VetInfo Digest      August 1999
 
 
This issue

Hyperadrenocorticism ( Cushing's Disease)
Who develops Hyperadrenocorticism?
What are the Signs of HAC?
Complications Associated with Cushing's Disease
Diagnosing Hyperadrenocorticism
Treating Hyperadrenocorticism
Is Cushing's Disease Always Fatal?
Revolution (TM), a New Medication for Prevention of Heartworms and Fleas
 

 

Hyperadrenocorticism ( Cushing's Disease)

Guide to Abbreviations in this issue:

HAC        Cushing's disease or hyperadrenocorticism

PDH        pituitary dependent hyperadrenocorticism

AT        adrenal tumor (adrenal gland origin hyperadrenocorticism)

ACTH        adrenocorticotropic hormone

CRH        corticotropin releasing hormone

LDDS        low dose dexamethasone suppression (test)

HDDS        high dose dexamethasone suppression (test)

SAP        serum alkaline phosphatase

PU/PD        polyuria/polydipsia (increased drinking and urination)

Several subscribers have written in the past month and asked that we provide an update on hyperadrenocorticism (Cushing's disease). This is a disorder that is common in older dogs and occurs much more rarely in cats. All of the clinical signs of Cushing's disease can be produced by
administering corticosteroids, such as prednisone, chronically. When a dog or cat has the symptoms of hyperadrenocorticism (HAC) but the cause is corticosteroid use, the syndrome produced is referred to as "Cushing's-like syndrome" in some textbooks.

When the adrenal glands are functioning normally, their action is regulated by a feedback mechanism involving the level of cortisone in the blood stream, the hypothalamus (part of the brain), the pituitary gland (another part of the brain) and a hormone it produces, ACTH (adrenocorticotropic
hormone). When cortisone levels in the body decrease, the hypothalamus produces a hormone CRH (corticotropin releasing hormone) that stimulates the pituitary gland to release ACTH, which stimulates the adrenal gland to produce cortisone. When cortisol levels in the bloodstream are high, the hypothalamus and the pituitary gland stop the release of ACTH and the adrenal gland stops releasing cortisones into the bloodstream. This is a complex process and a lot can go wrong with it.

Problems within the pituitary gland account for about 90% of the cases of hyperadrenocorticism. The most common pituitary gland problem is cancer. There are several types of tumors that affect the pituitary gland, all of which can lead to an overproduction of ACTH and Cushing's disease. In studies of dogs with Cushing's disease that have brain imaging scans using computerized tomography (CT) or magnetic resonance imaging (MRI) between 50% and 75% of the dogs with HAC either have, or develop, visible pituitary gland tumors (Feldman, et al, 1998). It is unclear what causes HAC in the remaining dogs that have pituitary dependent Cushing's disease (pituitary dependent hyperadrenocorticism or PDH).

While the tumors that develop occur in the pituitary gland, there is evidence that the stimulation for tumor formation may be due to the release of excessive corticotropin releasing hormone (CRH) from the hypothalamus. This effect may be age dependent, since the regulatory mechanism seems less sensitive in older patients, making over stimulation of the pituitary gland more common in geriatric patients.

Adrenal gland cancer causes the remaining 10% of cases of hyperadrenocorticism in dogs. The best treatment for adrenal gland cancer is probably removal of the affected gland(s). Lab testing can help to determine whether HAC is due to adrenal cancer or due to pituitary gland effects. It is best to try to confirm if adrenal gland cancer is present using standard X-rays or in some cases, ultrasound, CT or MRI scanning.

Hyperadrenocorticism is much less frequent in cats than in dogs. This may be due to the fact that cats appear to be more resistant to the effects of cortisone than dogs and therefore less likely to respond to the age related stimulation of the hypothalamus and pituitary gland that seems to contribute to the development of Cushing's disease in dogs.
 

Who develops Hyperadrenocorticism?

