Molly, diagnosed November 4/2015

[Mollys_Mom]

Molly is my 10 year old Border Collie X that I adopted when she was 4 months old. It has been a very rough year.

In May, I lost Mickey my BC/Sheltie X at 11 years of age unexpectedly to a mass in his spleen that had spread to the heart. There were no signs until one night when the sac around his heart had filled with blood, and I woke up to him struggling to breath. Diagnostics told us what was wrong, and that there was nothing we could do. I am grateful we had the time to diagnose and say our goodbyes.

A short four months later, I lost Jersey my 8 year old Border Collie. We went to bed around 11:30, and I woke up to her gasping at 12:30am and taking her last breaths. This one I think hurts the most - it was too sudden. She was gone before we could reach the vet office.

Now in November, Molly, the last dog from my "original pack" was diagnosed with Cushings through routine bloodwork. She just had her retest done yesterday, and so far is responding great to the medication (Vetory @ one 60mg capsule once a day and Hepatosupport @ 2 capsules once a day). The vet is very happy.

What I am currently struggling with is the cost of to treat this disease. For a 30 day supply of the Vetoryl, it is costing me $150, and the Hepatosupport is $54 for 60 capsules. So a rough total of $204 a month.

Are there are any resourceful links for legitimate places to get this medication cheaper online, and one that ships to Canada? Any input would be greatly appreciated. Thank you!

Molly: http://i64.tinypic.com/2a7d7xh.jpg

[labblab]

Hello and welcome to you and Molly! I cannot tell you how sorry I am about the loss of your two precious dogs. It must be incredibly difficult for you now to be dealing with illness in Molly, as well.

One of our Moderators, Sharlene, is the mom to another "Molly," :) and I'm certain she will be stopping by to welcome you, as well. A big "plus" is that she also lives in Canada and is treating her Molly with compounded trilostane, which is much less expensive than namebrand Vetoryl. Hopefully, she'll be able to give you some hints in that regard.

In the meantime, it will help us a great deal if you can give us more specifics as to Molly's diagnostic and monitoring test results. If you can give us actual numbers for any blood panel results that were abnormal (along with the reference range), that will be much appreciated.

Does Molly exhibit any outward symptoms of Cushing's? The reason why I ask is because there remains debate among clinicians as to the advisability of starting treatment in the absence of any symptoms other than lab abnormalities. I believe a large reason behind this is because the possibility of misdiagnosing Cushing's looms rather large if a dog doesn't display any observable symptoms. I do not mean to be questioning your vet's treatment recommendation, but am just wanting to clarify any abnormalities that have pointed in the direction of Cushing's for your girl.

Once again, welcome. And we very much look forward to learning more about your sweet (and beautiful!) girl.

Marianne

[Mollys_Mom]

Hi Marlene! Thank you for your reply. I don't have those numbers handy, but I will get them and post them here. :)

I didn't really notice her symptoms until a few months ago and they have mainly been increased thirst and urination. I honestly didn't think much of them though, and bloodwork was just routine (which was then followed by the ACHT stimulation test). I figured maybe stress in the house with the loss of her back was making her pick up odd habits. She's a very anxious dog, and is easily stressed.

I don't mind the questions at all. This vet is who is deal with for our rescue dogs (I'm the director for a charitable dog rescue) and she has frequently seen Molly in the last little while.

I will get those results posted as soon as I can! Thank you so much. <3

[molly muffin]

Hi, I'm the Canadian who also has a molly. Welcome to the forum.

I get compounded trilostane from ThePetPharmacy.ca at a cheaper price. There are actually several compound pharmacies that the vets use, but this one I've found to be a better price and they will mail to my door. You can send them an email and inquire about the price and they will respond. They can't do 60mg, as that is a patented amount by the makers of vetroyl, but they can do 59 or 61mg. Keep in mind too that some dogs respond better to vetroy than to trilostane (trilostane is the main ingredient in vetroyl). Your vet has to call in the prescription.

Wow, what a horrible time you have had. I can't imagine the heartbreak of losing 2 of your pack. :(

[molly muffin]

okay just checked and you can get the vetroyl, 60mg, 30 days for $99.08 CAD, so sure the trilostane would be cheaper than that. (still it's cheaper than your vet)

Hepato Support is $54.78 CAD for 180 pills. So definitely better pricing.

[Mollys_Mom]

Hi guys! Thanks for the info.

Attached is the bloodwork/paperwork the vet sent me. Let me know if you need anything else.

http://i64.tinypic.com/x24adl.jpg

http://i66.tinypic.com/ac5veu.jpg

[lulusmom]

Hi and a belated welcome to you and Molly.

I share Marianne's concern with a possible misdiagnosis. It appears that the vet did not do a full senior screening which would include a full blood chemistry panel, a complete blood count (CBC) and a urinalysis. The results you posted is a Catalyst DX test that is done inhouse as a presurgical precaution, primarily for dogs older than 6 or 7 years old. This test really is inadequate but I can tell you that the ALT and ALKP elevations are definitely the pattern we see in cushing's; however, as Marianne has already mentioned, there is a real concern with confirming a diagnosis based solely on lab abnormalities, in Molly's case only two on a very limited test. This becomes a greater concern for me because the post stimulated number on the acth stimulation test is borderline. The interpretation clearly states that cushing's is possible. That possibility is unlikely if the dog is asymptomatic.

You mentioned that you noticed recently that Molly is drinking and peeing more. Is she having accidents in the house? In order to determine if the drinking or peeing is the result of cushing's or some other condition, a urinalysis and a urine culture should have been done to check urine specific gravity, which is normally low and to rule out a UTI. Dogs with cushing's have very dilute urine and a standard urinalysis will not pick up all the white blood cells. A urine culture will do that, as well as identify the bacteria so that an appropriate antibiotic can be prescribed.

