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There is a study by Dr. Victor Castillo at the University of Buenos Aires veterinary school that used a 180 day treatment and showed tumor shrinkage through MRI. Does anyone know of this treatment being done in the US? The cost is similar to Vetoryl. The study indicates remission and a cure? Please comment.
Hello and welcome! We have had a bit of discussion here previously about retinoic acid and this particular 2006 study. However, none recently. This leads me to believe that the "question marks" that are noted in the thread below must remain. But if you can find any newer info, that would be great. Here's the related thread:
http://www.k9cushings.com/forum/showthread.php?t=2000
Do you have a dog who is currently being treated for Cushing's?
Marianne
Thank you for the thread link. I've directly contacted Dr. Castillo and he told me that they have been treating Cushings for nearly 10 years this way with success. He estimates the cost to be $40 to $90 for 30 capsules at 14mg (the dosage required for a 7kg dog). I am waiting for the pharmacy contact information from him.
Yes, I do have a 8 1/2 year old 15lb intact male Cairn Terrier currently being treated with Trilostane along with Homeopathics and a raw low purine diet. We're on the 2nd stim test from a whopping 70 his first stim prior to treatment, down to 15 with 5mg 2X. My vet suggested liquid form Trilostane to raise the dosage to 7.5mg 2X. He has definitely improved. His thirst changed in just a few days. Less panting now that he's been on the Vetoryl for a total of 4-weeks. I am thinking about trying the Retinoic Acid once more of his symptoms lessen and his stim gets below 5. It's been slow getting replies from Dr. Castillo but he does answer eventually.
That's very interesting that you've been able to contact Dr. Castillo directly. It will also be interesting to get the pharmacy info, since it appeared that obtaining the drug at an affordable price was a big issue here in the U.S. I have just now emailed an expert veterinary endocrinologist here in the U.S., requesting an update re: current use of retinoic acid here. He usually answers very promptly, and I'll definitely post any related info here as soon as I receive it.
Marianne
I went to read the abstract of the article and I am by no means an expert or even anything close :) Yet, it left me with some questions and I did try to look for them on the internet but couldn't find anything.
In the abstract they mention the trial was done with 22 dogs receiving retinoid acid and 20 dogs receiving ketoconazole as treatment. To me, this is strange, since ketoconazole isn't the most effective treatment in canine cushings. In my layman mind, I would think "Yeah right, compare a possible new treatment to a not very effective treatment...and chances are the outcome will be beneficial for the new treatment" So I would like to know how the retinoic acid compares to treatment with Vetoryl for example...yet, I cannot find any study on this. In fact, I cannot find any other studies on treating canine cushings with retinoic acid after this one from the abstract, which was 10 years ago in 2006. This too, seems strange to me. I did find a much more recent study of a trial with human cushings patients and retinoic acid. https://www.hindawi.com/journals/ije/2016/8173182/ In that article there is no mention either of trials in canines from a later date then 2006. They only refer to the 2006 trial. And humans and canines are different of course so you cannot compare those results one on one but eventhough it does seem beneficial to certain human cushings patients, it is not to all. So there still is a long way to go :)
I am notoriously curious, I appologize...but could you explain why you would want to change the Trilostane treatment (who seems to be working well from what you write) for the retinoic acid? I couldn't find anything indicating that treatment with retinoic acid would/could cure cushings. In fact, as far as I understood it, the dogs were treated for 6 months (180 days) but what happened after that. Was treatment stopped all together? It doesn't say in the abstract...but perhaps you have the full article available and there it said maybe more? :)
Anyway, to me personally, it just gave me more questions then that it seemed to be a lasting solution to treat canine cushings disease.
Love a good exchange of ideas and thoughts... :D
Saskia :)
OK, I've already heard back from Dr. David Bruyette who is the medical director of VCA Animal Hospital in West Los Angeles, has been instrumental in pioneering surgery for canine pituitary macrotumors at UCLA, has been a consultant to Dechra re: Vetoryl, and is also conducting ongoing clinical research himself. Apparently the cost of obtaining retinoic acid in the U.S. remains prohibitive and that has cast a pall on further research here. This is what he wrote to me:
I am not familiar with these other two chemicals, so I need to read more about them. But apparently cost is an issue with them as well, since when I asked him further about them, Dr. Bruyette said they do work in dogs but are also very expensive.Quote:
No one has really advanced the therapy very far given the costs and the availability of paseriotide and mifepristone which recently became approved for use in humans.
