Lady Update

[voss001]

Hello to you all. My lovely dog Lady, an approximately 13 year old Kerry Beagle, was recently diagnosed with Cushing's (pituitary) after suffering symptoms for over a year without a positive ACTH test. Sonigram revealed equal enlargement of the adrenals so diagnosis was pituitary.

A little background - Kerry Beagles are very rare in the US (she may be the only one and I found her so not sure how she got here) though common in Ireland. She is about 55 lbs - large for a beagle but medium in general. She also has amazing genes and looks and acts about 8. Over the past 2 years, her hearing has about 85% failed and she's been having a bit of trouble with her back legs giving out from time to time, something I've seen in other dogs when they age that I guess is just part of aging. She is extremely spry and playful and we hike 3 miles, half of which is steep uphill, every other day and she loves it.

About 4 weeks ago we finally got the positive test for Cushing's and after hearing the options from our vet decided to put Lady on Vetoryl. She started out on 60mg once a day. I saw immediate results - the first 3-4 days, she was tired a lot a few hours after the pill and generally calmer with little panting and less water intake - I thought it was the beginning of a miracle. However, by week 3 the symptoms seemed to be returning - anxiety, constant panting, excessive thirst/hunger, etc.

We went back to the vet for follow up testing and they found that her cortisol was now too LOW. So we changed to 25 mg of Vetoryl (from compounding pharmacy) 2 times a day. I give her a dose at 7 AM and the 2nd at 7PM. It's been about 10 days now, and we don't go back for re-testing until 3 weeks have gone by, but I don't see much if any improvement.

My question: if the Vetoryl works, how long would it be before we'd see noticeable and/or sustained improvement? My poor dog is really suffering and her being so sick is really stressing me out to the point that I don't know how much longer I can take it.

Thank you all for your support,

Mike

[Harley PoMMom]

Hi Mike and welcome to you and Lady from me and my boy Harley.

I was wondering if you could post the latest ACTH test results here and any other test results that had abnormal findings. You see, excessive thirst and excessive urination are symptoms of hyperthyroidism and diabetes, which share some of the same symptoms of cushings...were these non-adrenal illnesses ruled out?

Also, when was her ACTH test performed? According to Dechra US Product Insert:
conduct a 4-6 hour post dosing
ACTH stimulation test.

Re-examine and
conduct an ACTH stimulation test 10-14 days after every dose alteration.

You can find this and more information here at this link:http://www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Vetoryl.pdf

We are here for you, Mike, so hang in there and we will help you in any way we can.

Love and hugs,
Lori

[voss001]

Hi Lori - Just to clarify, Lady does not suffer from excessive urination, only thirst. Indeed, she can easily go without urinating for 12 hours and has always been that way. (I never make her do so, but we've been on planes and such at times and she has not peed in the house once in all our years together)

Her primary observable symptoms are thirst, hunger, anxiety, and panting.
She is JUMPY all the time - if she's lying comfortably on the floor and sees me move my seat, she JUMPS up abruptly. It is extremely disconcerting. Since she is deaf, it is very hard to keep her safe at times because of this.

Her last ACTH test was performed 4.5-5 hours after the dosing of the med.

I didn't see the test results, but I am sure I could get them and post if it would be helpful. If anyone has general observations about how long Trilostane should take to work, that would also be very helpful to me.

I should also mention that Lady suffers from acid reflux and has been taking 10mg of Famotidine (Pepcid) daily for about 7 years. Without it, she throws up as many as 10 times a day. With it, she's fine.

Thanks.

[frijole]

Trilo does tend to work rather quickly. I am trying to follow the timeline. You said she was doing great and then 3 weeks into it the symptoms returned. Was the acth test (where she was low) before or after the symptoms returned.

If after it makes no sense because if the cortisol is low then one would assume the appetite and thirst would have gone away. Signs of low cortisol are lethargy, lack of appetite.

Yes, getting the numbers for all tests done and the dates would really help us help you. Like Lori - I am wondering if something else is causing this. Cushing's is often misdiagnosed. Getting the tests will give us more information to work with.

I got the impression that the weak hind legs was a symptom before starting trilo right? Is that still an issue? Do you see signs of muscle wasting or do you think it is more like arthritis? When you say increased thirst - how much water does your dog drink a day?

