New Member with recently diagnosed Bigley

[Seaweedsally]

Hi guys my name is Jennifer and my dog was diagnosed with Cushings on 12.22.12. Your site has been a tremendous help. It's so informative and kind. My baby is about 7 years old and a lab mix. He was abandoned by a neighbor 2 years ago in the dead heat of summer malnourished, flea infested an left to die. My husband and I quickly took him in and started giving lots of medical attention and love. He has been so greatful ever since and such a good baby.

We started noticing some unusual sign last November with a skin irritation that wouldn't heal. Then by mid December he was presenting with excessive thirst and urination and weight loss. My vet ran a senior blood profile and urinalysis. His bloodworm was good and vet ran additional thyroid test to rule that out. He did have diluted urine at this time. Vet called us and said he wanted to test him for Cushings....so here we went.

He tested positive for Cushings on 1.10.12 with a value of 28.6. The vet put him on Trilostane 120mg once daily. Within a week the excessive drinking and peeing had stopped and everything seemed to be going fine.

His next ACTH stim on 1.27.12 was 4.2. We noticed his appetite had decreased and he had become more lethargic (he's never been active). He has pretty bad arthritis and with the decreased cortisol he was definitely starting to feel bad.

He went in for another ACTH stim on 2.10.12 and had a value of 7.7. By this time he was down to 60.5 lbs. with his values being in therapeutic range he kept him on 120mg Trilostane.

Fast forward to 2.23.12 and Bigley had stopped eating and had dropped down to 56.7 lbs. He was not feeling well at all. I had the vet do some blood work and everything was fine. He was X-rayed and no signs. Get did an ultrasound and there were no tumors on adrenals.however, he does have serious arthritis in hips and thoracic area.
I was really getting a strong feeling it was the Trilostane that made him quit eating. The vet and i agreed to take him off the Trilostane to see if we could get him to eat. He prescribed Mirtazepine to stimulate appetite.
I got home and gave him the Mirtazepine and in 30 minutes he was eating. We have been feeding canned food and we got the weight back on him.

Forgot to mention he has been on Tremadol 50 mg for pain since 1.10.12.

So we took a week off the Trilostane and put the weight back on and the vet said to hold the Mirtazepine to see if he would eat on his on. After being back on the trilostane for 4 days and and the appetite stimulant he didn't eat on his own. Again I gave him the Mirtazepine and within an hour he was eating. We are in this for the long haul and we are not giving up on him.

QUESTIONS: Has anyone seen serious anorexia with the use of Trilostane?

Is Tramadol an effective med for pain and arthritis?
The vets think it is pituitary and he has been exhibiting some odd behaviors like pacing in the house and has peed in house twice.

I have more questions but I don't want to be overwhelming. Thanks for any help you can offer

[Harley PoMMom]

Hi Jennifer,

Welcome to you and Bigley! So sorry for the reasons that brought you here but glad you found us.

According to Dechra's US Product Insert:
The most common adverse reactions reported are poor/reduced appetite, vomiting,
lethargy/dullness, diarrhea, and weakness. The link to where this info and much more can be found: Dechra's U.S. Product Insert. (http://www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Vetoryl.pdf)

I was wondering if your vet told you that the Trilostane has to be given with food to be absorbed better and that the ACTH stimulation test has to be performed 4-6 hours after the dose of Trilostane.

It does seem that Bigley's ACTH stim results are well within the therapeutic ranges, if done correctly.

Has Bigley been checked for pancreatitis? Are his kidney levels within the normal limits? What about his liver enzymes? If you could get copies of the chemistry/CBC results and the tests that were done to confirm the Cushing's and post any abnormalities here that would really help us.

I was also wondering when the ultrasound was done if the adrenals were visualized?

Tramadol is good for pain but don't really believe it helps with arthritis pain. Some members use adequan shots, Glucosamine, Chondroitin, and fish oil.

Please know we will help in any way we can so do not hesitate to ask any and all questions.

Love and hugs,
Lori

[labblab]

Hi Jennifer,

Welcome from me, too! A couple of quick questions for you. How was Bigley's appetite before you began the Cushing's treatment? I believe you said he was already showing weight loss before the trilostane was even started. Was diabetes definitely ruled out for Bigley, since the combination of excessive thirst and weight loss is much more common with diabetes than with Cushing's. Also, more recently, has he been "off" both the trilostane and the appetite stimulant simulataneously? If so, how did he do?