It does seem a shame if all these chemical alternatives might otherwise present a safe and therapeutic treatment alternative, if it were not for expense. Anyway, I guess this explains why the research has not yet gained additional traction in terms of veterinary use.
Marianne
Thank you for your comments regarding the study and I appreciate the exchange of thoughts. Here are my concerns: Trilostane is a perpetual treatment of symptoms, manually down-regulating cortisol. Cortisol is also beneficial and necessary. This may contribute to the hind leg weakness my dog is showing. It concerns me that the drug is very potent and dosage must be closely monitored and precisely dosed especially for a 7kg dog. Life expectancy for Trilostane is only a median of 540 days. My dog is only 8 1/2 years old, he should do better than that I hope.
If the Retinoic Acid performs as stated in the paper it could be a cure. It states there were no negative side effects. There are several before and after MRI images showing visible shrinkage of Pituitary Masses. At best, in optimism the paper in summary says: "some 6–12 months after completion of the trial and cessation of treatment, none of the dogs treated with retinoic acid has shown evidence of recurrence of Cushing’s disease."
Mitchell
Unfortunately no reply from Dr. Castillo yet with the pharmacy contact information. I will post once I receive the information. Thank you for asking Dr. Bruyette about this.
On another note, would you know Dr. Bruyette's thoughts regarding splitting dosages since Vetoryl peaks at 4-6 hours? I contacted Dechra and although in their handbook there are references to studies where splitting dosage was done, according to the person I spoke with 'do not officially recommend it'. The reference studies do state that it lessened the side effects with more consistent UCR measurements.
Mitchell
Yes, we do know Dr. Bruyette's thoughts about this :). He was actually a member here for a short time, and here's a reply that he posted to that very question. It's been a couple of years since he visited us here, but I believe his current approach remains consistent.
The question of once vs. twice daily dosing has consistently remained a topic of debate among clinicians throughout the years, and different folks have different perspectives and preferences. In my own mind, the research remains somewhat equivocal in terms of lessening ill effects. It seems to be the case that certain side effects may be lessened by the lower total daily dose that can be associated with twice daily dosing. Also, some clinicians speculate that longterm systemic damage may be lessened when cortisol levels are kept consistently lowered throughout the duration of each day. However, as Dr. Bruyette notes, twice daily dosing may carry an increased risk of driving cortisol levels too low, which to me is actually the most worrisome potential side effect of all.Quote:
With regards to once vs twice a day dosing if we look at all the studies throughout the world you will see that about 80% of dogs will feel better with once daily dosing. One huge advantage of once daily dosing is owner compliance which goes up substantially when owners only have to dose once a day. While twice a day dosing may result in a lower amount of trilostane being used per day it will require closer monitoring as the ACTH stimulation tests tend to be lower so we have to look for both hypocortisolemia and electrolyte abnormalities.
Given the fact that every dog metabolizes the drug a bit differently, my personal belief is that some dogs will feel better on once daily dosing (allowing their cortisol to rise somewhat throughout the course of 24 hours), and others will do better with cortisol levels that remain more consistently flat. If I were starting out all over again, though, unless I had a diabetic dog for whom twice daily dosing is generally always recommended, I think I'd ask to start off with one dose each morning and I would only shift to twice daily dosing if symptoms rebounded again later in the day. In my own daily life and schedule, it is just much easier for me to remain consistent with a single dose each morning, especially since trilostane needs to be administered along with a full meal in order to be metabolized properly. I see that you are dosing twice daily, however, and if that regimen seems to be working well for you, there are certainly many clinicians who favor that approach.
