Lost control on Trilostane

[punk88]

Hi all - I have a quick question for trilostane users. My toy poodle has been on trilostane for 2.5 yrs and her cortisol level has been well controlled (4-6 range). Her recent ACTH stim result showed a post result >50 (pre 6.5). She is currently taking 30 mg trilostane (once daily). Has anyone had a similar experience where the cortisol level has gone so far out of range while being treated with trilostane? Just wondering if trilostane will maintain control moving forward, or if it may not be an option long-term(?). Her Internist has increased the dose of trilostane. Any comments or thoughts would be greatly appreciated!

Thank you,
Punk's mom

[frijole]

Hi and welcome.

I am a lysodren user but that is a huge swing! Are you sure that the result is 50? Be sure that the units being measured are the same from the lab. Do you have a copy of the test?

Also, did your dog exhibit any symptoms of cushings returning? Finally when was the last test you had? If it was recent I would really question the result.

Please give us as much info as you can and I'm sure a trilo user will throw out an idea or two. Hang in there! Kim

[labblab]

Hi and Welcome! :)

It's great to hear that Punk's cortisol level was so well controlled for such a long time, so it must be really disappointing and confusing to receive a result that is so far out of the desired range. :(

A few quick questions for you. First, how long ago was Punk's previous ACTH? Secondly, what dose of trilostane has she been increased to? And third, have you seen an increase in her symptoms, as well?

Thanks for this additional info,
Marianne

[punk88]

Thank you for your quick response. Her last ACTH stim test was 5 months ago and the results were within range. Prior to that, the internist did increase her dose from 20 - 30 mg, as her cortisol increased to 15 ug/dl (one time).

Her symptoms have always been subtle (no increased thirst, hunger, etc). Her coat has thinned slightly more, panting has increased slightly and she has gained about 5 oz. She remains very active (runs, swims).

I did receive a copy of the report and her post cortisol is >50 ug/dl (same units as previous results). The internist has increased her dose to 40 mg and wants to repeat the stim test in 2 weeks. She indicated that she may have to increase the dose to 60 mg, but wants to do a recheck prior to doubling the dose.

Thanks again for your thoughts!

[lulusmom]

Hi and welcome.

Can you give us some information regarding Punk's original diagnosis? Was she diagnosed with pituitary or adrenal based cushing's. I ask because adrenal tumors are highly resistant to both Trilostane and Lysodren. It is not uncommon for a dog to have both a pituitary and adrenal tumors so if Punk had an adrenal tumor that has enlarged or if she has developed an adrenal tumor after the initial diagnosis, this could explain the rather sudden and large increase in circulating cortisol. It is also possible that an undiagnosed underlying non adrenal illness could be causing a spike in cortisol. An abdominal ultrasound would be a useful tool in ruling both scenarios out or in. If an adrenal tumor is involved, Trilostane would not be the treatment of choice.

We will be looking forward to receiving more information that will help us in providing more appropriate feedback.

Glynda

[SaxLady]

Hi Punk,
Before you go to the expense of more testing, it might be a good idea to see if there has been any recall or problems with that specific batch of Trilostane.
Candy

[punk88]

She was originally diagnosed with pituitary based cushing's, which was confirmed with an ultrasound (no tumors/enlarged adrenals - similar in size). She had a liver ultrasound in Nov 2007 (Alk. Phosph. was 1400) and kidneys/adrenals were checked at that time (kidney's shrunk slightly/no other change). She has not had any further ultrasounds.

I will look into the batch of Vetoryl to see if there were any problems. I picked up a new prescription and already started her on the new lot.

I appreciate the advice and will inquire about an abdominal ultrasound, too. Any thoughts on what type of non-adrenal illness could cause a spike in cortisol?

Thanks so much!!

[labblab]

I will look into the batch of Vetoryl to see if there were any problems. I picked up a new prescription and already started her on the new lot.

Have there been any changes in the source or form of Punk's Vetoryl along the way? Since brand-name Vetoryl does not come in 20 mg. or 40 mg. capsule strengths, I am wondering whether a pharmacy has customized Punk's dosage, or whether you've been using combinations of 10 mg. and/or 30 mg. capsules as her dose has changed. I know it's a very long shot -- that the Vetoryl itself may have been more or less effective -- but I just thought I'd ask...

Also, out of curiosity, what issues led you to test Punk for Cushing's originally? It sounds as though she has never exhibited some of the more common symptoms. With an ACTH result as high as this last one (assuming that the test itself was not flawed in some way), I would have expected Punk to be more openly symptomatic. But it sounds as though this has never really been the case with her?

Marianne

[lulusmom]

Hi again,

To answer your question regarding what types of conditions can cause increase in cortisol, here is a perfect example that was related to another member by Leslie (Squirt's Mom):


Cushing's is a complex condition that is often very difficult to confirm, even with several tests. The ACTH can show high cortisol levels that have nothing to do with an adrenal illness, which Cushing's is. In fact, all those tests can come back positive for PDH or ADH when something else altogether is at work. My Squirt is proof of that.