The typical patient with Cushing's disease is over nine years of age but it has been reported in dogs as young as six months of age. To give some perspective on this, over 90% of the cases of HAC occur in patients nine and over. In dogs there does not appear to be sex related predisposition
to this disorder. In cats the current information, from a small number of patients, indicates that female cats are slightly more likely to have Cushing's disease than males. The breeds most likely to develop HAC include poodles, dachshunds, beagles, boxers, Boston terriers and German shepherds.

Cushing's-like syndrome occurs in patients who are given corticosteroids such as prednisone in a manner that causes symptoms of hyperadrenocorticism. Patients with itchy skin disease whose owners give them prednisone on a daily basis rather than an every other day basis sometimes develop symptoms of HAC. Dogs on chemotherapeutic dosages of prednisone may also develop Cushing's-like syndrome. A less frequent cause of Cushing's symptoms in dogs is the use of corticosteroid eye drops on a daily basis. The dose seems too small to lead to problems but there are several reported cases of Cushing's like syndrome from the use of cortisone ophthalmic drops. Treatment consists of lowering the dosage or discontinuing the cortisone, if possible.

What are the Signs of HAC?

The most common symptom of Cushing's disease in dogs is increased drinking (polydipsia) and increased urination (polyuria). You may see this in a patient's record abbreviated as "PU/PD". Some clients notice the increased drinking but see no corresponding increase in urination while other clients
notice that urination frequency and amount have changed but don't notice a change in drinking behavior. Despite this, these conditions occur concurrently. Variations in observing these clinical signs probably occur due to the ability of some patients to stand more urine retention in the
bladder, the presence of incontinence that makes urination obvious or the availability of water sources that are hard to monitor.

Many dogs have increased appetites due to the higher levels of cortisol in the blood stream.

A pendulous abdomen is also commonly seen in patients with Cushing's disease. This is partially due to redistribution of fat due to the effect of cortisol and partially due to muscle weakness that occurs for the same reason. This is particularly noticeable in patients who also have hair loss in the abdominal region, making their abdomen even more noticeable.

Symmetrical hair loss along the flanks is often the first sign the skin effects of HAC. The hair loss may get so severe that the only hair is on the head and feet. Dogs with Cushing's disease are more susceptible to skin infections, which may lead to itchiness. Some patients with HAC develop a specific skin condition in which calcium deposits occur in the skin, known as calcinosis cutis. This may be an extremely pruritic (itchy) condition. The skin may develop areas of pigmentation that were not previously present and bruising is also common.

Both dogs and cats with Cushing's disease are more likely to have diabetes than non-cushingoid patients. It is harder to regulate insulin levels in pets that have concurrent HAC and this is the first sign that Cushing's disease is present in some patients, especially in cats.

Panting is frequently seen in patients with hyperadrenocorticism. The same effects of cortisol that lead to the pendulous abdomen lead to the panting --- muscular weakness of the muscles of respiration, fat redistribution in the chest and weakness of the heart, since it is a muscle, too. Pulmonary
embolism can cause severe respiratory signs in HAC patients.

Complications Associated with Cushing's Disease

There are certain illnesses in older dogs and cats that are frequently associated with HAC. When these illnesses are present it is a good idea to keep a high degree of suspicion for Cushing's disease as an underlying cause or concurrent illness.

Both cats and dogs with Cushing's disease are more prone to diabetes mellitus. Cushing's disease can make it very difficult to regulate blood sugar using insulin therapy, so in patients with difficult to manage diabetes it is especially important to consider the possibility of HAC.

Pancreatitis is more common in patients with hyperadrenocorticism. A pattern of recurrent bouts of pancreatitis should also raise suspicions about HAC. Due to the difficulty in diagnosing pancreatitis in cats it is harder to make this connection in feline patients but it may occur.

Persistent or frequently recurring cystitis is a common complication of HAC. This is a serious complication of Cushing's disease as it is very uncomfortable and sometimes fatal if unrecognized. Calcium oxalate bladder stones are more common in patients with hyperadrenocorticism, as well.

Cushing's disease can make it harder to maintain stable control of congestive heart failure in patients afflicted with both conditions. This is probably due to weakening of muscle brought on by the HAC but is also partially due to circulatory changes associated with the disease.

