Cushing's Disease Treatment

Question: Hello Doctor,

I am a suscriber and I come to you once again for some guidance. Macha, our 10 years old chow mixed has been diagnosed a few months ago with Cushing. We have followed our vet's suggestion of putting her on Lysodren. During the holidays, we have travelled to VA to visit family. There she stopped eating and started feeling weak. I have called the vet who told us to boost her with cotisone pills. We did that, unfortunately it turned for the worst as she began a severe episode of Addison. Knowing that something was very wrong with her, we cut short on our vacation and came back home. We dropped her off at the emergency where she was kept for three days. Talking to my vet today, i stated that I was really uncomfortable with lysodren now, to say the least, I fear it. It took us by suprised and we almost lost our dog. I now have to face the big choice of taking her of the drug and let nature follow its course or risking another episode such as the one we have known a few days ago. When cushing was diagnosed, i was told that it was a disease that can be easily controlled, nevertheless this episode has left us very bitter. I should say that she has never has, to my knowledge, any of the symptoms known to cushing. She was diagnosed before a minor surgery. I come to you today hoping you can give me a few words of advice on wether or not I should stop the lysodren treatment and what i should expect if she is not treated. Will she be more enclined to suffer from symptoms because she use to receive treatment? What is her life expectancy with treatment as opposed to not being treated?

Thank you for you reply, Louise

Answer: Louise-

I am reluctant to treat patients for Cushing's disease unless they have symptoms that are causing difficulties for them, such as increased drinking and urination, hair loss, muscular weakness, skin disorders and neurologic signs. My basic reasoning for this is that there isn't much evidence that treatment prolongs the life span of patients with Cushing's disease, if you don't count euthanasia due to problems like increased urination. So the major benefit of treatment is not prolonged life but comfort in the remaining life span. With this in mind, if there are no symptoms, there seems to be no strong reason to treat the disorder. On the other hand, there is good evidence that it makes patients with clinical signs feel better and some evidence that starting treatment early helps to control symptoms over the long run, so some vets feel differently than we do about when to treat.

There is an alternative approved treatment for Cushing's disease, which is the use of selegiline (Anipryl Rx), a medication that works well in about 40% of Cushing's disease cases and has less potential for harmful side effects and for causing hypoadrenocorticism (Addison's disease). It may be worth considering the use of this medication if there are future problems with clinical signs associated with Cushing's disease.

At the present time, most vets still favor the use of mitotane (Lysodren Rx) for the treatment of Cushing's disease, primarily because it is effective more often than selegiline but also because some veterinary endocrinologists question whether selegiline works at all, because it doesn't improve the results of standard tests used to assess the treatment of Cushing's disease even though it does appear to alleviate clinical signs in many patients. So your vet's choice of this medication is not really unusual. It is important to monitor for signs of hypoadrenocorticism and to know that it may occur when using Lysodren.

I have no problem with waiting until clinical signs appear before deciding to treat with Lysodren or Anipryl, since there isn't much evidence to indicate a longer life span when using these medications (there is a little evidence for this when using Anipryl, but only for one small subset of Cushing's disease patients). It would not bother me much if a client opted to discontinue treatment for this condition and see what happened, as long as they realized that we would have to repeat the initial stages of medicating, in which regular lab work (ACTH response tests) would have to be done to ensure that we have the correct dosages, when they decided to start the medication again due to the occurrence of clinical signs. I know of no evidence that suggests that stopping treatment and then restarting it is any more likely to cause problems or that there might be an increased chance that Lysodren would fail to work the second time around.

It would be best if you can schedule some time to discuss all this with your vet. The choice to use Lydodren was almost certainly made in good faith based on your vet's experiences with this disease and this medication. The outcome was scary for you and it was probably scary for your vet, too. I'm pretty sure your vet will remember this and inform future clients about the risk of Addison's disease when using Lysodren. I know that I have sometimes had to deal with a bad outcome prior to really understanding the risk of a treatment and properly conveying that to my clients.

