Recovering from possible too high dosage of Vetoryl

[SpringerX2]

Hello! My dog Chloe was diagnosed last January with Cushings. She is an English Springer Spaniel, 10 years old, about 55 pounds. She was put on a dose of 60mg if Vetoryl. This worked great. Within a week her symptoms basically disappeared. I might add her only symptom was excessive thirst and excessive urination and leaking. That dose worked well for her for six months or so. If we forgot a dose she always presented symptoms within 24-48 hours. After her second follow up ACTH test our vet said her levels were borderline to increase her dosage. If she wasnÂ’t presenting symptoms we could keep it the same. At that time she wasnÂ’t so we didnÂ’t increase. But after about a month she started leaking again so we increased by 10mg. After a few months she started skipping meals. We didnÂ’t think much of it because our other dog was doing the same thing. We had recently switched foods and thought they didnÂ’t like the new food. Well just over a week ago we had a little snowfall and Chloe flipped out. She loves the snow, she whined to go out as soon as she woke up and had a blast running Around in it all weekend like a puppy. On Monday she didnÂ’t eat any of her food all day. On Tuesday she was vomiting yellow bile all day and refusing all food. This is the day we stopped giving her the Vetoryl. She has barely ate since until today but she did stop vomiting. We took her to vet and they did blood draw to check cortisol levels which were at 1.5 on Thursday, two days after stopping the Vetoryl. We are scheduled for ACTH test on Thursday. Does anyone have experience with this and recovery after too high of dose? IÂ’m just assuming that was the cause anyways. We have no other explanation.

[Harley PoMMom]

Hi and welcome to you Chloe!

I am so sorry to hear that your precious girl is not feeling well and we certainly will help in any way we can. On the forum we have observed many dogs with cortisol dropping too low when their Trilostane dosage was too high and we even have seen cortisol fall too low when no increase in dosage was made. Some of these dogs go months before those adrenal glands start producing enough cortisol for clinical signs to reappear.

That 1.5 ug/dl ACTH stimulation test result, I'm assuming, is the post blood draw? It makes me a bit uneasy when I see a dog's post cortisol level drop below 2 ug/dl and according to a renown veterinarian that specializes in endocrinology, Dr. Peterson, he feels the same way too:

Dosage adjustments — lowering the dose

In this report (13), trilostane treatment was continued in dogs with a post-ACTH cortisol concentration less than 1.5 μg/dl, as long as no adverse clinical signs were reported. I disagree with that regime.

When using trilostane, it has become increasing clear that we do not want the cortisol values to drop too low, because that may indicate early or mild adrenal necrosis (1,11,12). In contrast to the protocol used in this reported study, I recommend stopping the drug in all dogs that develop a ACTH-stimulated cortisol values less than 2.0 μg/dl, and repeating the ACTH stimulation test in 1- to 2-weeks in those dogs. Some of these dogs will require that the drug be restarted at a lower dosage, but others will maintain low to normal serum cortisol concentrations for prolonged periods of time. And a subset of these dogs, presumably because of mild adrenal necrosis, will never need any further trilostane treatment to control the signs of Cushing's syndrome.

https://endocrinevet.blogspot.com/20...rilostane.html

When a dog's post cortisol level is < 2.0 ug/dl those adrenal glands may not be able to produce enough cortisol and/or an imbalance in the electrolytes could occur. Did the vet draw blood to verify that the electrolytes (mainly sodium and potassium) were normal? Was she started on prednisone? How is her appetite now? Any episodes of diarrhea?

Regarding Chloe's ACTH stimulation tests timeline, could you clarify for me when she had her cortisol rechecked as it looks like Chloe never had an ACTH stimulation test done 10-14 days after the Vetoryl was started, and she had no follow up cortisol rechecks until she was on the Trilostane/Vetoryl for six months, is that correct? Also could you get copies of those ACTH stim tests and post those results here? Two more questions I have; is Chloe getting her Trilostane/Vetoryl dose with a meal and are those ACTH stimulation tests being performed 4-6 hours after she has had her Trilostane/Vetoryl?

I apologize for so many questions, but your answers will help guide our additional thoughts and feedback. Once again, we're really glad you've found us.

Lori

[labblab]

Lori has started you off with some great info and questions, so right now I’ll just offer you and Chloe a big “Welcome!” I’m so glad you are able to join us here, and I’ll be watching for your next reply.

Marianne

[DoxieMama]

Welcome to you and Chloe! Lori covered all the questions so I just wanted to say hello. I look forward to hearing more about your precious girl.

Shana

[SpringerX2]

Okay let me see if I can clarify all of the questions above.

First, the 1.5 ug/dL reading was her level on Thursday last week about 10:15 AM, basically a resting blood draw not part of an ACTH stimulation. Her last dosage of trilostane was given on Monday evening at about 6:00 PM. Her Potassium was at 6.3 mmol/L and her Sodium was at 136 mmol.L on this date as well.

I've gotten her results from the last year and below are what her readings have been.
2/2/17
Cortisol Resting 11.4 ug/dl

3/7/17
Cortisol Resting 1.8
Post ACTH 7.5

6/14/17
Cortisol Resting 3.4
Post ACTH 7.4

9/14/17
Cortisol Resting 4.8
Post ACTH 5.9

We typically were giving her medication after dinner or right before bed with some bread. It was not ever given 4-6 hours before the ACTH test and was never recommended by our vet to do so. She started on 60mg in February 2017 and it was in October 2017 that we increased it to add an additional 10mg. This was due to her symptoms of excessive thirst and urination returning even when taking the 60mg daily. However, we never brought her in to have her levels retested after increasing which I believe is a miss since everything I am reading now says that you should always retest after changing doses. So here we are now in January 2018. Yesterday we bought some Science Diet AD wet food from the vet to feed her because she has been eating so little. She ate that right up and I got her to eat some other Blue Buffalo canned food. This morning she would not touch any food again and spit up clear liquid (flemmy water). Pretty much over the last week I can get her to eat minimal food, she would eat a homemade food of chicken and bone broth. Will not touch any dry dog food, and with the exception of yesterday and one day last week, would not touch any wet dog food either. Her weight is now at 48 pounds and she was at 58 this time last year.

