Help - my dog isn't responding to Veroryl!

[gaby]

Hi everyone! My dog was recently diagnosed with Cushing's and I am getting really frustrating because despite my best efforts to get him well, he is not responding to Vetoryl. SORRY FOR THE LENGTHY POST! I am trying to put as much details as possible (not knowing if it's important). Also, I love our vet; he has been so kind, helpful, and supportive in all of this. He goes above and beyond to help with our situation.

My dog is a 6.5 pounds chihuahua named Alfonso.

Here's our story:
We fostered Alfonso in March 2020 from the SPCA. They didn't know his age because someone found him in the street, but they estimated him to be 9 years old. He needed to be in foster care because he had a problem with his liver. I don't know the exact problem, but his liver enzymes (I think that's the term) were way too high. We put him on medication. He got all but 5 teeths removed because they were really in a bad condition. When the operation was over, they redid some tests and apparently everything was fine with his liver. We did notice he had 1 episode of epilepsy (we didn't know it was that at the time) but the SPCA told us not to worry if it didn't happen again. It did not, and we finally adopted him in May 2020. From May 2020 to December 2021, he had 1 episode of epilepsy every month, around the same time every month. There were no triggers, and after running a bunch of tests at the vet, he said there were no tumors or illness causing this. We just had to monitor him, and we would put him on medication if he had more than 1 seizure per month. He finally stopped having seizures in December 2021.

In December 2021, we noticed his lymph nodes in his neck were really big and hard (we were on vacation out of the country and waited 2 weeks before going to the vet). We went to the vet end of January 2022 to make an appointment to remove some of the teeth he had left (in bad shape), and the vet suggested we run tests before doing the operation. It was not cancerous and nothing to "worry" about, but there was definitely something going on with our dog's health. We decided to move forward and remove 2 other teeth because we were worried this was causing infection and that was the reason behind his lymph nodes being very big. The morning we left him at the vet, in April 2022, the vet did blood tests to make sure he was in a good health to go under anesthesia. He called us and said his liver enzymes were quite high. Not alarming, but higher than the norm. The surgery was riskier than anticipated. We decided to still move forward with the surgery, and everything went well. Our vet then asked us if our dog was drinking more water than normal, because he suspected a Cushing's disease. It is true that our dog had been drinking more than usual for the past 1-2 weeks, but we didn't really think it was anything because he was doing great (we noticed because he usually rarely drank any water at all). We did the Cushing's tests (the one where he stays the whole day at the vet) and it was negative. He also tested for other things such as diabetes, which were all negative. He said to monitor his condition and attributed the high liver enzymes to an infection from his bad teeth. Fast forward to June 2022, he was still drinking lots of water and peeing a lot. We did an ultrasound in July 2022 to see if he had any tumors and it was confirmed that there was a small tumor in the pituitary gland and that it was most probably Cushing's disease (at 95%). The vet suggested we re-do the Cushing's test to re-confirm and it was indeed positive (his liver enzymes more than doubled since the first test).

First week of August, we started him on 5 mg of Vetoryl: 1/2 a capsule in the morning, and 1/2 at night. Always given with a meal, but opened capsules (the vet said it was fine, since we don't have smaller sizes of Vetoryl here). We did not see any improvements after 2 weeks. We increased it to 1/2 a capsule in the morning and 1 at night (7.5 mg total). We did not see any improvements after 2 weeks. We then did 1 capsule in the morning, and 1 at night (10 mg total). Still no improvements... We are now doing 1.5 capsules in the morning and 1.5 at night (total of 15 mg). The vet says that's really high for a dog his weight and doesn't understand why he is not seeing improvements. He even now seeks help from a specialist in small-animal diseases (Dr. Lisa Carioto) but so far we haven't been able to determine what's wrong. He thinks we might need to increase his dose again...
**We tested his urine multiple times, and he still doesn't have diabetes, or any infections.**

