Trembling - please help me interpret

[WriterAshley]

Hello, all! So happy to have found this community! I have a 29(ish) pound Cocker Spaniel who is 13. He developed an infected toenail that resulted in amputation, and during his pre-op bloodwork, elevated enzyme levels raised a red flag for Cushing’s. He underwent the all-day suppression test which confirmed Cushing’s but his level was only slightly raised, at 1.9. Clinical signs included excessive water drinking, excessive thirst, and at times breathing in an exaggerated way (though not so dramatic as full-on panting). He also seemed more fatigued to me, but he was still up for walks, and I suspect he developed the infection bc of the Cushing’s.

We started Vetoeyl at 30 mg once per day about a month ago. He developed lethargy and loss interest in food after a few days. The vet discontinued use of the medicine and have him a low dose of prednisone for a week, which caused lots of the heavy and fast breathing from before. We then started him on the 10 mg dose, once daily.

On the whole this has worked great. He’s acting like his old self again, is still interested in food, and is resting so much better.

Problem is, about a week in, he started having minor tremors. They seem to be happening around 10 hours following his morning Vetoryl. They last around an hour, and then he’s fine again. Today he even wanted me to hold him during the tremors which is unlike him.

My vet told me to watch it and see if it worsens. He’s not due for bloodwork for couple weeks on this new dose, but I wonder if I should ask for it sooner?

Can someone help me navigate the difference between tremors as a serious sign of addison’s developing, versus tremors as a benign side effect? From what I’ve read, the fact it’s happening 10 hours post-medication versus right after medication is probably a good thing. Are there any other signs or connections I can look for? Could it be he’s adjusting to the medicine? Should I ask the vet about switching to 5 mg twice per day?

Thanks so much in advance for your help!

[labblab]

Hello, and welcome to you and your sweet boy! I’m afraid it will be later today before I’ll be able to return and write a lengthier reply. But I wanted to at least stop by this morning to let you know we’re very glad you’ve found us! So stay tuned, and I’ll be back again later on to add more thoughts ;-).

Marianne

[WriterAshley]

Thank you so much, Marianne! I could really use the help and I appreciate it so much!

Talked to my vet tech this morning, and he said he thinks it’s Schroeder’s cortisol levels coming back up as the meds wear off, or he wonders if it could be arthritis. I doubt it’s arthritis though because it seems very odd it would be happening on a pattern.

I’m going to go ahead and give him this morning’s dose and go from there. I’ve got a suppression test scheduled for Monday, so while he is there I’m going to have them do other bloodwork to check on all his other levels.

I just want to help him and not make anything worse. It’s so challenging to interpret!

Ashley

[Squirt's Mom]

Hi Ashley and welcome to you and your sweet baby boy!

First, I am very concerned about the validity of the Cushing's diagnosis in your baby. Testing for this disease should NEVER be done while the dog is sick or under any major stress because those things will impact the results, often returning false positives. Meaning the dog does NOT have Cushing's but the other illness/stress caused the test to show as if it does. Cortisol is what these tests look at and cortisol is one of the fight or flight hormones in the dog's body, and ours for that matter. It's job is to rise when faced with any stressful situation to help the body be able to cope. This is why our cortisol rises when we get jet lag or are in a stressful situation at work or home. And this happens when the dog is sick with other illnesses of any kind, has had surgery, or simply is one of those dogs who become extremely stressed when they go to the vet or get in a vehicle. It is NORMAL for the cortisol to be high just after any surgery and any time something like an infection is present. So I am not in the least surprise at the positive LDDS result due to the timing of that test. Sadly, your vet just cost you money you didn't need to spend at that time and put your dog under more stress than was warranted at that time. Your baby should have been allowed to completely heal from the surgery and return to a normal life before any testing was even considered. Some illnesses will cause the same signs as Cushing's as well so signs that are present when an infection is present don't count nor do any signs seen just before or following any surgery. The signs would become important AFTER the dog has healed completely. THEN if you see signs it is time to look at testing. The fact that you baby has reacted to the Vetoryl in the way he has tells me the possibility of a false positive is VERY real for your baby. I know...it happened with both my dogs who were diagnosed with Cushing's. One did eventually develop Cushing's but the second one never had it. Both had other issues -a tumor on the spleen for one and a host of other health issues in the other. I learned the hard way how unreliable these tests are in the presence of any other health issue. The LDDS, while considered to be the "gold standard" for testing is the test that is most apt to return a false positive when other illnesses are present. The ACTH will also do the same. So I would simply stop treatment for now and let my baby recover fully and then if signs are present start looking into Cushing's...with new testing sadly because the value of the LDDS that has been given is close to nil.