A very serious complication of hyperadrenocorticism is the development of blood clots in the circulation from the heart to the lungs (pulmonary thromboembolisms). This problem is a serious complication that often results in death of the patient when it occurs. Usually a dog that
develops this condition will develop obvious respiratory difficulty (rapid or distressed breathing patterns, weakness, blue coloration to the gums or conjunctival tissues.) Cats with pulmonary thromboembolism may just suddenly die, with very few warning signs. This disorder is difficult to
treat successfully, especially if it is not recognized very early.

Diagnosing Hyperadrenocorticism

General lab testing sometimes gives an indication that Cushing's disease is present. A general blood chemistry panel with elevations in the serum alkaline phosphatase (SAP) levels and not much other disturbance in lab values should be suspect for HAC. High cholesterol levels and increased
lipids in the serum are also commonly seen in dogs with Cushing's disease  Sometimes there are slight elevations in blood sugar. This is a more common sign in cats and in this species is sometimes the only laboratory abnormality seen in general blood work. Consistently dilute urine is also
a strong indicator of Cushing's disease, although this is not a very specific sign, since it can occur with a number of other conditions

When Cushing's disease is suspected there are a number of lab tests that are used to try to confirm the diagnosis. Each of them has advantages and disadvantages.

Low Dose Dexamethasone Suppression Testing:

The "gold standard" for diagnosing naturally occurring HAC in dogs is considered to be a test referred to as low dose dexamethasone suppression testing. This test is less sensitive in cats but is still considered to be useful. Dexamethasone is a cortisone. Increased cortisone levels in the
blood stream should cause the hypothalamus and pituitary gland to stop stimulating the adrenal gland to release cortisone. This leads to lower than normal (suppressed) cortisol levels measured at 4 to 6 and 8 hours after injection of the dexamethasone. This test will detect about 95% of
the cases of Cushing's disease in dogs and about 60% of the cases in cats.

Protocol for Low Dose Dexamethasone Suppression Testing (LDDS):

1) Draw blood from the patient.
2) Inject the patient with a low dose of dexamethasone IM or IV.
3) Draw blood at 4 to 6 hours post injection.
4) Draw blood again at 8 hours post injection.

Resting cortisol levels are less than 4 or 5 ug/dl in most dogs and less than 4 ug/dl in most cats. A high resting cortisol value is not sufficient to diagnose Cushing's disease so the rest of the test must be run no matter what the level is. If the eight hour blood level is less than 1 ug/dl then
adrenal suppression has occurred and Cushing's disease is not likely. If the level is greater than this the HAC may be present. If the eight hour serum cortisol level suggests that HAC is present looking at the four or six hour level may help to determine if pituitary gland dependent HAC is
present. If this is the case, the level of suppression should be less than 50% of the level of the baseline cortisol level. Sometimes a lab will provide an expected value that PDH should suppress to. This test seems to work reasonably well in cats but is not as accurate as it is in dogs.

ACTH Stimulation Test:

ACTH stimulation testing is also commonly used to try to confirm the presence of Cushing's disease. In this test, blood is drawn for a baseline sample and ACTH is injected intramuscularly. A second blood sample is drawn an hour later (some vets use 90 minutes later and some draw a sample one
hour and then two hours later). Since ACTH should increase the cortisol level by stimulating the adrenal gland, the test is considered positive for HAC if the cortisol level rises above the range specified by the laboratory doing the testing. This test will detect about 80% of the cases of HAC in
dogs and about 60% of the cases in cats. It is a faster test to use as it takes only one hour, making it attractive in some situations.

Protocol for ACTH response testing:

1) Draw a baseline blood sample
2) Inject ACTH gel or Cortrosyn (Rx), a synthetic ACTH
3) Draw blood in one hour (or according to alternative protocols). In cats,
two samples are recommended, one at 60 minutes and one at 90 minutes after
administration of Cortrosyn.

The post-ACTH cortisol level in normal dogs is between 8 and 20 ug/dl. If the level is greater than 20 ug/dl, then there is a high degree of suspicion for Cushing's disease. In cats, HAC is suspected if the post injection level is greater than 16 ug/dl in either blood sample.
 