All her tests - LDDS, HDDS, ultrasound, and ACTH - confirmed she had PDH, pituitary Cushing's. However, a splenic tumor and part of her spleen had to be removed and since then (9/08) her cortisol level has returned to normal. Her docs now say the stress from the tumor could easily have been the cause of the results that determined PDH, when in fact she may not be. She is being treated for her Atypical Cushing's only today and has been since 8/08.


Glynda

[punk88]

In an effort to find her source of proteinuria, the vet ran an ACTH stim test and the post result was 39. They expected the proteinuria to resolve after the cortisol was under control, but it didn't (UPC ratio shot up to 6.0). We're battling protein-losing nephropathy along with cushings. We've been able to maintain a UPC range of 1.8 - 2.6 with a combination of enalapril, chinese herbs, homeopathic remedies and acupuncture.

I purchased 10 mg caps from Masters, UK for the 20 mg dose. When they bumped her up to 30 mg, I started with 30 mg caps from Masters, but ended up with 30 mg caps from the internist's office (Master's would not refill the prescription once it was approved in the US). This is the first ACTH stim test on US purchased Vetoryl.

Thanks!

[Dawn]

hi please keep me updated on what happens - very interested, I think our boy will be going on trilostane this week possibly, and it will his first course of treatment thanks

[Harley PoMMom]

Hi Punk's Mom,

Welcome from me too! I have an almost 13 y/o pom. boy named Harley who was losing protein in his urine. His first UPC was 2.3 :eek:

He was suffering from high BP, from the gentle and loving urging of these amazing and knowledgeable people here, we finally got that under control and his last UPC results were 0.6, he takes Amlodipine.

I see Punk takes enalapril, is this for high BP? If so, is it under control?

As you can see we are pretty nosey here :D so if you wouldn't mind telling us your name..."Hey you" is so impersonal and we are so friendly here. :p:D

Hugs.
Lori

[punk88]

Thank you!

[punk88]

Hi - I apologize, my name is Arlene! Punk is taking enalapril 5 mg (BID) to reduce the proteinuria (she does not have high BP). We were able to reduce it from 6.0 to 3.9 with the enalapril and then down to 1.8 with alternative treatment. It is currently back up to 2.6, but it may be due to her increased cortisol.

I will keep you updated. I appreciate everyone's comments and thoughts!

Regards,
Arlene

We keep a close eye on her electrolytes, since enalapril should be used with caution in dogs treated with trilostane.

[Harley PoMMom]

Hi Arlene!

There is another test that can be run on Punk that measures the levels of the 5 intermediate/sex hormones. Trilostane can and usually does elevate one or more of these intermediate/sex hormones. This test is the UTK full adrenal panel. If you would like more information about it, let us know.

Love and hugs.
Lori

[punk88]

Dawn - good luck with the trilostane treatment! There were no visible side effects when Punk started her treatment, but it does increase the intermediate and sex hormones.

Lori - a UPC of 0.6 is fantastic!

[punk88]

Thanks, Lori. We did have the full adrenal panel done and the intermediate/sex hormones were very high!

Do you know if anyone has ever commented on the long-term effects of having these other hormones elevated?

[Harley PoMMom]

Hi Arlene,

Yes, Dr. Oliver himself has done studies on this, these elevations of these intermediate/sex hormones can be a serious problem for your dog.

My Harley suffers from high elevation of estradiol since Harley's cortisol is not elevated, Dr. Oliver believes his elevated estradiol is causing his high BP. Elevated estradiol can cause havoc on your dogs body and cause many issues.

If all or any of Punks intermediate/sex hormones are elevated and she were my dog, I would give this great concern.

Love and hugs.
Lori

[labblab]

Hi again, Arlene.

Thanks so much for all the additional info. Boy, if it were me, I do think I would be interested in pursuing another ultrasound -- as much to view Punk's kidneys again as to see the adrenal glands. Since Punk's proteinuria never resolved as expected once her cortisol was lowered, it does make one wonder whether there is something else at play in terms of kidney dysfunction.

Since you have already mentioned the caution about combining enalapril with trilostane (due to possible detrimental effect on electrolytes, blood volume, and renal perfusion), I feel certain that you and your vet are also aware of the general warning against using trilostane itself in animals suffering from renal insufficiency. I do not know whether this warning is solely due to the same ill effects associated with too-low aldosterone levels, or if there are other issues as well. This may very well be a conversation that you have already had with your vet, though, and you may know the answer.

Regardless, if Punk were my girl, I'd be interested in pursuing another ultrasound if for no other reason than the peace of mind that nothing has changed significantly since 2007. This sudden leap in cortisol -- to a level even higher than at the time she was initially diagnosed -- seems odd to me after having been so well controlled for so long a time. Given what you've told us, I wouldn't think the Vetoryl itself is the problem. I believe that all Vetoryl is manufactured in the U.K., regardless of whether or not it is being distributed here in the U.S. So unless there was a flaw in the ACTH test itself, I'd sure be questioning what is going on (just like YOU are!).