Marianne
Hi Mitchell,
thank you for your reply :) Like you, I too would research anything and everything when my dog was sick, so I fully understand :) I was just curious and well, being Dutch... I speak my mind easily :)
Wishing you and..... (your Cairn, what's his name please? :) ) all the best,
Saskia :)
Thank you, From Datsun (his name means speedy rabbit) and I all the best of luck to you too. Does your dog has this illness as well?
Mitchell
Datsun...a fitting name for a speedy Cairn :D No, my current dog doesn't have Cushings thankfully. Many years ago, Boncuk, a little Lagotto mix had Cushings and he's the one that brought me here... and I just never have left :) Like many of us here, even after our beloved dogs pass, we stay around because throughout the years, through years of shared sadness, joy, grief and sucesses....we have formed a family :) A weird family perhaps but very loving and caring :) Impossible to stay away... So, don't say I didn't warn you :p
Saskia and Quincy (a former Polish stray dog, now my certified service dog :D )
Reenvío Farmacia Galénica
Riobamba 923
Ciudad Autónoma de Buenos Aires-Arg.
Tel: ++54-11-4811-4325 // 4648
Mitchell,
I just posted a similar question and I feel like you and I think alike. Why not try to cure this rather than just control symptoms? I do agree in your case that 8.5 years is too young to have to settle for symptom management without asking about what else is out there. My Chihuahua is 14 and I am out there looking for a cure anyway. If he were 8-9 I might consider the mris, the radiation therapy etc.
Hoover, 6.5-7 lbs is currently on 5mg of Vetroyl 2x a day. I started him on 5mg 1x a day even though the vet suggested 10mg 1x a day because aside from the peeing and thirst he seemed to be healthy and I was feeling conservative. After reading the recent studies that twice a day was more effective, that the drug has a short half life, and that my dose is a little under the 1mg per pound standard anyway, I decided to listen to the internist I consulted who reitterated the studies of the effectiveness of twice a day dosing.
That's where I'm at right now. Thanks for sharing your correspondences with the specialists.
Mitchell,
Have you started with the Retinoic Acid? Is it hard to have it shipped over here?
I'm curious about contacting this pharmacy.
Thanks,
Yvonne
Hoover's mom:)
Hello Yvonne,
I have called Farmacia Galénica and spoke with Linda Prrozic, they require a prescription written to the owner with the pets name and will ship to the US. Here is the email address to send the prescription to: Farmacia_galenica@yahoo.com.ar
The VA-MD College of Veterinary Medicine may have tested with the 9-cis retinoic Acid...
VA-MD College of Veterinary Medicine
205 Duck Pond Drive
Blacksburg, Virginia 24061
540-231-7666
When I called them, was told that your vet will need to ask to speak with a Clinician…
Unfortunately my dog Datsun has been experiencing Cushings's Myopathy and had been having difficulty walking and standing. Since his symptoms were advancing more quickly than any of the herbals and homeopathics were able to resolve, Datsun began treatment with Vetoryl before I received the response from Dr. Castillo and Farmacia Galénica. Datsun has already had 5 stim tests and through gradual increases in dosage, has reduced his post stim result to 7, getting very close to the desired 1.45 - 5.5 range. Due to the expenses from the medication and testing, UTI treatments and necessity to resolve his Cushing's Myopathy as quick as possible I've not been able to begin treatment with the 9-cis retinoic acid. Besides, I'd rather wait until his Cushing's Myopathy resolves and think continuing the Vetoryl is the quickest route at this point. He is able to stand and walk/hop better now that he's been on the Vetoryl for 9-weeks already. He needs to continue to improve and can get to a point where I think he can withstand the switch to 9-cis Retinoic Acid. He'll need further stim testing for this as well. Please let me know if you will be using the 9-cis Retinoic Acid.
Best Wishes For You and Your Dog,
Mitchell
What is the contact number for Dr Castillo?
Sorry, I do not have a direct phone number to Dr. Castillo. Here is the University of Buenos Aires Veterinary School number:
Tel./fax: 011 54 11 4524 8496.
Mitchell, thanks for your help.
You're welcome, please let me know how it goes with Dr. Castillo and if you begin to treat with the 9-cis Retinoic acid.
