Addison's Disease: The (Not So) Great Pretender: This symptoms of this disease can make it difficult to pin down.
THE ENDOCRINE SYSTEM
The medically descriptive name for Addison's disease is hypoadrenocorticism, referring to inadequate adrenal gland secretion.
The adrenal glands are part of the very complex endocrine system, which is a chemical messenger system that helps regulate and modulate the function of the dog's organs.
The endocrine system begins in the brain, at the hypothalamic axis. The brain releases chemical signals, which, in turn, start a cascade of other actions. The brain secretes corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to secrete adrenocorticotropin hormone (ACTH), which normally stimulates the adrenal glands to make and release Cortisol hormones into the blood.
The small, peanut-shaped adrenal glands are positioned just above the kidneys. They are divided into two areas: the cortex (outside) and the medulla (inside). Each part releases different substances when cued to do so by the ACTH.
The adrenal medulla produces catecholamines, including adrenaline, norepinephrine, and small amounts of dopamine. These hormones are responsible for all the physiological characteristics of the so-called "fight or flight" response.
The adrenal cortex produces a variety of steroidal hormones, including mineralocorticoids (which help maintain electrolyte balance and blood pressure) and glucocorticoids (including Cortisol, which helps regulate body metabolism). Without these hormones, all sorts of body functions will go awry.
HOW ADDISON'S DEVELOPS
Addison's disease occurs when the adrenal glands or brain axis are not functioning properly. It can be divided into two categories: primary and secondary.
In primary Addison's disease, the problem is the adrenal glands themselves. In the case of 75 to 95 percent of Addisonian dogs, the problem begins when the immune system damages the adrenal glands so that they can no longer release their important hormones In a small subset, only the glucocorticoids are affected. This is called atypical Addison's.
Secondary hypoadrenocorticism occurs at the level of the brain. Trauma, infection, inflammation, and cancer can all cause abnormalities in the axis. These cases are not common. A much more likely cause of secondary Addison's disease is when a dog has been given steroids long-term for problems like allergies or autoimmune disease, and the steroids are suddenly withdrawn.
When a dog is given supplemental steroids, the body downregulates its own production of these steroids. When the supplemental steroids are stopped suddenly, the body does not have time to adjust and produce more. This causes a crisis, but it is not permanent. This reaction is why long-term steroids must always be weaned slowly.
SYMPTOMS AND DIAGNOSIS
The symptoms of Addison's disease can be insidious and chronic. A dog will have episodes of gastrointestinal upset with or without weight loss. Sometimes weight loss is the only sign, or there are very few symptoms other than occasional listlessness. It is easy for these to go unnoticed.
These vague symptoms are why many dogs are diagnosed only when they experience an Addisonian crisis. In this case, the lack of steroids and/or mineralocorticoids causes an acute, life-threatening collapse with severe electrolyte imbalances, dehydration, and gastrointestinal disease. A dog may seem normal then suddenly start vomiting, experiencing bloody diarrhea, and collapse. This is an emergency. The signs are not specific to Addison's disease and can represent other conditions such as anaphylaxis or acute hemorrhagic gastroenteritis; these conditions, too, call for emergency medical care.
The diagnosis of an Addisonian crisis is made based on clinical signs, history, signalment (age, breed, and sex), a physical exam, and Woodwork. Typical Addison's disease causes highly characteristic changes found on the dog's blood tests. Electrolyte changes are present including very elevated blood potassium in conjunction with a low sodium level. A sodium:potassium ratio should be evaluated by your veterinarian. A ratio of less than 27:1 often indicates Addison's.
Other changes can include low blood sugar (hypoglycemia), mildly elevated kidney values, and a normal white blood cell count in the face of illness. In an ill or stressed dog, the white blood cell count should be elevated, indicating a bodily response. However, in Addisonian patients, this doesn't occur. It's important to know that these changes are in typical hypoadrenocorticism, in which both Cortisol and mineralocorticoid levels are low.
In atypical Addison's, only Cortisol is involved. Bloodwork may be mostly normal. Electrolytes will not be affected. Sometimes the only change is a low blood sugar and a lack of elevation in white blood cells. This makes recognition and diagnosis a challenge.
The definitive test for both typical and atypical is the ACTH stimulation test. In a patient with Addison's disease, the glands cannot secrete Cortisol and mineralocorticoid because they are not functioning or are atrophied.
The patient must stay at the veterinary clinic for several hours while the test is administered. An initial baseline Cortisol level is drawn. This is typically very low in Addisonian patients. The dog is then given an injection of substance that mimics ACTH in an effort to stimulate the adrenal glands; the Cortisol levels are checked two hours later.
In a patient with hypoadrenocorticism, the adrenal glands do not respond and the "post-cortisol" level is close to zero, confirming the diagnosis. Note that the blood samples for this test must be sent to an outside laboratory; this is not an in-house test.
Initial treatment will depend on whether a dog is typical or atypical and on the severity of the condition at presentation.
If a dog is diagnosed while stable, initial treatment is with oral steroids, usually prednisone. This is true for both typical (deficiencies in Cortisol and mineralocorticoids) and atypical (deficiency of just steroids). Due to the many side effects they can cause, therapeutic steroid dosages should be adjusted over time to the lowest possible dose.
If a dog is atypical, steroids are usually sufficient treatment. It is important to note that some dogs who initially present with atypical Addison's will progress to the more typical disease, eventually requiring the mineralocorticoid supplementation, as well.
