Introducing KeeKee - looking for ideas on managing her trilostane intolerance

Hello.
KeeKee has been a Cushing’s dog for almost 11 months, so I thought I would share KeeKee’s journey with Cushing’s and to ask the community for ideas on managing her trilostane intolerance. Her current state is that her gastrointestinal tract is becoming increasingly intolerant to trilostane. The trilostane does help with her water consumption and panting, but her GI tolerance of the medication is dropping. So we are wondering how others that have run into this have managed their treatment. If you are taking breaks from trilostane, how long a break are you taking? Has anyone had success managing Cushing’s symptoms with anything other than trilostane, including alternative treatments?

KeeKee details:
Weight: 65 lbs
Age: 11-12 years (a bit unknown as she was an adult rescue)
Breed: Hound/Cattle dog mix
Other health conditions: hypothyroid (on low dose of thyroxine), periodic acute back pain

Here is KeeKee’s treatment journey:
In September 2024, we noted a significant increase in the amount of water she was drinking and excessive panting on walks. Also extreme drive for more food.
Full blood panel labs all looked good
Urine specific gravity abnormally low
Diabetes Mellitus ruled out (blood sugar was fine)
11/4/2024 Diagnosed with Cushing’s
LDDS test 4.4 → 2.9 → 3.7
Cause: Adrenal ultrasound showed adrenal hyperplasia, but no adrenal tumor. Diagnosis was that Pituitary tumor was driving the condition.

11/13/2024 started trilostane 30mg x2 day (we use the name brand Vetoryl and provide her doses at meal times about 12 hours apart)
12/3/2024 ACTH stimulation test 2.3 → 6.7
12/9/2024 trilostane 35mg x2 day
12/30/2024 ACTH stimulation test 2.8 → 6.8
1/6/2025 trilostane 45mg x2 day
1/9/2025 – 1/10/2025 multiple vomiting episodes
1/10/2025 stopped trilostane
1/11/2025 – 1/14/2025 Managing vomiting with Cerenia. Full blood work shows no issues.
1/11/2025 trilostane 35mg x2 day
1/17/2025 vomit at lunch. Stopped trilostane
Paused on trilostane through 2/16/2025 (due to intolerance to trilostane and surgery to remove a sarcoma tumor unrelated to Cushings)
2/17/2025 trilostane restarted at 15 mg x2 day
3/15/2025 trilostane 20 mg x2 day
3/29/2025 ACTH stimulation test 2.5 → 7.6
4/21/2025 ACTH stimulation test 5.3 → 7
7/17/2025 ACTH stimulation test 3.4 → 6.5
Water consumption at historic good level (< 2L per day)
8/23/2025 Probiotics started due to diarrhea
Last week of August 2025 had consecutive days of diarrhea, ending with vomiting
Ruled out Giardi
9/1/2025 – 9/8/2025 held trilostane
9/9/2025 Started back on trilostane 20mg x1 day
9/19/2025 Diarrhea came back
9/20/2025 Holding trilostane

Any ideas on how to manage this?

Thank you,
Greg

Hello Greg, and welcome to you and KeeKee. I’m so sorry she’s having these GI issues, especially since you’ve worked so diligently to try to perfect her treatment regimen — many kudos to you!

Our first worry when we see diarrhea or vomiting in a dog taking trilostane is the possibility that cortisol has dropped too low. But all of your conscientious monitoring has ruled that out. So we’re left with the dilemma of trying to decide whether it’s the trilostane itself that is upsetting her, or whether there is some other yet undiagnosed condition that may be contributing to the issue. Since her episodes do seemed to be linked to the periods of time when she’s taking the med, though, I can surely see why that’s your chief suspect.

As far as other well-researched treatment alternatives, Lysodren (mitotane) has historically been the other primary option. It preceded trilostane, but is now prescribed far less frequently due to the perception that it may result in even a greater frequency of side effects, including GI issues as well.

By any chance, has your vet contacted the U.S. offices for Dechra, the maker of Vetoryl? I don’t know what their current responsiveness is, but in the past they encouraged vets to contact their technical reps directly to discuss any questions or issues. Perhaps they’d recommend some GI-soothing med to be given on a daily basis (in the vein of Pepcid or Prilosec for humans). I think I’d try that first before abandoning the trilostane altogether. For sure, I’ll try to think of some other options or suggestions for you, as well.

In the meantime, though, we’re so glad to have the two of you here with us.
Marianne

Thank you Marianne for the Welcome and advice.

Historically the GI upset has seemed linked to trilostane, but this latest diarrhea is taking longer to resolve even while off trilostane. So we are working on trying to determine the right diet to reconcile this issue prior to using GI medication. Once this stabilizes, we will have a conversation with our vet on the best path forward. Not sure if they have reached out to Dechra, but they may need to do so for ideas.

Thanks,
Greg

Something else I wanted to mention about KeeKee since she has been on triostane this year is that her diet has been a bit unpredictable. This is from a dog who has never been picky about her food, eating and tolerating most any food.

A food that she had liked for years (Hill's Science Diet Oral Care), she started to refuse to eat. We then cycled through 3 other high quality limited ingredient dry kibble. She would initially be excited about the food, only to stop eating it weeks later. By July/August we were off any dry kibble and trying out Weruva canned chicken and Go! Solutions stew mixed with steamed long grain white rice. This is where she is now, and likes it a lot. However it is apparently not GI friendly enough, so we will be trying out GI specific food to see if it helps.

Thanks,
Greg

Hi again, Greg! Just wanted to check back and see how KeeKee has been doing during this past month. I’m surely hoping that she’s been getting some relief from her GI problems. We’ll welcome an update any time you might stop by once again.

Continuing healing wishes being sent your way,
Marianne