Mike Richards, DVM 1/15/2001

Cushing's disease - early treatment

Question: Dr.Richards, Thank you so much for having this great resource for our animals. My question is about cushings disease. My mixed breed smaller collie like dog (36 lbs)y, originally from the shelter, so I really do not know his age but probably around 12 years. I have had him for 10 years. He was panting a lot so my vet did some tests: chest Xray which was not outstanding, but alk phos was 700, so she did an ACTH which was elevated then a high dose dexamethasone suppression test which showed he has pituitary dependent cushings. The vet is great and is recommending lysodren treatment. My question is the only symptom he has now is panting otherwise he is healthy and happy (if he gets a car ride each day). I know this treatment may make him sick. Would it be OK to wait until he has more symptoms? My vet has not used anipryl but said she would reach it and let me know. What is your advice on that also? I appreciate your time. Gail

Answer: Gail-

There is no solid evidence that I know of that early treatment of hyperadrenocorticism prolongs life or reduces the likelihood of future clinical signs. So I don't have any problem with waiting to see what happens when a dog has minimal clinical signs but lab work confirms hyperadrenocorticism.

On the other hand, if I understand correctly the manner in which selegiline (Anipryl Rx) is supposed to work, it theoretically should help in slowing the progress of the disease and possibly in averting it, if started early. It is supposed to cut down on the overstimulation of the pituitary gland by the hypothalamus. There is still some controversy about whether Anipryl actually works, among veterinary endocrinologists, but we have had several patients have really big improvements in clinical signs on the medication, so I like it, so far. It is an easier medication to use than Lysodren (Rx) and it seems to be reasonably safe.

This is a wishy-washy answer but I think it comes down to this: if the panting doesn't bother you, there isn't any evidence that I know of that early treatment helps significantly in important things like longevity BUT if you don't mind spending the money for Anipryl, it might help --- it's just that no one knows that for sure right now.

I do wish I could give a more precise answer but right now there isn't enough information to do that.

Mike Richards, DVM 8/4/2000

Cushing's treatment

Question: Dear Dr. I am sorry I have not responded earlier, but we were on vacation. Your e- mail on July 9 was the first one I received. We have begun receiving the newsletter tho. I am still confused about the cushings. Would it be too late to wait for him to be tested until he starts drinking excessively, or the sooner he gets treated the better. I understand there is no cure. The reason people treat their pets is to basically stop them from urinating all over. We have switched him to a low protien diet and he takes 2 aspirin a day plus vitamin E and C. He started trotting aroung again, and runs to the lake when we take him swimming. I hate to start him on medication that may make him sick until the right quantity is figured out. I hate to keep asking you basically the same stuff, but this is pretty hard to figure out. Thanks, Dolores

Answer: Dolores-

Prior to the introduction of selegiline (Anipryl Rx) I could see no real benefit to treating Cushing's disease prior to the time that bothersome symptoms appeared, as long as it was due to pituitary problems rather than adrenal cancer. However, if the hypothesis for how selegiline works is correct, it may be possible to prevent some of the pituitary (brain) changes associated with hyperadrenocorticism (Cushing's disease) and that may be beneficial over the long run. So now, if expense isn't an obstacle, I tend to want to start treatment with selegiline as early as possible. Selegiline is expensive enough that cost is prohibitive for some of our clients.

I am not sure enough that the potential beneficial effects actually occur for me to feel bad if clients wait to see if further signs develop. I just think it is a good option for clients who can afford the cost and want to try to prevent progression of the disease.

I am not aware of any problems with lab testing caused by feeding the low or moderate protein diets recommended for kidney or liver disease. The fat content of these diets is higher than that recommended for Cushing's disease patients, though. If there is evidence of ongoing kidney problems I would opt to stay with the diet for that problem but if the kidney problems do seem to be resolved and if Cushing's disease does seem likely based on lab tests, switching to a lower fat diet might be helpful.

