In most cases, canine Addison's disease, or primary hypoadrenocorticism, is likely caused by immune-mediated destruction of
adrenal tissue in response to an unknown trigger, resulting in primary adrenocortical failure with glucocorticoid (cortisol)
and mineralocorticoid (aldosterone) insufficiency. Administering mitotane or, rarely, trilostane to treat canine hyperadrenocorticism
can also result in primary adrenocortical failure.
David S. Bruyette, DVM, DACVIM
Secondary hypoadrenocorticism, which is caused by a lack of ACTH secretion from the pituitary gland, is usually iatrogenic
and results from abruptly discontinuing long-term glucocorticoid therapy.
SIGNALMENT AND TYPICAL FINDINGS IN DOGS WITH ADDISON'S DISEASE
Primary hypoadrenocorticism can occur in dogs of any age, sex, or breed but occurs most often in young to middle-aged female
dogs. Breeds with a higher risk of developing the disease include poodles (standard and toy), rottweilers, West Highland white
terriers, Wheaton terriers, Great Danes, and Portuguese water dogs.1,2 The clinical signs are related to glucocorticoid and mineralocorticoid insufficiency and include a waxing and waning illness,
with lethargy, depression, anorexia, vomiting, diarrhea, melena, weight loss, polyuria and polydipsia, weakness, and abdominal
pain. Routine blood tests and urinalysis may reveal anemia, lymphocytosis, eosinophilia, hyperkalemia, hyponatremia, hypoglycemia,
hypercalcemia, and prerenal azotemia.
IDENTIFYING, TREATING, AND MONITORING ATYPICAL ADDISON'S DISEASE
About 5% to 10% of dogs with primary hypoadrenocorticism have a glucocorticoid deficiency only.3 These dogs tend to have a mild clinical presentation, with intermittent signs of a gastrointestinal disorder, such as anorexia,
vomiting, and weight loss. And because cortisol counteracts hypoglycemia, dogs may also present with hypoglycemia, particularly
in already small or thin animals. You may also identify a history of weight loss, which may precede the electrolyte abnormalities
that occur as the disease progresses and mineralocorticoid deficiency develops.
Perform ACTH stimulation tests to rule out hypoadrenocorticism in all dogs that exhibit vague waxing and waning clinical signs,
general malaise, and weight loss, even in dogs with normal serum electrolyte concentrations. In general, most animals with
Addison's disease have pre- and post-ACTH cortisol concentrations < 1 µg/dl. In some animals with severe nonadrenal illness
and in animals with early adrenal dysfunction, you can see pre- and post-ACTH cortisol concentrations within the normal basal
resting range (1 to 5 µg/dl). In these cases, it may be necessary to repeat the ACTH stimulation test in four to eight weeks
to document progressive adrenal dysfunction or recovery of the pituitary-adrenal axis after resolution of the nonadrenal illness.
If the ACTH stimulation test results indicate hypoadrenocorticism, provide glucocorticoid supplementation (0.2 to 0.4 mg/kg/day
orally), and monitor these dogs every three or four months for 12 months. Perform serum chemistry profiles that include electrolyte
measurements to monitor for hyperkalemia and hyponatremia, which may indicate mineralocorticoid deficiency and disease progression.
The sodium-potassium ratio can be used to evaluate possible mineralocorticoid insufficiency, but the sensitivity and specificity
of such ratios are affected by whether a ratio of 27 or 23 is used to diagnose adrenal insufficiency. If clinical signs of
mineralocorticoid insufficiency and alterations in the sodium or potassium concentrations, or both, develop at any time in
an animal with atypical Addison's disease, consider evaluating aldosterone concentrations pre- and post-ACTH stimulation and
instituting mineralocorticoid replacement therapy.
THERAPY DURING AN ADDISONIAN CRISIS
On the opposite end of the clinical presentation spectrum, if a dog is presented that you suspect is having an addisonian
crisis, obtain blood and urine samples to perform a pretreatment complete blood count, a serum chemistry profile, urinalysis,
and a baseline cortisol measurement. Then administer synthetic ACTH (Cortrosyn—Amphastar Pharmaceuticals; 5 µg/kg intravenously
or intramuscularly; maximum of 250 µg regardless of the dog's size), and obtain a blood sample one hour later to measure the
post-ACTH cortisol concentration.