If you don't mind, could you post the test results from the LDDS and the ACTH that apparently resulted in the reduction to 10mg. Being on the medication for a month means your baby should have had at least one ACTH by now. Also any testing that was done that shows things like BUN, CHOL, T4, etc. and the CBC that shows things like monocytes, eosinophils, etc. This will help us help you better. ;)

I'm glad you found us and look forward to learning more as time passes. I hope your sweet boy is recovering nicely!
Hugs.
Leslie

[labblab]

OK, I made it back again! I’m so glad that Leslie has had the chance to welcome you, as well, and to express her concerns. I definitely agree with her that diagnostic testing for Cushing’s should not be undertaken during a time of illness or stress. In that vein, I’ll ask if you could please elaborate some more on the timeline of Schroeder’s infection/amputation vis-a-vis his Cushing’s symptoms and the testing. For instance, if he was exhibiting the Cushing’s symptoms prior to the onset of the infection, that gives us more confidence about the accuracy of the diagnosis. Likewise, if the all-day LDDS test was performed during an office visit *after* the hospitalization for the amputation, that also makes us more comfortable that it wasn’t stress or non-Cushing’s illness that was skewing the cortisol level. So if you can tell us more about the testing timeline, that’ll help us a lot in terms of clarifying possible concerns.

For the sake of argument, though, I’m going to offer the following thoughts based on the assumption that the Cushing’s diagnosis is accurate. During our years here, a fair number of members have talked about unexplained episodes of tremoring or shivering, and in honesty, a lot of the same question marks still remain. I’m going to paste in a related quote that I’ve posted here before:


Tremors and "shivering" episodes are indeed complaints that we've heard before. My own Cushpup was one who suffered unexplained tremors before starting treatment, and for a period of time afterwards. There is still a lot that is unknown about Cushing's, and episodes like this seem to remain one of the mysteries. As Leslie says, tremoring has been listed as a possible side effect of trilostane, but my own dog started his tremoring before he was even placed on the medication.

Under the "Adverse Reactions" portion of Dechra's U.S. Product Insert for Vetoryl, "shaking/shivering" was reported in 10 dogs out of a total of 107 animals included in an American clinical trial. The big question, of course, is whether the shaking was truly caused by the drug or instead by something else. Since the shaking was observed in dogs during the time period they were taking the medication, it had to be listed as a possible side effect. But I don't think Dechra knows of a specific mechanism that would cause this effect.

As I say, my Cushpup definitely started tremoring prior to being treated with trilostane, so the drug couldn't have been the original cause. However, the tremoring did worsen after treatment was begun. So who knows exactly what was going on. For what it’s worth, here’s a related reply I posted to another member a while back.



Through the years, we have had other members who have worried over unexplained tremoring episodes. My own Cushpup, a Lab, suffered from intermittent involuntary tremoring episodes across his shoulder blades that made him look as though he was shivering. For him, the episodes happened most often when he was sitting down or at rest -- even when he was sleeping. Sometimes he would jerk himself awake, they were that severe. But just as is true for your boy, he would usually just stretch afterwards and never seemed to be in any particular pain or discomfort. The tremors began before he started trilostane treatment, worsened significantly when he first started the drug, and then ended up stopping entirely a few months down the road.