I have been involved in senior and special needs rescue for most of my life and had two of my own cushdogs and have fostered two rescued cushdogs. I used a rescue vet for acth stim tests but I had to teach the vet how to assess it for monitoring treatment. I'm not sure the vet you are using is that well versed in the diagnosis or treatment of cushing's either. Could it be that she is trying to save you money by taking short cuts? If Molly were my dog and I wasn't sure that her only symptom (increased drinking and peeing) was really a clinical symptom of cushing's, I personally would not start treatment until adequate testing has been done.

Dr. Mark Peterson has a website entitled Insights into Veterinary Endocrinology. This is an educational site, primarily for vets but Dr. Peterson graciously answers questions from pet owners as well. I asked a question on one of his pages where he discusses diagnosing cushing's. I presented a hypothetical dog who had all the usual abnormalities on blood tests and urinalyses and even a positive ldds test but no symptoms. Here is his response to my question as to whether he would treat that dog:


I am not a proponent of treating dogs with asymtomatic Cushing's disease, unless they have secondary hypertension or proteinuria.

Low dose trilostane may be helpful, but I am not aware of any studies that even suggest that, let alone prove that to be the case. With any drug, we have to weight the concerns of side effects.

In general, most dogs with Cushing's syndrome develop a high alkaline phosphatase, with is "induced" to rise because of the cortisol excess. In other words, the fact that this liver (and bone) enzyme is high only means that it is a marker for Cushing's and does not reflect liver damage. So to me, that is not a reason to treat, especially since this value rarely normalizes after successful treatment with trilostane or mitotane.

You may want to have some additional discussions with your vet before starting treatment, and you may even want to share the quote above. Just my two cents.

Glynda

[Mollys_Mom]

Hi Glynda,

So you're suggesting we do a urine culture? Molly has already started meds, and has been on them for about 1.5 months.

Those bloodwork results were from her repeat Mini CHEM 10 on November 1. We did a full CBC/CHEM 17 + LYTES on October 10 which showed she had elevated ALKP. The mini recheck showed that her ALT was now elevated as well, even after being on hepatosupport for several weeks.

What would other suggestions be for abnormal ALT/ALKP numbers and borderline ACHT stim results that go along with increased thirst/urination? She is having no accidents in the house - she just asks to be let out more often to urinate.

[tank&kat]

Do you have results from a more current ACTH test? I have to agree that the even though PU/PD (excessive thirst/urination) are primary symptoms of Cushing's, you don't want to diagnose a dog with only these symptoms present. The ACTH that was done on 11/4 is borderline at best. I would not have used this as a positive result. You could do a urine culture to check for bacteria/UTI.

Have her symptoms improved at all since treatment with trilostane? Does she have any trouble with back end weakness?

[Mollys_Mom]

Yes, the vet did say she was in the "grey area", but high end for her first stim test.

A UTI wouldn't cause liver levels to elevate though, so that wouldn't answer why those are high.

We are at the vet now for a repeat CHEM 10 and urinalysis/culture. My vet was very open to doing both.

Katforever83, she has no hind end weakness. Some days the symptoms seem better, some they don't. But I've read that it can take months for those to go away. I'm new at this though so I'm still trying to learn everything!

Thank you for the advice thus far everyone! I will keep you posted.

[lulusmom]

We are at the vet now for a repeat CHEM 10 and urinalysis/culture. My vet was very open to doing both.

That's great! Will be waiting for your updates.

Glynda

[Mollys_Mom]

Okay, I uploaded Molly's entire vet file including today's CHEM 10 bloodwork: http://www.filedropper.com/mollyhansen

In short:

ALT
Oct 10/15: 97 U/L
Nov 01/15: 130 U/L
Dec 08/15: 155 U/L

ALKP
Oct. 10/15: 755 U/L
Nov 01/15: 1245 U/L
Dec 08/15: 520 U/L

ALB
Oct 10/15: 36 g/l
Nov 01/15: 37 g/l
Dec 08/15: 41 g/l

Urinalysis showed very little bacteria, but they've also sent it out for a culture. No glucose, red or white blood cells.

[lulusmom]

Thank you for posting those results. Again, the Chem 10 panel is limited in scope and it includes few of the blood serum enzymes and blood counts that are assessed when diagnosing a dog. I will say that it is very unusual to see the steep drop in ALKP without the benefit of treatment. There was no correlating decrease in ALT which one would expect if these enzymes are being driven solely by cushing's. ALT has actually increased a bit.

Did your vet give you the results of the urine specific gravity? This is normally part of a urinalysis and is also very key if a dog is suspected of having polyuria/polydipsia (PU/PD) as a result of cushing's. Those are technical words for peeing lakes and drinking buckets of water. While USG can fluctuate at any given time, it would be uncommon for a dog with cushing's who has true clinical PU/PD to have a normal USG.

Unfortunately, these results do not increase my personal comfort level with the diagnosis. It actually raises more questions than it answers. I'm hoping others will give you their opinion as well. At this point, it is still possible that a UTI could explain Molly's frequent urination. I can't remember if I asked you or not, is her pee clear like water and odorless?

Glynda

[tank&kat]

Is Molly being treated with trilostane or lysodren? You mentioned she was on meds for 1.5 months.

[Mollys_Mom]

Glynda,

The specific gravity of her urine was normal, and her pee always looks normal as well.

The vet would like to do an ultrasound next, but honestly at this moment in time, I have no excess cash to do this right away. I have sent Molly's files to another vet hospital for a second opinion, but will continue with the Vetoryl and Hepatosupport for now.

Is an elevated ALB seen in cushings dogs?

