Vetoryl no longer working

Cate our now 10yr old border collie was diagnosed with Cushings in Nov 2019 at UT Vet School. She was started on 40mg of Vetoryl. With in 3 days the excessive drinking and peeing was eliminated. She had lost a lot of fur and they had shaved her belly but within 6mos her fur had grown back and things were great. She started playing again etc. In June of 2020 I thought maybe we could back off a bit on the Vetoryl to 30mg (less drug better right) but my Oct2020 I realized that her water consumption was increasing and her fur was looking rather unhealthy. So after a cortisol check which was 2.9 we went back to 40mg a day. By December 2020 still no real improvement. Cortisol at 3.3. We have been inching up on Vetoryl. 12/3/20 45mg, 12/17/20 50mg. 1/12/21 55mg and 1/19/21 60mg.
Tested cortisol 2/2/2021 Cortisol3.5. Vet is doing the prevetoryl check to hold the cost down.
Question 1 does Vetoryl just stop working?
Question 2 Weighing 44# then 60mg is a middle of the road dosage. Continue to increase dosage?
Question 3 Other than her excessive drinking 120 oz/day water and peeing(amazing no accidents), some fur loss,
Cate has no other obvious signs blood pressure normal electrolytes normal, energy level (walks 4-6miles/day) .
Change to Lysodren??
Any comments would be appreciated.

ACTH at dx 29.5ug/dL

Just wanted to share my experiences with the PVC test. When I was doing it it was showing at the lower end of normal for my Cush girl. However her drinking and hunger were getting worse and so a week after we did the latest PVC test we did the ACTH Stim test. The Stim test showed that her cortisol was actually very high - I think it was around 155nmol. She was usually around 90-100 nmol which is where she liked to be. It may be worth getting an ACTH Stim test and seeing what that result is. I am assuming a full blood panel has be done to look at kidney function and a urinalysis to check for UTI, glucose in urine and specific gravity.

Thanks and the vet recommends we go back to UT for consult. Of course they will probably run all tests again to a tune of $1600.
Even if her cortisol is higher the question still is why is the Vetoryl is not working anymore and upping the dosage isn't showing any improvement in symptoms(120oz + water and urinating a lot.)
Kidney function good, UTI no indication in catch sample, No glucose, Specific gravity very dilute. Electrolytes normal, blood pressure good.
We are upping dosage to 70mg(split am/pm) of Vetoryl with fingers crossed today. It is a lot of pills when we only have 10 & 5mg pills.
We get Vetoryl from Walmart petrx. Any concerns???

Hello to you and Cate! I’m soooooo glad that Laura has had the chance to greet you and to share her thoughts, and I’ll be writing more myself later on today or tomorrow — unfortunately this has just turned out to be a busy day for me. But I’m so glad you’ve joined us, and I’ll be adding a proper reply as soon as I can.

In the meantime, welcome!
Marianne

It is common for dogs to have to have the dose increased/decreased over time. My girl was pretty stable for about 5 years and then we had to increase her meds about 3 times in a few months. I know that I always got a urine culture done as the dipstick method usually done at the vets didn't show up the bacteria in a UTI since the urine was so dilute. I have seen some small dogs on some pretty hefty doses of Vetoryl so I wouldn't be too worried about 70mg. Can you not get the the 30mg Vetoryl or the compounded version called Trilostane (so much cheaper than Vetoryl). If you got Trilostane you could get 35mg tablets if doing a split dose (for a total of 70mg a day). I imagine getting 10mg and 5mg is VERY expensive.

Yes! Everything about this disease is expensive but until we can see Cate respond to a dosage then we will order in cheaper quantities.
Question ! I have been reluctant to do the UTI culture for various reasons(no peeing urgency even with the amount of water she is drinking, no obvious pain or discomfort, no licking or concern by Cate to that area) but...
Would a UTI result in elevated cortisol readings.???
If yes I will have them culture immediately.

OK, I finally made it back! First of all, I think Laura is totally spot-on with her thoughts and suggestions. As she says, the need for Vetoryl dosage adjustments over time is quite common. However, before getting caught up in continuing increases, I think her suggestions of a urine culture and a full ACTH make great sense. As to how much a simmering UTI would increase cortisol readings, I cannot say. We’re always told that any systemic illness or stress has the potential to elevate cortisol. As to whether or not Cate’s cortisol actually would be significantly affected in this instance, I don’t know. But of equal importance is the fact that an untreated UTI could absolutely account for the increased thirst/urination. Since that is really her only real issue at the moment, a urine culture is the first place I would start if Cate were my own dog. If she does have an infection, I would hold off on the Vetoryl increases for the moment because antibiotic treatment may solve all of your obvious problems. If the culture is negative, then I would next proceed with a full ACTH as a more complete gauge as to the status of her cortisol. Returning full circle, if her cortisol is simply edging upward, this is not an unusual situation and you’d be back to upping her dose until you find the sweet spot.

