What is Addison's disease?
Addison's disease (also known as hypoadrenocorticism) is caused by decreased production of two hormones from the adrenal gland: cortisol (a stress hormone) and aldosterone (mineralocorticoid), a hormone that controls the body's water balance through its effects on sodium and potassium.
What causes Addison's disease?
Addison’s disease, also known as hypoadrenocorticism, can have several causes.
Primary Addison’s disease is considered the most common type in pets. It occurs when the adrenal glands are damaged and cannot produce enough cortisol and aldosterone.
This malfunction in the adrenal glands is believed to be caused by an autoimmune response in which the immune system wrongly recognizes the adrenal gland tissue as “foreign” and destroys it like it would destroy a virus.
Less common causes of damage to the adrenal glands include:
- Trauma
- Bleeding
- Infection
- Cancer
Atypical Addison’s disease occurs when only the cortisol-producing part of the adrenal gland is damaged. Levels of sodium and potassium (electrolytes) are usually normal because aldosterone production is not affected. However, some affected dogs develop reduced aldosterone over time, causing electrolyte abnormalities, so they are often monitored for electrolyte changes.
Secondary Addison’s disease develops when the pituitary gland does not make enough ACTH, the hormone that tells the adrenal glands to produce cortisol.
One cause of reduced ACTH is the long-term administration of corticosteroids. Corticosteroids have effects like the natural hormone cortisol, telling the pituitary gland to reduce ACTH secretion.
Depending on the dose of corticosteroids and how long they are given, the pituitary gland may lose the ability to produce ACTH (usually temporarily). If corticosteroids are stopped abruptly, the adrenal glands don’t receive the ACTH signal to produce cortisol, resulting in secondary Addison’s disease.
Other, more rare causes of secondary Addison’s disease include trauma, brain surgery (hypophysectomy), inflammation, immune-mediated disease, tumors of the pituitary gland, and tumors near the pituitary gland.
In secondary Addison’s disease, cortisol is low and aldosterone is usually normal. Dogs with secondary Addison’s disease are not at risk of losing aldosterone production.
Iatrogenic Addison's disease is caused by medical intervention. It may occasionally develop after treatment for Cushing's disease (hyperadrenocorticism).
What tests are used to diagnose Addison's disease?
The signs of Addison's disease are often vague and may mimic other diseases, so 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.
What can these screening tests indicate?
Common screening tests are the complete blood count (CBC), serum biochemistry profile, and urinalysis.
Complete Blood Count (CBC)
A complete blood count (CBC) is a simple blood test that provides information about the different cell types in the blood. These include the red blood cells, which carry oxygen to the tissues; white blood cells, which fight infection and respond to inflammation; and platelets, which help the blood to clot. 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 pets will have characteristic changes in their white blood cell populations. These changes can be brought about by the effects of cortisol (a stress hormone), and 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, kidneys, and pancreas, and measuring them can give an indication of the function of these organs.
Changes seen with Addison's disease are usually related to the lack of hormonal effects on organs (cortisol and aldosterone), rather than actual organ damage. Cortisol is required for maintenance of proper serum glucose (blood sugar) concentrations, so cortisol deficiency may result in hypoglycemia (low blood sugar).
Aldosterone regulates the body's fluid balance by affecting sodium and potassium. A lack of aldosterone may be reflected by changes in the amount of sodium and potassium in the serum, causing an abnormal sodium:potassium (Na:K) ratio, 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 kidney values, 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.
The changes outlined above are not specific to Addison's disease; they may also be seen with dysfunction of other organs because cortisol and aldosterone have multiple effects on body organs. Therefore, if a pattern of changes is found that supports a diagnosis of Addison's disease, that diagnosis will need to be confirmed using an 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 to produce cortisol and how much to produce.
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 a specific length of time apart. In dogs, the first blood sample is taken before injecting synthetic ACTH (Cortrosyn™ or Synacthen®), and the second sample is taken one to two hours after the injection. In cats, this time frame may be shorter. Cortisol levels in the two samples are measured and compared to assess the response.
What result is expected if the patient has Addison's disease?
In a pet with Addison’s disease, the first test (taken before the ACTH injection) shows a low amount of cortisol. The second test (taken after the ACTH injection) shows little or no increase in the amount of cortisol. A lack of response to synthetic ACTH confirms the diagnosis of Addison's disease. Regardless of the underlying cause of Addison's disease, the results of the ACTH stimulation test are similar.
Why would my veterinarian ask to check a resting cortisol level before running an ACTH stimulation test?
Many illnesses can have signs like those caused by Addison’s disease, so your veterinarian may recommend checking your pet’s resting or baseline cortisol level. If resting cortisol is elevated, it can rule out Addison’s disease without the additional expense of synthetic ACTH. This test does not diagnose Addison’s disease.
How can the cause of Addison's disease be differentiated?
Medication review: It is essential for your veterinarian to thoroughly review all medications your pet has been receiving (both oral and topical). If your pet has suddenly stopped receiving medication containing corticosteroids, they may have a temporary Addisonian condition that only requires treatment for a short time.
Treatment history: 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 their lifetime.
Measuring ACTH: Endogenous (naturally produced) ACTH levels help determine whether the problem is in the adrenal glands or the pituitary gland. When the adrenal glands are damaged (primary Addison’s disease), cortisol production decreases, prompting the pituitary gland to secrete more stimulating hormone (ACTH) to increase cortisol production.
- High endogenous ACTH typically occurs in pets with primary Addison’s disease (adrenal gland disease).
- Low endogenous ACTH typically occurs in pets with secondary Addison’s disease (low production of ACTH by the pituitary gland) or iatrogenic disease due to medications that suppress production such as corticosteroids (prednisone, dexamethasone).
Both cortisol and aldosterone are usually decreased with Addison's disease, so should aldosterone be measured as well?
Studies have shown that measuring aldosterone concentrations does not reliably differentiate the different causes of Addison's disease, so it is rarely indicated.
