Trilostane just not working :(

[Biochemistry]

Hey everyone. This is my first thread on this site after about a month of looking around - I hope I can be much help to others as well. Anyway, my 13 year old Shih Tzu, Romie, has been diagnosed with Cushings on Feb. 9th. I took him to the vet thinking it might be malignant skin cancer (because a small tumor-like growth on his front paw kept getting irritated) but the vet had recommended ACTH stimulation tests because of some of the symptoms he was showing. As it turns out, he did have abnormal ACTH levels and we started him on the standard course of Trilostane (3mg). But in about four days, he started to have bloody, and sometimes jelly-like diarrhea, threw up and couldn't keep his head up. This happened very suddenly at night and it made me stay up all night (until the vet opened at 9 am) reading journals about Trilostane, etc.
When we got to the vet, the vet told me that these symptoms were very rare (the journals that I've read also confirmed this; saying the side effects were shown in only 3-5 percent of cases) and she recommended him to take another hormone test along with an electrolyte imbalance test which came out normal.
Well, she sent me home with some medicine which could help with his diarrhea and told me to just continue with the treatment. But I just couldn't give the regular 3 mg to him so I halfed the medicine. This had better results. After the trial period, I took him to the vet again, but this time, two days before the promised date, I went back to the 3 mg regimen. He seemed fine and there weren't any problems with his stool. The results of his hormone tests were thus: his cortisol levels did drop but it wasn't at a normal level and the vet recommended to raise the dose to 5 mg. I agreed and brought him a month's worth of medicine.
BUT again, he had bloody diarrhea even before I restarted him on the 5 mg dose. When I called the vet, she recommended that I reduce the trilostane as I did before. So, I divided the 5 mg dose given from the vet into three. In about 3 weeks or so, he started to have diarrhea again - even on the dose that amounts to 1.6-1.7 mg per day.
Does this mean that Trilostane is just not for Romie? I'm very worried because as I am aware that this is the safest (most non-invasive) treatment to Cushing's that there is. If we can't use it, wouldn't it be very harmful to Romie? This is just so frustrating..
Well, I know it was a super long post and I appreciate all of you who read it. He has never really been sick (except for a few skin conditions) and my heart just breaks every time his stomach even growls signaling diarrhea.
If you guys have any inputs regarding Romie, please share. I would really be grateful.
BTW he's also taking Samylin because his ALT levels were very high (does this have anything to do with it?)
Thanks again everyone!

[goldengirl88]

Welcome to the forum. Sorry your baby is having troubles. First I just want to say I am really upset with your vet. You never give trilostane to a sick dog, especially
with diarrhea, and bloody at that. We need to start at the beginning. What tests were performed to diagnose Cushing's? Has you dog had any other illnesses he was or is being treated for? Have you had him tested for diabetes or thyroid disease? They share similar symptoms. What are the symptoms your dog presented with? How old and how much does he weigh? Are you dividing this trilostane yourself? If these are capsules and you are opening them, it is dangerous to you and your dog. The diarrhea your dog experienced is one of the signs their cortisol is going low. Thank goodness they checked the electrolytes. I would not give this dog anymore trilostane until you get all your testing together, and post the abnormal numbers for us, and until the dog is well, and the dose is right for the weight, and you are not splitting capsules yourself. These are powerful drugs, there is a correct protocol that must be followed, and I am not sure that even happened in this case. Your vet has let you and your dog down telling you to continue to medicate a sick dog. Please no more trilostane until you have gotten up to speed on things. Blessings
Patti

[Harley PoMMom]

Hi and welcome to you and Romie! I am so glad you came out of the shadows and started a thread about your sweet boy. I have replied (in blue) within the body of your post.



Anyway, my 13 year old Shih Tzu, Romie, has been diagnosed with Cushings on Feb. 9th.

Could you get copies of all tests that were done on Romie and post those results here with the reference ranges and units of measurement...i.e...ALT 150 U/L (5-50)...Thanks! We are also very interested in the results of any diagnostic and monitoring tests for Cushing's



I took him to the vet thinking it might be malignant skin cancer (because a small tumor-like growth on his front paw kept getting irritated) but the vet had recommended ACTH stimulation tests because of some of the symptoms he was showing. As it turns out, he did have abnormal ACTH levels and we started him on the standard course of Trilostane (3mg).

