Elevated liver enzymes and Cushings.

[Donna Missy's Mum]

Hello
Thank you for this forum and site!!
I found it an amazing comfort when our little girl was first diagnosed.
This is my first post. My girl was diagnosed with Cushings 7 weeks ago.
Her liver enzymes were astronomical and climbing and ultrasound showed spots on the liver. Her Vet said that she only seemed well because the massive amounts of cortisol were masking her liver disease.
She also said Missy's results were overwhelmingly positive for Cushings but liver disease was our immediate concern.
We decided on open liver biopsy as this is the gold standard for diagnosis of liver disease.
We did not know if she would survive the surgery but she did and recovered so quickly.
She was immediately put on a liver support diet, Ursodiol and Denamarin while we waited for results.
Results came in. No liver disease!

We started on Trilostane 5mg twice daily and maintained liver treatment.
Her ACTH? test 2 weeks later showed her cortisol was at the high end of normal!! Happy days!!
She has put on weight, her hair is growing back and her fat Cushings belly is slowly shrinking!! Only the odd tremor from time to time.
However....... a follow up liver function test shows her enzymes have come down but are still massively elevated.
Her first liver panel:
ALP 5591
AST 496
ALT 1767
GGT 900
(Not a misprint)

Last weeks results:
ALP 3427
AST 222
ALT 1083
GGT 420

Do these enzymes take time to come down?
Our regular vet is away and the vet I spoke to seemed baffled?
Has anyone had experience with enzyme values like these coming down slowly.
We were just starting to believe our girl was going to be ok but are now worried we were just being too hopeful.
Any advice would be so appreciated.
Thank you
Donna

[Harley PoMMom]

Hi Donna,

Welcome to you and Missy! I am so sorry for the reasons that brought you to us but glad you found your way here. Could you tell us what test/s were performed that diagnosed the Cushing's and could you also post those results? Were her adrenal glands visualized on the ultrasound, and if so, what were those findings? Does Missy have any of the most common symptoms of Cushing's such as an excessive thirst/urination, ravenous appetite, and/or panting? How much does she weigh? What were the results of her latest ACTH stimulation test? Also, is Missy getting her Trilostane with a meal? And was that monitoring ACTH stim test done 4-6 hours post pill?

A very elevated ALP is generally found in cushdogs but we usually do not see the other liver enzyme levels so high as in Missy's case and I am relieved that liver disease was ruled out. Sometimes the ALP never returns within the normal ranges so that particular one may never normalize in Missy, as for the other ones, I'm just not sure because as I mentioned we, or at least I, haven't found those other enzymes to be so high in dogs with Cushing's but the fact that they are coming down is encouraging.

When is the vet planning on rechecking her liver enzyme and cortisol levels again?

Lori

[Donna Missy's Mum]

Thanks Lori
I don't know which Cushings test she did but she was tested 4 hours after her morning dose. I am waiting for another vet to get back to me so I can ask questions about the test and the values.
She weighs 5.8kg and I give her the trilostane with her meals and the Denamarin an hour before the evening meal.
She did urinate very frequently and only goes out about 3 times a day now down from up to 10 times. Her fur was thinning and she had the classic Cushings belly (well still does, just not as bad).
Since the trilostane and liver support started she has been really well. She has regained muscle too. Her rump was feeling really bony but is great now.
It seems like the Cushings is under control but those liver panel enzymes are still scary.
I understand the cortisol can damage the liver, maybe it takes time for the liver to repair.
She has a great regular vet who I'm yet to speak to but I do like to do my research.
She was prescribed a starting dose of Trilostane of 10mg twice daily but after looking at the Dechra recommendations I suggested we start lower at 5mg twice daily as I was scared of her going into Addison crisis. Turns out the lower dose was OK.
I have been searching to see if anyone else's pup had liver enzymes that high.
We had just started believing we would have her for a while longer before this last test.
I will repost when I have more info.

Thanks again
Donna

[lulusmom]

Hi Donna, and a belated welcome to you and Missy.