Mike Richards, DVM 7/24/2000

Cushing's treatment

Q: Dear Dr. Richards, I have recently subscribed to your newsletter and have read through all of your answers to questions regarding Cushing's Disease. Your page is a great source of information. I'm not as knowledgeable as some of the other pet owners but here goes. My dog, Lucy, who is a large (95-100lbs)black lab/golden retriever mix is now 11 yrs old. About a year and a half ago we first suspected Cushings after several urinary infections, increased thirst, appetite, excessive panting, hair loss and all the classic symptoms. She was tested for thyroid, diabetes and a few other things but they came up negative. That's when Cushings was first mentioned. With 3 young kids,limited means and a farm family that does not spend much on pets, I was pressured to forgo the definitive testing to confirm cushings and it's cause. We were also given an estimate of the cost of both the chemo drug with all the blood testing or the newly approved Anipryl(?) for a dog her size. After being told of her normal life expectancy (we were told 10-12 yrs) along with the cost, we felt compelled to let nature take it's course. It was an agonizing decision but Lucy didn't seem to be having any trouble. No skin problems, never has been on predisone or cortisone, only excessive thirst and appetite. Now she is having considerable trouble getting up and sleeps a lot (insists on the cold tile floor!)During a recent visit to the vet, I was told she looked just like a classic Cushing's dog and that her liver was enlarged. I was also told that the price of, I think, Anipryl has come down a good bit. I'm now feeling guilty since we are a bit better off this year. My question is: If I gave Lucy treatment now, would it change anything? Is any of the damage reversible? How would it change her quality of life? She's still a happy dog, just looking and acting very old. She seems to be drinking a bit less and her appetite has dropped a bit. I don't know if she is just too tired to get up as much or if it is a real decrease. I give her doggie multi-vitamins, glycoflex and, for a short time, buffered aspirin but thought it may upset her stomach since that is when she stopped eating as much. (Her skin and hair are looking much better after the vitamins) I'd really like a gut reaction/advice even if it isn't pleasant. I just keep getting options. What would you do?

Thanks K A: K

Most of the people who treat their dogs for Cushing's disease in our practice are looking for one of two benefits: 1) decrease in drinking and urinating 2) increase in hair coat. These are the two symptoms that bother owners most, although panting is a close third. Our experience with selegiline has been that it helps with all the symptoms when it helps and it totally fails when it doesn't. Selegiline also is used in the treatment of canine cognitive dysfunction and one effect appears to be an increase in organized activity (response to owners, playfulness) in many patients, so this symptom may improve even if others do not. Remember that our experience is fairly limited at this time. I am pretty sure we have treated less than ten patients but at least five or six (counting the two we didn't confirm the disease in).

I think that selegiline is still in the $50 to $60 per month range for most patients. They just sent us a package in which they have a one month free trial offer for patients that have not been on the medication, though. You might ask your vet about that.

Mike Richards, DVM 9/19/99

Cushing's treatment - part 2

Q: Thank you for writing back so quickly. I really appreciate some straight answers. I do have another question. When you say "good results", what kind of things are you referring to? Worst case, Lucy sees no improvement. Best case, could she regain some muscle strength? Would her coat thicken back up? Would the thirst, panting and appetite return close to normal? How about her energy level? After stopping the buffered asprin and starting her vitamins, she is looking and eating better but she still sleeps a lot and has trouble getting up on smooth floors. Also, you confirmed that the price for the drug selegiline (Anipryl Rx) has come down. How much would a dog Lucy's size need? What might that run where you are? I'd love to see Lucy enjoy another winter with us and, hopefully, another summer but without sucessful treatment, I'm not too optimistic. Thanks again and I look forward to hearing from you. K

A: K

I don't think that there is really much problem with delaying treatment of Cushing's disease, except when it is due to adrenal tumors (which is the less common form of the disorder). There is no evidence at the present time to show any improvement in lifespan due to treating for Cushing's disease, although some of the advocates of selegiline (Anipryl Rx) do point to evidence in laboratory species that this medication MIGHT prolong life in Cushing's patients. Treatment can make a big difference in the quality of the remaining lifetime, though.

We have had some really good results with Anipryl and some cases in which it did absolutely nothing that we could see. It is safe enough to use that I will prescribe it based on clinical signs alone, if the owners simply can't afford testing but want to try to treat a pet with clinical signs. So far, we have done this twice --- and had one success and one failure. The bad part about this approach is that I don't know if the failure is because the medication didn't work or because my diagnosis was wrong. That is bothersome but the dog's owners are content that they did what they could in their circumstances so they are happier than I am.

Anipryl is still pretty costly but it has come down in price some. If you can afford to try it for a couple of months and your vet thinks it is OK to proceed without testing, I really can't see any reason not to give it a try. But you might want to be sure it fits in the budget long term. It might be worse to know that it did help but that it is too expensive to continue than to not try it at all.

Hope this helps. If you need more clarification, feel free to write to me until you feel you have a clear understanding of the information on Cushing's disease.

Mike Richards, DVM 9/21/99