The cat presented for severe lethargy and depression, complete anorexia, and bloody diarrhea. On physical examination, she was 8-10% dehydrated and was severely depressed and weak. Her mucous membranes were slightly pale and tacky. Her only past history was a fungal infection causing hair loss on her face and neck, which has responded to itraconazole treatment with partial hair regrowth.
Results of a complete blood count revealed a hematocrit of 30%, and a white blood cell count of 14,300 with a normal differential. A serum chemistry panel showed a urea nitrogen of 22 mg/dl and a creatinine of 1.8 mg/dl. The serum concentrations of sodium (145 mEq/L), potassium (5.3 mEq/L), and chloride (107 mEq/L) were all within reference range limits. A basal serum cortisol value was slightly low at 0.8 μg/dl (normal, 1-4 μg/dl).
Based on the clinical presentations coupled with the low serum cortisol value, I made a diagnosis of hypoadrenocorticism and started the cat on prednisolone (5 mg, bid PO). There has been only a minimal response to treatment, and now the cat has developed ataxia. Repeat serum chemistry panel and survey radiographs were normal.
Why hasn't the cat responded better to my treatment?
In cats, as in other species, hypoadrenocorticism results from deficient adrenocortical secretion of glucocorticoids, either alone or concurrent with reduced secretion of mineralocorticoids. Hypoadrenocorticism can be a naturally occurring disease or can be iatrogenic and is extremely rare in cats (especially the naturally occurring disorder). The first cat with primary hypoadrenocorticism was described approximately 30 years ago (1), and since then, fewer than 20 well-documented cases of naturally occurring adrenal insufficiency in cats have been reported (2-9).
It's highly unlikely that this cat has primary hypoadrenocorticism (Addison's disease) for the following reasons.
- First of all, this is an extremely rare disorder of cats.
- More importantly, all of the reported feline cases of Addison's disease have had serum electrolyte changes consistent with mineralocorticoid (aldosterone) deficiency (hyperkalemia, usually with hyponatremia and hypochloremia) (1-9). The fact that this cat has normal serum electrolytes alone tends to rule out the diagnosis of Addison's disease.
- Thirdly, the serum cortisol of 1.1 μg/dl may be slightly low to low-normal, but cats with naturally occurring Addison's disease should have undetectable levels of circulating cortisol (1-10). So the fact that cortisol was detected alone goes against Addison's disease. However, I suspect that we may actually be measuring the prednisolone in the cortisol assay, since that steroid will cross react in the cortisol assay to produce a "falsely high" cortisol reading (10).
- To diagnose Addison's disease, we would need to do an ACTH stimulation test. To do that, however, we would need to stop the prednisolone for at least a week (a month would be best) to allow the pituitary gland and adrenal glands to recover.
It's highly likely that you have induced secondary hypoadrenocorticism in this cat.
- Remember that administration of any glucocorticoid to a cat will feed back to the cat's pituitary and suppress ACTH secretion. This can lead to secondary hypoadrenocorticism, with low circulating cortisol concentrations (10,12). In this scenario, however, aldosterone secretion would be be affected since pituitary ACTH has little stimulatory effect on aldosterone secretion. Therefore, normal serum electrolytes would be expected (10,12).
- In addition, it's quite possible that itraconazole that you have been giving is also blocking normal cortisol production, leading to iatrogenic hypoadrenocorticism. Antifungal agents, such as ketoconazole and itraconazole, interfere with the synthesis of steroid hormones and can block cortisol synthesis. Again, as long as you are giving the prednisolone, the cat is covered and should not show signs of hypoadrenocorticism.
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