Using prednisone to treat atypical cushings

[corkie'smom]

Hi, I have a 12 year old Boston Terrier that was diagnosed with Cushings. She was put on trilostane and her cortisol levels dropped substantially and she became sicker. We sent blood for a hormone profile to Univ of Tenn and she has atypical cushing. So definitely no trilostane. She's been on the hmr lignans and melatonin for about 2 months and doesn't seem very happy.
Has anyone put there atypical Cushing's dog on physiiological dose prednisone? Read a paper that studied this and the intermediates that are high in atypical dogs went down to normal. We started our dog on this and she seems a little happier.
Anyone heard of this or tried it?

[Squirt's Mom]

Hi and welcome to you and your baby!

Please, please, please in the name of all that is holy get that study and post it here. I cannot fathom why any vet with a head on their shoulders would use pred to treat Atypical. Pred will CAUSE another form of Cushing's not to mention cause all sorts of problems that never needed to happen. The treatment for Atypical is melatonin and lignans and it takes at least FOUR months for this treatment to work. There is absolutely no way in you know where any vet would put my baby on pred to treat Atypical. I would take my baby and run as fast as I could from any vet who tried, too. So please get that study and post it here...I admit I could be way out of touch and off base but I don't think so. ;) So let's take a look quickly before your baby pays a price she didn't need to at all.

Hugs,
Leslie and the gang

[corkie'smom]

Hi,
the article is found here:

http://www.petcarebooks.com/pdf/Atypical-Cushings-treatment.pdf

All the abnormal values for the dogs listed here were similar to Corkie's values. If it's true that high estradiol can mimic high cortisol symptoms, which is basically the thoughts behind using the lignans and melatonin, and physiologic levels of prednisone seem to alleviate them as well, it may be another treatment.
Physiological doses of prednisone is not the same as giving an anti-inflammatory dose.
Corkie's cortisol is low normal. She acts Addisonian.

Any thoughts on this?

[labblab]

Hello and welcome from me, too. I am wondering whether the article you are referencing was written by either Dr. Alfred Plechner or Caroline Levin? If so, yes, we have had previous discussions about their theories re: "adrenal exhaustion" and "Plechner Syndrome," and you can use our forum "Search" option to plug in their names and find those posts. You will find threads that mention their theories in conjunction with both "Atypical Cushing's" and also a condition called SARDS. SARDS is a poorly understood illness that involves sudden blindness that can occur in conjunction with adrenal hormone abnormalities.

I will try to come back later to write more, but unfortunately my personal impression is that their theories fall pretty far outside of validated scientific research and I have always felt that the recommendations to treat elevated adrenal hormones with supplemental steroids has the greater potential to do damage rather than good. In my memory, we have had a couple of folks who followed Dr. Plechner's recommendations in treating their dogs. One member believed that her SARDS' dog's blindness improved, although I don't believe any objective testing confirmed this. The other member was treating his dog with steroids in conjunction with elevated intermediate hormones, and the dog ended up developing diabetes, which I personally suspected might have been steroid-induced. I don't know the ultimate outcome.

I may be totally missing the boat here and you may be referencing some other research. So I'll not say more until we find out about the specific research you are citing.

In the meantime, can you tell us more about your dog's actual diagnostic and monitoring testing in conjunction with the trilostane? How much does she weigh, what dose of trilostane was she taking, and how did her monitoring ACTH tests turn out? What makes me especially nervous here is that I have to assume that your girl has elevated cortisol in addition to elevations in other adrenal hormones. If so, I think most conventional clinicians would say that administering additional prednisone to a dog with elevated cortisol is like pouring gasoline on the flames. So if she is truly doing better now with the supplemental prednisone, I have to wonder whether perhaps she was being overdosed on the trilostane and thrown into an Addisonian condition.

Anyway, the more details you can share with us the better. And once again, welcome. We will do our best to help you sort things out!

