Before prescribing Trilostane...(Discussion of UTK adrenal panel)

[O'Riley]

This has been bothering me for the past several days because I have read of several recent accounts of dogs that are testing positive on either the ACTH and/or the LDDS, are started on trilostane without knowing whether a dog also has Atypical Cushing's Syndrome.

Is it possible to have both Atypical and regular Cushing's at the same time?

If it is possible, then before starting a dog on trilostane, shouldn't it be standard operating procedure to do the University of Tennessee full adrenal panel? It is my understanding that a serious side effect of trilostane is that it can adversely affect levels of intermediate sex hormones in dogs that have Atypical Cushing's.

Doesn't it stand to reason that a vet could not prescribe trilostane without first knowing what's going on with the intermediate hormones?

[zoesmom]

You are right. That is possible and many owners are now taking that route before starting their pups on trilo. It's like a preemptive strike. But there are also many here who haven't done that but over the last couple of years, we've gotten wiser, thanks to all of the members who have consulted with Dr. Oliver. So I've noticed several here are now suggesting that kind of testing to new members. But for those dogs already on trilo who haven't had the UT panel would continue to have symptoms after a few months on the drug, then of course, it's still not too late to get the testing of intermediate hormones done. But I believe that then, the question arises: Do you take the dog off of trilo for a month or so and have UT do the combo panel as if starting from scratch (I think that's what Dr. O recommends.) Or do you just test the intermediate hormones, and assume that any out of range hormones are a result of the trilostane?. 'Cause really . . . those intermediates could have been out of whack even before the trilo was started or could be MORE messed up because of the trilo. We had a big discussion on this in Zoe's thread a couple of years ago - on the 'old' cushings forum. I might still be able to get it, if I kept the links to her recovered thread. Sue

PS - this is not to say that trilostane has that effect on every patient who is taking it. In fact, I think it's not that common, although I did suspect it might have been the case with Zoe. Never went ahead and tested her thru UT though. She'd been on trilo for at least two years at the time I considered it. And eventually, a drug she was given for something else (tylan for SIBO) finally brought her drinking and peeing under good control. She had improved somewhat after starting trilo but was still above the norm with the PU/PD - until the tylan.

[Squirt's Mom]

Good questions, and I feel the same as you about prescribing Trilo without the UTK panel first.

One problem is that many GP vets aren't even aware of Atypical Cushing's. Several of us here have had the pleasure of educating our vets on the topic. Me included.

Another problem is that Lyso is going to be phased out in the US, making Trilo the only real option for Canine Cushing's so vets are being introduced to Trilo and encouraged to use it.

This is one area where I believe educating yourself before starting treatment is so important.

As for whether a pup can have both true and Atypical Cushing's, the answer is technically no. True Cushing's means that only the cortisol is elevated while Atypical means only intermediate hormones are elevated with normal cortisol levels. If a pup has both elevated cortisol and intermediate hormones, then that pup is considered to have true Cushing's with concurrent elevated intermediate hormones. For true Cushing's the treatment is either Lyso or Trilo (sometimes Ketochonazole). For Atypical the treatment is lignans and melatonin, sometimes along with a maintenance dose of Lyso. For both elevations, the best approach is Lyso, including the loading phase plus maintenance, along with the lignans and melatonin.

The UTK panel and abdominal ultrasound are, to me, the most important tests in diagnosing Cushing's and determining which form the pup has.

Hugs,
Leslie and the girls

[zoesmom]

OK, funny. Your first two answers and you get a yes and a no. I will defer to Leslie on this one, since she's actually had the panel done. It sounds like more a matter of semantics - i.e. what to call the concurrent conditions??? But I did e-mail back and forth with Dr. O about Zoe and he suggested we stop the trilo before doing the full panel on her. However, she was complicated and had had the PU/PD all her life So I was questioning whether she could have had DI (diabetes insipidus) OR atypical cushings long before the regular cushings manifested and also trying to figure out why her PU/PD didn't totally resolve after starting trilo. Like I said . . . . complicated.

