Addison’s Disease - Testing and Monitoring

What is Addison's disease?

Addison's disease (the common name for hypoadrenocorticism) is caused by a decreased production of two hormones from the adrenal gland. These hormones are cortisol, a stress hormone, and aldosterone, a mineralocorticoid hormone that regulates the body's water balance through its effects on sodium and potassium.

What causes Addison's disease?

In humans, Addison's disease is usually caused by immune-mediated destruction of the adrenal glands – primary hypoadrenocorticism). The immune system wrongly recognizes the gland tissue as "foreign" and destroys it as it would destroy a virus. This is also thought to be the main cause of Addison's disease in the dog. Less common causes of damage to the adrenal glands include trauma, bleeding, or infection. Regardless of the cause of adrenal gland destruction, the levels of cortisol and aldosterone will be decreased, resulting in clinical disease.

Addison's disease may also result from decreased stimulation of the glands by the pituitary hormone ACTH, called secondary hypoadrenocorticism. Secondary Addison's disease is rare, and may be related to trauma, inflammation or tumors near the pituitary gland. Decreased cortisol production is the main feature of this form of Addison's disease, while the production of aldosterone is less affected.

If a dog receives corticosteroid-containing medications such as prednisone over a prolonged period, the normal production of cortisol by the adrenal glands is reduced. If this medication is withdrawn rapidly, the adrenal glands will not be prepared to suddenly resume cortisol production. Therefore, a temporary condition similar to Addison's disease may result.

Finally, Addison's disease may occasionally occur following treatment for hyperadrenocorticism (Cushing's disease). This form of Addison's disease is termed iatrogenic (caused by clinical intervention).

What tests are used to diagnose Addison's disease?

"The signs of Addison's disease are often vague,
and may mimic other disease conditions."

The signs of Addison's disease are often vague, and may mimic other diseases. Therefore, it is important to perform initial screening tests that evaluate blood and urine samples to help rule out other disease conditions and to establish further evidence of Addison's disease. Given the slowly progressive nature of this disease, the number of changes or 'clues' to Addison's disease that are found in this initial testing are variable.

Complete blood count (CBC):

The red blood cell, white blood cell, and platelet cells are evaluated. Occasionally a mild anemia (low red blood cell count) is noted with Addison's disease, as cortisol is required for optimal red blood cell production by the bone marrow.

Often, sick or otherwise stressed dogs will have characteristic changes in their white blood cell populations. These changes can be brought about by the effects of cortisol (a stress hormone), as well as by the effects of an ongoing infection. When cortisol decreases in Addison's disease, these characteristic stress-induced changes may disappear.

Serum biochemistry profile:

Serum (the liquid portion of blood) contains enzymes, proteins, lipids (fats), glucose (sugar) and metabolites. These serum components are derived from different organs such as the liver, kidney and pancreas, and their measurement can give an indication of the function of these organs.

Changes seen with Addison's disease are usually related to the lack of hormonal (cortisol and aldosterone) effects on organs, rather than actual organ damage. Since cortisol is required for maintenance of proper serum glucose (blood sugar) concentrations, cortisol deficiency may result in hypoglycemia (low blood sugar).

Aldosterone regulates the body's fluid balance by its effects on sodium and potassium. A lack of aldosterone may be reflected by changes in the proportion of sodium to potassium in the serum, and by a decrease in total body fluid. This decreased body fluid makes it difficult for the kidneys to rid the body of waste products. An increase in metabolic byproducts such as blood urea nitrogen and creatinine may be seen in the serum.

Urinalysis:

The decrease in total body fluid related to Addison's disease cannot be measured directly but can be estimated by the concentration of urine that an animal produces. A special instrument called a refractometer is used to evaluate the concentration of the urine. The kidneys generally produce concentrated urine when water is less available.

Because of the multiple effects of cortisol and aldosterone on body organs, the changes outlined above are not specific for Addison's disease but may also be seen with dysfunction of other organs. Therefore, if a pattern of changes supportive of Addison's disease is found, diagnosis will need to be confirmed using a specific diagnostic test, called the ACTH stimulation test.

How does the ACTH stimulation test work?

ACTH is a hormone naturally produced by the pituitary gland (located in the brain). The purpose of ACTH is to tell the adrenal glands when and how much cortisol to produce.

"This test requires two blood samples taken approximately 2 hours apart."

As the blood level of cortisol increases, it causes the pituitary gland to decrease its production of ACTH, which results in a lowering of the cortisol level. The ACTH stimulation test mimics this natural stimulatory pathway and demonstrates the ability of the pet's adrenal glands to produce cortisol in response to an injection of synthetic ACTH.

This test requires two blood samples taken approximately 2 hours apart. The first blood sample is taken prior to injecting synthetic ACTH, and the second sample is taken 2 hours following the injection. Cortisol levels in the two samples are measured and compared to assess the response.

What do we expect to see if the patient has Addison's disease?

Regardless of the underlying cause of Addison's disease, the results of the ACTH stimulation test are similar.

This test is characterized by a low amount of cortisol in the blood sample taken prior to the administration of the synthetic ACTH, and either little or no increase in the amount of cortisol measured in the sample taken after the ACTH injection. A lack of response to synthetic ACTH administration confirms the diagnosis of Addison's disease.

How can we differentiate between the causes of Addison's disease?

A thorough review of all medications that your pet has been receiving (both oral and topical formulations) is essential. If your pet has received medications containing corticosteroids that are suddenly stopped, he may have a temporary Addisonian condition that only requires treatment for a short time.

If your pet has been treated for hyperadrenocorticism (Cushing's disease), the adrenal glands may become incapable of producing cortisol and aldosterone. This condition is permanent and your pet will require treatment for his lifetime.

Most cases of Addison's disease that are not related to the effects of medication are caused by immune-mediated destruction of the adrenal glands. As the function of these glands decreases, the amount of cortisol in the blood also decreases. Decreased blood cortisol levels prompts the normal pituitary gland to secrete more stimulating hormone (ACTH) in an attempt to 'beef up' cortisol production. Over time, this effort becomes futile, but an increased blood ACTH concentration can be measured. The amount of this endogenous ACTH is typically increased in dogs with Addison's disease due to adrenal gland disease. Conversely, with cases of Addison's disease due to lack of production of ACTH by the pituitary gland, the endogenous ACTH concentration will be decreased.

Since both cortisol and aldosterone hormones are usually decreased with Addison's disease, do we need to measure aldosterone as well?

Studies have shown that measuring aldosterone concentrations does not reliably differentiate amongst the different causes of Addison's disease. Therefore it is rarely indicated.