Best Wishes to You and Griffey,
Mitchell
Tried calling the number you gave but they didn't speak English and hung up on me. Do you speak Spanish?
Mitchell, was the pharmacy you posted recommended by Dr Castillo?
Yes, the pharmacy posted is the one suggested by Dr. Castillo. I do not speak spanish and used online translation software through Microsoft to corrospond with Dr. Castillo through email. You will need a prescription from your US Vet to purchase from the pharmacy. Ask to speak with Linda, she speaks english.
I couldn't get the pharmacy number to work. I must be doing something wrong.
This is how I dial the number:
Dial 011 54 1148114648
Alternate number:
Dial 011 54 1148114325
Okay thanks. I will try again tomorrow.
Mitchell,
I couldn't get the pharmacy email to work. I'm very interested in trying this if I can get hold of someone there.
Hello,
Datsun is a 9-year old Cairn Terrier being treated with Trilostane which was started late October 2016. He is being given Trilostane 2X daily, 12 hrs apart. He weighs 6.5kg and is being given 15mg in the morning and 15mg in the evening. We began in October with 5mg 2X. Very carefully his daily total has been incrementally increased by 5mg approximately every 14-days and has gotten a good result from the Trilostane. His most recent Pre STIM number most recently was 6.3 and Post STIM was 6.1 (his first post STIM was at 70!). We are now going to wait 25-days for a STIM recheck along with Blood Chemistry to check ALT levels etc.
My question is, has anyone found anything that can be done to help Datsun with his Cushing's Myopathy in the meanwhile.
I'm very concerned especially since following the administration of his Trilostane at about 1 1/2 hours he becomes very wobbly, almost unable to stand up. This condition is temporary lasting about 1 hour, but consistently happens with each time he's given the Trilostane. This began occuring at about the point in time he was administered 10mg 2X.
Thanks to Everyone at K9Cushings,
Mitchell
Hello Mitchell, and welcome back to you and Datsun. You'll see that I've merged your newest post into your original thread about Datsun. We like to consolidate all replies in a single thread so that a dog's history and discussion and can be easily found and summarized in one place.
May I ask how recently this last ACTH test was performed? Also, what was the timing relative to the trilostane dosing on the day of the test? The reason why I ask is because trilostane is reported to begin exercising its maximum effect around 1.5 hours after dosing -- exactly the timeframe in which you are observing the ill effects in Datsun. This would normally lead one to believe that his wobbliness may be an adverse effect from his cortisol dipping too low at that time, although a post-ACTH result of 6.1 would make that a bit puzzling (depending upon the testing protocol you are following).
Dechra recommends that testing be performed 4-6 hours after trilostane is given along with a full meal. Is that the protocol you have been following? Let's start with that question, and then go from there.
Marianne
Hi Marianne,
Datsun's most recent STIM was performed on Wednesday, February 8th. The STIM was performed at 4 1/2 hours after his morning dosage as were his 6 other STIM's since October 2016 all tests were performed at the same Veterinary Hospital, UF in Gainesville, FL.
Thanks So Much For the Quick Reply!
Mitchell
And yes both dosages are given with food.
Did Datsun eat breakfast alongside his trilostane on the day of the test (as well as on other days, as well)? If so, the results should indeed be accurate. However, one possibility I might suggest is talking with UF about perhaps moving up the timing of his ACTH the next time around. Dechra acknowledges that there is a fair degree of variability in the manner that individual dogs metabolize trilostane, and perhaps Datsun's cortisol is "bottoming out" and then rebounding more quickly than is the norm. It might be interesting to see where his cortisol level is at that 1.5 hour timeframe, especially if his myopathy is otherwise much improved since starting treatment.
Have you reported the wobbliness to the vets at UF? If so, do they have any thoughts about it?
Marianne
Whoops, we were posting at the same time! Thanks for the info about the food.
