Cushing`s disease and elevated liver enzymes

Photo Gallery - Advanced Cushing`s Disease

Cushing`s disease page 2 Page 2 is a continuation of our Cushing`s page and has more recent Q&A and informatio

Cushing`s disease is probably more accurately referred to as hyperadrenocorticism -- the production of too much adrenal hormone, in particular corticosteroids. It can be naturally occurring or due to over administration of corticosteroids such as prednisone (iatrogenic Cushing`s). The latter is easy to cure - just cut out the corticosteroid administration slowly to allow the body to return to normal function. The former is more difficult.

Hyperadrenocorticism occurs for two reasons --- a tumor of the adrenal gland that produces adrenal hormones or stimulation of the normal adrenal glands from the hormones that control it. The primary reason for this to occur is a pituitary gland tumor that produces excessive ACTH, which stimulates the adrenal gland to produce corticosteroids. Adrenal gland tumors account for 15% of the cases of spontaneous hyperadrenocorticism. Pituitary tumors account for 85%.

Cushing`s disease causes increased drinking, increased urination, increased appetite, panting, high blood pressure, hair loss - usually evenly distributed on both sides of the body, pendulous abdomen, thinning of the skin, calcified lumps in the skin, susceptibility to skin infections and diabetes, weakening of the heart and skeletal muscles, nervous system disease and other symptoms. Most owners reach a point where the water consumption and urination become bothersome to them.

The diagnosis of Cushing`s can be done with several blood tests. A general hint of Cushing`s can be obtained by a blood panel. To confirm it, a test known as a low dose dexamethasone test is done. A baseline blood sample is drawn in the morning, an injection of dexamethasone given and a follow-up blood test done 8 hours later. In a normal dog, the dexamethasone should suppress cortisol levels in the blood stream. In Cushing`s disease this effect does not occur. Once the disease is diagnosed, it is possible to differentiate between the adrenal tumors and pituitary gland tumors using a second test, a high dose dexamethasone suppression test. Most dogs with pituitary tumors will have cortisol suppression on this test. There are other tests used, including ACTH response tests and urine cortisol/creatinine ratios to diagnose this disease. X-rays and ultrasonography can help determine if an adrenal gland tumor is present.

If it can be determined that there is an adrenal gland tumor, it can be removed. Many veterinarians prefer to have a specialist attempt this since the surgical risks can be high. Pituitary gland tumors are not usually removed in veterinary medicine. This situation is treated using Lysodren (o`p`-DDD, which is a relative of DDT) or ketaconazole. Some research with Deprenyl for treatment of this is being done, too, I think. Lysodren selectively kills the outer layer of the adrenal gland that produces corticosteroids. By administering it in proper amounts it is possible to kill just enough of the gland off to keep the production of corticosteroids to normal levels. Obviously, close regulation of this using blood testing is necessary since overdoing it can cause severe problems with Addison`s disease - hypoadrenocorticism. Adverse reactions to Lysodren occur at times but it is the standard treatment at this time. Over medication with Lysodren can cause inappetance, vomiting, diarrhea, lethargy and weakness. If any of these signs occur then your veterinarian should be immediately notified.

Treatment of Cushing`s disease caused by pituitary tumors is symptomatic therapy -- it does not cure the pituitary tumor. The average lifespan of dogs diagnosed with Cushing`s, with or without treatment is estimated at 2 years by Dr. Mark Peterson, but in a recent conversation with another endocrinologist I came away with the impression that this was an "educated guess" rather than the result of extensive survey of Cushing`s patients. At present, though, I think that treatment should be viewed as a means of providing a better quality lifestyle rather than as a method of extending longevity.

Michael Richards, DVM Cushing`s

Q: Dr. Mike:

I have an 11 yr old poodle mix (Tina) (14 lbs, epileptic, female, spayed). She has been on pheno most of her life, now 30mg twice a day. A year ago, found hypothyroid, and vet has been trying to adjust levothyroxine dosage. (We are due for new blood test soon on this).

She had been vomiting for quite a few months, incidences started out to be every month have been getting to be every 3-4 days, she would vomit early in the AM before food or meds and could not digest some of the treats, carrots, grapes that we had been giving her for many years.

Also, she has been steadily losing fur on her back and the skin shows through, sometimes the skin changes color but she does not itch or scratch.

Vet thought possibly Cushings but after testing, she showed normal ranges. In subsequent conversations, however, he said he is still not ruling out Cushings for the future. He doesn`t seem to be too sure.

Sugar was high but urine test showed she is not diabetic. Also, ultrasound showed a couple of nodules in the spleen. Vet said he discussed this with radiologist but that more than likely benign. (Even if they were not, I am not prepared to remove the spleen or do exploratory surgery on her).

Vets conclusion was that the vomiting was probably due to pancreatitis due to the high numbers on the amylase panel. She had high numbers once before and old vet asked if she threw up a lot but at that time she didn`t. I don`t know if pancreatitis causes vomiting or vomiting causes pancreatitis.

Right now, I have finally gotten her stabilized by virtue of Reglan in the AM and before bedtime. The vomit is usually clear frothy or yellow. It takes a lot out of her and this may be the first time in months that we are able to get through a week without her vomiting. I am prepared to keep her on the Reglan forever but I am afraid that there may be underlying problems that my vet doesn`t know about.