[labblab]

I will say that it is very unusual to see the steep drop in ALKP without the benefit of treatment. There was no correlating decrease in ALT which one would expect if these enzymes are being driven solely by cushing's. ALT has actually increased a bit.
I am puzzling over the same thing. It sounds as though Molly has been taking the Vetoryl for about a month, and with that big a decline in the ALKP, I am surprised to see the ALT continuing to go up. That makes me wonder whether there is perhaps an unrelated primary liver problem involved in some way...

Marianne

[labblab]

Is an elevated ALB seen in cushings dogs?
Low albumin can be associated with several different serious problems, but I'm not aware of high albumin being a particular health issue. Dehydration at the time of a blood draw can increase the ALB level, I think. It does seem a little odd that Molly's ALB keeps going up, though.

I can't view her entire blood profile. Are her globulin levels within normal limits, such that the albumin-globulin ratio is also within normal limits, or is the ratio unbalanced?

[Mollys_Mom]

Hi all.
I spoke with two other vets from two different clinics who reviewed Molly's entire file and both agreed that her cushings was caught in early development stages.

Neither seem too concerned about the elevated ALB. General consensus between the three vets is recheck liver values in a couple of weeks and do ultrasound.

Molly seems to be doing pretty good lately.

[molly muffin]

That is excellent news. :) I tell you, there is nothing like having a plan. I think that is a good one by the way.

[Mollys_Mom]

Molly went in for her bloodwork today.

ALB has stayed the same at ALB, so that's better than it continuing to elevate.

ALT has come down 130 from 155.

ALKP, however, has jumped up to 1062 from 520. Last time we had tested the blood, this number was cut in half.

The vet gave me three options:
1) Try Zentonil and recheck values in one month. However, money is getting tight and this medication for one month is $120.
2) Do the ultrasound.
3) Repeat ACHT stim test.

I think at this point it makes the most sense to go ahead with the ultrasound to ensure that it is cushings we are dealing with or if something else is going on. I am hoping there is nothing else (as clinically she seems to be doing just fine at home), and that she will just need adjustment of her cushings meds.

We will also be likely switching her over to a hepatic diet from Royal Canin.

One thing I am curious about - one of my other dogs is on a steroid spray for her paws due to allergies. Molly is a big licker, so I am wondering if that could be affecting her at all from picking it up in the house.

Where diet is concerned, should I be avoiding anything? Molly absolutely loves pizzle sticks but I am not sure if lots of protein is okay for cushings dogs?

Looking forward to input. :)

[Mollys_Mom]

Anyone?.... I expected a bit more support and advice from this forum. Maybe I shouldn't I bother.

[molly muffin]

I do apologize that it has taken so long for someone to get back to you about your questions.

I checked thepetpharmacy.ca where I buy my dogs drugs from and Zentonil Plus is cheaper through them than the price you where quoted by your vet.

http://thepetpharmacist.ca/product-list?title=Zentonil%20Plus&title2=Zentonil%20Plus

I've had good luck with them and they will ship direct to your door.

As for what to feed her, I usually stay away from high anything and go for moderate protein and moderate fat.

I like the ultrasound option as I think you get a lot of bang for your buck with an ultrasound in that it can show you what is going on with the internal organs.

I'm in canada and the initial ultrasound was more expensive but then follow up ultrasounds are only running around 79. each CAD. I get this via the Internal Medicine Specialist clinic.

Most vets don't worry so much about high ALKP in cushing dogs, but when there is a big jump, I personally like to rule out sludge in the gall bladder causing it, and that is something that an ultrasound can rule in or out.

Hopefully that helps some as far as what I would do. Again I apologize for the time it took to get back to you.

[Budsters Mom]

We are family here. Many of us have jobs, careers, numerous responsibilities, families etc. Basically, we have lives away from the forum and cannot be here ALL the time. Our administrators and moderators do all they can to keep this forum running as smoothly as they are able, helping as many fur babies and pet parents as humanly possible. However, they are all volunteers. They selflessly donate their time to help others. Even many of us, non-staff members donate our time as we are available, doing what we can.

If you do decide to stick around, you will soon discover that our members are extremely knowledgeable and have excellent ideas. We will do everything we can to help you and Molly. The rest is up to you.


Kathy


I expected a bit more support and advice from this forum. Maybe I shouldn't I bother.

[labblab]

Molly's Mom, I am sorry you felt overlooked. But as Kathy has said, we are an all-volunteer staff that must balance our time spent on the forum with all the other responsibilities in our lives (including issues that may arise with our own human and canine family members :o), and holiday seasons can be time periods when we all are stretched especially thin. Having said that, our goal is to provide accurate and timely information and support to all our members. If you or anyone else here feels as though they have gone unnoticed for too long a time, please do go ahead and add an additional reply in order to "bump up" your thread and bring it back to our attention. I see that all your previous replies had multiple responses within 24 hours, and that is really our goal. So I hope you will cut us some slack on those occasions (which we hope will be rare) when the response is not as swift.

Moving on to your questions, yes, I agree with you and Sharlene that an ultrasound seems like a reasonable "next step." If Molly were mine, that is probably how I would proceed, myself.

As far as diet, we often recommend lower levels of fat because dogs with uncontrolled Cushing's may be more vulnerable to pancreatitis, and pancreatitis may be triggered by high (especially sudden high) fat intake. The research in all of this is not conclusive, but it seems like a reasonable precaution to take. We also recommend moderate levels of protein because higher levels of cortisol can cause a particular type of protein-losing kidney abnormality which may be worsened by a high dietary protein intake. If you have your dog's urine tested and no protein loss is found, this risk may be minimal at the moment. But still, it is another caution that we voice.

I do hope you will remain with us, and we will try our best to be as responsive as we can to your questions and concerns.

