids for a variety of dermatologic or behavioral reasons. These cats do not show signs of adrenal insufficiency unless the mediation is stopped too abruptly. This is also known as iatrogenic hypoadrenocorticism (see, "What causes this disease in cats," below).

What are the missing hormones in cats with hypoadrenocorticism?
Like dogs or people with Addison’s disease, cats with hypoadrenocorticism are unable to produce one or two steroid hormones, both secreted from the adrenal cortex (outer layer of the adrenal gland).
  1. The first hormone that's missing is cortisol, which is very important in maintaining a normal metabolism, as well as a general sense of well-being.
  2. The second hormone that's missing is aldosterone, which manages the water balance and serum electrolytes in the body.
What are the different forms of hypoadrenocorticism in cats?
Hypoadrenocorticism can be divided into primary and secondary subtypes:
  • With primary hypoadrenocorticism (Addison's disease), the problem lies in the adrenal gland itself, with atrophy or destruction of the gland.
  • With secondary hypoadrenocorticism, the adrenal glands are normal, and the problem lies in the pituitary gland. The pituitary gland normally secretes a hormone called ACTH (adrenocorticotropic hormone) that stimulates the adrenal gland to secrete its hormones. In secondary hypoadrenocorticism, ACTH is not secreted in needed amounts, leading to the secondary adrenal insufficiency.
What causes this disease in cats?
In most cats with naturally occurring hypoadrenocorticism, the exact cause for the adrenal failure is never known for certain.  

Many cats, however, develop the problem because of iatrogenic causes. The term iatrogenic means that the disease is caused by, or results from, a medical or surgical treatment for another problem (i.e., the disease did not develop spontaneously).  
In cats with primary hypoadrenocorticism, the following causes must be considered.
  • Most cats that develop Addison’s disease spontaneously appear to have an autoimmune condition in which the body destroys part of the adrenal cortex.
  • Infiltrative conditions such as lymphoma (a form of cancer) can destroy the adrenal gland to cause Addison’s disease.
  • Surgical removal of both adrenal glands for treatment of feline Cushing’s disease will result in iatrogenic Addison’s disease, but this is a rarely used operation for cats.  
  • Rarely, primary adrenal failure can occur secondary to trauma. This may be temporary or permanent.
In cats with secondary hypoadrenocorticism, the following underlying causes should be excluded. Again, all of these conditions are associated with deficient secretion of the pituitary hormone, ACTH.
  • Congenital deficiency of ACTH secretion (not yet reported in cats).
  • Pituitary tumors, inflammation, or trauma that have destroyed most of the ACTH-secreting cells in the pituitary gland, leading to deficient ACTH secretion.
  • Iatrogenic hypoadrenocorticism that results from administration of large doses of cortisone-like hormones (glucocorticoids or progesterone-like drugs), which are then withdrawn too rapidly. In this case, the term iatrogenic means that the hypoadrenocorticism is caused by the high-dose glucocorticoid or progestin (megestrol acetate; trade names, Ovaban or Megace) treatment.   
Chain of events leading to severe hypoadrenocorticism in cats
With primary hypoadrenocorticism (Addison's disease), cats develop complete adrenocortical destruction with both cortisol and aldosterone deficiencies.

Aldosterone is the main mineralocorticoid hormone, and it affects the levels of potassium, sodium, and chloride in the blood. Low levels of aldosterone cause potassium to gradually build up in the blood and, in severe cases, cause the heart to slow down or beat irregularly. Some cats have such a slow heart rate (50 beats per minute or lower) that they can become weak or go into shock.

More commonly, cats will develop iatrogenic, secondary hypoadrenocorticism (see above, What causes this disease in cats) to treatment with steroid-like drugs used for anti-inflammatory purposes. This subgroup of hypoadrenal cats is only deficient in cortisol and maintains a normal aldosterone level. These cats are more difficult to diagnose because their signs are milder and the serum potassium, sodium, and chloride values all remain normal.

What are the clinical signs and symptoms of feline hypoadrenocorticism?
Signs of hypoadrenocorticism may include repeated episodes of vomiting and diarrhea, loss of appetite, dehydration, and gradual, but severe, weight loss.