His last suggestion is to put her on the Hills i/d diet which I have started. I will also pick up some flax seed oil for the fur and see if that helps.

I am sorry to be so lengthy but I wanted to give you the whole story. Thank God, she has not had a seizure as of lately or that would have complicated the story even more.

I don`t know if the years of pheno can be the cause of her problems but vet rules out liver disease from tests done. I don`t want to put her through any tests than are not necessary and I am aware that she is an older dog but I just want to make sure that the time she has left are quality time for her.

Eileen

A: Eileen;

Hyperadrenocorticism will produce clinical signs in some dogs whose lab values never reach the cortisol levels necessary to be sure that that the disease is present. I can`t explain that but when the clinical signs are highly suggestive (and your dog`s clinical signs are highly suggestive) of the disease, it is sometimes necessary just to treat for the condition to see if it is present. This has gotten a lot easier to do with the introduction of l-deprenyl (Anipryl Rx). It isn`t nearly as toxic as mitotane (Lysodren Rx), which is the other approved treatment for hyperadrenocorticism (Cushing`s disease). It is hard to decide when the clinical signs justify treatment without supporting lab values but if your vet really feels strongly that Cushing`s disease is present and suggests treatment for it, I think that there are times when it is reasonable to try that approach.

I also think it is really important to be sure you aren`t causing Cushing`s disease. Once in a while I forget that a patient is on prednisone and has been for some time. Patients that have been on prednisone chronically often have symptoms of Cushing`s disease. If you aren`t using this medication then it isn`t the cause of the symptoms but if you are, be sure to remind your vet. Even corticosteroid eye drops can lead to Cushing`s symptoms in some patients -- so any source of chronic corticosteroid use has to be considered.

High amylase levels are sometimes present when pancreatitis is present and pancreatitis can be chronic so that seems like a reasonable assumption, too. Since dogs with Cushing`s disease are more prone to pancreatitis, having both conditions is not unusual.

It is OK to use metoclopramide (Reglan Rx) chronically when necessary. You are correct that it is better to find and treat an underlying condition whenever possible, though.

Mike Richards, DVM 5/3/99 Please also note that Tina has been eating grapes as well, now known to be toxic..

Grape and Raisin toxicity

Cushing`s in Rottie

Q: Dr. Mike, I have a 5 year old female Rottweiler, Regal, who possibly has Cushings, but we are not sure. She has most of the classic symptoms: excessive drinking and urination, pot bellied abdomen, panting, excessive eating, loss of muscle mass and strength and skin problems. She is allergic to pollen, dust and fleas, so to combat her allergies, she has been on Prednisone pretty regularly for the past two years. 20 mg per day, the minimum effective dosage. She has been off of the pred. for almost a week and the initial blood tests were inconclusive of Cushings. Her skin problems are VERY bad with open sores and calcifications on her skin. This is very painful for her and she is constantly licking herself. I am bathing her every other day, with a bezoil peroxide shampoo our Vet prescribed, but it is not helping, and the sores are only multiplying. She also smells very bad in these areas. I have tried Benadryl spray topically, tablets orally and nitrofurzone topically to try to ease the pain, but nothing seems to help. I`m afraid to keep putting anything on her, since she keeps licking it off, that can`t be good for her. I am told by our vet, that until the prednisone is completely out of her system, ( a month, minimum) the blood tests won`t be totally accurate, and that once you go on medication for this, there is no turning back, you`re on it for life. It also seems that Cushing`s is more common among small dogs and not big ones like mine, so I am very skeptical whether this is it.

Is there anything you can suggest in the interim to help her. She is on antibiotics, and we`ll be swinging back and forth from Clavamox to another (can`t remember name) for the next few weeks, and I started her on Atarax today to help with the itching. Any other suggestions would be greatly appreciated.

Thank you for your help. Wanda and Regal

A: Dear Wanda (and Regal)

I suspect that your Rottweiler is very likely to have Cushing`s disease. I also suspect that after a month or so your Rottweiler will no longer have Cushing`s disease. How can this be?

Probably the most common cause of the Cushing`s disease syndrome is administration of prednisone or other corticosteroids at levels sufficient to induce clinical signs of Cushing`s disease. This is not a "true" case of hyperadrenocorticism since the adrenal gland isn`t producing excessive cortisone. But it is the same syndrome. The only difference is that you have been giving the corticosteroids instead of her body producing them. Most dogs will not develop clinical signs of Cushing`s disease if prednisone is administered every other day at anti-inflammatory dosages. Unfortunately, prednisone works better if it is given everyday and many pet owners ignore the admonition to give it on alternative days and their pets develop signs of Cushing`s disease. Veterinarians will sometimes resort to gradually increasing the dosages of prednisone when pets don`t respond as expected to lower dosages. Eventually the dose administered exceeds the anti-inflammatory dose and gets into the immunosuppressive range, which is high enough to produce signs of Cushing`s disease. Sometimes, prednisone is being administered orally at appropriate dosages but ear medications or eye medications containing a corticosteroid are being administered at the same time and this leads to an overdosage situation. In a few instances eye drops containing potent corticosteroids have induced Cushing`s disease symptoms in dogs without administration of any oral or injectable corticosteroids.