Marianne

[Mollys_Mom]

I understand everyone here posts as they can. Often, however, I will check in and plenty of other posts have been answered and mine has drifted to the bottom, or even the next page.

Anyhow. Molly is now on the Royal Canin Hepatic dry food.

She had an abdominal ultrasound on Tuesday. The vet said her liver looks like the liver of a typical dog her age/cushings dog. There may be some nodules forming on the right side and fat deposits on the spleen, but he is not worried. He said her liver, spleen and kidneys look good.

In conclusion, he feels we should simply repeat the ACHT stim test because he thinks she just needs her meds adjusted (she is 47.96lbs and on 60mg of Vetoryl once a day).

[spdd]

I do not want to sound harsh, and I am sorry if it comes across that way. I had a very, very sick dog and the information I got here was far beyond anything that any veterinarian could give me. Read my posts and you will see the horrendous experience I was having. There are many sick dogs on this forum as well as on the facebook account handled by the same people and as mentioned everyone is voluntary. They do research on our behalf, ck out pharmacies, matter of fact I think they are genius's on here, so I'd cool my jets a little and let the wonderful people on here look after ALL the dogs and people that need excellent advice. I saw on one of your posts 5-6 replies in one day. Now that is service when there are others that need good advice too. People have their own issues with their own dogs that are giving their knowledge freely, so if you have to wait a couple of days for a reply, then so be it. This is not a chat forum or social forum, but a great place and the only place you will find such generous, caring and compassionate people, along with the knowledge.
I am truly sorry you are having issues with Molly, but if it can be sorted out, this is the place. My pup has since died, and some of our advisors here have dying dogs, so please be a little more compassionate with them, as they have been with you. One actually today has to put her beloved pup down, and her other one is very sick, so hopefully you understand.

[molly muffin]

Did you out Molly on the hepatic support supplement too?

Is she still drinking and peeing a lot?

She was diagnosed in December and you had an ACTH afterwards. Was that the two week test after starting? If so she will be needing another ACTH soon.

Sometimes the liver values never come down a lot. Other times they do. My dogs has never really come down much. If they do then they go back up

The ultrasound sounds like a good report in that no masses or obvious tumors where seen.

I think I would have the retest of the ACTH when it is due. And see what the numbers show there. You want to be under 250nmol post ACTH but I don't like to go too low post so for me not under 70nmol although technically it can be lower.

I only have a moment as I have to get to work and didn't see the last ACTH results posted. Only the vet said she is responding well.
Did they give you the avtual results?
They like to start the dogs on 1mg/1lb so she is a bit over that and cortisol will continue to decrease on the same dose for 30 days usually.

[Mollys_Mom]

Yep, Molly has been on the hepatosupport supplements since October.

Looking in what I have available, Molly's reading from her stim tests:

Nov 4, 2015
Post injection: 588 nmol/L (read pre injection was just marked as --- nmol/L)

Dec 1, 2015
Pre-injection: 124 nmol/L
Post-injection: 150 nmol/L

Oct 10, 2015 bloodwork showed her ALKP at 755 u/l.
Nov 1, 2015 bloodwork showed her ALKP at 1245 u/l.
Dec 8, 2015 bloodwork showed her ALKP at 520 u/l.
Jan 4, 2016 bloodwork showed her ALKP at 1062 u/l.

** Molly started 60mg of Vetoryl once a day on November 4

Her drinking seemed to improve in December, but over the last few weeks increased (seems to follow the rising ALKP). Peeing more, but I feel I can't claim that as a symptom because her drinking has increased and the two go hand in hand. She's very, very moochy for treats. Other than that she really has no clinical symptoms. Has some lumps popping up but they've all tested fatty. Coat and skin in good shape.

[Harley PoMMom]

Hi and a belated welcome to you and Molly,

I just reread your thread and saw that one of your dogs is on steroid spray, is this still being given? Depending on how much Molly is digesting this could yield a higher ACTH post number and since a majority of dogs have a steroid induced isoenzyme of ALP this may cause an increase in the ALP.




One thing I am curious about - one of my other dogs is on a steroid spray for her paws due to allergies. Molly is a big licker, so I am wondering if that could be affecting her at all from picking it up in the house.



Hugs, Lori

[Mollys_Mom]

I have stopped giving the steroid spray to my other dog. It made me too nervous with Molly having cushings.

[molly muffin]

They drink more because their kidneys are working over time, and this can be partly due to the liver and cushings, it all ties together. Then of course they pee more. Sometimes this clears up in dogs, but not always, and it can take time too.

I would if it where me, repeat the ACTH at around the end of jan, first part of feb, it was a month after the first one that the dec 1 test was done and she'd dropped quite a bit. So see if that has stabilized.

Dec 1, 2015
Pre-injection: 124 nmol/L = 4.4ug
Post-injection: 150 nmol/L = 5.4 ug
(this is converted for our US members to more easily see where she is at now)

The post can come down a bit more since symptoms haven't cleared up and they might have done so by now. I'd also at that time have a check of things like the BUN and Creatinine (kidney related) and just make sure that is okay too.

Those would be my watch for with the only symptoms being the drinking and peeing and the liver enzymes. (recheck those)

So this would be my future plans based on what you have said.

It seems that over all she is doing very well clinically and just a matter of keeping an eye on things and see where she is going and what needs to be worked on still. Liver enzymes especially can take quite awhile in most dogs to come down (if they do, again it isn't a given that they will or won't)

But it's a plan at least and I like a plan.

[Harley PoMMom]

They drink more because their kidneys are working over time, and this can be partly due to the liver and cushings, it all ties together. Then of course they pee more. Sometimes this clears up in dogs, but not always, and it can take time too.

