I started the dog on oral prednisone (0.15 mg/kg once daily) for glucocorticoid coverage. For mineralocorticoid supplementation, I administered a single dose of desoxycorticosterone pivalate (DOCP; Percorten-V, Novartis) at the recommended dose of 2.2 mg/kg intramuscularly.
The dog has done very well, with a complete clinical response. We have monitored the dog's serum chemistry panel at 15, 25, 35, and 51 days after the initial Percorten-V injection, but the dog's serum potassium value remains within the high-normal range (between 4.5-5.5).
Now on day 53, the dog is acting more lethargic and is not eating well. I just instructed the owner to administer the second Percorten-V injection; the owner is a nurse so they are able to give the injection at home.
I'm confused. Does this dog have Addison's disease or is my diagnosis incorrect? Can Addison's disease ever go into remission? Why is the serum potassium concentration still within the normal range?
In answer to your first question, it is clear that this dog does indeed have primary hypoadrenocorticism (Addison's disease) (1-5). That diagnosis is based on the following data:
- Signalment (i.e., young adult female dog)
- History and clinical signs (anorexia, vomiting, lethargy)
- Routine laboratory findings (hyperkalemia, hyponatremia, prerenal azotemia)
- Low basal cortisol concentration
- Lack of a serum cortisol response to ACTH stimulation
- Complete response to glucocorticoid and mineralocorticoid treatment
In answer to your last question, I do not know for certain why an occasional dog will have a prolonged response to the Percorten-V injection, but it certainly does occur. Remember that circulating potassium concentrations are controlled by factors other than just aldosterone. That's one reason we sometimes see dogs with "atypical" Addison's dogs that have persistently normal serum potassium concentrations but no measurable aldosterone concentrations (6-9). Most of those dogs will eventually go on to develop hyperkalemia or hyponatremia, but in some dogs it may take months.
Dogs like this indicate that there are mechanisms which allow normal potassium and sodium balance to be maintained even without the presence of circulating aldosterone. This phenomenon is also recognized in human medicine, where it has been shown that up to 25% of human patients with primary hypoadrenocorticism may have normal serum potassium concentrations. However, all of these Addison's patients will have a high plasma renin to aldosterone ratio, which indicates a failing zona glomerulosa (10,11).
What's the mechanism for this maintenance of normal potassium concentrations in dogs or humans with Addison's disease? Well, that's not clear, but the following physiological mechanisms have been proposed (11-13):
- Hyperkalemia itself will increase potassium excretion; this may help maintain normal serum levels of potassium.
- A high renal tubular flow rate with increased distal delivery of potassium can increase the urinary excretion of potassium and again help maintain normokalemia.
- An increased sensitivity of the distal tubule to aldosterone will enhance the urinary excretion of potassium. Again, this would help maintain the whole body levels of potassium.
- Insulin may also act to compensate for aldosterone deficiency by promoting the transfer of potassium from the extracellular to intracellular space, thus maintaining normokalemia.
Based on my studies done 2 decades ago, it's clear that most dogs with Addison's disease can be maintained quite well with DOCP when given at much lower monthly doses than 2.2 mg/kg/injection (4,5). In one study (4), the final median dose of DOCP needed in 33 dogs was 1.69 mg/kg/month, with a range of 0.75-3.4 mg/kg/month (Figure 1, below).
If this was my case, I would not waste any more time or money trying to determine the longest interval you can go between Percorten-V injections. Remember, it's not necessary for hyperkalemia to redevelop before the next injection; in fact, you don't want that to ever happen! Rather, I recommend that you treat with low dose of Percorten-V once monthly. It's very difficult to "overdose" Percorten-V, so we don't have to worry about giving the injections too frequently, especially when we are giving a smaller monthly dose.
How low can you go with the monthly Percorten-V injections? I'd start by lowering the dose by about 10-20% and then check the serum electrolytes again in a month. If they remain normal, then I'd continue to decrease the dose by another 10-20%. Again, in my studies, over half the dogs did very well on a monthly dose of Percorten-V <1.6 mg/kg. Almost all dogs need a monthly dose of at least 1.0 mg/kg/month to maintain normal serum electrolytes on a long-term basis (Figure 1).
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