Marianne

[labblab]

Hi again -- we were typing at the same time. And yes, as I was suspecting, I see your article was written by Caroline Levin. Now that I know she's the author, I'll try to write more re: my concerns later on.

But first and foremost, I have to wonder whether Corkie is perhaps truly Addisonian as a result of trilostane overdosing. That is an entirely different situation than the "adrenal exhaustion" theories of Ms. Levin and Dr. Plechner. If so, her blood chemistries (specifically potassium and sodium) may also be imbalanced as a result of damage to adrenal function. How recently has a blood chemistry panel been performed? Were her levels all normal when they were tested? Are you working with the same vet now who was overseeing the trilostane treatment?

We really do need to know more about the course of her Cushing's diagnosis and trilostane treatment. The thing is, if Corkie's cortisol was previously elevated but now is very low subsequent to trilostane treatment, she is NOT suffering from Atypical Cushing's -- she instead may be genuinely Addisonian. So thank you in advance for telling us more specific details about her diagnosis, treatment and testing.

Marianne

[Squirt's Mom]

ahhhh what I also was afraid of. Caroline Levin is a human RN, not in the animal medical profession at all. She has some good thoughts on living with blind dogs but not on canine Cushing's. So I beg you to please stop the pred and if your vet insists on following this cockamamie treatment approach, find a new vet as quickly as you can.
;)

[corkie'smom]

Hi, her blood panels were normal except for elevated ALP and AST.
She was given only 10 mg of trilostane, and her weight was 25 lbs.
She developed diarrhea, shaking and malaise. The ACTH stim test was in the low normal range (can't find the result right now)
Took her immediately off the trilostane and sent a blood sample to Unive of Tenn. Unfortunately, the vet sent it too soon, since trilostane can affect some of the hormones and their intermediates. So, the values about 6 weeks after stopping trilostane:
Baseline Post ACTH
cortisol(ug/dl) 2.3 *5.0
androstenedione (ng/ml) **.77 1.65
estradiol **83.9 67.7
progesterone and testosterone were normal
17 OH progesterone ng/dl **1.7 **3.22

*low
**high

[corkie'smom]

Well to be honest, there isn't very much out there that is sound science concerning Cushing's treatment. At least Ms. Levine has an endocrinology background and isn't selling something.

[Squirt's Mom]

Oh honey, there is LOTS of sound info out there about canine Cushing's. Here is a good start for you - http://www.k9cushings.com/forum/forumdisplay.php?f=10

Ms. Levin may have training in endocrinology but she is an RN, a human RN, a nurse, not a doctor of any kind and with no training in animal care. ;) And she is certainly selling something - herself. She has gained attention by this "theory"...and harmed no telling how many dogs in the process sadly.

[Squirt's Mom]

Had to get to my laptop. :D Here are some more links with solid information on canine Cushing's.

Kate Connick*
http://www.kateconnick.com/library/cushingsdisease.html

Long Beach Animal Hospital*
http://www.lbah.com/canine/cushings.htm

Drs. Foster and Smith*
http://www.peteducation.com/article.cfm?c=2+2097&aid=416

Newman Veterinary*
http://www.newmanveterinary.com/CushingDiag.html

Cushing’s signs and pics*
http://www.newmanveterinary.com/CushSignFrame.html

BMD Health Library*
http://www.bestbeau.ca/bmd_health_links_4.htm
(scroll down to see Endocrine Diseases)

Mar Vista Animal Medical Center*
http://www.marvistavet.com/html/cushing_s_disease.html

Washington State Uni. – College of Veterinary Medicine
http://www.vetmed.wsu.edu/cliented/cushings.aspx

[labblab]

If Corkie's cortisol had only rebounded to 2.5/5.0 six weeks after stopping the trilostane, I do have to suspect that her natural adrenal function may be somewhat blunted on a long-term basis. If so, that could again explain why she may feel better with some supplemental prednisone onboard.