Urine cortisol/creatinine ratio:

Urine cortisol/creatinine ratio is sometimes used by veterinarians as a less expensive screening test for Cushing's disease. Most dogs with HAC will have elevated cortisol:creatinine ratios but so do many dogs with non-adrenal illnesses. A dog with a normal cortisol:creatinine ratio in
the urine is not likely to have Cushing's disease, though.

A single urine sample is all that is necessary to run a urine cortisol:creatinine ratio. If the ratio of cortisol in the urine to the level of creatinine in the urine is elevated (usually greater than 100:1) the likelihood of Cushing's disease being present is pretty high. If the level of cortisol to creatinine is low (less than 8:1) then the likelihood of Cushing's disease is very low. Ratios in-between these levels sometimes indicate non-Cushing's stressful illnesses and sometimes indicate Cushing's disease. This test is a nice screening test because it is inexpensive. Low ratios make HAC pretty unlikely. High ratios are not specific enough to be sure hyperadrenocorticism is present.

Once it has been determined that HAC is present in a dog it is necessary to try to determine if the cause is a pituitary tumor or problem or adrenal gland cancer. High dose dexamethasone suppression testing and plasma ACTH levels can help in determining which disorder is present. In most cases of
pituitary dependent HAC, a high enough dose of dexamethasone will cause suppression of the blood cortisol levels. This effect does not occur when adrenal gland tumors are the cause of the Cushing's disease, allowing the cause to be diagnosed.

Protocol for High Dose Dexamethasone Suppression (HDDS) Test

1) Draw a blood sample for baseline cortisol level
2) Inject a high dose (0.1mg/kg) of dexamethasone IV
3) Draw blood at 6 hours and 8 hours after the dexamethasone injection
(some vets just do the 8 hour sample)

In dogs in which PDH is present, the post-injection blood sample should be less than 50% of the baseline value for that patient. In dogs with AT, there is usually no suppression in cortisol levels. This test is sufficient to differentiate AT from PDH in about 85% of dogs.

Plasma Adrenocorticotropic Hormone Level Test:

This is a test in which the level of ACTH in the plasma is tested. This test can differentiate between pituitary dependent HAC and adrenal tumors in about 90% of dogs. Special sample handling requirements make it hard to do this test in many practices but most universities and referral practices probably can do this type of testing.  In dogs with PDH the plasma ACTH level is usually greater than 45 pg/ml. In dogs with AT, the plasma ACTH level is less than 20 pg/ml. There is a gray area between these dose ranges.

Imaging (Radiographs of the Abdomen, Ultrasound and CT or MRI Scans)

X-rays are useful in diagnosing adrenal gland tumors in some cases. Mineralization of the adrenal glands, visible on radiographs, is suggestive of adrenal gland tumors.

If a tumor of the adrenal gland seems likely, or to rule out this possibility, ultrasound imaging of the adrenal gland is a reasonably accurate screening test. The more experience the ultrasound examiner has, the more likely an accurate evaluation of the adrenal gland will occur with ultrasound exam.

CT is not as accurate in evaluating soft tissue as magnetic resonance imaging. It is more accurate than plain X-rays, though. Both the adrenal gland and the pituitary gland can be evaluated with CT scans. The adrenal gland is better visualized than the pituitary gland. MRI scans can detect
pituitary tumors in at least 50% and possibly as high as 75% (with repeated scans) of dogs and cats with PDH. Adrenal tumors are also detectable with high success rates using magnetic resonance imaging. Where it is possible to have these scans, they are a very useful tool in differentiating PDH
from adrenal tumors.

Treating Hyperadrenocorticism

The treatment for HAC will vary depending on whether or not the disease is due to the pituitary gland or the adrenal gland and on the patient's condition at the time the diagnosis is made.

The recommended treatment for adrenal gland tumors is removal of the affected gland or glands (adrenalectomy). This is considered to be high risk surgery. Dogs undergoing adrenal gland surgery need to be carefully monitored during surgery and at least a couple of days after surgery. For
this reason, it is best to have this surgery done at a hospital with twenty-four hour a day care and surgeons familiar with the procedure. Supplementation of mineralocorticoids and corticosteroids may be necessary for several weeks following removal of one adrenal gland and are usually
necessary for life if both glands are removed.