[labblab]

This is a question that has been "chewed over" quite a bit by our staff here in recent months. For a period of time, I was one of those who recommended UTK testing to most "newbies" since it is true that trilostane does inevitably increase some of the intermediates. But now my own impression has shifted: I don't think there is yet consensus among veterinary clinicians as to whether or not the elevations in intermediate hormones caused by trilostane necessarily result in any problematic symptoms for the majority of treated dogs, nor is it clear which dogs will actually exhibit symptoms as a result of naturally-occuring intermediate elevations.

I'm one who likes to know as much about the "big picture" as I possibly can. So in terms of testing, if it were my own dog, I would like to have a full adrenal panel performed as part of the initial diagnostic Cushing's work-up. That way -- especially if both the ACTH and an LDDS came out "negative" for my dog with Cushing's symptoms -- I would already have an indication as to whether it may instead be the intermediate hormones that are creating the problems. So for folks who come to us and have not yet had an ACTH performed, I do often suggest that they consider the combined ACTH/full adrenal panel instead. That way, they wouldn't have to backtrack and repeat any part of the testing in the event that the "stand-alone" ACTH (and/or LDDS) turn out "negative."

But for members who have already had "positive" diagnostic ACTH or LDDS tests performed, I am backing away from encouraging them to incur the expense of having a repeat ACTH/full adrenal panel done upfront, prior to beginning trilostane treatment. Presumably, they are going to go ahead and treat the elevated cortisol, regardless. And the status of the intermediates, even if elevated, may not end up actually causing any clinical problems for their dogs. Plus, for members not living in the U.S., it is not anywhere near as easy to ship the blood samples to Tennessee for analysis.

If, however, a member consults us about a pup who had originally been well-treated with trilostane but who starts exhibiting worrisome symptoms again even though the cortisol is well-controlled (or for whom symptoms never fully resolve) -- then I definitely do encourage them to consult with Dr. Oliver about the advisability and timing of performing the full adrenal panel. When being performed for diagnostic purposes, he does generally recommend that the trilostane be suspended for at least a couple of weeks before performing the test.

So those are some of my thoughts to throw into the mix!

Marianne

[jrepac]

I'm dealing with the concurrent situation as well....elevated cortisol AND elevated intermediate hormones....I tend to think of it as having both typical and atypical Cushings. But, I think it tends to get classified simply as cushings.

Still, knowing that the other hormones were elevated led me to a very different treatment path....bless the UTK and their test!

[I'm the oddball owner using anirpyl + lignans + melatonin, which seems to work pretty well...at least so far]

Jeff

[Roxee's Dad]

I am now in the throws of having Rozee going through diagnostics for cushing's (probably Atypical) Met with the vet earlier this week to discuss further testing and he wanted to do the ACTH stim test. I disagreed and asked him to do the full UTK adreanal panel. One vet visit, one blood draw, and a full page of answers in return. My Roxee (Rozee's littermate sister) had PDH and was on Trilo, I wish I had done the full UTK with her but I just didn't know enough about it at the time.

But I did get a great education here.

[lulusmom]

After doing quite a bit of research in the last year on this subject, I've changed my position even more so than Marianne. I personally will no longer encourage members to have a UTK panel at all, unless conventional tests such as ACTH stim and LDDS are negative. Dr. Oliver himself states in his paper entitled "Steroid Profiles in the Diagnosis of Canine Adrenal Disorders" that steroid hormone profiles are indicated when other routine tests of adrenal function are negative (ACTH stim; LDDS; combined dexamethasone suppression/ACTH stim) and the dog still exhibits signs of cushing's syndrome, indicating the likelihood of atypical cushing's disease being present. Dr. David Bruyette prescribes Trilostane to the vast majority of his patients and has all but abandoned Lysodren, reserving it for those dogs that cannot handle Trilostane. He also lectures that you should not jump at having a UTK panel done unless all other tests are negative for cushing's.