One of the paradoxes of treating skin disease with corticosteroids is that dogs will develop extremely itchy sores known as calcinosis cutis when they are exposed to corticosteroids at high enough dosages or long enough to produce signs of Cushing`s disease. These sores often look like allergic reactions or skin infections and so the vet tries even harder to control the situation by increasing the prednisone more. I have been caught in this scenario once or twice myself.

It is a very good idea to discontinue the prednisone in a situation like yours, in order to try to rule out iatrogenic (caused by the veterinarian or client administering medications or treatments) Cushing`s syndrome. It isn`t a good idea to just abruptly stop prednisone, though. After two years of regular prednisone administration your Rottie`s adrenal glands are not used to having to work hard to make cortisone. You have been administering it and doing their job. Stopping the cortisone administration suddenly can leave your dog in a situation in which she does not have cortisone source and can`t make adequate quantities. There is a purpose for corticosones in the body and sudden withdrawal of prednisone can leave a dog vulnerable to shock, high serum potassium levels and even heart failure. I am hoping that you withdrew this medication slowly.

The dermatologist we send patients to currently likes a shampoo, Etiderm (TM), better than the older antibacterial shampoos such as benzoyl peroxide. We don`t have very much experience with its use yet but we do trust the dermatologist. In addition, clemastine (Tavist Rx) is currently considered to be the best antihistamine for control of itching. Hydroxyzine (Atarax Rx) is often effective and there is no need to switch if it is working.

I don`t see the need to test for Cushing`s disease if the symptoms improve after withdrawal of prednisone. It is far more likely that the signs you are seeing are due to administration of prednisone than to naturally occurring Cushing`s disease.

The most likely scenario is that you will see a lot of improvement but that you won`t see total improvement because you were using prednisone to treat an existing skin condition and it may not be gone. In a young dog it is worthwhile to consider allergy testing and hyposensitization with injections of small amounts of the allergen instead of using prednisone. Some Rottweilers appear to have difficulty controlling normal skin bacteria. In these dogs control of the infection with antibiotics can sometimes be achieved with long-term use.

If withdrawing the prednisone doesn`t help it may also be worthwhile to ask about referral to a veterinary dermatologist. Sometimes it really can help to see a specialist.

Video: Elevated Liver Enzymes

Mike Richards, DVM

Cushing`s disease- seizures and skin rash

Q: Dear Dr. Mike,

I really marvel at the information available on your site and as a new subscriber to VetInfo Digest I look forward to receiving the information.

I went back over previous material on Cushings Disease and found some helpful information, but not on my current problem.

Psaltee is a 14 yr. old neutered Staffordshire Bull Terrier female. She had a serious bout with seizures several years ago which were finally controlled with phenobarb 30mg twice a day. She was pretty "dopey" so I gradually cut back to 30mg once a day which has held the problem in check.

Almost a yr. & a half ago she was diagnosed with Cushings. She`s been on 500mg Lysodren twice a week since then. I also mix Solid Gold wate-on, seameal, flaxseed oil and a combo of yeast and garlic powder in her food, anticipating possible skin and joint problems. (I also have a young mini-bull terrier who gets `crusty skin` occasionally- so the mix is for him too.)

Lately, the hair on her forelegs has fallen off and she has developed what appears to be an infected rash on her chest, feet, and on both sides of her face. A new vet in the office gave me clavamox 250mg. twice a day and said the rash was a result of mites and that the Lysodren dosage would have to be increased. She was tested in January and the levels were slightly elevated but the dosing schedule remained the same. I hate to put her through the all day event if it`s not absolutely necessary.

Is there any kind of shampoo I can use that would make her a little more comfortable and ease the redness? What else can I expect in the latter stages of this disease? I`m already the only dog owner on the block whose pooch has her own litter tray to use while I`m at work, and a full-time air conditioner!

Thanks for any direction you can give me.

Pam

A: Pam;

There are several things to consider with the skin rash.

The first is to be sure that mites really are the problem, or at least part of the problem. The reason this is important is that the most likely mite problem to suddenly appear in an older dog that has not been exposed to other dogs is demodecosis (infestation with Demodex mites). If skin scrapings have been done and this mite has been identified as a problem it would be a good idea to consider treating for the mites. It is a little more complicated to treat for mites in a dog that has hyperadrenocorticism but it can be done.

The second thing to consider is that Cushing`s disease can produce itchy scaly skin lesions all by itself. There is a specific skin condition associated with hyperadenocroticism, called calcinosis cutis and the only cause I know of is the Cushing`s disease. It may be necessary to obtain a skin biopsy in order to test for this condition since the lesions are not easily identified in many cases without microscopic examination of the tissue. The sores usually look like a cream colored (from calcium deposition) plaque at first, then often become scaly and itchy. It is easy to miss the initial stage of the disorder, though. The sores are usually most prevalent in the inquinal area and surrounding abdomen, near the base of the tail and on the top of the neck. If calcinosis cutis is the problem it will be necessary to try to adjust the dosage of mitotane (Lysodren Rx) to better control the Cushing`s disease or to consider switching to one of the other treatments. If your vet is used to treating with Lysodren it is probably best to stick with it. We have recently had some success using l-deprenyl (Anipryl Rx) for pituitary dependent Cushing`s disease which is the type that affects most dogs. Ketaconazole inhibits the release of cortisones from the adrenal gland which also helps to resolve the clinical signs of hyperadrenocorticism in some dogs.

