Around 80% of animals with Cushing's disease have a problem with the pituitary release of ACTH. Tumors of the pituitary gland account most of these cases however spontaneous pituitary depended Cushing's can also occur, the cause of which is unknown. The over stimulation of the adrenals by excessive ACTH release causes them to enlarge, leading to over production of cortisol. Cortisol secreting adrenal tumors account for the cases of non-pituitary related disease. Long term, high dose use of corticosteroids (cortisone) can also produce the signs of hyperadrenocorticism (iatrogenic Cushing's syndrome).

Signs of hyperadrenocorticism usually develop slowly. Excessive drinking (polydypsia) and urinating (polyuria) are one of the most common signs recognized by owners. This can reach extremes as high as ten times the normal intake of water. Appetite can also increase significantly. Muscle weakness and fatigue can be a mild sign however weakness of the abdominal muscles in combination with swelling of the liver results in abdominal enlargement giving a "potbellied' appearance. Changes to the coat and skin may also be seen. Generalized hairloss in an even pattern can develop over an extended period of time. The skin becomes thin and fragile and is slow to heal. Secondary skin infections are not uncommon. The testicles can become small and spongy in male dogs while females will often stop cycling. Panting and shortness of breath while apparently resting may also be noted.

Diagnosis of hyperadrenocorticism is base on measuring changes in blood cortisol levels following administration of either ACTH or Dexmethasone (corticosteroid). Animals with pituitary related Cushing's disease will have an significantly increased production of cortisol following the injection of a large dose of ACTH. This is because the adrenal glands have become enlarged in these animals and therefore can produce much greater amount of cortisol than normal size adrenals. The ACTH test will also identify cases of iatrogenic Cushing's where the blood cortisol level is low having been suppressed by long term administration of corticosteroids, and has little or no response to the administration of ACTH. The administration of dexamethasone stimulates a drop in the level of circulating blood cortisol in the normal animal. Where Cushing's disease is present this drop is less pronounced or follows an abnormal pattern. Neither the ACTH or dexamethasone tests will detect all cases of hyperadrenocorticism and both can be effected by drugs such as anticonvulsant medications.

Animals diagnosed with adrenal gland tumors are usually treated by surgical removal of the tumor. The two adrenal glands sit under each of the kidneys and can be difficult to access. Adrenal tumors are mostly cancerous, spreading to the liver and lungs so attempts should be made using Xray and ultrasound to ensure there has been no spread before surgery is performed.

Pituitary dependent Cushing's disease is treated with the drug o,p'-DDD (Lysodren). This drug causes damage to the adrenal gland reducing its ability to produce cortisol. The enlarged glands seen with Cushing's seem to be particularly sensitive to o,p-DDD. Initial therapy is twice daily and lasts on average from 5 to 16 days. Response to treatment is monitored by a reduction in clinical signs, especially water intake. If no response is seen within 21 days it may be necessary to increase the dose. Some animals have taken up to 60 day to fully respond to treatment. Maintenance therapy with o,p-DDD is continued on a weekly basis however it may be necessary to taylor the dose to suit the individual animal.

Other drugs which have been used to treat Cushing's in humans include Cyproheptadine, Bromocriptine, Trilostane, Metyrapone and Ketoconazole. Of these Ketoconazole appears to be the only one with potential for use in veterinary medicine. Given at 30mg/kg daily it has been shown to produce clinical improvement in dogs with both pituitary dependent Cushing's and adrenal tumors.