What about recent testing of her blood chemistries? As I wrote above, I am especially worried about the balance of potassium and sodium. Trilostane overdosing can affect aldosterone production in addition to cortisol. If that occurs, the balance of the electrolytes can be thrown off and this can actually become life-threatening.

Can you tell us more about the Cushing's-specific testing that diagnosed the disease back before the trilostane was begun? An ACTH or LDDS test, for instance? Given her poor response to the trilostane, one does wonder whether that was the correct diagnosis, originally.

I am not in any way trying or wanting to offend you, but I am very worried that Corkie's current pressing problem is not one of elevated intermediate hormones, but instead one of cortisol (and perhaps aldosterone) production. If so, she may be in need of the prednisone, but not for the reasons given by Ms. Levin. Plus, she may be in need of additional treatment, too. Are you consulting with a vet now about her abnormalities of behavior and labwork? At a minimum, I repeat that I really think she needs to have a panel of blood chemistries performed ASAP.

[corkie'smom]

Well, she's had 4 blood panels since her diagnosis, and 2 after stopping the trilostane. On the repeat panels, everything was normal except for ALP and AST. The 2 values are still high but did go down somewhat.
The family vet suggested the LD dexa test. I feel he has a tendency to over medicate (he would have started her on 30 mg trilostane!!)so I went to an internal medicine vet and had another blood panel, ultrasound and thorough exam. Adrenals were very slightly bilaterally enlarged. Everything else normal. Her drinking, urinating, panting and physique suggesting Cushings. I don't know what the reults of the test were, but I could find out. Corkie is very sensitive to everything, so she started her on 10 mg trilostane. In 2 days drinking, urinating and panting were normal. Diarrhea, malaise and shaking started at about 12 days. The stim test were low normal (don't have the results right now) continued

[labblab]

Are you still consulting with the internal medicine specialist? What are her thoughts as to how to proceed since Corkie is still unwell?

[corkie'smom]

The vet wanted to repeat the stim test in 2 weeks. Unfortunately, she went on to bigger and better things and I found another internal medicine vet. She agreed with the diagnosis and protocol.
Did major blood bio panel, urinalysis - fine except for liver enzymes. Sent The blood to U Tenn, but they felt the results were affected by the trilostane so we had to redo it.
Not seeing much for 2 months of the melatonin and lignan, although it still is early. She is just so droopy and shaky and vet thought the prednisone may help. She has other atypical dogs, but Corkie seems different. The prescribing had nothing to do with the Levine article.
Corkie is an interesting dog. Very sensitive to feelings of others. She sits on a chair at the kitchen table, not for food but to be involved with the action. Gets very upset with driving in the car, visiting the vet, storms, wind, etc. She probably has anxiety related bowl issues.
I didn't mean to offend anyone about the lack of research. There is a lot of stuff circulating out there. Not much in the way of scientific papers. I have a doctorate in a science field and I know how easily information that isn't fact can be construed as fact because of not understanding the science or the logic behind it. This vet stuff seems to really bring this home to me. It's worrisome. Also, the melatonin dose is really high. Any justification for that?

[corkie'smom]

Yes the vet is keeping in touch. I just started the prednisone last Friday. I have to call her weekly and describe how Corkie is doing. Taking her to the vet is so stressful for my baby.

[corkie'smom]

Another interesting physical problem with Corkie is that the vet shaved her to do the ultrasound and the hair hasn't grown back. That's been over 4 weeks. Also, she does this lip smacking thing. Vet thought it may be that her stomach is upset?

[labblab]

I'd be super interested in knowing what an ACTH result prior to beginning the trilostane might have been, but it sounds as though the ACTH testing did not begin until after treatment was begun. That's not a criticism of anybody, because the LDDS is considered to be the preferred diagnostic test by many folks. But as things have unfolded, it would just be interesting to have had a pre-treatment ACTH for comparison purposes.