I would if it where me, repeat the ACTH at around the end of jan, first part of feb, it was a month after the first one that the dec 1 test was done and she'd dropped quite a bit. So see if that has stabilized.

Dec 1, 2015
Pre-injection: 124 nmol/L = 4.4ug
Post-injection: 150 nmol/L = 5.4 ug
(this is converted for our US members to more easily see where she is at now)

The post can come down a bit more since symptoms haven't cleared up and they might have done so by now. I'd also at that time have a check of things like the BUN and Creatinine (kidney related) and just make sure that is okay too.

Those would be my watch for with the only symptoms being the drinking and peeing and the liver enzymes. (recheck those)

So this would be my future plans based on what you have said.

It seems that over all she is doing very well clinically and just a matter of keeping an eye on things and see where she is going and what needs to be worked on still. Liver enzymes especially can take quite awhile in most dogs to come down (if they do, again it isn't a given that they will or won't)

But it's a plan at least and I like a plan.

Sounds like a really good plan, Sharlene.

[Mollys_Mom]

Does a stim test have to be done at the 4 hour mark after meds are given? Or is just at least four hours after? What is the timeline for blood draws and injection typically?

My vet is open until midnight with no emergency fee. Molly eats supper and gets her meds at 5pm. My dogs only eat once a day and not in the mornings because my hours change and I am not always there for the morning.

The vet suggested I switch her to the morning because the time I currently give them poses a problem for a proper test. But it is difficult for me to be able to give meds at a consistent time in the morning. Is is detrimental to give her meds to her earlier one day (like 3 or 4pm) instead of 5? I would really prefer to not have to change our routine.

[Squirt's Mom]

MODERATOR NOTE: I have merged your post about ACTH timing into Molly’s original thread. We like to keep all posts about each pup in a single thread as it makes it easier for members, and parents, to refer back to the pup's history when needed. Thanks!

[judymaggie]

Hi! The ACTH test needs to be administered 4-6 hours after a meal followed by the trilostane dose. Let's say Molly eats at 5 and gets her trilostane by 5:15. Then the earliest the first draw can be is 9:15 followed by the injection. Then the second draw would be at 10:15. Since your vet stays open until midnight, I don't understand why this would pose a problem for them.

I don't think it would matter if you fed and dosed Molly an hour early on the day of her test if that hour would make a difference to the vet.

[Harley PoMMom]

Judy is correct, Dechra, the makers of Vetoryl, recommend that the monitoring ACTH stim test be performed 4-6 hours post pill. However, one of the renowned endocrine specialists, Dr Peterson, has a different opinion:
Most of the initial studies recommended that the ACTH stimulation test be done 4-6 hours after dose administration times, but more recent investigation indicate that the drug generally has a peak effect earlier (1). I like to have my dog owners make the appointment at 2-4 hours because this interval ensures that we are testing at close to the peak effects of the drug (2).

Four important points here:

First, trilostane should always be given together with food. It has been shown that feeding immediately after the administration of the drug significantly increases its absorption (1,2).

Second, It's very important to be consistent in timing when using ACTH stimulation test to make dosage adjustments. We don't want to start one test at 10 AM, then do the next follow-up ACTH stimulation test at 2 PM and compare the results. Because of the relatively short-acting effects of trilostane, the results of ACTH stimulation testing varies considerably with the time of testing relative to dosing.

Third, when we state that the ACTH stimulation test be done 2-4 hours after the morning dose, that's when the basal serum cortisol is collected and the ACTH injected.

Fourth, the form of ACTH injected makes a difference. If synthetic ACTH (cosyntropin or Cortrosyn) is used, the post-ACTH cortisol sample is usually collected at 1 hour after ACTH administration. If the ACTH preparation used is a gel, the post-cortisol sample is usually collected at 2 hours.

If we use ACTH get and start the test at 4-6 hours after the morning dose, we have a good chance of missing the time of the peak action of trilostane. Remember that after administration of trilostane, peak concentrations are seen within 1.5 hours and decrease to baseline values in about 18 hours (less in some dogs).
In addition, many of the ACTH gel products are formulated by compounding pharmacies, and these may not always be reliable (3).
For these reasons, I prefer using synthetic cosyntropin over ACTH gel when doing an ACTH stimulation test to monitor trilostane therapy.

Bottom Line:

When monitoring dogs on Vetoryl (trilostane) for Cushing's disease, start your ACTH stimulation test 2 to 4 hours after the morning dose of the drug has been administered.
The dog should never be fasted on the morning of the test. Trilostane is a fat-soluble drug and must be given with food to help increase its absorption.
Ideally, use synthetic cosyntropin to do the ACTH stimulation test to ensure consistent and reliable results.


This article can be found here: http://www.endocrinevet.info/2013/11/protocol-for-acth-stimulation-testing.html

Although I believe it is strongly recommended that the Trilostane be given with the morning meal, I think it is more critical, and this is JMO, that one needs to be consistent with their administration of the Trilostane capsule...same time every day, and those ACTH monitoring tests need to performed the same way too.

Hugs, Lori

[molly muffin]

I make sure that on the day of the test, I give molly her pill and then have her at the vets about 4 - 4.5 hours afterwards to start the testing. That is consistent.
On other days though, an hour or so earlier or later if medicating once a day is not usually an issue.

[Mollys_Mom]

Thank you everyone! I will let you know how the next test goes.

Overall, Molly is doing well. She's had quite a few lumps appear over the last several months but all have shown to be nothing but fat. :)

Her symptoms of cushings are still limited to increased drinking and urination, and being moochy (but she's always loved food). Her coat is actually probably the nicest it has been in a few years and her skin is still good. I am really hoping we can finally work out her dosage and go on living our lives with as few bumps in the road as possible with this.