I have seen skin disease associated with the use of phenobarbital. It seems very likely that if 30mg of phenobarbital once a day appears to be controlling the seizure activity that your dog may not need it at all. The only way to see if the dosage of phenobarbital is less than that needed to control seizures is to test the blood level of phenobarbital. So far, when we have tested dogs that had lower than the needed blood levels and weren`t having seizures we have been able to stop the medication after tapering it off for a month or so without any of the dogs suffering a return of seizure activity. Withdrawing the phenobarbital if it is unnecessary may help with the skin problems.

It may not be necessary to do an all day test to monitor how well the Lysodren is working. Once we know that Cushing`s disease is present we usually use the ACTH response test to monitor the response to treatment. It is usually possible to do this test in an hour (although some vets recommended two hours). Many of our clients come, let us draw the blood and give the ACTH and then walk their dog around our clinic property for an hour or go on a short errand and return. This test takes less time than a dexamethasone suppression test which is usually thought of as the best way to diagnose Cushing`s disease and is the initial test that many dogs get, for that reason.

To get to the actual question you asked, there are definitely shampoos that help with itching. I personally like tar and sulfer shampoos like Lytar (tm) and oatmeal shampoos like Relief (tm). There are a number of both types of shampoos available. Other anti-seborrheic shampoos may be helpful for calcinosis cutis. Antihistamines can be helpful in relieving itchiness, too. Currently clemastine (Tavist Rx) is the antihistamine that many vets favor but there are many others and there is no way that I know of to predict which antihistamine will work best in any particular dog. Antibiotics are often necessary if the itchiness has led to secondary skin infections.

I hope that you and your vet can work through this problem. I realize that I have suggested a lot of testing (skin scraping, skin biopsy, phenobarbital levels and ACTH response testing). If money isn`t an object you could easily have all of this done in one morning if your vet has the time to cooperate in the venture. The two blood tests would be very easy to do at the same time since you have to drawn an initial sample for the ACTH response test and it can be used for both tests.

Hope this helps some.

Mike Richards, DVM

Cushing`s Disease and corticosteroids

Q: Dr. Mike

I have recently moved and my dog`s new vet. has said that my chow could have cushings disease. We transferred and Kenya (my chow) has been treated by the same Dr. for several years. At the time I took her to the vet she was constantly chewing herself to the point of bleeding and causing "hot spots". After 3 months with her new Dr. she stopped chewing, regained her personality and all in all began to get healthier everyday. This was due to shaving her hair, conditioning her skin, and allergy shots. When I discussed this with her Dr. I was told that the shots could shorten her life span a couple of hers. Well, I made the difficult decision to allow the shots and let her life be enjoyable and to best quality I was capable of suppling verses quanity. When she needs a shot she will let me know and is relieved within a 24 hrs of that shot. Kenya has never had to suffer thru any hot spots or sleepless nights since I made this decision, she is now 10 years old and yes, age is taking somewhat of a toll but no more than any other at 10 yrs and maybe not even as much as others her age. I do not regret the decision I made and I know by her loyalty and love she feels the same.

To set some history, I fed my chow whatever was on special from the grocery store(not really knowing any better) and all table scraps she wanted. Well, needless to tell you she became very fat. But was happy and content. My Vet. suggested that she lose 25 pounds and that began my research on premium foods. She was on Prescription r/d and lost her weight. She now eats Nutro Lamb & Rice (because of allergies) and is maintaining this weight very well. Results of her being over weight and then losing 25 pds is some wrinkles and saging here and there. (which unfortunately we all experience).

Kenya does not drink accessive amounts of water (except a couple days after recieving her shot), she does not eat fast, urinate alot or show any signs of cushings. I have loved Kenya for 10 years and will do whatever is best for her. The Vet here basically accused me of killing my dog. They said that every shot I give her is killing her more and more. That she has the classic signs of cushings. (thining hair,saging skin, and something about her abdomen) As I told you she lost alot weight and that allows for the sagging, she is ten years old and I shave her for the summer to allow her skin to breathe and keep her more comfortable in the heat.

They had also suggested thyroid problems. Well, I purposely gave her vet records to them so they would know her past. The whole conversation let me know they didn`t read her records and didn`t even know how old she was. They thought her short hair was of natual causes I guess. She was tested for thyriod problems years ago and results were nortmal and after hearing the statement that I have cut my dogs life in half, I could only assume that they thought she was young??!! It absolutely blew my mind. My heart sank that allowed my dog to stay with them a week while I was out of town.

I know I seem to be rambling on and going no where with this conversation but this was so upsetting to me. I looked up cushings disease on the net and ended up here, please give me any suggestions you have, I know in my heart I have done the best with kenya, but after going through something like this I can only question her diagnosis, please respond and restore my faith in myself and the vet. that I have always referred to as saving kenya.

Thank you for taking the time to read this letter and the access to this page. I look forward to hearing from you.

Sharon

A: Dear Sharon;

It is possible that Kenya could have Cushing`s disease. If so, it is possible that the Cushing`s disease (hyperadrenocorticism) is due to the injections or that it is occurring due to natural causes. Hyperadrenocorticism is not that unusual in older female dogs. Signs of hyperadrenocorticism occur with some frequency in dogs treated with corticosteroids on a continual basis for an extended period. This happens most frequently when prednisone is used on a daily basis rather than every 48 hours but can happen with the injectable corticosteroids as well, especially if they are used more frequently than once a month.