At no time has Dr. Oliver ever suggested that pet owners should always have a UTK panel before starting treatment with Trilostane. I think the rationale behind that is that if a dog has been properly diagnosed with cushing's, it is pretty safe to say that a number of the intermediate steroids are also elevated. So with that being the case, Trilostane would rarely, if ever, be prescribed.

Some of you may recall that we asked Dr. David Bruyette if he had any concerns about prescribing Trilostane for dogs that have significant elevations in intermediate steroid/sex hormone levels and in those instances, did he recommend an alternative treatment? He answered; "Any adrenolytic agent or enzyme blocker can raise steroid intermediates to some degree. Whether this is an issue clinically depends on the given dog, the dose of medication used, the duration of treatment and concurrent diseases and/or medications." When talking about Trilostane, even Dr. Oliver admits that the long-term effects of elevated intermediate steroids remain ill-defined. Add on top of those opinions that we've never had a member treating their dog with Trilostane report a return of symptoms, despite having perfect 24 hour control of the cortisol.

I switched my own dogs from Trilostane to Lysodren because Lulu's coat and skin never got better and Jojo's PU/PD never resolved on Trilostane. Well guess what??? It's been a year or better since then and neither one has improved. Lulu is still bald and Jojo is still a drinking fool and a great big pee bucket.

The veterinary community at large has come a long way in accepting the fact that there are dogs out there with atypical cushing's but I think it's going to take a lot more convincing evidence before the endocrinologists, world reknown or otherwise, will subscribe to the theory that you need to know if intermediates are elevated before prescribing Trilostane. I'd like to see some of that evidence myself.

[Harley PoMMom]

My boy Harley dx'd positive for Cushings in April 09 with a LDDS test. His former vet wanted to start him on Trilostane immediately. At the gentle urging of these wonderful and knowledgeable people I had the UTK full adrenal panel ran first. The UTK panel showed that Harley's estradiol hormone was very elevated but his cortisol was within the normal range. His treatment, at that time, was melatonin and flax hulls with lignans. Harley also suffers from high blood pressure which Dr Oliver says the elevated estradiol is the reason.

Harley has since had another UTK full adrenal panel done in Nov. 09 and now all his intermediate/sex hormones and his cortisol are elevated. His treatment still consist the melatonin and flax hulls with lignans plus a maintenance dose of Lysodren 3X a week.

Love and hugs,
Lori

[labblab]

Add on top of those opinions that we've never had a member treating their dog with Trilostane report a return of symptoms, despite having perfect 24 hour control of the cortisol.

Glynda, for the most part, I do think you and I hold similar views about the advisability of UTK testing. But we diverge here, because I do believe that we've had a few occasions of "unexplained" symptom rebound. And I think that it happened with at least one member fairly recently (although of course I can't remember who ), because I know that I recommended UTK testing -- and that is since I've adopted my new strategy of recommending it more selectively. What I am talking about are not instances where the symptoms were reappearing only later in the day, which would instead point to less than 24-hour control and the need for twice daily dosing. This doesn't happen very often, but Dr. Oliver has spoken of a subset of dogs who may start out fine on trilostane, but who potentially end up experiencing problems down-the-road from the inevitable elevations.

Trilostane reportedly offers effective control of Cushing’s syndrome, but the long-term effects of the elevated intermediate steroids remain ill-defined. Some dogs do have return of clinical signs of Cushing’s syndrome while on trilostane.

So I do think that obtaining the UTK profile for that subset of dogs may be enlightening. And maybe in those instances, the testing could occur without suspending the trilostane treatment? For people whose dogs are already being treated with trilostane, I always encourage people to have their vets consult with Dr. O in advance of testing to make sure what his recommendations are re: advisability and timing.

Marianne