Felipedia

Cushing Disease is rare in cats compared to dogs. One reason is because they tend to be more resistant to higher levels of cortisol, especially if given as a medication for other diseases such as skin allergies. Most feline Cushing's develops most commonly in middle-aged to older cats (mean age = 10.4 years; range 6–15 years). Of the 26 reported cases of feline Cushing's syndrome and one previously unreported case,21 (78%) have been females. This female sex predilection resembles the human syndrome and contrasts with canine hyperadrenocorticism, where no sex predilection occurs. It can affect the ability to control the blood sugar level in cats with diabetes mellitus concurrently. Cushing's may be caused by a pituitary tumour (90% are adenomas), pituitary hyperplasia, adrenal tumours, adrenal hyperplasia, by non-endocrine tumours (usually lung) or may be iatrogenic (external corticosteroid use).

Cats do not show as much drinking and urinating as dogs do, unless they have diabetes mellitus concurrently. Most cats are presented in a more advanced state of Cushing's disease because the early symptom of drinking and urinating are not observed. They might also have hepatomegaly, weight gain, pot-bellied appearance, and muscle wasting.

Sometimes the skin is easily bruised and torn. This is called the fragile skin syndrome.

Cats do not routinely show any specific changes on a regular blood panel or urinalysis, although it is common to see hypercholesterolemia, hyperglycaemia, mild leukocytosis and erythroid regeneration (nucleated RBCs). The most consistent finding on a blood panel is hyperglycaemia. An elevated alkaline phosphatase occurs in only a minority of cases. Often the elevated alkaline phosphatase is due to liver changes from unregulated diabetes mellitus. The urine cortisol: creatine ratio test is helpful in cats, especially since it is a relatively stress free test compared to blood sampling. If the test is normal then there is much less of a chance that Cushing's is present. It the test is elevated it might be Cushing's, but there are also other situations that cause this elevation.

The ACTH stimulation test is used, but two blood samples need to be analysed at 30 and 60 minutes, instead of the 1 sample at 2 hours for the dog. This is because the increase in cortisol is variable in the cat. False negatives are common. False positives occur in stressed cats or those with non adrenal illness.

Advantages - The ACTH stimulation test is the best screening test for distinguishing spontaneous from iatrogenic hyperadrenocorticism. In spontaneous hyperadrenocorticism, the ACTH stimulation test reliably identifies more than 50 per cent of dogs with adrenal-dependent hyperadrenocorticism and about 85 per cent of dogs with pituitary-dependent hyperadrenocorticism. It is a simple and quick test to perform and documents excessive production of glucocorticoids by the adrenal cortex in cases of hyperadrenocorticism. The information gained is also useful in providing baseline information for monitoring mitotane therapy, although different criteria are used to interpret cortisol results during treatment.

Disadvantages - The ACTH stimulation test does not reliably differentiate adrenal-dependent from pituitary-dependent hyperadrenocorticism. A diagnosis of hyperadrenocorticism should not by excluded on the basis of a normal ACTH response if the clinical signs are compatible with the disease. Occasionally, an animal under chronic stress may develop some degree of adrenal hyperplasia, which produces an abnormal ACTH response. This may be seen for example with diabetes mellitus or pyometra and a normal cortisol response to ACTH stimulation will be obtained after treatment of the underlying disease in these cases.

Interpretation - It is essential to use absolute values for pre- and post- ACTH plasma cortisol concentrations rather than a ratio or percentage increase in post-ACTH cortisol concentration over the basal concentration. In normal dogs, pre ACTH cortisol concentrations are usually between 20 and 250 nmol/l with post ACTH cortisol concentrations between 200 to 450 nmol/l. Regardless of the pre-ACTH cortisol value, a diagnosis of hyperadrenocorticism can be confirmed by demonstrating a post-ACTH cortisol concentration greater than 600 mmol/l in dogs with clinical signs compatible the disease.

The LDDS test is used but the dexamethasone that is injected needs to be given at a higher dose. This test, when used in conjunction with the ACTH stimulation test, is one of the best ways to diagnose Cushing's in the cat.

Advantages - The low-dose dexamethasone suppression test is more reliable than the ACTH stimulation test in confirming hyperadrenocorticism, since the results are diagnostic in all adrenal-dependent cases and in 90 to 95 per cent of dogs with pituitary-dependent hyperadrenocorticism.

Disadvantages - The low-dose dexamethasone suppression test is not as accurate as the ACTH stimulation test for the detection of iatrogenic hyperadrenocorticism. The test is also affected by more variables than the ACTH stimulation test, takes 8 hours to complete and does not provide pre-treatment information that may used in monitoring the effects of mitotane therapy. The low-dose dexamethasone suppression test does not reliably differentiate pituitary-dependent from adrenal-dependent hyperadrenocorticism.

Interpretation - Interpretation of the results of a low-dose dexamethasone suppression test must be based on the laboratory's normal range for the dose and preparation of dexamethasone administered. If the dose of dexamethasone fails to adequately suppress circulating cortisol concentrations in a dog with compatible clinical signs, a diagnosis of hyperadrenocorticism is confirmed. While basal and 8-hour post-dexamethasone samples are most important for interpretation of the test, one or more samples taken at intermediate times (for example, 2, 4, or 6 hours) during the test period may also prove helpful. If a plasma cortisol concentration determined two to six hours after dexamethasone injection is suppressed normally or near-normally (to below 40 mmol/l), while the 8-hour sample shows escape from cortisol suppression, then a diagnosis of pituitary-dependent hyperadrenocorticism is indicated (Peterson, 1984).

The HDDS test to differentiate PD from AT has not been refined to the point that is of diagnostic value.

In general, results of these tests can be variable, and must be interpreted in conjunction with the history and clinical findings. In light of the fact that Cushing's is uncommon in cats, these tests need careful interpretation.

If the above tests suggest Cushing's then radiology can be helpful since up to 30% of feline adrenal tumours are mineralised. Other radiographic findings include hepatomegaly and obesity. Ultrasonic evidence of an enlarged adrenal gland (especially if unilateral) or changes in internal adrenal architecture is strong evidence of an adrenal tumour (AT).

Adrenal tumours occur in about 20% of feline Cushing's. They can be malignant or benign.

Serum cortisol levels high and low dexamethasone suppression tests. In a healthy individual, the administration of a low dose of oral dexamethasone (0.5mg 6-hourly) will lead to suppression of cortisol levels below 50nmol/L. No fall occurs in patients with ectopic adrenocorticotropic hormone (ACTH) syndrome, even with high doses of dexamethasone. This contrasts with the responses seen in patients with pituitary-dependent disease in whom inadequate suppression after low-dose administration of dexamethasone, and at least 50% suppression after administration of a high dose of dexamethasone (2mg 6-hourly) are characteristic.

Medical therapy is generally unrewarding. Ketoconazole can be used, but the effects are variable, and side effects can occur. Mitotane might help, along with metyrapone. Metyrapone may be more helpful as a pre-surgical stabilization prior to surgery. Anipryl has not been used in cats.

Surgery is needed to remove one of the adrenal glands if the gland has a tumour, and both glands if the problem is PD. If both glands are removed the cat has to be on supplemental cortisone and mineralocorticoids for the rest of its life. Some cats with concurrent diabetes mellitus will no longer have the disease when their adrenal tumour is removed.

Unfortunately, cats with Cushing's can be poor aesthetic risks due to diabetes mellitus and fragile skin. When this occurs we sometimes will use medical therapy to help control the problem and make our patient a better anaesthetic risk.