I did mention to UF about the wobbliness following his dosages, the Doctor feels that it may or should (not sure or definite) resolve once he is "stimming" in the recommended range. Due in part to his wobbliness, the Doctor wants to see if his upcoming blood chemistry will be a better indication of Datsun's symptoms resolving rather than solely relying on the STIM since he is so close to optimum treatment reference range. I'm concerned about raising dosage. Testing him at 1 1/2 hours would be very interesting to see the results. I will ask him about the variability in the rate at which the Trilostane effects Datsun. Interestingly, I did ask the Doctor about 3X dosing early on when the treatment was begun. The Doctor was not in favor of this due to concerns over being able to consistently measure stims. I also asked if obtaining the treatment range was the main measure, than why not single dose until treatment range was obtained.
Anyway, once his blood chemistry shows improvement the Doctor thinks the Myopathy should improve. I'm wondering if anyone has noted Myopathy improvement once their dog is within treatment range and how long before improvement was noticeable? And is there anything else that I can do for Datsun to increase the chances of improvement of the Myopathy. I do massage his hind leg quads to the point where he will relax his leg muscles enough to allow the knee to bend and relieve the stiffness temporarily.
Perhaps water therapy could be tried?
Datsun's blood chemistry has significantly improved, in September 2016, before Trilostane Therapy,
His numbers:
ALP 617 5 - 160 U/L HIGH
ALT 202 18 - 121 U/L HIGH
AST 77 16 - 55 U/L HIGH
CREATINE KINASE 640 10 - 200 U/L HIGH
GGT 63 1 0 - 13 U/L HIGH
BUN 33 9 - 31 mg/dL
Trilostane Began October 31st, 2016.
After Trilostane Therapy, March 9th, 2017
ALK PHOS 127 U/L H 8 - 114
ALT P-5-P 80 U/L H 18 - 64
AST P-5-P 72 U/L H 15 - 52
T BILIRUBI <0.1 mg/dL 0.1 - 0.4
CREATININE 0.7 mg/dL 0.6 - 1.7
BUN 27 mg/dL H 8 - 25
Unfortunately his Cushing's Myopathy has gotten worse, he no longer walks. My Vet thinks this may be permanent. Very little information available, does anyone one know someone who is an expert with Cushing's Myopathy?
It sounds as though Datsun may be in the very miniscule number of dogs with cushing's who have a condition known as pseudomyotonia. Unlike the usual muscle wasting that is commonly seen in cushing's pseudomyotonia can be quite devastating. If this is what you are dealing with, your vet is correct that it does not always improve with treatment. The specialist you would need to consult for this rare symptom would be a board certified veterinary neurologist who would run a number of test to determine if Datsun does have pseudomyotonia. Has your vet ruled out other possibilities such as degenerative myelopathy, IVDD, etc.?
Hi Mitchell,
In my ongoing Cushing's research I stumbled on these two articles, one written by Dr. Mark Peterson, an endocrinologist.
http://www.vmsg.com/wp-content/uploa...domyotonia.pdf
http://www.endocrinevet.info/2011/02...-cushings.html
Another thought is to email Dr. Bruyette in CA and ask if he could recommend anyone in your area, including your IMS, with whom he could consult to treat Datsun. I don't have his email but I am certain others here do.
Also, if you search this forum for myotonia, there are or were other folks whose pups were diagnosed. I'm really sorry as it seemed that Datsun was doing well before this condition emerged. This disease truly sucks and I'm thinking of you and Datsun.
Thank you for the information. The article written by Dr. Peterson was very interesting, but apparently there is no known treatment. Datsun has a follow-up appointment tomorrow with the neurologist at UF. He has been on a steady decline with regard to his mobility over the past 8 months. His myopathy symptoms worsened last week. In August, Datsun was able to jump up onto the couch or bed and would occasionally run after a squirrel. It's been such a short time that his condition has worsened to the point where now he will not walk. I still wonder if the Trilostane treatment which began the end of October is involved. I still wonder if I should change course and treat with the Retinoic Acid... I am going to try and decide if we should temporarily stop the Trilostane to see if it will make a difference. Possible revert to micromanaging each of Datsun's Cushing's symptoms. After his neurological exam tomorrow I'll relate any new information...