Because the clinical signs of hypoadrenocorticism are vague and nonspecific, it can be difficult to diagnose in the earlier stages of disease. Therefore, severe consequences, such as shock and evidence of kidney failure, can develop suddenly in some cats with complete adrenocortical destruction.

In cats with secondary hypoadrenocorticism, the clinical signs generally are not as severe and are usually not life threatening.

How is feline hypoadrenocorticism diagnosed? 
A veterinarian may suspect hypoadrenocorticism based on the cat’s history (including past treatment with steroids or progestins), clinical signs, and certain laboratory abnormalities, such as low serum sodium and high potassium concentrations. However, one must specifically evaluate adrenal function to document low cortisol levels to definitively diagnose hypoadrenocorticism.

The diagnosis of hypoadrenocorticism is confirmed by lack of cortisol response to ACTH administration. It is important to recognize that the reference range for the post ACTH cortisol is lower in cats than in dogs. To confirm a diagnosis of hypoadrenocorticism, however, the serum concentrations of both the basal cortisol level and ACTH-stimulated cortisol levels are low (generally less than 2 μg/dl).   

How is primary hypoadrenocorticism (Addison’s disease) treated?
Untreated, primary hypoadrenocorticism (Addison’s disease) can lead to an adrenal crisis.  An adrenal crisis is a medical emergency that requires intravenous fluids to restore the body’s levels of fluids, salts, and sugar to normal.  Once stabilized, the cat can then be treated with hormone replacement therapy (either orally or by injection).  With proper treatment, the long-term prognosis is excellent.

Long-tem treatment of primary hypoadrenocorticism (Addison’s disease) includes treatment with either both missing adrenal hormones.  For mineralocorticoid replacement, either oral fludrocortisone (trade name, Florinef) or injectable desoxycortisone privalate (DOCP, trade name, Percorten) are given. In cats, glucocorticoid replacement is best given as oral or injectable prednisolone.   

Response to treatment is similar although clinical signs such as anorexia, lethargy, and weakness may sometimes take longer to resolve than in dogs. Prognosis for long-term survival is good with the exception of cats in which the underlying cause is adrenal neoplasia.

How is iatrogenic hypoadrenocorticism (secondary to overtreatment with steroids or progestins) treated?
In cats with iatrogenic hypoadrenocorticism due to overtreatment with steroids for nonendocrine problems, treatment simply involves reinstituting glucocorticoid replacement at a gradual tapering dosage over weeks to months. This allows the pituitary ACTH-secreting cells to recover and stimulate normal cortisol secretion once again.


doughgirl said...

My cat had the ACTH stimulation test which confirmed secondary renal insufficiency. He was on prednisone for 18 months (its a long story). Is the maintenance dose the same for cats as dogs? I have been giving him 1.25 mg/day. He weighs 10 pounds. He seems good except his legs seem weak. Also, given the length of time he was on steroids (5 to 10 mg/day), do you expect his adrenal function to return with time? In other words, should I attempt to wean him off steroids? Thank you for your help.

Dr. Mark E. Peterson said...

Should you stop steroids? That depends if he needs steroids to treat other problems. The dose you are giving now is small.

doughgirl said...

Dr. Peterson.

Thank you so much for your reply. My vet and I are struggling to determine the proper dose of prednisolone for my cat. The only reason I am giving the pred is because of the hypoadrenocorticism diagnosis. My vet cautions not to give more than a metabolic dose of prednisolone as my cat also has stage 2 renal disease. Do you think 1.25 mg is less than the metabolic dose for a 10 pound cat?

Here are his test results:
baseline cortisol: less than 1 ug/dl (reference range 1-4.5)
post acth stimulation: 4 ug/dl (reference range 7-20)

After reading your blog article again, I am wondering if you think he even has iatrogenic, secondary hypoadrenocorticism since his ACTH-stimulated cortisol level was 4.

Dr. Mark E. Peterson said...

That ACTH response test is NOT diagnostic for Addison's. I'd stop the prednisone (or you can continue the 1.25 mg if you want -- it won't hurt anything).