His symptoms:
1- His hair doesn't grow back if it's cut
2- Sometimes he has a crust on the top of his nose, as well as on his paw pads (a lot of cracks and yellow crusts).
3- He can't jump on the bed / couch or walk up stairs anymore. When he runs and is super excited, his will faceplant on the ground. His back legs sometimes shake for no reason. (we started doing hydrotherapy at home in our bathtub to strengthen his legs and giving him CB2 oil)
4- Excessive thirst (he drinks 45 seconds each time, multiple times a day).
5- Excessive hunger (always looking for food, can bark indefinitely until we give him food).
6- Excessive urination (he was peeing in bed multiple times a night, so the vet suggested we remove his water bowl before going to work, and he stopped).
7- A couple weeks ago, his tongue was bright red in some areas, as if he had an allergic reaction (not sure if it's related). It went away after 4 days.
8- He licks his paws very often. At night, he wakes up and licks his paws for a long time. If we try to distract him, he will start licking anything he can find (the bed sheet, our hand, his cotton blanket, etc). He seems to be in a trance... (the vet said he might have acid reflux, we gave him medication and it didn't help).
9- He has a bit of a pot belly (we used to give him lots of treats and stopped - seems better now). He hasn't gained weight since being diagnosed with Cushing's.
10- Flaky skin on his tummy (that's better than it was before).

Apart from all of this, our dog is doing great. He has a lot of energy for an 11 year old, he loves going on walks (although he is not as much of a fast walker as he was 2 years ago, but maybe that's just his age!), he eats very well (we make him homemade food, and the vet says that's fine), and he is just a really sweet dog in general! :) He doesn't look sick.

My questions: am I missing something? Are there tests we should do that we didn't do? Any other treatments to consider apart from Vetoryl?
I am not questioning my vet's decisions or competence. I really love him. I am just trying to seek advice from people that might have been in the same situation and had success stories!

Thank you so much!
- Gaby

[labblab]

Dear Gaby,

Welcome to you and sweet Alfonso! Your membership has now been officially approved, so if you receive an email request for additional registration confirmation, you can just disregard it.

Thanks so much for all the info you’ve supplied. Every bit of it is helpful to us. I surely understand why you all are puzzled by the situation, and I’ll come back later on after I’ve had a chance to think things over in more detail. But I wanted to at least have the chance this morning to welcome you both to our family!

Again, we’re really glad you’ve joined us,
Marianne

[gaby]

Thank you so much Marianne!

[labblab]

OK, I’m back again, and you’re very welcome if I’m able to provide any help to you!

First of all, how huge-hearted of your family to adopt little Alfonso, especially since some health issues were possible for him. And you’ve done a great job of advocating for him ever since, so kudos to you for sure :-).

Turning to his treatment history, I definitely understand why you’re puzzled. I’m afraid I don’t have any definite answers, but here’s a few thoughts and observations to throw out. First, you mention that an ultrasound confirmed a small pituitary tumor, and that raises a couple of questions for me. In conjunction with Cushing’s diagnostics, abdominal ultrasounds are commonly performed in order to visualize the adrenal glands in search of any tumors there, and also to assess the health of other internal organs such as the liver, kidneys, spleen and gallbladder. However, since the pituitary gland is in the head, it cannot be viewed unless you do an MRI or a CT scan of the head. Either of those tests are typically quite expensive and not commonly done. So I’m hoping you can clarify whether a scan of Alfonso’s head was actually done, or whether it’s just assumed that he must have a pituitary tumor that’s causing Cushing’s. If no masses are seen on his adrenal glands during an ultrasound, a pituitary tumor is assumed by default in a dog who exhibits many outward symptoms that are consistent with Cushing’s. And I can’t argue with the fact that Alfonso does indeed exhibit many outward symptoms that are consistent with Cushing’s!

Secondly, has Alfonso’s cortisol level been monitored since starting the Vetoryl? Monitoring is done via blood testing. In the U.S., the favored monitoring test is the ACTH stimulation test. In the U.K. and many parts of Europe, taking a baseline cortisol reading one hour prior to the next Vetoryl capsule is now the favored alternative. It’s recommended that monitoring in either form be done 10-14 days after starting treatment and also after any dosing changes. At a minimum, the testing should be done no later than 30 days after starting treatment. You don’t mention any monitoring test results for Alfonso, and this raises a big question mark, both in terms of safety and also in terms of judging how much his medication is affecting his adrenal function. Cortisol levels can continue to drop over time, even when a dose is unchanged. For this reason, it’s important to hold off on increases until you have an accurate assessment of what the current dose is doing.

The thing is, you can’t rely on outward symptoms alone in terms of judging how much any given dose may be lowering cortisol levels. Alfonso has had three dosing increases now in a short amount of time, and it would be very important to know the actual effect on his cortisol before increasing further. His current dose does sound big, but the research literature states that a range of 1-3 mg. per pound has been associated with effective control in past studies. So although his dose is big, he’s not yet at that upper border. But as I say, without first testing his cortisol, I don’t think it would be safe to increase his dose any further at this stage.

