CVC 2008 Highlights: Managing atypical and critical cases of primary hypoadrenocorticism in dogs
Two things you may not know about canine Addison's disease: A history of weight loss or hypoglycemia may precede the typical electrolyte abnormalities, and DOCP can be administered immediately in dogs that may be having an addisonian crisis.
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.
During that hour, start treating the dog's hypovolemia and hypotension with fluid resuscitation (0.9% sodium chloride solution at 60 to 80 ml/kg for the first one or two hours), administer a glucocorticoid in the form of a dexamethasone salt (1 mg/kg dexamethasone sodium phosphate given intravenously) rather than prednisone so it won't interfere with your ACTH stimulation test results, provide thermal support (e.g. forced-air warming with a Bair Hugger [Arizant Healthcare] or a warm-water- circulating blanket), and administer a mineralocorticoid, such as desoxycorticosterone pivalate (DOCP; Percorten-V—Novartis Animal Health) (1 mg/lb given intramuscularly), right away. Data show that giving DOCP daily to healthy dogs is not harmful,4 and there is no medical disadvantage to giving this drug during a potential addisonian crisis. Administer DOCP intramuscularly during an addisonian crisis because the drug may be poorly absorbed in dehydrated, hypovolemic, hypotensive patients if given subcutaneously.
As an alternative to DOCP, you may administer fludrocortisone acetate (Florinef—Bristol-Myers Squibb), which has mineralocorticoid and glucocorticoid activities. But this drug must be given orally, and addisonian dogs are already likely experiencing gastrointestinal dysfunction such as vomiting or gastric bleeding. Furthermore, DOCP corrects the electrolyte abnormalities that occur with hypoadrenocorticism better than fludrocortisone does.5
After one or two hours, decrease the saline solution administration rate to meet the dog's fluid replacement needs. If the dog doesn't respond well to the above therapy within 24 hours, reassess your diagnostic test results thoroughly.
MAINTENANCE MINERALOCORTICOID AND GLUCOCORTICOID THERAPY
As you transition to maintenance therapy for hypoadrenocorticism, recheck dogs two weeks after the first DOCP injection and every week thereafter, and measure serum electrolyte concentrations. By assessing patients for hyperkalemia and hyponatremia, you will be better able to determine the DOCP administration interval. The frequency of DOCP administration is determined by the time the sodium or potassium concentration, or both, is no longer in the reference range after the initial dose of DOCP.
In my experience, some dogs may require a DOCP dosing interval of every two weeks and others may require a dosing interval of every eight weeks (the labeled dosing interval is every 25 days). Furthermore, I have found that large dogs (> 50 lb) may need only 0.5 mg/lb DOCP, and if their electrolyte concentrations are normal at four weeks after the first injection, you may be able to effectively treat these patients with an even lower dose. DOCP is also effective when given subcutaneously,6 and we have taught our clients how to administer these injections at home, thus saving the expense and time of a trip to the hospital for dogs that are stable.
Fludrocortisone acetate may be used as maintenance mineralocorticoid replacement therapy, but it is inferior to DOCP with respect to normalization of serum sodium and potassium concentrations. And in dogs weighing > 20 to 25 lb, it will be more expensive than DOCP.
In dogs with stable disease, perform a recheck examination and laboratory tests every four to six months and anytime the dog becomes ill.
Glucocorticoid supplementation (0.2 to 0.4 mg/kg prednisone given orally once a day or every other day) will be needed as part of lifelong treatment in dogs receiving DOCP. Instruct clients that the dose will need to be increased in times of illness or other stress, such as hospitalization or boarding. When a stressful episode is anticipated, administer additional glucocorticoids the day before and two or three days after the event.
David S. Bruyette, DVM, DACVIM
VCA West Los Angeles Animal Hospital
1818 S. Sepulveda Blvd.
West Los Angeles, CA 90025
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2. Oberbauer AM, Bell JS, Belanger JM, et al. Genetic evaluation of Addison's disease in the Portuguese water dog. BMC Vet Res 2006;2:15.
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5. Kintzer P, Peterson M. Treatment and long-term follow-up of 205 dogs with hypoadrenocorticism. J Vet Intern Med 1997;11(2):43-49.
6. McCabe MD, Feldman EC, Lynn RC, et al. Subcutaneous administration of desoxycorticosterone pivalate for the treatment of canine hypoadrenocorticism. J Am Anim Hosp Assoc 1995;31(2):151-155.