As you can tell from my avatar, my Cushpup was a Lab, too. Unfortunately, we lost him to what we assume was an enlarging pituitary tumor that ended up putting pressure on other important areas of the brain -- including the area that controls appetite. I do not want to alarm you unnecessarily, but this line in your reply really caught my attention:


The vets think it is pituitary and he has been exhibiting some odd behaviors like pacing in the house and has peed in house twice.

While anorexia is indeed listed as a possible side effect of the trilostane itself, it can also be a symptom of an enlarging pituitary tumor. And there are a couple of aspects of your boy's situation that are similar to my experience. First, the weight loss. It is very unusual for Cushpups to lose weight. A ravenous appetite is a very common symptom of the disorder, and most dogs gain weight prior to diagnosis. However, even though my dog did have the ravenous appetite, he was inexplicably losing weight, too. Either way, I am curious about Bigley's appetite before beginning treatment.

Moving on, we also started on trilostane, and the excessive thirst and urination quickly resolved. My dog was treated several years ago, and the dosing guidelines were different. He weighed about the same amount as Bigley, and also started out on 120 mg. For both our boys, that is a higher starting dose than many specialists are now recommending. But even at that higher dose, his cortisol level was still higher than we wanted. So we increased the trilostane even more. But at no time did his cortisol level ever fall below around 6 ug/dl, even on the higher dose. However, for a time, everything still remained fine. But after about nine months of treatment, he lost his appetite and low cortisol was not the culprit. And then we started to see a combination of neurological abnormalities including pacing aimlessly around the house, lack of coordination, soiling himself for the first time in his life, and finally a loss of the desire to eat and drink entirely. There are possible treatments for enlarging pituitary tumors which some of our members have undergone successfully. But for a variety of reasons, we decided not to try to treat, however, and sadly euthanized instead.

I know this is a sobering story and I hesitate to spell it all out for you. But there are some parallels with your boy that caught my attention, although they may be purely coincidence. And in retrospect, one thing I wish we had done was to completely withhold the trilostane for a bit longer time period, in order to see whether that would have made any difference at all in his appetite. And so returning full circle to where I started out this reply, that is why I'm wondering whether, without the appetite stimulant, his natural appetite would return while off the medication -- or whether he needs the appetite stimulant either way.

There is reason to believe that Cushing's treatment actually has the potential to hasten the growth of pituitary tumors because of disruption to the normal pituitary feedback loop. For most dogs, this does not present any real problem because the tumors are usually so tiny to begin with. But for a small subset of dogs, the growth can present a problem. I suspect my dog was one who fell in that category. And I do wonder if that might be the case for Bigley. But I never knew for certain how much the trilostane itself might have been affecting his appetite. That's why, if I had a do-over, I wish I could have experimented with a longer "break" from the drug in order to see whether his appetite would have improved on its own. It is also possible to know, for certain, whether the size of the pituitary tumor is an issue. Either an MRI or CT scan of the head can be done. Both of these procedures are expensive, but they can tell you definitively whether or not that is the source of the problem. And if so, there are treatments that can be considered which are more likely to be successful if performed sooner rather than later.

I see I've written a book so will end here. But I did want to throw these thoughts out for you consideration. And also to get a bit more info about Bigley's appetite history. And also to ask whether you are seeing any other "odd" changes in his behavior...

Marianne

[Seaweedsally]

Thanks Lori and Marianne for the quick reply. I am so worried and overwhelmed and it's comforting to have your guys support. I'm going to try and address your questions individually but there may be some overlap.
NOTE: Bigley never presented with hair loss or ravenous appetite

Re Lori:
The bet did not tell me to give the trilostane with food nor did he tell me to give him the trilostane in order for him to do the ACTH stim. I gave him the trilostane about 7:00 pm and then would drop him off at 9:30 the next morning and he would stay until 2:00pm.

How much would this throw his levels off?

As far as I know he was not checked for pancreatitis. Is there a specific test for that?

Latest blood work as of 2/21/12: abnormalities as follows
EOS----- LOW. 0.07 k/ul. Range (0.10-1.49)
ALT-----HIGH. 102 U/L. Range. (10-100)
AMYL---LOW. 461 U/L. Range. (500- 1500)

When the vet did the X-rays combined wih the ultrasound he did say both adrenals were enlarged. He said if it were an adrenal tumor on gland would be larger. Is this is true and is this what they mean by testing for pituatary or adrenal dependency?

I hope this helps. If there any more info you need let me know.