I too share your concerns with the abnormal liver enzymes. This is definitely not the pattern we see in cushing's so Missy definitely has something other than cushing's affecting the liver. We have seen dogs with ALP increases in the 5,000's but AST is usually normal, ALT is mildly elevated and GGT is often normal or mildly elevated. I'm glad to see they have come down but not enough. I see that your vet did an abdominal ultrasound and it appears that Missy may have something called hepatic nodular hyperplasia. These are usually benign nodules on the liver that are commonly seen on imaging in senior dogs. These nodules don't usually cause any clinical signs, meaning a dog is usually otherwise healthy. Can you get a copy of the abdominal ultrasound interpretation and share them with us? We have seen more than a few dogs with gall bladder mucoceles which can cause more severe elevations so I would be interested to know what the gall bladder looked like. I have shared my life with many Maltese and this is a breed that is definitely over represented in gall bladder mucoceles. Ursodiol is often prescribed for this so I am wondering if this drug is one of the liver meds prescribed? Was a needle guided liver biopsy done? This is not a benign procedure so it's possible your vet opted to treat the numbers. With respect to your concerns about the high levels of cortisol's effect on the liver, cushing's does not damage or kill liver tissue, it affects the body's metabolic processes and causes an over accumulation of glycogen (fat) in the liver. This is what causes the liver to the enlarge in dogs with cushing's and while the liver may have to work a bit harder, it does not cause liver disease. It is also not uncommon for the ALKP to never return to normal in dogs with cushing's, despite liver support supplements, but other liver enzymes usually return to normal range. I hope this helps and I look forward to hearing a lot more about your precious Missy.

I'm sorry for the reasons that brought you here but I'm really glad you found us. You just happened to land in the best support group on the net. There is lots of collective experience and a whole lot of reference material that will help you understand the disease and its treatments a lot better. When you get a chance, take a look around at our Helpful Resources subforum. Since you are treating with Vetoryl, I'll get you started on a great reference (link below) that summarizes Vetoryl dosing and monitoring protocol. This is very important as you play a critical role in administering the drug and making sure proper protocol is followed for every acth stimulation test. Let us know if you have any questions and we'll do our best to answer them. It is extremely rare that our staff and/or senior members would be unable to answer the vast majority of questions that are commonly asked by members.

http://www.k9cushings.com/forum/showthread.php?8925-GENERAL-GUIDELINES-for-Dosing-and-Monitoring-Treatment-with-Vetoryl-(trilostane)

Glynda

[labblab]

Hey Glynda, I’m not Donna of course ;-), but here’s the answers to a couple of your questions:


We decided on open liver biopsy as this is the gold standard for diagnosis of liver disease.
We did not know if she would survive the surgery but she did and recovered so quickly.
She was immediately put on a liver support diet, Ursodiol and Denamarin while we waited for results.
Results came in. No liver disease!

So Missy actually had an open biopsy and has also been taking Ursodiol. Those high liver numbers across the board are puzzling for sure, but at least the good part is that they are coming down. It also seems to be a really good sign that she is outwardly looking a lot better, as well. So perhaps with more time, there’ll be continued decrease in those abnormal values. I think your question about the gall bladder is very well taken, though, and something I’d also encourage Donna to take up with the regular vet upon her return.

Marianne

[Donna Missy's Mum]

Thanks Marianne and Glynda
I will need to get the hang of posting quicker. This is my 3rd attempt. I keep being timed out.
I appreciate your replies.
I will certainly ask about the gall bladder and the ultrasounds as I think we have nowhere else to go with the liver. Four large samples were taken and all were normal but the liver did look enlarged.
Missy is going in for her next ACTH on the 15th June so we will see how well we are managing the Cushings. Our regular vet was away when she had her last one done and that vet said it was all ok.
Our regular vet rang last night finally and said that the liver enzymes were coming down and could take a while. I asked about the numbers on the previous ACTH test and she said 160 but they like it to be under 100 (nmol/L I guess).
We are using liquid compounded Trilostane (from a reputable chemist through the clinic) so it will be easy to tweak the dose if need be.
Thank you for giving ideas about the right questions to ask the vet and me the confidence to question Missy's treatment.
Donna

[labblab]

Hi again, Donna.

Thanks so much for this additional info, and here are some hints to keep from timing out — that is sooooooo frustrating when it happens. But these tips should keep it from happening any more.

http://www.k9cushings.com/forum/showthread.php?1329-Attention-Members-How-to-stay-logged-in-while-typing-long-replies

I do think there’s cause for optimism with Missy. The fact that all her liver enzymes have declined since starting the trilostane seems to imply that the pretreatment elevated cortisol was certainly contributing to the problem if not the sole cause. Lowering of enzymes can indeed take time, and as mentioned above, they may never return to their pre-Cushing’s baseline.

Those next ACTH results will indeed be helpful, but you girls are definitely on the right track if Missy’s post-ACTH cortisol has already lowered to 160 nmol/L (5.7 is/dL). So I think there is good reason to feel optimistic at this point. Please do keep us updated!

Marianne