We never did figure out what caused them. Through the years, other members here have reported similar issues with their dogs under a variety of circumstances: some using trilostane, some using Lysodren (another medication), and also dogs not yet being treated at all. For this reason, it has been hard to point to a single "trigger." It is true that tremors are now listed as a possible side effect of trilostane. But I've always wondered whether such tremors more often just somehow relate to rapidly changing cortisol levels. But the good news is that they didn't really seem to bother my dog at all -- it was ME who was going crazy trying to figure them out!

Since apparently Schroeder’s tremoring didn’t start until after he began taking the Vetoryl, it does seem more likely that it’s a side effect of the medication itself, or perhaps some sort of a physiological reaction to the rapid lowering of previously high cortisol levels as mentioned above. If so, the tremoring may improve or cease as his body adjusts. As you note, tremoring can also be associated with a cortisol level that has actually dropped too low. But if Schroeder otherwise appears well aside from the brief tremoring, I wouldn’t feel as worried about that being the case. Anyway, we can talk more about all of these options. But I’ll quit what’s become a very lengthy reply, and look forward to getting more info about your diagnostic journey.

Marianne

[WriterAshley]

Thank you both so much for your help! I'm sorry for my late response... I wanted to get my info together before messaging again. I've asked my vet to send me copies of all his lab work, but I haven't gotten those quite yet, so I can't speak to specifics, but let me give you a more extensive history. I was unclear last time!

I am happy to report Schroeder's trembling has subsided! I think it may have been his body's adjustment to the medicine, because it always happened about 10 hours after administration. But I do need your help now on another issue!

In the fall (November?), Schroeder was way overdue for a dental (it usually takes him a solid two days to stop crying/acting strange after anesthesia so I was prolonging it). He had to have some teeth pulled and had a canine that was saved but did have an infection they had to really clean out. On that same side, he had a mysterious booger in his nose. I assume it had to do with the tooth infection. The vet flushed it all well (and I think they checked for polyps with a scope) and didn't find any reason to be concerned. After the surgery, the nose booger came back once more, then it resolved. Around that time, Schroeder broke a toenail while on a walk, and I noticed he was licking the area A LOT. When he had bloodwork done before surgery, his levels indicated an elevation that could mean Cushing's developing, but it was so slight the vet didn't worry about it at that time because it could be anything.

The vet tech did let me know that the x-rays showed a slight respiratory infection. He said we probably would not have even known about it if not for the x-rays, but that the post-op antibiotics should clear it up.

In December, Schroeder would have periods where he seemed to be breathing quickly and with extra effort (sort of like a slight puffing). He sometimes would have a runny nose, but it was always clear. At one point, I remember him sounding congested like he had a stuffy nose, and I did some Googling to see what normal respiratory rates are and if I should take him to urgent care. (Speaking of which, what ARE normal respiratory rates? My vet said to let them know about anything over 15, but what I've read online says 15-35 is fine. I'm so confused!) I put him in the bathroom with some hot water in the background to clear the congestion, and it helped quite a bit. I'm wondering, in retrospect, if this was a respiratory infection that could have even been connected to the initial slight respiratory irritation shown on x-rays. Or maybe a secondary respiratory thing. Who knows.

In late December, Schroeder started limping. (Amazingly, he was still jumping on things, which really shocked me when we did x-rays and discovered the culprit! But that's how he is. Anyway, I digress...) When I took him into the vet, his broken toenail had become infected. They started him on antibiotics, and it was amazing how much more "himself" he seemed... but the swelling did not subside, so they took x-rays and found bone degregation! As you can imagine, this was terrifying as we were looking at the possibility of cancer (and we lost our other dog to spleen cancer so this was a huge emotional trigger for me). Thank God- truly, thank God- the surgery to remove the toe was uncomplicated and showed a toenail infection was to blame. My vet said this can happen because the toenail and the bone there are so close at that joint. My guess is that Schroeder's terrible teeth at the time of the initial toenail break and all the licking he did is what started that infection. When they did prep bloodwork for the toe surgery, the enzyme level (the one that's the marker- I'm sorry I don't remember what it's called but I'm sure y'all know) had come way up. That's when the vet tech told me about the elevation and the possibility of Cushing's. The surgery was in early January.