Could you tell us what symptoms Romie was displaying that led you or the vet to test for Cushing's? If you could post the results of that ACTH test that would be great. Cushing's is one of the most difficult diseases to get a confirmed diagnosis for because there isn't one test that is 100% accurate at diagnosing it. A Cushing's savvy vet will perform multiple tests to validate a Cushing's diagnosis.



But in about four days, he started to have bloody, and sometimes jelly-like diarrhea, threw up and couldn't keep his head up. This happened very suddenly at night and it made me stay up all night (until the vet opened at 9 am) reading journals about Trilostane, etc.
When we got to the vet, the vet told me that these symptoms were very rare (the journals that I've read also confirmed this; saying the side effects were shown in only 3-5 percent of cases) and she recommended him to take another hormone test along with an electrolyte imbalance test which came out normal.

Adverse symptoms can happen when a dog is started out at a dose that is too high, we have seen many cases of that here on the forum so, unlike what your vet says, it is common


Well, she sent me home with some medicine which could help with his diarrhea and told me to just continue with the treatment. But I just couldn't give the regular 3 mg to him so I halfed the medicine.

You absolutely did the right thing when you withheld the Trilostane. It is important to never give Trilostane to a dog that is presenting symptoms of being unwell, which could be diarrhea, vomiting or the dog just not acting them self. It's a huge red flag to me that Romie's vet told you to continue with the Trilostane while he was ill.



He seemed fine and there weren't any problems with his stool. The results of his hormone tests were thus: his cortisol levels did drop but it wasn't at a normal level and the vet recommended to raise the dose to 5 mg. I agreed and brought him a month's worth of medicine.

Again, can you please post those ACTH stim results? Another thing, is Romie getting his Trilostane with food so it is properly absorbed? And are his monitoring ACTH stim tests being done 4-6 hours after his dose of Trilostane?



BUT again, he had bloody diarrhea even before I restarted him on the 5 mg dose. When I called the vet, she recommended that I reduce the trilostane as I did before. So, I divided the 5 mg dose given from the vet into three. In about 3 weeks or so, he started to have diarrhea again - even on the dose that amounts to 1.6-1.7 mg per day.

Is Romie's Trilostane being compounded? Is the Trilostane a liquid form or capsule? Trilostane capsules should never be split open and handled. Dechra, the makers of Vetoryl in which Trilostane is the active ingedient, state in their product insert to never split open the capsule.



Does this mean that Trilostane is just not for Romie? I'm very worried because as I am aware that this is the safest (most non-evasive) treatment to Cushing's that there is. If we can't use it, wouldn't it be very harmful to Romie? This is just so frustrating..

The two most rx'd drugs for Cushing's are Trilostane/Vetoryl and Mitotane/Lysodren. One is no safer than the other, they both can have adverse effects and they do work differently. Lysodtren has been around for centuries and has been used for the treatment for canine Cushing's for decades. Trilostane was only approved in the U.S. for the treatment for Cushing's in 2008.



BTW he's also taking Samylin because his ALT levels were very high (does this have anything to do with it?)

We rarely see high elevations in the ALT, on the other hand the ALP is often very high in a dog with Cushing's.

Please knowwe will help in any way we can so do not hesitate to ask all the questions you want. ;)

Hugs, Lori

[Renee]

Popping in to welcome you, second Patti & Lori -- and to express frustration and disappointment in your vet.

It boggles my mind how many vets are so cavalier about cushings medicines, and how woefully uneducated they are. It scares me and makes me very angry. I believe your vet is putting your dogs life in danger with his poor choices.

It is very possible Romie has something else going on, instead of cushings. I urge you to stop the medicine and start back at the beginning, so you can make sure to get it right.

[molly muffin]

Hello and welcome to the forum.

If there is anything else going on with Romie, then the ACTH test will register as high. That doesn't mean he has cushings. It means, something is going on. Usually a dog is taken in to test for cushings, because they have cushing symptoms, drinking tons of water, having accidents in the house, eating ravenously, pot belly and hair thinning, etc. The water intake and eating are usually the most prominent first noticed symptoms. In addition there could be a weakness in rear legs. You took Romie in to check for a possible tumor on paw correct?

