Atypical Addison’s Disease

By Doug Brum
angell.org/internalmedicine
internalmedicine@angell.org
617-541-5186

Canine glucocorticoid deficient hypoadrenocorticism or “Atypical” Addison’s disease is being identified in our canine population with greater frequency.  The term describes dogs with adrenal glands that still produce mineralocorticoids but lack sufficient glucocorticoid production.  Atypical Addison’s disease used to be considered a much rarer condition than the classical Addisonian but now is identified in up to 30-45% of dogs diagnosed with the hypoadrenocortisism.  Both types of Addison’s disease still occur with greater frequency in younger dogs with the average age of diagnosis about 4-5 years of age.  Female dogs account for about 70% of the cases, and there is a heritable component in Standard Poodles, Bearded Collies, Portuguese Water Dogs, and the Nova Scotia Duck Tolling Retriever.

Atypical Addison dogs usually have more subtle clinical signs and may be more difficult to diagnose.  Usually these dogs do not present in a crisis, nor are they severely dehydrated, bradycardic, or in hypovolemic shock as they still have mineralocorticoid function.  Their signs are glucocorticoid dependent and subtler.  Clinical signs vary but may include, vomiting, diarrhea, anorexia, lethargy, or weight loss.  The most typical history we see is a young dog with chronic intermittent histories of gastrointestinal issues.  They commonly have episodes or signs that “wax and wane.”   Some of these dogs have been sent in for GI work ups including the recommendation for endoscopic biopsies.  Atypical Addison’s should be ruled out before endoscopy.

Addison’s disease has often been called the “great imposter” as it can mimic many other diseases and is often difficult to initially diagnose.  Since dogs with atypical Addison’s disease still have mineralocorticoid function, they lack the typical electrolyte abnormalities commonly associated with hypoadrenocorticism.  Their sodium and potassium values are often normal, so other blood abnormalities need to be noted to guide in the diagnosis.  A lack of a stress leukogram in an ill animal is commonly seen in animals with a cortisol deficiency.

More subtle lab abnormalities signs include a mild to moderate hypoalbuminemia, and hypocholesterolemia, once again pointing to GI disease, but decreased cortisol levels can also be the problem. When a young dog presents for only hypercalcemia or eosinophilia, atypical Addison’s needs to be considered.  Other dogs, especially toy breeds, may present just with hypoglycemia.  A dog could have only one of these lab abnormalities, or multiple.  It is important to rule atypical Addison’s out before getting into more extensive work ups in all these conditions.

An excellent, and cost efficient way to rule out atypical Addison’s disease is by running a basal cortisol level.  If your patient’s basal cortisol level is over 2 mcg/dl the dog unlikely will have Addison’s disease.  Values below 2 mcg/dl don’t diagnose the disease, it just means that the dog could have Addison’s disease and an ACTH stim should be run.  Even if the basal cortisol level is at the lowest level detectable for your lab, an ACTH stim needs to be done to diagnose the condition, as some dogs that have very low basal cortisol levels still will have cortisols that stimulate to acceptable levels.

Dogs with Addison’s disease usually have ACTH stims with the pre and post cortisol under 1mcg/dl, but if both values are under 2 mcg/dl, it is diagnostic for Addison’s disease.

Occasionally in dogs that are tested early in disease progression, the cortisol concentrations may be slightly higher.   “Flat-line” cortisol responses can be seen when a pre-ACTH cortisol level might be 3 mcg/dl, and a post-ACTH cortisol might be 3.3 mcg/dl). Retesting these dogs in 4-6 weeks might show more definitive results.

Another factor that could confound a diagnosis is if a dog has received prednisone before doing either a basal cortisol level or an ACTH stim.  Giving prednisone prior to doing a cortisol level will falsely increase the measured cortisol, possibly giving a false negative result.

The treatment of glucocorticoid-deficient Addison’s disease involves using the lowest effective dose of prednisone that controls the dog’s clinical signs and minimizes any long-term prednisone side effects.  Typically, after initially establishing a diagnosis, higher doses of prednisone may be used (up to 1mg/kg/day) but these doses may be rapidly decreased to a maintenance dose closer to 0.1-0.2mg/kg/day.  All dogs are different, and some dogs need less than 0.1mg/kg/day or only need it every other day.  As with typical Addisonian dogs, in stressful situations, the maintenance dose of prednisone is usually doubled.

Sometimes dogs receiving long-term prednisone for the treatment of their disease begin to show side effects of long term prednisone administration (the most common are polyuria/polydipsia/primary polydipsia (PU/PD/PP)) even at fairly low prednisone doses.  In these dogs changing prednisone to methylprednisolone may significantly improve their clinical signs.

The key in treating all atypical Addison’s dogs is to give them the smallest amount of prednisone or methylprednisolone to control their clinical signs and minimize any potential side effects of the corticosteroid.  If doses of prednisone significantly higher than 0.2mg/kg/day are needed to control a dog’s clinical signs, then it is possible that the patient may have another disease that the prednisone is treating.  The atypical Addison’s dog that had chronic intermittent GI signs, and requires higher doses of prednisone, may also have inflammatory bowel disease (IBD), and the higher doses are actually treating the IBD.  Establishing the diagnosis of IBD would allow you to treat the IBD with different modalities, allowing for a smaller dose of prednisone, and thus fewer side effects.

Dogs with atypical Addison’s disease typically live excellent quality lives and the disease does not affect the dogs’ life expectancy.  Dogs should be evaluated at least twice a year, and electrolytes should be monitored.  It is rare that a dog with glucocorticoid deficient Addison’s will develop classical Addison’s, with electrolyte abnormalities, but it has been reported.

Some have suggested that it is safer to prophylactically give these dogs DOCP to reduce the chance of an Addisonian crisis that could develop if a dog becomes mineralocorticoid deficient as well.  Most veterinarians no longer recommend this due to expense and the unlikely event that their disease will progress.  Routine monitoring with physical examinations, blood work and client education is usually sufficient.

Remembering atypical Addison’s as a possible cause of many subtle signs or specific lab abnormalities, can save you and your clients extensive diagnostic work ups and significantly improve the quality of life of our patients.