Re: Marianne:
His appetite was good before the Cush dx. When we took him in for annuals and to check on the skin irritation he was 73lbs and had not started drinking and peeing excessively until first of December. We didn't notice the increase overnight. It was just more gradual and combined with the skin irritation that hadn't healed we took him in on 12/22/11. The vet knew he had something going on but didn't mention Cushings at this time.

As far as diabetes being ruled out would that have shown up in his blood work?

I wasn't very clear about my explanation of appetite. We took away the 120mg trilostane and immediately put him on Mirtazepine. He has lost so much weight by then and quit eating that we had to get some weight on him fast. He started eating instantly and I guess we can't tell which worked. We then kept him off trilostane and gave him the Mirtazepine for 5 days in which he had a great appetite and gained 5lbs. After consulting with another vet he cut his dose in half to 60mg. Since the Mirtazepine has a long half life we went on extra day to see if he would eat on his own while taking the 60mg trilostane. And once again he did not eat so we dosed with the Mirtazepine and he started eating again. But one important note!!! I have noticed in today that his appetite has decreased some.

The odd behavior is scaring me a bit. Sometimes he just paces aimlessly around the house and he went out the other night and jumped in he creel behind our house. He was completely soaked...he has never done that. He used to come upstairs and bark to want to go out in he night. He has stopped this maybe because he can't get upstairs I don't know. Last night he peed in the kitchen floor but never barked to wake us up...and trust me I've been sleeping with one eye open ever since this started. He seems like he can't hold it as long anymore. He can't hold it much longer than 2 hours now.

Any thoughts??

Thank you guys so much for any help and ideas.

[Harley PoMMom]

Re Lori:
The bet did not tell me to give the trilostane with food nor did he tell me to give him the trilostane in order for him to do the ACTH stim. I gave him the trilostane about 7:00 pm and then would drop him off at 9:30 the next morning and he would stay until 2:00pm.

How much would this throw his levels off?

If the ACTH stimulation test was not done 4-6 hours after the dose of Trilostane, then the results are skewed.

According to Dechra's Product Insert:
After approximately 10-14 days at this dose, re-examine the dog and conduct a 4-6 hour post-dosing ACTH stimulation test. This information and more can be found here: Dechra's U.S. Product Insert. (http://www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Vetoryl.pdf)

Dr. Peterson, a renown Cushing's expert, has this to say and more about the best protocol for an ACTH stimulation test:
With trilostane, it’s extremely important to give the morning medication with food, and then start the ACTH stimulation test 3 to 4 hours later.

Fasting these dogs on the morning in which the ACTH stimulation test is scheduled should be avoided since it invalidates the test results.

This excerpt can be found here: What's the Best Protocol for ACTH Stimulation Testing in Dogs and Cats? (http://endocrinevet.blogspot.com/2011/03/whats-best-protocol-for-acth.html)


As far as I know he was not checked for pancreatitis. Is there a specific test for that?



The spec cPL test is the best way to get a confirmed diagnosis for pancreatitis. A link with info about this test: http://www.idexx.com/view/xhtml/en_us/smallanimal/reference-laboratories/testmenu/innovative-tests/spec-cpl.jsf?SSOTOKEN=0

My boy, Harley, had pancreatitis but displayed no symptoms. His pancreatitis was diagnosed from an ultrasound and confirmed with the spec cPL test.

With PDH (pituitary-dependent hyperadrenocorticism), both adrenals are enlarged but a chronic illness can cause both of the adrenal glands to become enlarged also.

With ADH (adrenal-dependent hyperadrenocorticism), one adrenal will usually be atrophied and one or both will have a mass. ADH accounts for about 15% of all cases of Cushing's in dogs, while 85% of dogs with Cushing's have PDH.

We are definitely here for you and Bigley and remember that you are never alone on this journey.

Love and hugs,
Lori

[labblab]

Thanks so much for this additional info! It definitely fills in several puzzle pieces. First and most importantly, I want to "second" Lori's worries about the monitoring ACTH testing. It is not at all your fault since your vet did not give you proper instructions. But given the time frame within which the testing was done, I am very afraid that Bigley has been overdosed on the trilostane -- and that would most certainly at least account for the anorexia, if not other odd behaviors. Trilostane has a very short half-life, and the "trough" in a dog's cortisol level will come within about 1 1/2 hours after dosing. By twelve hours later, the cortisol level will have rebounded significantly in most dogs. Here's a quote from that Product Insert that Lori gave you earlier:


Trilostane absorption is enhanced by administration with food. In healthy dogs, maximal plasma levels of trilostane occur within 1.5 hours, returning to baseline levels within twelve hours,although large inter-dog variation occurs.