[molly muffin]

I am sure that you will be able to go with only minor bumps now and then, once you know how she is doing on treatment and settle into a dosage.

A lot of dogs get the fatty lumps, called lipoma. I usually have them aspirate anything like that if it pops up and make sure that is what it is, but normally it is and is very common as dogs get older.

[Mollys_Mom]

Well, I am stressed out again.

Molly had a repeat stim test tonight. Her results were good and within the range of "continue current dosage". (sorry, I don't have the numbers handy but will post when I do)

However, her ALKP has increased more than the last check. Again, they didn't give me the numbers as they were closing but I will share when I get them.

I really cannot afford to add anymore medications at this point. I am literally tapped out and barely get by being able to buy her Vetoryl and Hepatosupport.

Her drinking and urination decreased but have increased again over the last two runs of bloodwork (so following the rising of the ALKP).

It is breaking my heart that I don't have more money to give her any more medications she may need. Other than the drinking and urination, she is a bit moochy but stable otherwise. I just feel like a terrible owner having restrictions financially.

Molly had her ultrasound in early January and everything looked fine.

The vet wants "time to think about our next step" and will be in touch with me.

:'(

[labblab]

Dec 1, 2015
Pre-injection: 124 nmol/L = 4.4ug
Post-injection: 150 nmol/L = 5.4 ug
(this is converted for our US members to more easily see where she is at now)

Gosh, I am sure sorry that Molly is still having some issues. You are being a great mom, though, and doing what is within your power to do. The darn finances can be a huge issue for most of us, and sometimes we have to pick and choose among different options because there is just no way we can swing them all. I've been there, myself, and I know it feels crappy :o. But you are doing the things that are most important, and Molly is lucky to have you for her mom!

I do have a couple of thoughts that might mean that things are not as bleak as you are fearing. First of all, it will be really important to get all those actual lab numbers just as soon as you are able. There are actually two categories of "Continue at the same dose" recomendations published by Dechra. The first is to stay on the same dose if the post-ACTH numbers fall within a range of 1.45 - 5.4 ug/dL. The second is to continue on the same dose if the post-ACTH falls within a range of approx. 5.4 - 9.1 unless clinical signs of Cushing's are still evident. If unresolved symptoms remain, then the dose should be increased.

In the box above, I posted Molly's ACTH numbers from December, and at that time, she was right at the very top of the lower range. So if she is any higher than that at this time, then her dose really ought to be increased since she is exhibiting increased thirst and urination. That may be the only simple fix that is necessary. Since you live in Canada where the cost of Vetoryl is quite excessively high, perhaps your vet would consider switching to a less expensive compounded version of trilostane if Molly does need a higher dose of the medication.

However, I must ask whether you are still dosing Molly only once a day at suppertime? If so, that may be the problem. Since trilostane has a short active life in the body, its effects are already diminishing in many dogs (and thus symptoms are rebounding) by the 12-hour mark after dosing. If Molly gets her Vetoryl with supper, by the time she wakes up the next morning, her cortisol may already be on the rise and continuing to rise throughout the day. So even if Molly's post-ACTH result fell within that lower range when tested in the evening after being dosed with Vetoryl at supper, higher cortisol the next day may be the problem. Given Molly's unresolved symptoms, I do think it would be worth it to switch to morning dosing, even if there has to be some inconsistency as to timing due to your job. The other option is to switch to twice-daily dosing by dividing her dose in half and giving her some medication both in the morning and evening. But that might make the drug cost even more expensive for you. If so, I believe I would first try dosing once in the morning, either at the same dose or at an increased dose, depending upon those actual post-ACTH test results. That just may solve the problem pretty easily, including putting a lid on the ALKP increase.

Marianne

[Mollys_Mom]

Yes, Molly still gets her dose once a day at supper (5pm). So you are saying that the body would most benefit from being dosed in the morning? Is there something that happens in the body for this to make it more effective? Not arguing, just trying to understand. :)

We are still doing hepatosupport at the same time as her meal, and she is eating Royal Canin hepatic food.

Dec 1, 2015
Pre-injection: 124 nmol/L = 4.4ug
Post-injection: 150 nmol/L = 5.4 ug

FEB 22, 2016
Pre-injection (baseline): 104 nmol/L
Post-injection: 87 nmol/L

Sorry, I am not sure how to convert them.

ALKP is following an elevating trend...
ALKP: 755 u/l (Oct 10, 2015)
ALKP: 1245 u/l (Nov 1, 2015)
ALKP: 520 u/l (Dec 8, 2015)
ALKP: 1062 u/l (Jan 4, 2016)
ALKP: 1811 u/l (Feb 22, 2016)

I have also noticed Molly pants quite a bit at night. I wouldn't call it distressing, though. Frustrating because for a very small window a couple of months ago, her symptoms were disappearing. :(

[labblab]

Thanks so much for this additional info. And no, I don't think you're being argumentative at all! I'm glad you are wanting to understand the rationale for what I wrote earlier. Here's a quote from Dechra's U.S. Product Insert for Vetoryl that describes the relatively short active life of trilostane in a dog's body:


CLINICAL PHARMACOLOGY: 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. There is no accumulation of trilostane or its metabolites over time.

So even though individual dogs can metabolize the drug more slowly or more quickly, on average trilostane only remains active in the body for approx. 12 hours. When dosed in the morning, some dogs exhibit sufficient symptom resolution throughout the day even though the drug's effect is wearing off by bedtime. So that's great and makes things simple. However, other dogs may see symptoms rebounding later in the day if the drug's effect wears off earlier for them. In that case, the recommendation is to shift to twice-daily dosing. Here's Dechra's published instruction in that regard:


Once daily administration is recommended. However, if clinical signs are not controlled for the full day, twice daily dosing may be needed. To switch from a once daily dose to a twice daily dose, the total daily dose should be divided into 2 portions given 12 hours apart. It is not necessary for the portions to be equal. If applicable, the larger dose should be administered in the morning and the smaller dose in the evening. For example, a dog receiving 90 mg would receive 60 mg in the morning, and 30 mg in evening.