[labblab]

Thanks so much for all this additional info. Upon reading it, though, I do feel more concerned that Chloe's cortisol level may indeed be too low. And under these circumstances, a baseline or resting cortisol level alone is insufficient -- unfortunately, a full ACTH is really necessary in order to determine whether or not her adrenal glands are truly functioning normally. For instance, if there is little or no increase in the post-ACTH level above the 1.5 baseline, then the adrenal glands are not responding properly to stimulation and Chloe may be suffering from a lack of appropriate cortisol reserves. This could definitely account for her lack of appetite and spitting up. For right now, I definitely think you need to continue to withhold her trilostane. And since her lack of appetite is continuing again today along with the vomiting, I think you need to contact the vet and, ideally, request an ACTH to be performed. If for some reason that can't be done, I would ask for a prescription of prednisone (or dexamethasone) to try giving her. If her cortisol level is indeed too low, then the supplemental steroid will act as a replacement for the cortisol she is lacking. If she starts perking up again after being dosed with the the prednisone, you have added reason to conclude that her cortisol has dropped too low. She does not need a large dose of prednisone in this situation -- just a small "rescue" dose that will replace any lost cortisol. I've forgotten the formula myself, but I'll try to come back and add it later. Ideally, however, you'll have an ACTH done before starting any prednisone. Prednisone will register in the same way as cortisol on an ACTH test, so a dog must be prednisone-free for at least 24 hours before being tested.

One question: were those sodium and potassium numbers that you gave us within normal range last week? I'm assuming (hoping) so. But even if they were normal, it can still be the case that Chloe's cortisol has dropped too low

Just so you'll know for the future, it is recommended that trilostane be given in the morning along with breakfast if it is dosed only once a day. Cortisol levels are at their lowest within the first few hours after dosing, and then typically start to rebound again within 12-18 hours. By the time 24 hours have passed, the drug has typically exited the body altogether. So if you dose only once daily in the evening, you have two problems. First, by the tie time the dog awakens in the morning, the medication effect is already starting to wear off and cortisol levels (and symptoms) can rebound during the day when the dog is most active. Secondly, by the time an ACTH test is performed the next day, again, you are catching the cortisol level at its highest rather than its lowest. For safety reasons, this is not a good thing, because you can be lulled into increasing a dose when it's not appropriate. This may be what happened with Chloe, and her adrenal glands may now be oversuppressed to the extent that they will need a total break from the medication for at least a while. And in addition, she may need the supplemental steroid to get her over the hump.

Please keep us updated as to how things go today, OK?
Marianne

Edited to add: Here's an article that gives the proper formula for steroid dosing for dogs suffering from Addison's Disease. You'll see that Dr. Peterson recommends a prednisone dose no larger than .2 mg/kg, which would translate into approx. .5 mg/lb. So in Chloe's case, she wouldn't need a dose larger than about 3.0 mg. total. So not very much prednisone at all.

https://endocrinevet.blogspot.com/20...-for-dogs.html

[SpringerX2]

Thanks for all of the feedback. We did give her prednisone for three days after I brought her in last week, so she took a dose on Thursday, Friday and Saturday. It did not really seem to perk her up any though. We do have an appointment to bring her in on Thursday this week to do the ACTH stimulation test. He wanted to wait a few days of her being off the prednisone before doing the ACTH.

According to her blood test chart her Potassium was high at 6.3 when the reference range is 4-5.4 and her sodium was low at 136 when the reference range is 142-152

[SpringerX2]

Hmmm. The prescription I was given for the prednisone show it is for 5mg tablets. I gave her one a day for three days.

[labblab]

The 5 mg. should have been fine, I’d think — not that far above Dr. Peterson’s formula. When you say she wasn’t better, she did eat yesterday, though? And now that she’s been back off the prednisone since Saturday, she’s not eating again. So perhaps it was making a difference after all.

Also, that potassium/sodium imbalance is consistent with an Addisonian condition, too. I don’t know how severely out of range her results were, but dogs with electrolyte imbalances often need an additional type of supplemental steroid (different from prednisone) in order to address that issue. Aldosterone is the adrenal hormone that controls that balance, and it can also drop too low with oversuppression caused by overdosing.

Bear in mind I am not a vet, but I would not wait until Thursday to have Chloe’s labs rechecked and the ACTH done. If she’s not had any prednisone since Saturday morning, it should no longer pose a risk as far as skewing the ACTH results. Since she’s not improving at all, I would want to move forward with the testing ASAP.

Marianne

[DoxieMama]

My dog's ACTH results did not show Addisonian but his electrolytes were out of whack. I went back through his results to remind me how that was checked. My dog's levels got down to 25.7, and we stopped Trilostane (compounded version of the active ingredient in Vetoryl).

With Chloe's sodium level of 136, and potassium of 6.3, that gives me an Na/K ratio of 21.6... which is REALLY LOW (reference range is 27-40).

I would like to echo Marianne's statement

Bear in mind I am not a vet, but I would not wait until Thursday to have Chloe’s labs rechecked and the ACTH done. If she’s not had any prednisone since Saturday morning, it should no longer pose a risk as far as skewing the ACTH results. Since she’s not improving at all, I would want to move forward with the testing ASAP.

Shana