We waited until Schroeder was fully healed and we got the biopsy results back that there was no cancer prior to doing the 8 hour Cushing's test. That one was done the beginning/middle of March. Schroeder continued to do the quick breathing thing and would sometimes look like his chest/stomach was sort of expanding with the breath... but no signs of actual respiratory distress... gums looked fine, no exercise issues. He maybe had some extra fatigue? But he was still begging for chicken dinner, walks, etc. After the suppression test in particular, he was breathing very heavily and panting. I attributed the quick breathing to Cushing's, especially from his reaction to the cortisol shot.

The test came back showing 1.9.

I took him in for a checkup prior to starting Vetoryl because I was worried about the breathing thing. When the vet listened to his lungs, he heard something (I assume fluid - I didn't ask directly) and went to look at the x-rays they'd taken before. He felt it was a respiratory infection that may be connected to what we'd seen in the x-rays. He put Schroeder on two different antibiotics... one that helps teeth bacteria and bones and also doxycycline.

We initially put him on 30 mg once per day of Vetoryl which he took for a few days before showing signs it was too high of a dose. He became lethargic, disinterested in food, and he threw up/his stool was soft. I do feel the Vetoryl helped the rapid breathing a bit, although looking back, I wonder if it was the antibiotics. The vet gave a very low dose of prednisone, the rapid breathing worsened, and so I asked if I could stop doing that since it was precautionary, and they told me I could. After seven days, we started the 10 mg dose of Vetoryl which has seemed to work very nicely. He has started chasing squirrels again, his appetite has become normal again (prior to Vetoryl he was SO HUNGRY) and he's shown interest in toys again.

Last week was the two week mark on the new dose, so we did the 1 hour test, and it came back showing his numbers are very well-regulated by the new dose with some room to come down further if they do continue to drop as he's on it longer... I know that can happen the first month. The only thing they flagged was a slightly elevated BUN, but creatinine and urine urine specific gravity were fine so they want to retest that in a month (but they said BUN is not at a level that they would worry about medicating). One thing they mentioned is that using wet food can sometimes help raise BUN, so I got some wet food toppers and tried on this last week, but it wreaked havoc on my boy's sensitive tummy and he had diarrhea all weekend. I took him in for a checkup on Monday to rule out any kind of parasites, and they said the stool was fine but they heard fluid on his lungs.

They put him back on the doxy for two weeks in hopes this is all connected to the respiratory infection and that maybe he just needed more antibiotics than he got. I will say that every time he's been on the antibiotics, he's seemed to perk up. I am VERY hopeful this has just been a stubborn infection and that the Cushing's has made it a little harder for him to kick so he needs an extra round of medicine. If after two weeks he is still having the fluid issue, they want to do x-rays to check heart disease.

He has had a slight heart murmur for a long time and has also had a cough for a long time. Since it has never inhibited his exercise (he can walk for looonnnnnggg periods without fatigue) the vet has felt he did not need medication.

He has some slight hair loss on his back limbs, I feel like he has a slight pot belly (but it may be from those couple months being SO hungry before meds), and he was drinking water like crazy prior to the Vetoryl. I do think he has Cushing's, but I'm very worried about heart disease as well.

I guess my question is... has anyone seen Cushing's cause quick breathing when cortisol is too high? Has anyone had respiratory infections to deal with while on Vetoryl - and what finally resolved them? And if this does end up being heart disease, what am I going to need to know about possible drug interactions with Vetoryl?

Thank you for reading such a long post... I hope that helps fill in the gaps. I appreciate you all so much! We lost our other dog very suddenly, so I'm grateful for the chance to care for Schroeder as he ages but I also feel I'm putting a lot of pressure on myself to not "miss" anything, if that makes sense.

Ashley

[labblab]

Hi again, Ashley! I’m so sorry for the delay in getting back to you. I’ve just had some things I’ve had to attend to over the last couple of days — nothing bad, but just busy. So I haven’t had the chance to post as much. But I’ll definitely return with a better reply shortly.

