Q & A: Addison's Disease in a Siamese Cat

I would like to discuss a problem case of feline Addison's disease that I diagnosed a few months ago. The cat is a 6-year old female-spayed Siamese weighing 3 kg.

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?

My Response

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.

1. First of all, this is an extremely rare disorder of cats.
2. 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.
3. 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).
4. 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.

One common protocol for ACTH response testing in cats is to collect blood for determination of circulating cortisol concentration before and at 60 minutes after administration of 0.125 mg synthetic ACTH (cosyntropin; Cortrosyn) IV (10,11). It is important to administer ACTH intravenously, especially if the cat is dehydrated. In addition, findings in healthy cats indicate that ACTH given by the intravenous route induces a greater and more prolonged adrenocortical stimulation than does intramuscular administration (10,11).

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.

Bottom Line: Overall, I do not know the cause of this cat's illness, and it's obvious that she is seriously ill. But I do not think this cat has naturally occurring hypoadrenocorticism — either primary (Addison's disease) or secondary (pituitary ACTH deficiency).

References

1. Johnessee JS, Peterson ME, Gilbertson SR: Primary hypoadrenocorticism in a cat. Journal of the American Veterinary Medical Association 1983;183:881-882.
2. Peterson ME, Greco DS, Orth DN: Primary hypoadrenocorticism in ten cats. Journal of Veterinary Internal Medicine 1989;3:55-58.
3. Berger SL, Reed JR. Traumatically induced hypoadrenocorticism in a cat. Journal of the American Animal Hospital Association1993; 29:337–339.
4. Ballmer-Rusca E. What is your diagnosis? Hypoadrenocorticism in a domestic cat. Schweizer Archiv für Tierheilkunde 1995;137:65–67.
5. Brain PH.Trauma-induced hypoadrenocorticism in a cat. Australian Veterinary Practitioner 1997;27:178–181.
6. Tasker S, MacKay AD, Sparkes AH. A case of feline primary hypoadrenocorticism. Journal of Feline Medicine and Surgery 1999;1:257–260,
7. Parnell NK, Powell LL, Hohenhaus AE, Patnaik AK, Peterson ME. Hypoadrenocorticism as the primary manifestation of lymphoma in two cats. Journal of the American Veterinary Medical Association 1999;214:1208–1211.
8. Stonehewer J, Tasker S. Hypoadrenocorticism in a cat. Journal of Small Animal Practice 2001;42:186–190.
9. Redden B. Feline hypoadrenocorticism. Compendium of Continuing Education for the Practicing Veterinarian 2005;27:697–706.
10. Peterson ME: Hypoadrenocorticism in cats. In: Mooney C.T., Peterson M.E. (eds), Manual of Canine and Feline Endocrinology (Fourth Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association 2012; in press.
11. Peterson ME, Kemppainen RJ. Comparison of intravenous and intramuscular routes of administering cosyntropin for corticotropin stimulation testing in cats. American Journal of Veterinary Research 1992;531392-1395.
12. Middleton DJ, Watson AD, et al. Suppression of cortisol responses to exogenous adrenocorticotrophic hormone, and the occurrence of side effects attributable to glucocorticoid excess, in cats during therapy with megestrol acetate and prednisolone. Canadian Journal of Veterinary Research 1987;51:60–65.