When surgery isn't possible it is sometimes necessary to treat adrenal gland tumors medically, in dogs. This is usually done using mitotane (Lysodren Rx), which is a relative of DDT, the infamous insecticide. Mitotane selectively kills adrenal gland tissue and can be used as a chemotherapeutic agent to eliminate adrenal gland tumors. It is hard to get the dosage high enough to consistently kill tumors without causing toxic effects but it can be done in many dogs. If the adrenal gland tumor is successfully destroyed, the normal adrenal tissue will be destroyed, as well. Due to this, supplementation of normal adrenal gland hormones will be necessary after mitotane treatment for adrenal gland tumors, as well. Some veterinarians use this technique (destruction of the adrenal gland with mitotane) as a medical treatment, on the assumption that it is easier to treat Addison's disease than it is to regulate HAC for a dog's lifetime.

In cats, adrenalectomy may be the best treatment regardless of the cause of the hyperadrenocorticism. Cats do not consistently respond to medications
used to treat pituitary gland origin HAC in dogs, although there are reported cases of success with medical treatment. Cats also require supplementation of corticosteroids and mineralocorticoids for several months after removal of one adrenal gland and lifelong supplementation
after removal of both glands.

Dogs with pituitary gland origin hyperadrenocorticism have more choices in therapy.

Mitotane has been used for many years to control Cushing's disease in dogs. The standard treatment is to use mitotane to reduce the size of the adrenal gland to the point where it produces a normal amount of adrenal hormones. Then a maintenance dosage to keep the hormonal levels adjusted is given for life. It is usually necessary to give mitotane once a week during the maintenance stage. Some dogs have severe reactions to mitotane and dogs need to be monitored closely during the initial therapy. Since the dosage necessary to control hormonal levels varies widely from dog to dog, it is
necessary to continue to do ACTH response testing on a periodic basis during the initial stage of treatment and throughout the dog's life. It is possible to give enough Lysodren to completely destroy the functionality of the adrenal glands. Some vets do this in order to try to lessen the need to
do maintenance ACTH testing and use Lysodren on a lifelong basis. It is still necessary to do some maintenance testing to regulate Addison's disease and medication costs are often close to the same. Either approach is probably acceptable but I still prefer to use Lysodren long-term over
treating Addison's disease, in my patients.

Protocols for use of Mitotane:

An induction dosage of mitotane is administered for 10 to 14 days, or until signs of hypoadrenocorticism occur (weakness, decrease in appetite, vomiting, diarrhea and depression). The earliest sign of a need to stop the induction dosage is a decrease in appetite. At this point, ACTH response testing is performed. The ideal stopping point is when the ACTH response test indicates a slightly lower than normal cortisol level and little to no rise with ACTH stimulation. It may take several ACTH response tests before proper blood levels are achieved.

Maintenance treatment with mitotane is accomplished using mitotane at a dosage of about 50mg/kg/wk. Usually this dose is divided into two to three treatments during the week. In some cases it is possible to use less frequent dosing intervals or lower maintenance doses. Often, as time goes on, it will be necessary to increase the maintenance dosage. Due to the potential for lack of control and for inducing Addison's disease, it is necessary to monitor the success of therapy on a regular basis using ACTH response testing. The recommended guideline is to test 3 months after
establishing a maintenance doses and at six month intervals for life.

An alternative protocol is to give mitotane on a continuous basis at a dosage of 50 to 75mg/kg for 25 days or until dosing must be stopped due to adverse reactions to the mitotane or ypoadrenocorticism from its use. The goal is to produce an induced state of hypoadrenocorticism and manage that,
rather than managing hyperadrenocorticism. Dogs treated with this protocol require supplementation with glucocorticoids and mineralocorticoids in the early stages of the treatment protocol and must be maintained on these medications for life. There is about a 40% relapse rate in dogs treated in
this manner when PDH is the cause and a slightly higher relapse rate with adrenal tumors. This means that ACTH response testing should probably be done on about the same schedule as the protocol for maintenance with mitotane.