Turning to Molly's specific ACTH results, we see that this most recent test did show results that are squarely within the lowest of the listed therapeutic ranges (to convert from nmol/L to ug/mL, we divide by 27.59):


Pre-ACTH: 104 nmol/L (3.7 ug/mL)

Post-ACTH: 87 nmol/L (3.2 ug/mL)


Given those results, we don't want to be increasing Molly's daily trilostane total any further, because we don't want her cortisol to drop any lower at any time of the day. So in this situation with rebounding symptoms, I think you have two options to try. The first is to shift to dosing her once daily in the morning in the hope that the single dose will carry her symptom-free throughout the waking day. In making the shift, you'd be structuring the dosing so that her cortisol is at its lowest during the daytime hours instead of at its highest. If that doesn't help, the other alternative is to divide her daily total and give a portion in the morning and a portion in the evening in an effort to keep her cortisol consistently lower throughout an entire 24-hour time period.

Of course, this is all assuming that her rebounding symptoms and ALKP are solely a result of her Cushing's. Out of curiosity, what's been happening with her ALT during this same time period?

Marianne

[Mollys_Mom]

Thank uou so much for all of your information, Marianne, and for being so supportive.

Unfortunately they only tested the ALKP levels, not ALT. There was a miscommunication.

The vet said we are in a bit of a catch 22 situation. She said: "we are controlling the over-production of cortisol with a medication that is also metabolized by the liver, which in turn can cause the liver enzymes to creep up."

She suggested possibly adding a supplementation of SAMe or Silbyn (or Zentonil or Denamarin). It would be an additional $130 to buy from the clinic per month. :(

She said diagnostic wise the next step could be a surgically invasive liver biopsy.

Other than that, for monitoring she recommended rechecking chemistry in 6 months as long as she seems to be doing well.

What do I do? :( With Molly's levels and current symptoms, would you consider her safe and "stable"? Do I have to worry about losing her in a couple of months if I take some time to see if her values adjust at all? Or is that negligent of me?

[labblab]

Well, if Molly were my own dog, I believe this is what I would do at this point...

First, I'd switch her Vetoryl to morning rather than evening dosing for a couple of weeks so as to see whether that resolves her rebounding symptoms.

Second, if Molly shows no improvement after a couple of weeks of revised dosing, I would want to have a complete blood chemistry panel run on Molly. If your vet is concerned enough about Molly's ALKP that she is suggesting an invasive liver biopsy, I am pretty much astonished that she would want to wait for six months before rechecking the ALKP and also evaluating Molly's other liver markers. That makes no sense to me at all. In the presence of continued excessive thirst and urination, I would also want to be checking Molly's glucose level (diabetes can be associated with Cushing's), her kidney markers, and also her electrolytes (potassium and sodium levels). The electrolytes can become unbalanced with Vetoryl treatment, and need to be checked alongside the other blood chemistries.

If Molly's other liver markers show new elevations in addition to the ALKP, then I'd want a bile acids test to be done. It is a blood test that measures how well the liver is actually functioning. The liver enzymes on a blood chemistry panel don't do that.

If it were me, I'd want this blood testing all performed prior to considering a liver biopsy. And I definitely would not wait longer than a month to have it done. I really hope that shifting to morning dosing will help resolve Molly's issues. If not, shifting to twice daily dosing is a further option. But in the meantime, I'd really want to be checking her blood chemistries in order to evaluate other possible problems.

Marianne

[molly muffin]

I've had my vet mention liver biopsy too but it's not a road I've chosen to go down and don't expect to, unless something shows up on an ultrasound.
I'd do what Marianne suggested too as far as the additional chemistry and urinalysis test goes. In fact I have done those for the exact same reasons, liver enzymes going up.
Things can change very quickly in their chemistries.
Did you look into ordering from thepetpharmacist? I save quite a bit going through them rather than buying from the clinic. Money is always something that has to be considered, as it's not just todays test but the next one that I feel like I'm always saving for.

[Wuchi]

Hi

A couple quick suggestions:
- to keep the cost of meds down ask your vet for a prescription and have it filled directly from a pharmacy that sells or compounds dog medicine. Was buying trilostine (10mg) from vet at $165 per month now buy it directly from compounder for $60.
- my dog had a super high liver count and it started coming down after being on the trilostine for about 3 months (takes a while for it to drop). I've also been using liquid milk thistle which my dogs naturalpath recommended -- you can buy at any drug store or on amazon -- get a non concentrated dose and one that is alcohol free (I get mine from Pharmica). It's around $8-10. It doesn't seem to bug the dog as much as the Denamarin/SAMe did (kinda made her wiggy) and have read about a lot of success stories about it on it helping animals and humans.
- panting: my dog had some of that when adjusting to the higher doses of Trilo -- it went away after about 4 days after she went up a dose (Have a very small dog who has a sensitive stomach). I had to drop the dose down once because she was panting so hard -- just stopped it a day and then increased it a little slower over a period of 3 weeks. Once my dog got to her right dose of Trilo the panting stopped.

Hope this helps some. Best of luck on your journey.

[Mollys_Mom]

Hi all!
Again, thank you for all of the input and support.

Molly seems to be symptomatically be balancing out again. Still some excessive drinking/urinating, but it doesn't seem as extreme and I am guessing maybe she will just always be this way. She doesn't seem to be *too* stressed by it.