Since Bigley wasn't being tested until more than fourteen hours after his trilostane dose, the maximal effect (and lowest cortisol level) would have occurred many hours before the test was conducted. And since his fourteen-hour (baseline) results were as low as 4.2 and 7.7, we can assume that his level right after dosing may have been WAY too low for safety and comfort. It is actualy perhaps a lucky fluke that you were not giving the trilostane with food (as it ought to be given), or else it would have been metabolized even more efficiently and the cortisol results even lower.

I know it presents a very awkward situation, but your vet really owes you two free ACTH tests since you were not given proper instructions! And most importantly, what is Bigley's cortisol level now, on the 60 mg.?

I still also have some concerns about the original diagnosis. The original diagnostic ACTH test is indeed elevated, but as Lori has pointed out, other illnesses besides Cushing's can also result in a "false positive" for Cushing's. Diabetes can be ruled out by routine blood testing (it's the "Glucose" reading on a blood panel). So if that was still normal on 2/21, then diabetes shouldn't be the problem. But I'm still not sure about this -- was Bigley losing weight even before he started the trilostane? If so, that is still unusual. Also, Bigley does not have the elevations in liver enzymes that are typical of Cushpups (apparently no elevation in ALKP and only a tiny elevation in ALT). Do you know whether those liver readings were higher before he started on the trilostane?

Is Bigley still taking the 60 mg.? If you are seeing a decrease in appetite again, I'd be worried that his cortisol is still/again dropping too low. On one hand, I'd be wanting to know an accurate cortisol on this current dose. But that will require shifting to morning dosing for at least a few days, and the trilo given with food 4-6 hours prior to testing on the day the ACTH is performed. And if Bigley is doing poorly even on the 60 mg., the better approach may be to take him off the trilostane all together until you see his appetitite stabilizing again *without* the need for an appetite stimulant. And an ACTH test performed before you consider putting him back on the trilo -- to make sure that his cortisol has indeed rebounded to a level where it is safe (or necessary) to resume the medication. Even though the effects of trilostane are supposed to be short-lived, the manufacturer acknowledges that some dogs can end up with long-term suppression of the adrenal glands that is not currently well-understood.

Please know that I am not a vet, so these are all suggestions for you to consider. But truly, your vet does owe you some free ACTH tests!

Marianne

[Seaweedsally]

Thank you guys so much for the fast replies. I talked to the bet today and he did agree on the improper ACTH stim. After reading more I did ask him if it was possible that he couldn't take the trilostane and he said yes. He did say there were a small number of dogs who could not tolerate the trilostane. Since he has only been on the half
Dose of 60mg for 5days and his appetite has gone down again even with the stimulant he does want me to stop the trilostane. And I couldn't agree more because I just don't think he can handle it. He's having a really bad day today not feeling good, no appetite, and very out of sorts and pacing when he does get up.

And yes he was losing weight even before the Cushings diagnosis and no appetite stimulant. And after talking to you it is more evident that he may have had something else going on before.

In his initial blood work (12.22.11) before the cushings diagnosis ALT was higher at 141.0 U/L range (12-118) compared to 102.0 on feb 21.
His initial ALKP was 186.0 U/L range (5-131) compared to normal 118 U/L range (23-212) on feb 21.

The vet told me today that not treating the Cushings was an option for that cushpups could live a long time. He said the option to treat was sometimes more to relieve the inconvenience to the owners. This was a little freighting because wouldn't a Cushings dog be uncomfortable untreated? And he did say if we didn't treat it he could give him some kind of anti-fungal drug that would decrease the drinking and peeing some.

He also said that if he can't tolerate the trilostane we might be able to try the Lysodrn or mitotane but he doesn't like to use these because they are not as safe. Thoughts?

And "yes" he was losing weight before the Cushings diagnosis. And maybe I just didn't want to hear or believe it but he did say last week "since he was already losing weight before, we might be 'chasing' cancer".

I don't know if I'm making any sense because I'm so nervous and scared. I don't want to let him go if i think there is something i can do for him, but i also don't want to be selfish and let him suffer.