I guess one part that remains a puzzle for me is why folks seem to be primarily focused on those other adrenal elevations right now. Have the original Cushing's symptoms rebounded even with a cortisol level that is low? I was thinking your worries about Corkie's current symptoms correspond more closely with adrenal oversuppression rather than undersuppression. Are you instead seeing a different set of problems now? Lack of hair regrowth is typically a symptom of too much cortisol rather than too little, but what other problems are you seeing right now? And yep, lip smacking can be associated with nausea.

[labblab]

Just wanted to add that what we've seen and been told here is that all dogs who exhibit elevated cortisol will also exhibit elevations in other adrenal hormones, as well,if the full panel is tested. The big question is whether or not those other elevations are actually independently responsible for any behavioral or laboratory abnormalities. So that's where Corkie's situation gets more complicated for me. If her cortisol is now oversuppressed, what significance or concern should be attached to those other elevations? I definitely dunno, myself, but that's one of the big questions I have going forward. Are the lignans and melatonin even really called for right now, or are they making her feel even more dopey? I think a high dose of melatonin could definitely do that.

[corkie'smom]

As of last night, she starting drinking and urinating more. I think I should stop the prednisone. She has perked up though.
There has been no change in the pot bellied appearance since the beginning. She hasn't gained back any of the weight she lost since this started. Hind quarter muscle loss is the same or worse.

Not sure what to do.

[labblab]

How long ago was that last ACTH done (the one that had the cortisol result of 2.5/5.0)?

[corkie'smom]

The last ACTH stim test was done on 10/14. I gave the values previously

The previous ACTH stim test (being on trilostane, 10 mg from
8/8 -8-22) was on 9/10.

Cortisol baseline: 4.6 ug/dl
post ACTh: 7.7 ug/dl

Estradiol was 95.4 pg/ml, 93.1 pg/ml

[labblab]

So her cortisol was actually lower on this most recent test than it was in September, at which time the trilostane had already been discontinued for a couple of weeks....:confused:

You say that she's on a really high dose of melatonin? What dose is she taking? I don't know whether it could be having this much effect on her cortisol or not.

I know I keep repeating the same thing, but I'm feeling more worried about her cortisol than about those intermediates right now. It seems as though something really goofy is going on with the cortisol. Was an ACTH done in August, right at the time the trilostane was halted? The thing is, the 4.6/7.7 was really not too low at all for a dog being actively treated with trilo. It was right in the correct range. But the numbers are obviously not the whole picture if a dog's behavior is abnormal. Were there ACTH results that were lower, though, in August when the trilo was stopped?

[Renee]

I have to wonder if:

1. the cushings diagnosis was just wrong to begin with, and that's why the severe reaction? Remember, the cortisol range for a healthy dog is higher than the range we look for in a controlled cushings dog. While both of her stim results are in range for treatment, they are out of range for a healthy dog.

or,

2. Corkie is just one of the dogs that for whatever reason, just does not react well to vetoryl and cannot tolerate it at all.

Were any stim tests done while she was actively taking vetoryl? Or right after you stopped treatment due to her reaction?

It seems there has been a lot of up and down with medications. First vetoryl, then pred, then melatonin/lignans. Maybe she needs to get off of everything and do a little rebounding before pursuing additional diagnostics? Of course, first make sure it's safe to take her off the pred.

[corkie'smom]

I don't have a copy of the results of the stim test while on vetoryl , but it was in the low normal range. The vet was shocked after 2 weeks on such a low dose of vetoryl that Corkie was at that level. With the diarrhea, nausea and malaise, we decided to stop vetoryl and do another stim test in a few weeks. Results are above.

Her dose of melatonin is 3 mg twice a day. She's been on that since 9/10 along with 20 mg hmr lignin. The prednisone, 2.5 mg/day, was started a week ago today. We have been weaning her off the melatonin since she is so lethargic on it. My husband, who is a PhD in nutritional biochemistry was shocked about the recommended dose. In humans, .3 mg is the tested adequate dose.