With a cortisol level this high, I'm just really surprised (and glad!) that Punk is not exhibiting other outward symptoms. Please do keep us in the loop re: any additional testing or information, OK?

Marianne

[gpgscott]

Thanks, Lori. We did have the full adrenal panel done and the intermediate/sex hormones were very high!

Do you know if anyone has ever commented on the long-term effects of having these other hormones elevated?

Hi Arlene,

Right up front I need to tell you that we do not administer Trilostane as our Moria is strictly Atypical with elevations of estradiol only. Neither do we administer Lysodren.

I have a great distrust for Trilostane. Its action is not straightforward, it confuses the system into thinking that cortisol is not called for but in most cases causes elevations of hormones other than cortisol. There are also permutations of Trilo varying from Vetoryl to compounded versions and I suspect uniformity.

Me, I would do a washout, which is stop treatment for 30 days or until resumption of significant symptoms and then do another full adrenal panel from UTK.

Very sorry the treatment has become unstable. Please continue to let us know how you proceed.

Best to you and Punk.

Scott

[punk88]

Thanks for your great thoughts and concern!

Yup, I am aware that trilostane is contraindicated for renal insufficiency. Punk's renal function is well within the normal range, so she is able to eliminate the trilostane.

Scott, early on I purchased the trilostane from a compounding pharmacy, but received one refill with 2 different sizes caps, so I quickly scraped that idea!

My choices are continuing on with trilostane (and living with the fact that the other hormones will be elevated), or switching to Lysodren. I don't know if it's riskier to use Lysodren on a dog with kidney disease(?).

I will discuss an ultrasound with the vet and will certainly let you know how things progress. May all of your "sugar babies" continue to do well!!

Best Regards,
Arlene

[Harley PoMMom]

Hi Arlene,


My choices are continuing on with trilostane (and living with the fact that the other hormones will be elevated), or switching to Lysodren. I don't know if it's riskier to use Lysodren on a dog with kidney disease(?). I really don't know the answer to that question either, but the five intermediate/sex hormones which are: androstenedione, estradiol, progesterone, 17 OH Progresterone, and aldosterone, Lysodren lowers progesterone, androstenedione and 17 OH Progresterone.

Love and hugs.
Lori

[punk88]

It's difficult to know what to do. If we took her off of trilostane, all of her intermediate/sex hormones would resolve. I had sent an e-mail to Dr. Oliver early on, and he indicated that they do see a rise in these other hormones in dogs treated with trilostane. The internist was very reluctant to give her Lysodren because of her kidney disease.

I spoke with the internist yesterday and she believes that the spike in cortisol is a result of losing efficacy of the trilostane. She indicated that she would expect the pre-cortisol result to be elevated if there were something else going on. It may also be a result of the tumor on the pituitary growing larger. But, we will open it up to an ultrasound if the increased dose doesn't reduce the cortisol level.

Stay tuned!

[Barney's Mom]

Hey Arlene! Nice to meet you and punk. I have a dog that is on a med that is very similar to Enalapril, it is Benazepril, (they are both ACE inhibitors) and he takes it for proteinuria also although he does have some hypertension. My dog was originally on Trilostane, with the Benazepril and we had to stop the Trilostane because the Trilostane and the ace inhibitors will both raise your serum potassium, and together that effect is potentiated. High potassium levels can be very dangerous for your pet, they can cause cardiac disturbances and EKG changes. Sure enough Barney's potassium rose to a levels that were unsafe. We started Lysodren with no ill effects.
The use of ACE inhibitors and Trilostane together isn't an absolute contraindication, but the makers of Trilostane do state that extreme caution should be used when giving both medications together. For me, the risk of cardiac disturbances just wasn't worth the risk. I have never heard that Lysodren is contraindicated in animals with renal impairment, except for cases of overt renal failure where the dogs have poor appetite. That was the reason my IMS chose Lysodren.

Cheryl

[punk88]

Thanks for the information, Cheryl! We do keep a close eye on Punk's electrolytes and thankfully, they have been well within range so far. We have discussed benazepril vs. enalapril with the vet and was advised that they typically start treatment with enalapril, then switch to benazapril when renal function is impaired. Benazepril is eliminated mostly by the liver, whereas enalapril is eliminated solely by the kidneys.

It sounds as though Barney's proteinuria is due to high blood pressure? Punk has a condition called glomerularnephritis, which unfortunately will progress as she ages. Her kidney membrane is compromised, so the larger protein molecules are able to pass through to the urine. I think that this condition is worse than the cushing's disease. Since Lysodren kills off some of the adrenal glands, the fear is that it will do further damage to her kidneys.

If trilostane is no longer effective for her, we will have to consider Lysodren.

Thanks again!
Arlene