Okay, so my next game plan is to do full blood check on her and a urinalysis in the coming weeks; just need to save up some coin - please don't judge me. :(

Are there side effects to Milk Thistle? For some reason I thought I heard it wasn't good.

[Harley PoMMom]

Sweety, we are not here to judge you and we completely understand the financial hardship that Cushing's puts on pet parents, we do what we can and that's all we can do.

I know of no adverse side effects of milk thistle unless the dog suffers from allergies. Here's a link to a pretty good article about milk thistle: http://www.littlebigcat.com/health/milk-thistle-a-wonder-herb/

Hugs, Lori

[Wuchi]

My vet said the milk thistle shouldn't do any harm to my dog, but always good to check with your vet to see if it's ok to give it to your dog (since they know what other meds they are on, etc). FYI -- you might already know this, but the vet shouldn't charge you for a quick question like this, just use whatever communication method you're comfortable with (phone, email, stop by office).

[Mollys_Mom]

Hey guys! Molly had a full blood work up done and urinalysis. Urinalysis was normal, bloodwork is all good except the ALT and ALKP have creeped up a bit again since January 4.

ALT is at 191 u/l.
ALKP is 1817 u/l.

The hepatosupport capsule she gets has milk thistle in it (the dose she would get if she were just taking milk thistle), so there is no need to add more apparently.

A vet from a different clinic that I use with the rescue dogs suggested purchasing SAMe on it's own (as long as it has NN or NPN on the bottle) to use in conjunction with the hepatosupport. It work cost about $45 every 2 months. She also said she has had cushings dogs with consistently elevated liver values for years and years and ultrasounds and tests have always been fine.

Could I just be overthinking this and dwelling too much on perfect bloodwork?

[apollo6]

Yes! If most of the blood work is good,focus on that. We become so protective of every little upsetthat we forget to look at the big picture. So good work Molly.

[Mollys_Mom]

Yes! If most of the blood work is good,focus on that. We become so protective of every little upsetthat we forget to look at the big picture. So good work Molly.

Yes it is SO easy to get obsessed with the little things, eh? Time for a big sigh of relief. I'm sure Molly will appreciate me backing off her for a bit. ;) She HATES going to the vet that she literally hides from me whenever I try to take her out of the house now.

[Harley PoMMom]

It is nearly impossible not to obsess about our sweet furbabies ;) I do agree with the vet, the ALP and ALT in some cush dogs, even with successful treatment, will not return to normal levels.

[Mollys_Mom]

Hi all! Just wanted to do a quick update on Molly.

My stress/anxiety over this has been very low over the last couple of months. I was being very obsessive about Molly's levels and bloodwork being perfect. She HATES the vet and her own anxiety goes through the roof going there. It was to the point where she wouldn't even leave the house with me anymore. She would try and hide under tables, chairs, anything, expecting that I was taking her out to go to the vet.

Molly seems to have remained the same and I think that is a good thing. I think we have things under control.

For future, how often should stim tests be done to ensure her dose is still correct? Her last test was in February. Her ALT and ALKP were still elevated, but I am trying not to obsess over those since everything else, including her symptoms, have stayed be same and not become worse. Just looking for advice on what the "maintenance" care is for Cushings dogs. :)

[judymaggie]

Hi! I am glad that things are stable with Molly. With regard to your question about monitoring, Dechra (manufacturer/distributor of Vetoryl) recommends an ACTH every 90 days. This is assuming that everything remains stable and there are no dosage changes. Some dogs do need dosing adjustments after a period of time so you don't want to go too long without an ACTH. That said, some folks do extend this time frame out. I stick to it but am a bit OCD about things like this!

Couple of thoughts re Molly's anxiety about leaving the house -- you might try some conditioning to just sitting in the car. Take some special treats with you and see if you can entice her into the car (with it just stationery, not running). Then just sit there for a while, encouraging her. Then you can move to having the car running, but not going anywhere. Then see if you can drive around the block. When she is comfortable in the moving car, try taking her somewhere that she enjoys (pet store, park, etc.) so she realizes that not all car trips lead to the vet. I know of some folks who have done this and, at some point, go the vet's office and just hang out outside -- then progress to going inside, staying for a little while in the waiting room and then leaving.

[Mollys_Mom]

Hi all! Does anyone who has a cushings dog use Bravecto as well? I am waiting to hear back from my vet about it. I've done a lot of research on the drug and am comfortable administering it to my dogs, but I am unsure how I feel about giving it to a 10 year old dog with cushings/enlarged liver. Ticks are terrible here, and there is lots of Lyme disease and anaplasmosis.


(I moved this post so as to keep all the information about Molly within one thread.)

[Mollys_Mom]

Hi all. What is the life expectancy for dogs once diagnosed with cushings? I was told by my vet if the disease is well managed with medication, they will usually live their regular life expectancy assuming no other health problems arise. However, this weekend I was told by two different people that it is max 2-3 years..... I'm very upset to hear this and looking for clarification. :(

also, any thoughts to my previous post?

[DoxieMama]

Hi, I have not used Bravecto so cannot comment on that. But as for your other question, your vet is correct. It is not uncommon for dogs to live a normal life expectancy when Cushing's is under control.

How is Molly doing now?

[Mollys_Mom]

Thank you! Molly continues to do well. She had excellent readings on her last stim test. The ALKP and ALT are still elevated, but I'm not dwelling on them at the moment as she has very minimal symptoms of Cushings and no sign of anything else at this time. She has the odd day where she drinks a lot/pees a lot, but if that's all she has to deal with, I think we're both happy. :)

[molly muffin]

That is great to hear such a good report on Molly. Yay! :)

Sometimes those liver numbers never really come down much. My molly's bounce up and down all the time it seems.