Endocrine update: There's more to cats than thyroids and diabetes (Proceedings)
Hyperadrenocorticism (Hac, Cushing's disease)
Cushing's is a disease of middle-aged to older cats (7-12 years), and may be caused by a pituitary tumor (90% are adenomas), pituitary hyperplasia, adrenal tumors, adrenal hyperplasia, by non-endocrine tumors (usually lung) or it may be iatrogenic. Clinical signs in cats include uncontrolled diabetes: (PU/PD, polyphagia, weight loss), pendulous abdomen, lethargy, thin skin, recurrent infections and poor muscle mass are common. Thin skin is the hallmark of feline hyperadrenocorticism and these cats may develop open wounds just by grooming themselves. Often we see severe insulin resistance and this often predates the diagnosis of Cushing's by several months. Cushing's should always be on the differential with cats that need very high doses of insulin. The thin skin is another feature of the disease. This also occurs in the dog but it seems to be more pronounced in the cat perhaps due to later recognition.
Changes expected in the bloodwork are non-specific but include hypercholesterolemia, hyperglycemia, mild leukocytosis and erythroid regeneration (nrbcs). The serum alkaline phosphatase and alt will be elevated. In cats this is not a steroid effect; it is due to concurrent lipidosis or possibly pancreatitis. Decreased T4 and T3 caused by "euthyroid sick syndrome" and attenuated response to TSH stimulation caused by overcrowding of pituitary thyrotrophs by adrenocorticotrophs. Overt diabetes mellitus may result from the insulin antagonism caused by hypercortisolemia in about 85% of cats with hyperadrenocorticism. Urinalysis changes include glucosuria, possibly a low urine specific gravity and a secondary bacteruria.Diagnosis
In order to get the adrenals to suppress in the cat, the "Low-dose dexamethasone test" requires 0.1mg/kg dexamethasone sodium phosphate IV and sample plasma at times 0,2,4,6 and 8 hours after injection. Because cats may escape suppression earlier than 8 hours, so the plasma should be sampled at more frequent intervals than in dogs. Normal cats and cats with non-adrenal illnesses will consistently show cortisol suppression at this dose. However, unlike dogs, it may not suppress cats with pituitary dependent HA. Thus, we can't use it to discriminate between adrenal tumors and PDHA in cats. Rather, the feline "High-dose dexamethasone test", i.e. administering 1.0mg/kg dexamethasone IV and sampling at times 0,2, 4, 6 and 8 hours will differentiate PDHA from adrenal tumors in most cases. In the rare cat who doesn't suppress even at this dose, endogenous ACTH levels, abdominal ultrasound, CT or MRI are required to confirm the location of the tumour. There is controversy about the definitive test with some endocrinologists saying that ACTH stimulation test is the test of choice in cats. The majority of cats have pituitary dependent HA.
Ultrasound is very helpful. It can be used together with endocrine tests to provide a diagnosis of PDHA. With PDHA, one will see 2 normal or enlarged adrenal glands. With adrenal tumors there will be atrophy of the contralateral gland. In cats, adrenal calcification is a normal aging change unlike in the dog where calcified adrenals on radiography are cause for concern.
1. Control the diabetes with as much insulin as is required. This is important, not only from the perspective of glycemic control, but also because the immunosuppressive effects of glucocorticoids predispose an already prone individual to infections.
2. op-DDD (Lysodren): 25 mg/kg BID for 10 days. Check an ACTH stimulation test and if the values are below 5mcg/dl, then reduce the frequency of administration to once weekly. Retest ACTH stimulation after 4 weeks.
Note: when performing an ACTH stimulation test in cats, collect plasma at time 0, administer 2.2 units of porcine ACTH gel/kg IM (Repository Corticotropin injection USP) and collect plasma again at 1 and 2 hours post injection or administer 0.25 mg synthetic ACTH/cat IM (Cortrosyn) and collect plasma again at 30 minutes and 1 hour after injection. It is important that the reference laboratory being used has established feline reference ranges.
1. Metyrapone, which blocks adrenal conversion of 11-deoxycortisol to cortisol may be used at 65mg/kg PO q12h. Clinical improvement is expected within 5 days of initiation of therapy. Monitor blood glucose closely as diabetic cats will be prone to becoming hypoglycemic rapidly.
2. Recently, trilostane, a steroid synthesis inhibitor, has been reported for the treatment of PDHA.
Op-DDD, metyrapone or aminoglutasamine may be used to stabilize the patient prior to adrenalectomy. While the challenge is very real to stabilize these patients prior to surgery, adrenalectomy (unilateral for adrenal tumour or bilateral for PDHA) offers the best success.
Post-operatively, cats may develop sepsis, pancreatitis, thromboembolism, wound dehiscence, adrenal insufficiency and hypoglycemia. For patients who had a unilateral adrenalectomy, prednisolone 2.5mgPO q12h should be started in the evening after surgery, continued for several weeks before tapering. For bilaterally adrenalectized cats, lifelong mineralocorticoids will be required. Pituitary tumour enlargement may be treated safely and effectively with external beam radiation therapy.