It is also possible that Kenya doesn`t have Cushing`s disease. Most dogs with this disease drink a lot and urinate a lot. Not all of them, but most of them. Thinning of the haircoat, thinning of the skin itself, a pendulous abdomen (think of a pot-bellied dog), changes in liver enzymes, itchy skin sores, increased susceptibility to infection, lethargy and behavioral changes are some of the signs that can be seen with Cushing`s disease. Without seeing Kenya it is hard to evaluate how many of these problems may be present. It doesn`t sound like many in your note, though.

Hypothyroidism is fairly common in older female dogs, too. It also can cause thinning of the haircoat, failure of hair to regrow after being shaved, increased susceptibility to infections, especially skin infections, reproductive disorders and has been implicated in so many other clinical signs of illness that testing for it is easy to justify. Proper testing is pretty important with this condition because treatment requires lifelong supplementation and there are a lot of dogs on thyroid replacement therapy who never had hypothyroidism to begin with. I attended a seminar on endocrine disease once in which the speaker said that hypothyroidism was probably the most over-diagnosed condition and the the most over-looked condition at the same time. Meaning, I suppose, that it is missed many times when it should be found and diagnosed many times when it is not present.

Pharmacology professors at veterinary schools seems to universally abhor corticosteroids. I think this is because they don`t often practice veterinary medicine and when they do they don`t practice it in a real world setting. Their view is probably further skewed by a tendency to see the worst cases of everything at referral hospitals, including the worst cases of corticosteroid abuse. They teach students based on their view of the world. Many veterinarians graduate from veterinary school with a firm belief that the use of corticosteroids is highly dangerous and almost completely unjustified. This is a tragedy for a lot of dogs who could have relief from problems very responsive to corticosteroids without undue risk, as long as they are used with reasonable care. It usually takes new veterinarians a year or two to realize that corticosteroids are often beneficial and then a few more years to realize that they aren`t seeing all that many bad reactions, either. Pharmacology professors also tend to teach that the injectable corticosteroids are much worse than using prednisone on an every other day basis and to taper off the dosage when the allergy season is over. In theory this is probably true. In practice it doesn`t take too long to notice that a lot of clients ignore the admonitions to use prednisone on an every other day basis because it works a lot better if you give it every day. This can cause problems. Then clients often run out of the pills and simply stop dosing the prednisone rather than tapering it off. Most of the time this works out OK but I have seen some reactions that occurred from suddenly stopping the medications. The injections by-pass both of these problems but create some of their own. The veterinarian controls the frequency of the injections and if this is done conscientiously it is a good thing. There is a period of time when the injections suppress adrenal function but they naturally taper off which allows the dog`s body to start production of cortisones and limit the possibility of reactions from withdrawal. In general, if the dog is receiving less than five or six injections a year and is getting them at least a month apart there is not a huge risk of complications. More frequent use increases the risk of producing iatrogenic Cushing`s disease but the risk of this may be worth taking to provide comfort. If we have to use injections more than four or five times a year we do try to get the clients to switch to every other prednisone.

If you are not using Frontline (TM), Frontline Topspot (TM) or Advantage (TM) for flea control you should do so. Even if you don`t see fleas. Use of Frontline has drastically reduced the number of itchy dogs we treat at our practice, making the use of long-acting injectable corticosteroids pretty infrequent in our practice over the last two years.

It is relatively easy to test for both hypothyroidism and hyperadrenocorticism. If your vet really suspects these conditions are present it is reasonable to test for them. If there is any question about the results, an internal medicine specialist or endocrinologist can be contacted to help with interpretation and reassure you that the results are accurate. If Cushing`s disease is present and appears to be due to corticosteroids you or your vet are administering it is easy to "cure" the disease. Just stop administering the corticosteroids. This may present a lot of problems in keeping Kenya comfortable, though.

I think that keeping Kenya comfortable was the right approach to her problems. If your new vet can work out a way to keep her comfortable without the use of corticosteroids that would be even better. If not, I don`t see much reason to feel guilty about providing her with a comfortable life.

Mike Richards, DVM

Cushing`s disease in Corgi

Q: Dr. Mike: Our 7-year old Pembroke Welsh Corgi has been diagnosed with Cushing`s Disease. She is on Lysodren once a week, plus 1500 mg of L-Carnitine and 50 mg of Coenzyme Q-10 per day. I know there are many symptoms to Cushings, but the ONLY outward symptoms that we see on her is a loss of muscle, especially her rear end. She will not put any weight on her left hind leg now. When standing, she holds it straight out behind her. My concern is this: will Cushing`s affect one area (or side) of a dog more than another? I am afraid there is something else wrong with her leg besides the Cushings. Our vet feels that it is the Cushing`s causing this limping, and that swimming therapy may help. I have searched the San Diego area for a canine hydrotherapist, but can`t find one. Is there any other kind of therapy I could give her? Should her back be x-rayed? (Hip Displaysia has been ruled out.) Another thing, her orginal test in January for Cushings was negative, but came back positive in May. During this period, she was found to have over eighty bladder stones which were surgically removed. Upon no improvement in her limping after surgery, a more extensive test was done for Cushings (in May) and found to be positive. I guess my questions are this: can Cushings cause such severe muscle loss in one particular area of an animal, and is there a way I can help her get some muscle back? Is it just muscle loss that could cause her to not use her hind leg at all, or could it be something else? I know this is long-winded. Thanks Dr. Mike, Mary

A: Mary- I think Cushing`s disease can have some odd effects at times and I would not want to say it couldn`t cause the symptoms you describe. I would want to be really certain it was the cause, though. You may want to ask your vet about referral to a veterinary endocrinologist, or internal medicine specialist. There are very good endocrinologists at the University of California at Davis, if that is a reasonable trip for you to make.