Thank you guys so much for your love and compassion!
Jennifer



These were his symptoms before the Cushings diagnosis:
Excessive thirst
Excessive urination
Decrease in appetite
Skin irritation on under back left leg that didn't heal after antibiotics

What are the chances of a false positive for Cushings?

He has not had the specific test cPL for pancreatitis. Is it my understanding that the ultrasound wouldnt show anything and him have pancreatitis?

[labblab]

Jennifer, under the circumstances, I'm really glad you are stopping the trilostane, at least for the time being. In the future, if Bigley truly does have Cushing's, trilostane may still be a reasonable treatment option for him -- but at an appropriate dose. At this point, given the invalidity of the two monitoring ACTH tests, we have no idea as to what would actually be an appropriate dose for him. It might be a dose even smaller than the 60 mg.

But first things first, and that is to get a better handle as to what is really going on with Bigley. If he does not perk up quickly, at a minimum I would want the vet to do a simple test of his blood chemistries to make sure that they have not been thrown out of whack by a too-high dose of trilostane (the levels of sodium and potassium are the most likely to be affected).

And I still can't get the question of diabetes out of my head, given Bigley's original symptoms of a skin infection that was slow to heal, excessive thirst and urination, and weight loss. Do you have copies of the blood tests that have been performed since December? Can you look up "Glucose" levels? Also, do you have results of any urine tests that were run? Again, you'd be looking for the presence of glucose in the urine.

I'm also going to ask the administrator of our sister forum, k9diabetes.com, to stop by and see if there is any other testing that she thinks might be helpful in this situation.

So stay tuned, and please do keep updating us on Bigley is doing now that you've stopped the trilostane.

Marianne

[k9diabetes]

Hi Jennifer,

I am very happy to hear that you will be stopping Trilostane treatment, for all of the many reasons listed by others. I have seen a handful of dogs at the diabetes forum who did not do well at all on Trilostane and also whose Cushing's diagnoses were questionable, as it seems like Bigley's may be.

I hope you have copies of the bloodwork and can check the glucose levels to see if they are normal. I am assuming they are, though. It's pretty rare for a vet to miss that and I imagine you would have listed them if they were out of range.

The liver enzymes are very very mildly elevated. Almost any endocrine problem and a lot of other problems could raise the lever enzyme test results that much. And, as others have said, weight loss also does not suggest Cushing's disease. So there are plenty of reasons to question whether Cushing's treatment is needed at all.

Another possibility for the increased thirst and urination is diabetes insipidus. Though it shares the name with diabetes mellitus, insipidus is unrelated to blood sugar.

http://www.petplace.com/dogs/diabetes-insipidus/page1.aspx

The most problematic thing, I think, will be if the thirst and urination immediately return. I don't have any idea how Trilostane might impact something like diabetes insipidus... I suppose it could have an effect on the hormones involved. But if it's insipidus, there are other treatments for that.

As far as the pacing goes, while a brain tumor is one possibility, I could also see that kind of behavior being caused by pain made significantly worse by sharply reduced cortisol levels. Cortisol helps alleviate arthritis pain, for example, so Bigley's arthritis could be very painful right now and certainly could make him not want to navigate the stairs.

Another possibility for weight loss is an inflamed bowel. Could be he has some auto-immune issues involving both the bowel and the skin, for example. Maybe allergy related or just because he tends to auto-immune disorders.

So there are a lot of possibilities involved here and I think eliminating the Trilostane now is a good first step to sorting it out and will hopefully make Bigley feel a whole lot better. Several of the other dogs I know who have had problems with Trilostane have just felt awful while taking it and so much better off.

As far as Lysodren vs. Trilostane goes, I think a lot of vets have been misled in thinking Trilostane is "safer" than Lysodren. They each are powerful meds with potential side effects that can be a big problem and I don't think one is better necessarily than the other. So if he needs Cushing's treatment, I wouldn't be afraid to try Lysodren.

Natalie

[jmac]

Hi Jennifer,

While I don't have any advice to offer you (although that's fine because you already have gotten great advice from the experts), I just wanted to stop by to tell you that we are here to support you and Bigley. You have found a wonderful place with lots of helpful, kind, and supportive people, who are all hoping for the best for Bigley!

Julie & Hannah

[marie adams]

Welcome to the Family Jennifer and Bigley :),

Please do not ever think you will overwhelm us--just keep asking questions and sharing what is happening. The experts are already sharing and answering a lot of your questions. If they do not know they will research it for you.

Take care--you are doing a great job of helping Bigley!!! :)