Marianne

[labblab]

Alrighty, I’m *finally* back again — I’m so sorry for the long wait! And after this wait, I apologize because I’m not sure I can be all that helpful to you. Cardiac and respiratory issues are not ones that I’ve faced with my own dogs, so I’m afraid I’m not very knowledgeable at all in that regard. It does sound as though Schroeder has had an underlying, smoldering respiratory problem for some time now that has never fully resolved, and further diagnostics in that regard may certainly be important. I will confess that hearing about this chronic problem gives me pause regarding the validity of the Cushing’s test since, as we’ve discussed before, any illness or stress can cause elevation in cortisol levels. However, if you’ve actually seen outward improvement in Schroeder since beginning the lower dose of Vetoryl, then I’ll take comfort in thinking it’s helping rather than harming him.

As far as Cushing’s effect on respiration, panting is a very, very common symptom of Cushing’s. So I don’t know whether or not you’d characterize Schroeder’s rapid breathing as panting. But if so, most all of us have seen that in our untreated Cushpups. Before treatment, my own boy would even rouse from sleep throughout the night and pant. But given the possible issues with Schroeder’s lungs and heart, there may be other factors affecting his breathing.

In terms of his kidney function, there is a specific simple blood test you may want to request the next time he has blood drawn: the SDMA. It’s a relatively new test, but it can help evaluate the presence of kidney dysfunction even before significant abnormalities in creatinine and BUN are observed. Given Schroeder’s respiratory symptoms, I think it would be a good idea to evaluate his kidney function as thoroughly as is possible, too, since worsening kidney problems can contribute to the burden placed on the lungs and the heart. Here’s some specific info about this test:

https://www.idexx.com/en/veterinary/reference-laboratories/sdma/

By the way, has Schroeder’s blood pressure ever been checked? Cushing’s is a disease that can cause high blood pressure, and if so, of course that may also contribute to heart and lung problems. We’ve had a number of dogs here who have been placed on meds for high blood pressure. Some of those drugs do have the potential to interact with Vetoryl, so certain combinations are preferable over others. That may also be true of other types of cardiac meds, as well. Your vet can always consult with Dechra, the maker of Vetoryl, regarding possible interactions. Dechra maintains technical reps on their staff who are happy to consult with vets at any time, either via phone or email.

So, in summary, it sounds as though the most important thing right now is to get to the bottom of this smoldering respiratory issue, whether it be infection or some other heart/lung problem. If your own vet seems stumped, you might even want to request a referral to an internal medicine specialist, if there’s a specialty practice or a vet school in your area. Schroeder’s situation does sound complicated enough that some additional consultation may be helpful. Either way, of course do keep us updated.

Marianne

[Squirt's Mom]

Hi Ashley,

Just have a little bit to share with you in addition to what Marianne has already said so well.

I had a non-cush pup who had COPD and chronic pneumonia as a result. I smoked around her for years and her COPD was the result of my actions. (vet said not but I'm not an idiot. ;) she was just trying to ameliorate my guilt.)

Trinket was easy to pill until it came to the antibiotics for the pneumonia and I started finding them spit out all over the house. She was blind but an expert at finding the most difficult hiding spots for those pills! :D I ended up having to learn to give her antibiotics via injections twice a day to get a hold on the pneumonia. She also took Guaifenesen and Theophylline for the COPD which did help. It was a long road and a lifetime condition but we did finally get it to a manageable place after the injections got to work.

I strongly second Marianne's suggestion of the SDMA...it has made a world of difference for our dogs because we can now find kidney damage MUCH earlier than we could before. Based on the BUN and CREAT alone something like 75% of kidney function would be lost before there was any indication of a problem. With the SDMA we can see that much sooner and be able to take action much sooner giving the dog the optimal chance.

You are doing a great job, Mom, so keep up the good work! Your precious Schroeder is so lucky to have you on his team.
Hugs,
Leslie