If there is no UTI and her full ACTH is actually remaining within the desired therapeutic range, then the thinking cap needs to go back on. One question for you: did Cate’s original diagnostic testing point to the type of tumor that is causing her Cushing’s (pituitary vs. adrenal)? Simply based on anecdotal reports of our members over the years, it seems as though adrenal tumors may be somewhat more variable in terms of cortisol production over time although we’ve certainly witnessed many dosage adjustments with pituitary tumors, as well. Also, for dogs with pituitary tumors, there is another condition that can be created alongside the Cushing’s. It’s a disorder called “Diabetes Insipidus,” and its chief symptom is excessive thirst and urination. I’ll give you a link that explains more about this disorder, but I can tell you that we have had dogs here who suffer from both pituitary Cushing’s and DI. The treatment for DI is actually quite simple — the administration of some eyedrops. Also, often just a trial of the drops serves as the diagnostic itself. If the drops help, the condition is presumed to exist. Anyway, here’s the link. If Cate doesn’t have a UTI and her ACTH is within range, DI is definitely something I’d want to discuss further with your vet if she has already been diagnosed with a pituitary tumor.

https://vcahospitals.com/know-your-p...ipidus-in-dogs

Marianne

Thanks for info.
Yes UnivTenn diagnosed pituitary Cushings.
And since this latest increase of Vetoryl (70mg) has not decreased the amount of water drinking and urination at all,
we will pursue the urinalysis for a UTI. If nothing there back to UT.
The possibility of Diabetes Insipidus may be the answer. The tumor pressing on that part of the brain is a real possibility since Cate doesn't seem to have a lot of other symptoms.
Another question (oh so many) what is the Vetoryl doing? Why isn't it pushing her towards Addison?
Last vet visit (2/2) Cate gained a couple pounds. No vomiting or diarrhea. Healthy appetite.

I think it’s very good news that Cate is otherwise doing well aside from the thirst and urination. At least that relieves some degree of worry over her. Given her behavior and cortisol readings, it doesn’t appear that you’re currently risking an Addisonian condition from the increased Vetoryl. Instead, the situation may be the opposite: the higher dose of Vetoryl hasn’t yet lowered her pre-pill cortisol readings because her adrenal glands are now producing a higher level of cortisol than the current dose of Vetoryl is yet able to control. Cortisol production can change over time in Cushpups, often unpredictably.

As we’ve said above, I think you’re at the point where you really need to see the results of a full ACTH stimulation test, especially if it turns out that there is no UTI present that could account for the thirst/urination. The full ACTH will give you a more complete picture of the status of her cortisol production and cortisol reserves. So either with your own vet or at UTK, that would be my next step, especially if the urine culture is negative.

Marianne

Of course the UTI was negative. Without any symptoms I really did not think this was the problem.
After that stressful day at vets Cate's water consumption has increased again.

Continuing
128+ oz/day.
Questions
1 Increasing Vetoryl to 80mg/day. Should we not be seeing some improvement
2 Ordered drops for Diabetes insipidus. Any knowledge or comments?

Cate's overall health is good. No vomiting, no loss of appetite, no diarrhea, some hair loss and panting.

Is the Vetoryl being given with a full meal? This is a fat soluble drug that must be given with a meal to be absorbed and used by the body.

Having said that, there are some dogs that simply do not respond to Vetoryl and some that don't respond to Lysodren. These pups eventually need to switch to the other drug if at all possible (Lyso is not available in all parts of the world).

But I would wait until I tried the DI meds first and see how that works for her. If Cate improves then you have the diagnosis and know why she's continued to drink so much...tho excess urination usually goes along with DI. However....our babies don't usually read the rule book and the few that do seem to think it's poppy cock. :D

I endorse everything Leslie has written above. Have you yet had an ACTH stimulation test run, though? If not, I’m really getting worried about your continued Vetoryl increases, especially in such a short time frame. I think you’ve truly reached the point where it’s no longer safe to keep increasing without having a more complete picture of Cate’s adrenal function and cortisol reserves.

Additionally, I would hold off on any more increases until after you’ve tried the DI drops. If you try both simultaneously, you won’t know whether any improvement is due to the increase or the drops. You’d really be muddying the water. So for both safety and also the benefit of more clearly judging the effect of the drops, I’d hold off on any more creases for now.

Marianne

Yes Cate gets the Vetoryl with her meals. Morning meal and 12 hours later with supper meal.
Got the drops today for Diabetes Insipidus. Nervous. But with her increase of water (16more oz) for a 24hr total of 128 oz in the last week I think it is worth a try. Any considerations???

I sure wish I had some first-hand experience with the D.I. drops, but I don’t. I think it’s pretty straightforward, though — either they help or they don’t. I sure hope they do help because that would solve the puzzle. Since the repeated Vetoryl increases aren’t having any effect, I’m really questioning whether elevated cortisol is the driver of the thirst. For safety’s sake, that’s another reason why I’d hold off on any more increases for the time being.

Definitely let us know how things go, OK?
Marianne

update on cate
2/2/2021 prevetoryl 3.5
2/24/21 increased vetoryl to 80mg
3/3/21 increased vetoryl to 90m
3/9/21 prevetoryl test 2.6 (range 1.3 to 2.9) yes in range!!!
3/13/21 water intake down to 112oz (been at 156oz) vomited think maybe food.
still good appetite, catching frisbees and good poops
3/15/2021 water intake 88oz
of course ran out of 5mg today
will talk to vet today about another prevetoryl test
we are getting close!!!
note i emailed dechra and mandy called me that afternoon, we talked and she gave me a case number. she said she could call my vet but i said i would let the vet know that they could consult. my vet called them and talked to mandy and dr bradford a vet.
my vet said it really helped discussing cates case with them. her practice is small and she is not treating any other cushing dogs at this time. mostly because of cost prohibitive.
another note no caps because i broke my wrist on saturday. sheesh it is always something!!

I highly recommend getting a full ACTH stimulation test performed before any more Vetoryl dose increases are made. The pre-pill cortisol method is most useful in patients whose Cushing's has been successfully controlled and that are undergoing 6-month monitoring. Since Cate's symptoms are not being controlled on the dose she is on, I believe, it's time that an cortisol assay is done so that her actual cortisol level is known.

Have you tried the DI drops?

Sorry to hear that you broke your wrist, OUCH! Hope it heals fast!!

Hugs, Lori

Drinking excessive amounts of water can also be an unrelated, self-soothing idiopathic response to stress or discomfort. It can sometimes be habitual. I just realized I'm very late to the game here. Apologies and I hope it worked out.