Ketoconazole Protocol:

Ketoconazole (Nizoral Rx) has been used to treat Cushing's disease when it isn't possible to use mitotane in a patient. It works in an entirely different manner. While mitotane kills adrenal cells, ketoconazole simply stops them from releasing cortisones into the circulation. This is
effective in eliminating the signs of HAC in many dogs but will not work for about half of the dogs treated. Ketaconazole must be given twice daily. It is much more costly to treat a dog with ketoconazole than with mitotane, even with the cost of lab testing during maintenance of mitotane.

Ketoconazole is given at a dosage of about 10mg/kg twice a day. This is a higher dosage than ketoconazole is normally used at for its anti-fungal capabilities. It is probably only effective in about 40% of patients treated with it. Most vets use it when mitotane and/or selegiline fail.
Monitoring of the effect with ACTH response testing is done at 3 to 6 month intervals, depending on the clinical signs and the veterinarian's preference.

Selegiline or l-deprenyl

L-deprenyl, or selegiline ( Anipryl Rx), is the newest medication used to treat Cushing's disease in dogs. It works in a manner that is quite different from either mitotane or Ketaconazole. Selegiline in a monoamine oxidase inhibitor, which allows it to help the hypothalamus preserve
dopamine. This is beneficial to the function of the hypothalamus which helps it maintain a more normal sensitivity to cortisol levels. This leads to less chronic stimulation of the pituitary gland, which seems to lessen the probability of pituitary gland tumors and excessive ACTH production.
This mechanism of action has made the use of selegiline somewhat controversial among endocrinologists. There is at least one veterinary endocrinologist who has openly suggested that selegiline should only work in about 25% of the cases of PDH, based on interpretation of theories of
its method of action. However, the available lab data, most of which has been produced in studies funded by the company, suggest a much higher rate of success in at least partially alleviating the symptoms of Cushing's disease -- approximately 80%. Over time it will be possible to determine
which level of success is actually occurring but that will take some time. In the meantime, considering that selegiline appears to be safer to use than mitotane it seems reasonable to attempt to treat uncomplicated cases of Cushing's disease with it and use it if it appears to be effective.
Since there is little evidence that any of the treatments for Cushing's disease extend the lifespan of affected patients, a beneficial clinical response seems like a reasonable goal. Anipryl is currently the most expensive medication for treating Cushing's disease, probably.

Protocol for use of Selegiline:

Selegiline is given for one month at a dosage of 1mg/kg. If after the first month there is no decrease in clinical signs or no improvement in LDDS testing, the dosage is increased to 2mgkg for an additional month. If there is no improvement in clinical signs after that time and no improvement in
LDDS values, then the medication is stopped and alternative therapies should be considered.

When using selegiline there are a couple of things to remember. It is also effective in the treatment of canine cognitive dysfunction (CCD), which is probably present in a number of dogs with Cushing's disease since both problems occur in the same age range. It is highly likely that some of the
perceived improvements in clinical signs occur due to the abatement of CCD symptoms that have been confused with Cushing's disease symptoms. While this isn't a bad thing, it may point out a need to use selegiline AND an alternative therapy for Cushing's disease if only partial resolution of
clinical signs occurs. It is the only drug mentioned so far that doesn't change ACTH response tests very much. It is usually monitored using LDDS testing, if monitoring is desired. If the clinical signs are decreased to a level that is satisfactory to the client and the pet's condition appears to
be improved it is not actually necessary to do follow-up testing on a regular basis when using Anipryl, as there is not as much chance of causing harm with it as there is with mitotane.

Surgical Therapy for PDH ( transsphenoidal hypophysectomy)

With the advent of accurate diagnostic imaging using CT or MRI scans, it has become possible to locate and remove pituitary gland tumors surgically at some institutions. The Utrecht University in the Netherlands is one place where this surgery has been performed a number of times. While the
risk of surgery is pretty high, with 10% of dogs undergoing surgery dying from immediate complications and almost 10% of dogs having incomplete surgical excision of the affected portions of the pituitary gland, the two year survival rate of patients undergoing this procedure is still reported
to be close to 80% by Meij, et al, in the May/June 1998 issue of Veterinary Surgery. I am not sure how available this procedure is in the United States but it is likely that it will become more common due to the increased availability of high quality imaging and advanced surgical facilities.
Limited reports from surgeons in this country

Limited reports from surgeons in this country seem to indicate a higher death rate from surgical complications than has been experienced by the surgeons at Utrecht.