I do have one last concern. We’ve had other vets, too, who have OK’d opening the Vetoryl capsules. But Dechra, the maker of Vetoryl, really frowns on this. They don’t want humans to be risking exposure to the chemical in the powder, and they also tell us that there’s no way of knowing whether the medication is being metabolized effectively when given outside the capsules. The capsules are designed to be swallowed whole with the release of the effective chemical, trilostane, directly into the stomach and upper GI tract. All the dosing research was done with the medication being released and metabolized in that manner. If the dog is instead receiving the raw chemical in its mouth, it may instead be metabolized differently and this could affect the dosing.

You say you did give him one whole capsule both in the morning and night for a while with no improvement. But going forward, I’d encourage you to stick with whole capsules at all times, even if it means an uneven dose — for instance, 10 mg. in the morning and 5 mg. at night. Dechra says that uneven doses are OK if necessary; just give the larger dose in the morning.

OK, I’ll stop for now! But I’ll be anxious to hear back about my two questions. First, to clarify about any actual imaging of Alfonso’s pituitary gland. And secondly, have monitoring cortisol tests been done. And if so, what were the actual numerical results?

Marianne

[gaby]

Thank you so much for getting back to me! And thanks for your kind words :) It was important for me to adopt an older dog because they all deserve a loving home, regardless of their age or medical history!

1- You are right! Sorry, I was confused for a second. We did the ultrasound and there were no tumors in his adrenal glands so he assumed it was the pituitary tumor. He said we could do a CT scan to confirm the pituitary tumor, but considering it's more than $1000 and it would only be for our personal knowledge (wouldn't change anything in the treatment), it would be quite useless.
2- No we have not monitored his cortisol level. I believe he said we would monitor it once his symptoms were "under control". He mentioned that if he was in "overdose" he would have apparent symptoms such as lethargy, loss of appetite, etc.
3- The vet had never mentioned it was dangerous for our health to open the capsules, but brought it up during our last phone call (oups!). He then really recommended us to wear a mask and gloves when opening the capsules. He also suggested we buy empty capsules and fill them up with 1/2 of a pill to create 1/2 doses. We bought the capsules this morning.

I just emailed our vet and asked that we give him 2 capsules in the morning and 1 at night + asked for a ACTH stimulation test. We only did one before starting his treatment on Vetoryl.

[labblab]

Thanks so much for this additional info, and yes, you really need to press for the monitoring test. Blood testing is important because overdosing can cause cortisol levels to start dropping too low before overt symptoms are seen. You want to do everything you can to reverse the overdosing *before* a dog actually becomes ill. Not only does trilostane lower cortisol, but it can also suppress the production of aldosterone, which is the adrenal hormone that controls the balance of sodium and potassium in the body. So if cortisol is dropping too low, other blood chemistries can be destabilized as well. This results in an “Addisonian” condition which can become genuinely life-threatening. Here’s a list of overt symptoms of overdosing:


Pet owners must be vigilant in watching for signs that cortisol is too low. Symptoms of low cortisol include but are not limited to vomiting, diarrhea, lethargy, poor/reduced appetite, weakness, collapse and tremoring. Should you observe one or more of these symptoms, STOP treatment and contact your veterinarian immediately. In the event your vet is closed, contact or go to your local emergency facility. Withholding Vetoryl or trilostane, whether a few days or several, will not be detrimental to your dog.

So as I say, to the extent possible, you want to avoid cortisol to be lowered to the point that your dog becomes visibly ill. A dog experiencing an Addisonian crisis may require hospitalization and IV support. Also, some dogs may end up with permanent oversuppression of their adrenal glands due to overdosing, and require lifelong steroid supplementation. Through the blood testing, you will know to make dosage adjustments — both up and down — as is appropriate.

To better prepare you to discuss the actual procedures involved in the monitoring testing with your vet, please read through this link:

https://www.k9cushings.com/forum/showthread.php?8925-GENERAL-GUIDELINES-for-Vetoryl-(trilostane)-Dosing-amp-Monitoring-with-ACTH-Stimulation

[labblab]

And just to add a quick P.S... From the sound of it, Alfonso was given an LDDS (Low Dose Dexamethasone Suppression) test when he was first being diagnosed -- that's the 8-hour test that takes all day. It is only used for diagnostic purposes, and cannot be used for monitoring. He may have been given the shorter ACTH stimulation test in follow-up at the time of the second test. But I just want to stress that the only two monitoring blood tests are the ones discussed in that link that I gave you above: the ACTH, or the Pre-Vetoryl baseline cortisol sample.