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Mike Richards, DVM

Cushing`s possible

Q: Dr. Mike- First, thanks for developing such a wonderful web site. I`ve found it to be very helpful. I`m looking for more information on pancreatitis, or whatever the problem is that has my 14 year old, 15 lb. Terrier-Spitz mix, Melissa, so miserable. Over the last 3-4 weeks, Melissa has seemed to dramatically increase her consumption of water, pants heavily and constantly, and has begun sleeping on the cool tile floor of the bathroom. We assumed that it was her reaction to yet another unbearably hot Austin summer, so we made lots of water available to her, turned the air conditioner down, and bought her a little electric fan for her favorite sleeping spot. Nothing seemed to change with her behavior. Last week we came home from work to find little Melissa in a puddle on the bathroom floor, unable to rise to her feet. Once we picked her up, she was able to stand but she hobbled when she walked, favoring her back right leg. [This is getting long, but please indulge my continuance, as I`m quite distraught.]

The next morning, our trusted vet looked her over and was much more concerned about her panting than her leg problem. He ordered blood work which revealed: ALB 3.11 g/dl .ALKP 1719 IU .ALT 128 IU .AMYL 2334 IU .BUN 18.2 mg/dl .Ca 8.52 mg/dl .CREA .33 mg/dl .GLU 118.1 mg/dl .LIPA (vet`s note: "too high to read") .PHOS 5.22 mg/dl ,TIL .54 mg/dl .TP 7.58 g/dl .GLOB 4.47 g/dl .HCT 46.1% .HGB 16.5 g/dl .MCHC 35.8 g/dl .WBC 17.5 X 10(9)/L .GRANS 16.2 X 10(9)/L .%GRANS 93% .L/M 1.3 X 10(9)/L .%L/M 7% .PLT 476 X 10(9)/L .Her health history is pretty unremarkable other than she`s always had what both this Dr.and Melissa`s previous vets have called a "sensitive stomach"--off and on for years she`s had a gurgly tummy and refused to eat, but blood work as recently as Oct 95 ruled out pancreatitis. Furthermore, she was on cortisone shots and pills for years for itching, but we cut those out about a year ago b/c they seemed to cause her stomach upset. Our Dr. seems to think Melissa`s suffering chronic pancreatitis and probable liver disease/progressive failure. He gave her an antibiotic shot and an anti-inflammatory shot (from her vet records it looks like 0.5ml FLO/0.5 ml Dex and 0.2ml Cent/0.1 Torbutrol) and prescribed Amoxil tabs 100mg 2x/day- Centrine as needed for nausea (although she doesn`t seem to have any problem with nausea lately so we haven`t given her but one of these)- Pancrezyme 1/2 tsp. with each meal- Torbutrol 1 mg 2-3x/day as needed- and Vet`s Choice Sensitive Care food-- 2 heaping spoons 3x/day. Since beginning this treatment last Friday (6/20), her appetite has returned with a vengeance, but her heavy panting, labored breathing, and lethargy/depression continues. She has had three good spells of a couple of hours each where she seemed perky, met me at the door when I got home, followed around the house, and actually rolled over to have her tummy rubbed--all "well" Melissa behaviors.

The bad symptoms, though, have returned afterward each time. In fact, early this morning, her breathing was so loud and labored that it woke me up. I gave her a Torbutrol, assuming she was in pain, and within 30-45 minutes she was breathing quietly. To top all of this off, I also noticed today that she`s got tapeworms (darn these Texas fleas!!), so I`ve called in a request to our vet for one of those worm pills. Thinking that these continued symptoms are probably her response to pain, I`ve begun looking for ways to make her more comfortable. Our vet mentioned that the analgesic we`re giving her may be tough on her liver, so I`m hesitant to rely on that. On the suggestion of a couple of friends and with the OK of our vet, I`ve made an appointment for tomorrow with another vet who incorporates accupuncture into her practice. Since I don`t see that we have the luxury of a wait-and-see approach with this old doggie, I`m in search of as much information as I can get on pancreatitis and other problems that might present in the same ways. And, I guess, I`m looking for additional confirmation that we`re taking the right approach with Melissa. Any advice for reading materials, thoughts on her diagnosis, or additional or alternative treatment options, or words of reassurance? Many thanks in advance for addressing my question and for putting together such an informative web site. Leslie

A: Leslie- Based on the description of increased drinking and urinating, along with lethargy, I`d be suspicious of Cushing`s disease (hyperadrenocorticism). This can lead to pancreatitis and it is entirely possible that both problems could be present (or that my suspicion is off base). Cushing`s disease frequently causes elevations of the alkaline phosphatase level, too. It requires special testing specifically for this disease, most commonly a "low dose dexamethasone response test". Cushing`s disease causes panting, increased drinking and urinating, muscular weakness, promotes diabetes and pancreatitis and is associated with hairloss in many dogs, as well.I`m sure your vet has continued to think this through and has probably considered this possibility but it might be worth asking about.