Radiation for Pituitary Tumors

Pituitary macroadenomas (the type of pituitary tumor that is large and visible with CT or MRI scanning) are susceptible to treatment with radiation therapy. In the United States this seems to be a more common treatment approach than surgical removal of the tumor. This treatment
method is only available at a few facilities in the U.S. For a dog that has Cushing's disease and is showing neurologic signs, radiation should be considered after confirming that the neurologic signs are due to a pituitary macroadenoma, if the cost of diagnosis and treatment is not
prohibitive.

Is Cushing's Disease Always Fatal?

I get asked this question a lot. To the best of my knowledge, there is no evidence that treating Cushing's disease actually prolongs the lifespan of patients affected with the disease, with the exception of two cases: 1) dogs with adrenal tumors that are successfully removed prior to metastasis 2) dogs who have PDH and who have pituitary gland removal surgery or radiation therapy that is successful. The other patients with this condition do appear to die from it, or complications associated with it, if another cause of death doesn't occur first. Given the average age of the
patients who get Cushing's disease, death by other causes is not an infrequent problem.

The presence of pituitary brain tumors eventually leads to neurologic injuries in the 15 to 25% of dogs whose tumors are pituitary macrotumors rather than the more common microtumors. Cushing's disease helps to induce diabetes mellitus in many patients. Pancreatitis occurs more commonly in
Cushing's disease patients. Severe pulmonary embolism is a cause of sudden death in patients with HAC. Muscular weakness may exacerbate heart failure in a patient with both conditions. The cost of treatment and monitoring treatment leads to the decision to euthanize many pets with this condition.
Usually, one of these problems will occur eventually.

Despite this gloomy long term prognosis there is some hope. Some endocrinologists believe that early use of selegiline may help to reverse the process by which HAC occurs and that two months of trial use may actually be too short a time period in which to evaluate this effect. As more research is done, this will be interesting to follow. At present this is just a theory, though. There are many patients who live much longer than a year or two after the diagnosis of Cushing's disease is made and treatment started. In our practice, the longest period of successful treatment for Cushing's disease has been six years. Dogs that develop HAC early in their life seem to be the ones that respond the longest to
treatment, which does give them the chance for a nearly normal lifespan.

Most of our patients who have hyperadrenocorticism can be managed successfully for some time. They have normal activity levels and relatively normal lives except for medication administration and lab testing on a regular basis. My clients report that their pets feel much better with
treatment. While we may not be able to change the length of time a pet with Cushing's disease lives, we can make them comfortable and help them
maintain a good quality of life.

Revolution (TM), a New Medication for Prevention of Heartworms and Fleas

Recent announcements in the newspaper trumpeted the release of a new medication for prevention of heartworms, fleas and ear mites in both dogs and cats. In addition, the medication kills scabies mites in dogs and roundworms and hookworms in cats. The medication's generic name is
selamectin and its brand name is Revolution. It is manufactured by Pfizer, Inc. Some of you probably called your vet, whose response was very likely to have been, "I never heard of it." How does this happen?

The FDA prohibits advertising of a medication prior to its approval. The approval of a medication generates a press release, which makes it into the news immediately. The veterinarian has no advance warning that this medication will be approved, because of the advertising ban. So for a few
days to a few weeks, veterinarians field phone calls while having little to no information about a product. Fortunately, it usually takes a couple of months to get a product into production, giving vets time to catch up. Revolution will probably be available in September for sale by veterinarians.

Published by TierCom, Inc., P.O. Box 476, Cobbs Creek, VA 23035. All opinions are those of the author, Michael Richards, DVM. Thank you for your
support of our publication and website, www.vetinfo.com