There are currently two options for this: an oral supplement (fludrocortisone acetate) and an injectable one (desoxycorticosterone pivalate, better known as DOCP).
Fludrocortisone acetate, the less expensive choice, is given daily. It has both mineralocorticoid activity and some steroid activity, so certain patients can be maintained on fludro cortisone only. However, monitoring is more intense for the first 18 to 24 months, and in some cases, it just doesn't work well enough. The side effects of the glucocorticoid portion can also be very intense at higher doses (increased drinking, increased urination, panting, weight gain, and restlessness).
The better alternative is DOCP, given as an injection every 25 to 30 days. This is by far the preferred treatment option because of the long duration between injections and how well it works. With veterinary instruction, it can be administered at home. However, DOCP can be very expensive for big dogs. Also, it is intermittently unavailable, so in those cases, fludrocortisone acetate may be chosen as the initial treatment.
The treatment is different for a dog who is diagnosed due to an Addisonian crisis--unfortunately, this is not uncommon. A previously healthy dog may suddenly develop copious vomiting, hemorrhagic diarrhea, shock, and collapse. This is an emergency and requires immediate veterinary attention. Dogs are usually suffering low blood pressure, low blood sugar, and seriously unbalanced electrolyte levels.
Large volumes of intravenous fluids will correct low blood pressure and electrolyte abnormalities. A physiologic dose of a short-acting steroid (Dexamethasone-SP) is given. This will not interfere with necessary testing to confirm the diagnosis (while other, longer acting steroids will). Blood sugar is often low during a crisis and should be treated as well. Dextrose will be added to the fluids.
Patients will be in the hospital anywhere from two to five days, depending on the severity of shock and electrolyte imbalances. Serial blood-work is performed to monitor sodium and potassium, as well as blood glucose. Electrolytes may be checked as frequently as every four hours in the initial 24- to 48-hour period. Blood pressure is monitored closely. Treating an Addisonian crisis can be costly and stressful, and the prognosis is always guarded.
Once stable, dogs with hypoadrenocorticism must be monitored closely at home. Symptoms of impending crisis can be as subtle as shaking but also may include vomiting, loose stool, decreased appetite, and weakness. Any time a stressful event occurs and the body naturally requires more Cortisol, a dog is at risk for a crisis. Ask your veterinarian for information about increasing steroids in these times.
Serial bloodwork is needed to titrate treatment. This usually includes electrolyte monitoring, as well as periodically checking a full blood panel. Electrolytes are usually checked every three to six months initially; once they have normalized, the tests can be less frequent.
A full metabolic panel is recommended every six months. When a patient is maintaining well on DOCP, the dose is usually sufficient to manage symptoms for the rest of the animal's life.
Treatment is lifelong, but the prognosis for Addison's disease is positive overall. The limiting factor for many dog owners is the cost of repeated laboratory testing in the first 12 to 18 months. DOCP also can be expensive for large dogs. Once the disease is stabilized, however, dogs often enjoy a good quality of life with minimal follow-up testing and less expense.
After nine years in emergency medicine, Catherine Ashe, DVM, now works as a relief veterinarian in Asheville, NC.
A Note About Whipworms
The canine whipworm, Trichuris vulpis, is a nasty parasite that lives in the large intestine. The symptoms of a whipworm infection can be very similar to Addison's disease and include weight loss, vomiting, and bloody diarrhea. Further, they can cause the characteristic bloodwork changes of Addison's, particularly the telltale sodium:potassium ratio.
If you are in an endemic area (ask your veterinarian, or see the informative prevalence maps at capcvet.org/maps), keep your dog on a monthly prevention that protects against whipworms. Sentinel, Trifexis, Interceptor Plus, and Advantage Multi all contain ingredients that treat whipworm infections. Check the label or product insert on your dog's flea/tick and heartworm preventatives to see if they contain an agent that specifically targets whipworms.
A Pitch for Pet Insurance
Pet insurance is always a good idea, but even more so if your dog is diagnosed with a chronic illness such as Addison's disease. Since it is such an excellent mimic, it make take several lab tests before the correct diagnosis is made. Even if the diagnosis is made quickly, follow-up testing, medications, and monitoring can quickly add up (no pun intended).
Most pet insurances decline coverage for pre-existing conditions. With a diagnosis of Addison's disease, it is likely too late to find a company that will pay for diagnostics and treatment. If your dog was insured beforehand, however, insurance can be a literal lifesaver.
As a veterinarian, I wish more owners would consider pet insurance. Making a diagnosis under even the best of circumstances with unlimited funds can be challenging. It is even more so when finances are a major factor. Of all the chronic diseases, Addison's is one of the most easily treated and managed. Unfortunately, the cost of diagnosing, treating, and monitoring can be a burden, and sometimes hard decisions must be made. "Financial euthanasia" can be especially traumatic for everyone involved.
Dogs with Addison's disease can be tricky to diagnose, time-consuming, and test-intensive in the initial stages. Pet insurance can alleviate this strain dramatically. In this situation, we all win: the veterinarian, the pet owner, but mostly importantly, the patient!
For tips on buying pet insurance, see "Rest Insured," WDJ March 2018.
Caption: There is quite a long list of dogs who are at a higher-than-average risk of developing Addison's disease, including Rottweilers, but the condition can afflict a dog of any breed.
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|Publication:||Whole Dog Journal|
|Date:||May 1, 2019|
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