The other reason that Romie might have a bad reaction and the reason I mention the above statement is if he doesn't have cushings at all. In which case, giving cushing meds will be bad and cause what you are seeing. It doesn't seem that he is being over dosed on 1.6mg a day, but really need those ACTH numbers.

I am usually disgusted at vets who go directly to a cushings diagnosis and don't do adequate testing or check symptoms before prescribing medication. It can have very bad results and they should know better. grrrrrrr

Can you tell us more about Romie? Did he have those cushing symptoms? Whatever you do, with having bloody diarrhea, do Not give cushing medication. It's making a bad problem worse. With cushing nothing happens fast and making sure you have the right diagnosis is paramount to Romie's health.

You can ask to see an IMS, but it doesn't sound like your vet knows much about cushings or the medications used to treat. Sorry, if that sounds harsh, but thinking of you and Romie here, not the vet.

Sharlene and Molly Muffin

[goldengirl88]

Just checking in to see how Romie is today? Hope things are going well. Blessings
Patti

[Biochemistry]

Thanks everyone, for all your concerned replies. I have never seen any site in my life who are as considerate as you guys. Sorry for the late reply, I had to take Romie to the vet and had a very busy couple of days.
Well I wanted to give you guys a more exact look at Romie. So I took a picture of Romie's blood work, hormone panels etc. that I got from the vet couple of days ago.
But before that, for the symptoms Romie was showing.
He didn't show any visible symptoms (i.e., pot belly, drinking too much water, lethargy.. etc) but he did have loss of hair especially visible on his tail and his scans of his adrenal glans were enlarged.
But on Friday, when we went to the vet (we had changed our vet for some reasons though in the same hospital), the new vet said he also suspected thyroid hormone problems (he thought this because of the loss of tail fur and vacant expression that Romie has). So we conducted something called, "fresh T4 test" (if memory serves) but it came out as inconclusive (the results were 0.9, not sure about units). In order to be sure, we need to send his tests to the United States for a thyroid stimulating hormone test and the free T4 test. With the results that Romie received, the vet thought it wasn't bad enough (?) to send his results to the States (it's probably super expensive; BTW, I currently live in South Korea).
So the conclusion that we arrived on Friday is this; to continue with Trilostane for a week more on a much lower dosage along with some medicine to contain his diarrhea. (I'm not happy with this though.. I haven't given him the medicine yet, not until his diarrhea symptoms are totally gone)

Here are the results so far

http://lh4.googleusercontent.com/-LLMIGsU0kLw/UyT0xfDJnPI/AAAAAAAAAAk/pvo5q9V_27k/w346-h461/20140316_091757.jpg

So, what do you guys think?

[molly muffin]

I tried to see Romie's results on the jpg, but just couldn't make anything out clear enough.
Can you type in the abnormal results here?
For instance
02/15/2014
ALKP 1002ug range 50 - 110ug

only the results that are high/low, anything within normal range you can leave off.
I even downloaded and tried to enlarge, but then it's was just a blur completely, so couldn't make out numbers, etc.

If the thyroid is just a tad low, then that could be consistent with cushings, but I don't like that Romie had the bloody diarrhea right off starting the medication. That is not a good sign and I stated before, either it isn't cushings, or the dose is too much for him and has to be lowered.
I definitely wouldn't give while he is having any diarrhea at all. Are you giving an probiotic or something for his gastro? It could also be a bought of colitis, or a gastrointestinal bacteria causing it, but you don't want to give the meds for cushings while that is going on.

Sharlene and Molly muffin

[Harley PoMMom]

I couldn't make out Romie's blood panel results either and that was with enlarging and a magnifying glass!! :o It would be of a big help if you would post those results as Sharlene has mentioned...Thanks!

Since Romie does not have any of the common clinical Cushing's symptoms, if this were me, I would not give him any Trilostane. Trilostane is a strong drug and should not be administered to a dog that does not have a confirmed diagnosis of Cushing's.

Although I am not a vet, if Romie was my dog I would start the thyroid medication at a low dose and see if an improvement is noticed.