[Renee]

When you say "low normal range", do you know which range that would be? The 'normal' range for a healthy (ie non-cushings) is generally 8-22 ug/dl, while the 'normal' range for a cushings pup using vetoryl treatment is 2-5 (up to 9, if controlled) ug/dl.

All of this is to say -- if she was 'low normal' according to the healthy dog range (8-22), then that would indicate her cortisol has continued to steadily drop, even with the vetoryl being discontinued. That's an odd trend and not one that supports cushings, especially once the medication was halted.

It would be very, very helpful if you were able to round up all the stim test results, and post them chronologically. I am afraid we may see a trend of her cortisol dropping, and continuing to drop, even though she is no longer being treated with vetoryl.

[corkie'smom]

Cortisol was in the 2-5 range after being on vetoryl for 2 weeks.

[labblab]

OK, so here's the timeline that we have so far:


Trilostane (10 mg.) for two weeks, from 8/8 - 8/22

ACTH performed when trilostane was discontinued: Somewhere between 2 - 5

ACTH (approx. two weeks later) 9/10: 4.6 and 7.7

ACTH (approx. one month later) 10/14: 2.3 and 5.0


So the ACTH at the time the trilostane was discontinued was actually within desired therapeutic range for treatment. However, Corkie was feeling poorly. By two weeks later, the cortisol had rebounded higher. A month after that, the cortisol was lower again.

Question: At what point did you start the melatonin treatment? If it was between the September and October ACTH tests, perhaps the melatonin could actually account for the decline. And per the UTK melatonin dosing guidelines, 3 mg. twice daily is indeed the recommended dose for a dog weighing less than 30 pounds.

So here's some random thinking on my part...it is possible that Corkie's poor reaction to the trilostane was the result of "corticosteroid withdrawal" instead of a true Addisonian drop, meaning that when cortisol levels are lowered quite significantly and quite quickly, dogs can really feel crappy for a while even though their cortisol is not technically at a dangerously low level.

Her cortisol did head upward two weeks after the trilo was discontinued, but it subsequently dropped again in October, but perhaps as a result of the melatonin. Maybe the cortisol is again on the rise, though, since you are seeing some symptom worsening. If so, could be due to natural cortisol rebound, but perhaps it is instead the pred. Since her cortisol has never been dangerously low, though (at least, not yet), I guess I'd agree that I'd check with the vet about discontinuing the pred and watching what develops: seeing whether her Cushing's symptoms increase all on their own or not. At least, that's my thinking right at this moment. :o

Marianne

[corkie'smom]

Here are Corkie's results in one place.

LDDS Test: 8/6

Pre Dexa: 6.2 ug/dl (1-6 ug/dl normal)
Post 4hr : 6.1 ug/dl (<1.5 ug/dl normal)
post 8 hr: 5.7 ug/dl (<1.5 ug/dl normal)

ACTH Stim test 2 weeks of being on 10 mg vetoryl: 8/20
Pre-ACTH cortisol: 2.8ug/dl
Post-ACTH cortisol: 3.5 ug/dl

ACTH Stim Test: 9/10. Vetoryl stopped on 8/22
Pre-ACTH cortisol: 4.6 Ug/dl
Post-ACTH cortisol: 7.7 ug/dl

ACTH Stim Test:10/14
Pre-ACTH cortisol: 2.3 ug/dl
Post-ACTH cortisol: 5.0 ug/dl

[corkie'smom]

I started the melatonin on 9/11.

[corkie'smom]

I started the prednisone on 11/7.

[labblab]

Thanks a lot for gathering all that info together! So you did start the melatonin right after the second ACTH. So maybe it's the melatonin that is responsible for the subsequent downturn in cortisol on the October testing. I just don't know whether that decline is in an amount for which melatonin would typically be responsible.

Just as I wrote above, though, I think I agree with your suggestion about talking to the vet about stopping the prednisone for now and watching how Corkie responds.