Mike Richards, DVM

Cushing`s and Melissa - continued

Q: Dr. Richards- Thought you might be interested the latest twist in Melissa`s on-going saga. Her high-dex test to determine the origin of her Cushing`s came out inconclusive. Apparently she reduced her cortisol (or whatever the test is supposed to reduce) by 50.46%. The internist we have begun dealing with suggested an ultrasound to determine more definitively whether or not an adrenal tumor was the problem. No abdominal abnormalities were seen in the ultrasound with one big exception: she had a ~2.5 cm pocket of fluid in one lobe of her liver. Based on the surgeon and internist`s recommendations, exploratory surgery was done, the pocket removed and a biopsy of her liver was done. The hands-on examination of her adrenal glands showed them to be symmetrically enlarged with no signs of growths. Ironically, one end of Melissa`s pancreas appeared to be a little tough, so it, too, was biopsied. The fluid pocket in her liver was determined to be a cyst adenoma, and her liver tissue, according to the surgeon, looked to be very healthy. Her pancreas, on the other hand, was determined to be in the healing stages from an attack of acute pancreatitis. So, our weird little dog has both pancreatitis and pituitary-dependent Cushing`s. She`ll be in the doggie hospital for six days, working her way off of IV fluids and back to food during her last two days. We visited with her yesterday and she looked really good--perky and up for a mini-walk outside. Today, according to the internist, she looks even better--up schmoozing with the staff! Once she`s back home, I think the plan is to give her Pancrezyme supplements (haven`t confirmed this with the internist) and in few weeks we`ll probably begin treatment with Lysodren. Any thoughts on the choice of Cushing`s treatment options (Lysodren, Ketoconazole, or L-deprenyl)? Yet another big, warm thank you for spurring me to push further and harder into figuring out what was making sweet Melissa so sick! -Leslie

A: Leslie- We still use Lysodren therapy most of the time for Cushing`s disease because we are familiar with it, it costs less and it is easily available. I have used ketoconazole twice, once successfully. I wasn`t too disappointed that it didn`t work in the other case because it is supposed to have about a 20% failure rate in helping with Cushing`s. We chose it in both these cases because of reactions to Lysodren. So it is good to have a third choice and l-deprenyl looks good on paper but I haven`t tried it yet.

Mike Richards, DVM

Michal Response: Leslie, thanks for keeping us informed on Melissa`s care and progress.

Cushing`s Disease with immune mediated hemolytic anemia

Q: Dear Mike: Our bichon was recently diagnosed with Cushing`s Disease. The vet. put her on Anipryl or four days straight with one tablet each week thereafter, for four weeks. Into the third week she became very weak, and upon her vomiting...I rushed her to the vet... We have now been told that they think she has auto immune hemolytic anemia. She tested neg to the Coomes test....even thought that doesn`t mean she doesn`t have it. They began giving her steroids and within 34 hours her red blood cell count had climbed from 9,000 to 12,000.. they said they had hoped for higher...they will increase the amount of steriods today...her wbc is very high as well... My question....Do you think that the Anipryl brought on a drug -induced immune hemolytic anemia? or is this just a part of having Cushings? and lastly never having been down this road before...should I prepare myself for days of sadness ahead? I so appreciate having found this supportive site on the web...not in anyway do I discount the abilities of my vets...by asking you these questions...I only hope to gain further insight into this horrible disease that anyone has. With appreciation, Mrs. J.

A: Mrs. J- I think that it is necessary to consider the possibility that l-deprenyl (Anipryl Rx) could have lead to a immune mediated hemolytic anemia as a drug reaction. I am not familiar enough with this medication to know how likely that might be, though. I have forwarded your email to a veterinarian I know who is involved with the research on this medication and maybe he will know more. I`ll pass on any information I get.

There are other medications for hyperadrenocorticism (Cushing`s disease). Ketaconazole is pretty safe and mitotane (Lysodren Rx) has been used with success many times, although overall it is more likely to cause side effects than either ketaconazole or l-deprenyl, probably.

If the immune mediated hemolytic anemia is a drug reaction it will normally respond to treatment and it is not likely to recur with other medications. I hope that everything is improving now.

Mike Richards, DVM

Video: Symptoms of Liver Failure - liver enzymes symptoms

High Alkaline phosphate levels

Q: My 12 year old Maltese was diagnosed with Cushings the first of April. He has been taking Lysodren (daily 10 days, 2x wkly since). His alkaline phosphatase is now 1500, up from 1108 on Apr 1. the Vet did not retest until June 13. I now realize (from the various Web articles I`ve read) that retesting should have been done sooner. Have you had experiences with a similar situation? Any opinions? I live in Dallas, TX. Any opinions on speciality vets here who deal with Cushings?

Video: Why might someone's liver enzymes be high? Will this cause vomiting?