Please do keep us updated. ;)

Hugs, Lori

[goldengirl88]

Just some thoughts from me. my Tipper had a thyroid that was low. I could see the clinical symptoms and it was not off a lot. These symptoms could be from the thyroid and maybe you could talk the vet into using a low dose liken half the normal dose?? My dog takes half the normal dose and is doing so much better. I too would not be using the trilostane without a confirmed diagnosis. Bloody diarrhea is a signal to stop. You could put your dogs life in jeopardy continuing
with trilostane if your dog does not have Cushing's, or if the dosage is too high. Blessings
Patti

[Biochemistry]

Hey you guys. Sorry for the image. There are just so many tests that he did so I thought that rather than writing it down, it would be better for me to find a way to show you the copy of the blood work.
I think this will work now.

http://i.imgur.com/CwuB86q.jpg

The first column is the test name, the second indicating what the normal range should be, the third, fourth, fifth, sixth are the test results that Romie actually took on the respective dates that are indicated on the sheet.

Again, thanks to all of you for caring so much about Romie. We really, really appreciate it.

[Biochemistry]

To Patti:
Yeah, my vet did think that also.. The symptoms that he pointed out indicating thyroid problems were loss of tail fur, slight irregularities in motor functions (he thought it might be neurological symptoms corresponding with thyroid hormone imbalance) and vacant expressions. But Romie always had a somewhat of a quiet demeanor since he was a little baby so I'm thinking maybe the last one isn't a symptom. The motor functions part was in regards to Romie tripping easily. I also thought this was due to the loss of muscle in his hind legs due to Cushings. And before his Cushings diagnosis, I thought it was just due to slippery floors (he didn't trip often on concrete floors). I don't know which steps to take :/

[goldengirl88]

If this were my dog I would start with the thyroid. I am suspect of that and it can make a dog miserable, as it did my Tipper. All you need is a low half dose according to your dogs weight. My dog weighs less than 18 lbs and is on .05 Soloxine. It has made a huge difference in her. If his thyroid is not working how it should, he could have hormones out of balance, that can really make you feel bad, as I have it and know. Some of the tests for Cushing's can be skewed if there is something else going on. So I would go with what you do know for a fact, and that is the thyroid is slow. You could get a full thyroid panel done at Michigan State, or by Dr. Jean Dodds. You would have to fast the dog and get a blood draw, and have the vet send it away for testing. That would give you a full picture of what is going on. I would not give my dog any more trilostane period, until this is figured out. Then after that I would investigate the possibility of Cushing's by proper testing if your dog is showing clinical signs of the disease.You will need to give thyroid meds a while to work to get the thyroid up to par. It is a month now for my dog and hers are normal now. It could have serious consequences if you continue to use trilostane and your dog does not have Cushing's. Many other diseases have similar symptoms that is why Cushing's is so hard to diagnose.Just stop and think what you are doing for a minute, and I am sure you will want to do the safest thing for your dog. Whenever I do anything with Tipper her safety is always paramount to anything else. Talk to your vet, he already has suspicions of thyroid problems from what he said, ask him to send the tests away. Blessings
Patti

[Biochemistry]

To Patti:
We will talk to our vet about further thyroid tests.
Thanks so much for your concern. We were lost; now we have some ground to start on. THANKS!!

[goldengirl88]

Hope everything is going OK today. Let us know what else you find out about the thyroid. Blessings
Patti

[Biochemistry]

Hi everyone, I just wanted to update you on the results I received yesterday from the vet. Like what you guys have suggested, I did send for Romie's thyroid hormone tests to the United States (which was not cheap.. I wish I could move back to the States :eek:).

Here are the results:
Free T4 = 0.874 mg/dL
Total T4 = 0.887 mg/dL
TSH = 0.244 mg/mL

They were all within normal range. Now the vet believes firmly that it is Cushing's. What do you all think?
I have taken Romie off of Trilostane for some time, but is it time to start again? What if the diarrhea symptoms start again? :(:(

[goldengirl88]

Would you be able to post the normal values given by the lab on these tests? My dogs was said to be normal too, but when I sent her information to Dr. Jean Dodds she said it was low. She is a world renowned specialist with this. Blessings
Patti