First described in humans in 1932 by Dr. Harvey Cushing, the disease was originally thought to be a disorder of only the pituitary gland. Later studies showed "Cushing's Disease" as being caused by multiple factors. Canine Cushing's Disease (CCD) and Canine Cushing's Syndrome (CCS), all types of hyperadrenocorticism, have multiple pathophysiologic origins. The hallmark of the disease process is an overproduction of cortisol by the adrenal glands. Cortisol is a type of steroid produced by the adrenal gland which is necessary for normal body functions. Overproduction of cortisol causes many changes to normal metabolism. Some of the changes are readily apparent and some are very difficult to interpret. Onset is usually subtle with diagnosis often not made until quite late in the disorder. Hopefully, this article will allow some insight which may result in a more rapid diagnosis and earlier therapy.
Veterinary medicine recognized three main types of hyperadrenocorticism
I. Canine Cushing's Disease (CCD)
Pituitary dependent hyperadrenocorticism (PDH) is caused by the presence of a tumor in the pituitary gland. The tumor secretes an increased amount of adrenocorticotrophic hormone (ACTH) causing the adrenal glands (small glands near the kidneys) to increase their output of cortisol. The tumor in the pituitary gland is small and rarely are other signs of the tumor seen. PDH represents 80 to 85% of naturally occurring hyperadrenocorticism in dogs. According to the fourth edition of the Textbook of Veterinary Internal Medicine by Ettinger and Feldman, 1995, the top four affected breeds are Poodles, Dachshunds, Terriers and Beagles. About 75% of dogs with PDH weigh less than 20kg.
II. Iatrogenic Cushing's Syndrome
This type of Cushing's is secondary to use of steroids taken orally or by injection. The most frequent reason for steroid therapy is allergic dermatitis. Chronic usage will eventually cause the adrenal glands to atrophy, allowing the administered steroids to cause the clinical signs of hyperadrenocorticism. Attempts at desensitization and control of dermatitis without steroid usage can totally prevent this form of Cushing's. There is no weight predisposition for Iatrogenic Cushing's Syndrome.
III. Adrenal Gland Tumors
Several types of tumors can grow in the adrenal gland. Both cancerous or benign tumors may be present. The types are beyond the scope of this article, but it is important to know that tumors may be a cause of Canine Cushing's Syndrome. Forty-five to 50% of dogs with adrenocortical tumors weigh greater than 20 kg.
The three types of Cushing's all have one common factor -- the presence of elevated cortisol. Cortisol causes similar signs in all cases and a complete history, physical exam and laboratory test results will usually lead to a diagnosis. The testing is not 100% accurate and therefore it may be necessary to run several tests before a correct diagnosis is accomplished. Factors involved in diagnosis are multiple, and in many cases, only one or two signs may be present, while in other cases, the signs may be overwhelming. Many of the following statistics are from the Textbook of Veterinary Internal Medicine and some may be anecdotal from 22 years of practice.
Age -- usually older than 6 yrs -- 75% are older than 9 yrs for PDH, while dogs with tumors of the adrenal gland tend to be older.
Sex -- 55% to 60% of PDH are female and 60% to 65% of adrenal tumor dogs are female.
Breed -- smaller breeds (listed above) tend to get PDH, while adrenal tumors tend to develop in larger dogs.
History -- this is a disease with a slow onset and clinical problems are few in the initial stages. Frequently, the owner suspects diabetes or other skin related problems.
Physical findings -- increased thirst and increased appetite are very common findings. It is important to note that several signs of Cushing's may be normal behavior traits -- our Golden Retriever would eat any amount of food given as fast as possible, and if not dieted would be enormous. Because many of the dogs with Cushing's have such an excellent appetite, owners are reluctant to think that their dog is ill and tolerate many physical changes before concerns are great enough to have the dog checked.
Increased thirst and increased urine output are common findings. With Cushing's the urine is often very dilute and a simple urine specific gravity may be done as an initial screening test. It is strongly recommended that a refractometer and not urine dip sticks be used to determine the concentration of the urine. As with many of the tests, if this test is normal, but the disease is still questioned, more thorough testing is necessary. Urinary cortisol/creatinine testing is easily done and is a very good initial test, but it is also not specific - if the test is elevated, usually other testing is necessary.
A large distended (potty) abdomen and muscle weakness are seen in many advanced cases. The dog may develop an extremely potty abdomen -- this sign is in as many as 80% to 90% of the cases. Many cases are first seen because the owners think they appear obese, when, in reality, the abdomen looks larger due to muscle weakness and the extremities are actually much thinner from muscle wasting. Weakness, often a presenting sign, may be a sign that develops after treatment. The disease causes an increase in cortisol that helps to keep inflammation out of old arthritic joints -- treatment reduces the unwanted cortisol and may exacerbate signs of joint disease.
Several signs may be present in the skin to lead to a presumptive diagnosis of Cushing's. As many as 100% of the affected dogs will have some type of dermatological signs with up to 80% having alopecia (hair loss). Alopecia is usually evident in the flanks, sides of abdomen and around the anal area. The hair loss usually has bilateral symmetry ( the same on both sides). Poor re-growth of shaved areas, or re-growth with brittle sparse hair must be considered as clinical signs. Thin cool skin and infections like pyoderma or seborrhea may also be present. Calcium deposits in the skin (calcinosis cutis) which may feel firm to the touch may occur in the head and dorsal neck area, ventral abdomen and flanks. These deposits appear slightly raised and may be whitish to light pink with areas being quite small to very large.
Rapid breathing may be noted, but usually no cough is present. The respiratory difficulties may be related to enlargement of the liver putting pressure on the cardiopulmonary areas. Because small breeds may be affected, coughing may be present due to a collapsing trachea.
Many tests may be used to differentiate Cushing's from other endocrine disorders -- urine testing has been noted. Ultrasonography and radiology may image enlarged or calcium containing adrenal glands. Protocol for blood tests taken which use injections of ACTH and/or Dexamethasone can be found in veterinary textbooks. If you suspect Cushing's may be present and only one test has been done, it may be imperative to request further testing. If your veterinarian is not familiar with other testing methods, a veterinary teaching hospital or specialist may be necessary.
PDH cases may be treated with oral medication -- the protocol may vary according to practitioners, but the attempt is made to decrease the output of cortisol by the adrenal gland without completely stopping cortisol production. Timing meals or measuring water intake may be used in determining initial treatment end-point and used as factors to determine the maintenance dose.
Patience must be used during therapy -- each case is different. If initial results are not gratifying, or if the attending veterinarian gets frustrated, it may be necessary to start over with another protocol or another veterinarian.
Iatrogenic Cushing's Syndrome which is caused by excess oral or injectable steroids may often be helped by cessation of the steroid therapy and diet changes. Long term prognosis is poor.
Adrenal tumors, if in only one adrenal gland, may respond to surgical intervention. The possibility that cancerous tumors may have already spread to other organs necessitate a thorough pre-surgical work-up.
William E. Schultz, D.V.M., graduated from Michigan State University School of Veterinary Medicine in spring, 1973. Dr. Schultz has a companion animal practice in Okomos, Michigan.
Original Doc: cush04.doc
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