A: Teresa- It is not unusual for dogs with Cushing`s disease to have high alkaline phosphatase levels --- often in the range of your Maltese. This doesn`t always resolve with therapy but our experience has been that it rarely indicates a clinically serious problem. I know that there are good veterinarians on the staff at

Texas A&M, if your vet does not know of a specialist closer. Mike Richards, DVM

Cushing`s - no response to treatment

Q: Hi! I have a dog of ten years, diagnosed with Cushing`s, possibly due to a tumor in the hipofisis (adrenal glands have been seen by Ultrasound and they are normal in size- liver is enlarged). Yokie is a dog of 10 kilos of weight and is being treated with Lysodren. We have tried for ten days and it didn`t work (symptoms didn`t change: polydipsia, polyuria, polyfagia, pendulous abdomen, hair loss, panting...) We have begun again for ten days more and we are in our ninenth day and no change till now. We are going to continue five days more (in total 15 days this time) and then we will do an ACTH. Do you have any reference of dogs with Cushing`s that don`t react to the treatment? What can I do if my dog doesn`t react to the treatment? Thanks for your attention - from Spain

A: Some dogs do not respond to Lysodren and it seems likely that your dog may be one of them. There are several options in this case. The medical options are ketoconazole (Nizoral Rx) and l-deprenyl (Eldepryl Rx and Anipryl Rx). l-deprenyl will only work with pituitary dependent Cushing`s disease, so it is good that your dog appears to have this type. Both of these medical treatments have been pretty widely reported in the veterinary literature and I am pretty sure that your veterinarian will be able to find references for their use. l-deprenyl may be a little harder to find information on as its effects on cushingoid dogs has been a more recent discovery.

In a small number of dogs there may be operable tumors contributing to this condition - pheochromocytomas. It may be worth considering this possibility if the condition continues to be resistant to therapy.

Good luck with this. Mike Richards, DVM

Diet For Cushing`s

Q: Dear Dr.Mike, I don`t mean to make a pest of myself, but I forgot to ask if you there are any dietary recommendations in Cushing dogs. We have her on a strictly dog food diet.(Iams dry minichunks and canned science diet senior).I have absolutely forbidden family members from sneaking her any table scraps any more,as she did used to get more than a little dogs share of meat scraps,cottage cheese and anything that fell to the floor. Any special things I could do for her?? I have been led to understand that if her metabolic functions and enzymes are not normal she may not be absorbing the needed vitamins,proteins and fat that a dog needs for proper health. Thank You in advance for any help.

A: I have been reading some interesting articles on hyperadrenocorticism today. I found a recent issue of the Clinics of North America, "Adrenal Disorders", March 1997, edited by Peter Kinzer, DVM.

It has an article suggesting that the pathogenosis of pituitary dependent hyperadrenocorticism has not been fully worked out. This article, by Dave Bruyette, DVM et. al., mostly concerns the use of a new medication, l-deprenyl, for the treatment of Cushing`s disease. It suggests that it is possible that this is a neurologic degenerative disease similar to Parkinson`s disease in humans in the way it progresses, but with different effects and clinical signs. It is a different view entirely from the one I have held for a long time on how this disease occurs. It will take me a while to research this and I am sure that the university vets will already be aware of this hypothesis. Still, it is interesting and made researching this worthwhile.

The only dietary recommendations I can find are in Small Animal Clinical Nutrition III by Morris, et. al. It says to feed a high protein, low fiber, low fat, low purine diet. It suggests that it is important not to oversupplement calcium. It is also important to make sure potassium levels are adequate and that sodium is not restricted in any way if mitotane (o`p`DDD) is being used to treat the hyperadrenocorticism. Also, it is important not to restrict water intake, as you might imagine. Feeding Hill`s i/d diet is one way to meet the requirements for these things. One of the book`s authors is the son of the veterinarian who founded Hill`s, so there may be a little bias in the recommendations, at least as to the recommended diet.

Mike Richards, DVM

Seizures and Cushing`s Disease:

Q: Mikki is 15. She is a mutt...Terrier dominates. She has never been sick to any degree. An upset stomach might take place if she`s eaten sothing she shouldn`t have.....like the time she got into the chocolate chip cookies. Generally speaking, however, she is pretty healthy. She eats Vets dog food, half can in the morning and the other in the evening ....and milk bone bisquits. That`s it. We don`t vary the diet. She has always downed her food in about a minute..now I water it down so she will eat slower. Her appetite does not change. she has begun to display slight siezures lasting a few seconds. There is no change of weight, behavior, or appetite. Her vision is getting weaker but not worse than expected for a 15 year old. Nothing seems to be changed except very (infrequent) short seizures. Her Vet took a blood test and he`s looking at Cushings Disease..but from what I read he is on the wrong path....and there is no mention of seizures in Cushings. Any help would be welcome

A: My guess is that most seizures occurring in older dogs are the result of degenerative changes in the nervous system and cancer. However, Cushing`s disease is reported to be associated with an increase in seizure activity. This probably occurs because most cases of Cushing`s disease are caused by pituitary gland tumors in the brain. As the tumor grows, seizures can occur. Most dogs (about 80% if I remember correctly) affected with Cushing`s disease show a marked increase in drinking and urinating. It is relatively easy to rule this disease out with labwork and if other clinical signs of the disease are present, such as abdominal distension, hairloss, thinning of the skin, increased skin pigmentation, panting, excessive drinking, urination or appetite, it is a good idea to rule it out. I hope you find a treatable cause for Mikki`s seizures. My terrier mix, Maggie Mae, also has seizures. I haven`t been able to find a cause for them but they are infrequent and we are not treating her at the present time for them.

Mike Richards, DVM

Cushing`s disease page 2

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