Sorry to ask all these questions but it will help. Glad you found us. Hang in there and we'll help all we can! Kim

[Harley PoMMom]

Hi Mike,

It is very unusual for a dog with Cushing's Disease to not have polyuria as one of their symptoms. Excess cortisol increases the glomerular filtration rate: (GFR is the volume of fluid filtered from the kidney glomerular capillaries), thus initiating increased urination. Since the dog is urinating more the dog has to increase the amount of drinking water to keep up...usually what goes in has to come out?

Many of our members give their pups pepcid ac as both of the Cushing's medicines can irritate the stomach.

Was a ACTH stim test done before any Trilostane treatment began? And, yes, posting the results of the ACTH tests with the dates that they were done would be most helpful.

Was/is her liver enzymes high? Can you get a copy of her chemistry blood panel results and post any abnormalities here, with the reference ranges and the units of measurements...(ug/dl).

The more you can tell us, the better our feedback will be.

Love and hugs,
Lori

[frijole]

This is why I asked how much is 'alot' of water. My Haley was treated for cushings for over 4 yrs and she never had excessive water intake. No more than 1 1/2 cups a day and she was 16 lbs. When I first came online I was confused about this. People set me straight by defining 'lots' as in gallons. :p Normal water intake should be around an ounce per pound of weight. Kim

[voss001]

OK, let's see if I can cover everything asked in the last 2 posts.

Here is the basic timeline:

4Q of 2008 - Hearing loss discovered

2Q 2009 - Heavy panting and anxiety noticed and gradually become chronic

Feb 2010 - First ACTH test is negative, but Vet suspects Cushings. Lady is now drinking 5-6 20 OZ bowls of water per day as opposed to 1-2 max.

Early Nov 2010 - 2nd ACTH test is positive - Vet confirms Lady has Cushing's

Early Nov 2010 - Lady goes on 60 mg Vetoryl daily - good results first 3 days or so - she sleeps a lot, seems very calm and like her old self at times, and drinks much less water. By 2nd week, even 2 doses/day seems to not be helping much and she is back to heavy panting at times and drinking more. (I increased the dosage some days as a test to see if it would help after reading that 2 60 mg doses are not unusual for a 55 lb dog)

Early Dec 2010 - 3rd test shows Cortisol is now too low - vet changed to 25mg Vetoryl 2x daily attempting to get right level consistently. Note: could I have screwed up the vet's test by giving 2 doses in 1 day a few days before the test? My impression is that it doesn't stay in the blood long enough for that.

We are now about 9 days into this 2 x 25 mg/day routine and what I observe is that she slows down and sleeps somewhere around 3-4 hours after taking the med, but still has periods of HEAVY panting all day long and anxiety is very high. Drinking about 4-5 20 oz bowls of water daily. I know that any animal's hormonal axis takes time to adjust, but HOW LONG for a 55 lb dog??

I was an athlete for many years and used various kinds of steroids and other ergogenic aids which modified the hypo-gonadal axis. I know that there is about a 1-month +- adjustment period in humans and a degree of "rebound" as receptors re-attenuate, glands resume production, etc. Has anyone any idea as to how this goes in dogs?

As to the weakness in her rear legs - this started in the last 6 months. I see *no* sign of muscle wasting, so I am more inclined to believe it is related to arthritis, which previous x-rays have identified early signs of. She takes 1000 mg of glucosamine/condroitin daily, but I really don't know if that stuff has any efficacy to be honest. Bear in mind, this is a 14 year old dog, so she almost certainly has some degree of arthritis as she's already far outlived her demographic.

Now, for Lori's questions:

Yes, 2 ACTH tests (the 8 hour kind) were done before Trilostasne began and one after. (the brief kind where they just measure Cortisol and Cortrosyn) I definitely do not observe any increase in urination over the past year or, if any, so little as to be unobservable.

Now her liver is an interesting subject. 5 or 6 years ago, a vet observed her liver to be small, but no problems were found with it. In the last 2 months when we had the sonigram, etc., this vet found her liver to be enlarged, which they attribute to the Cushing's. I will get her latest enzymes and bloodwork on Monday to post along with the ACTH tests.

One other thing I should mention: Lady was 55 lbs all her life until the last 18 months or so when she went up to 60-65 lbs and had a lot of belly fat increase. Since starting Trilostane, she is down to 55 lbs and her belly looks better, even after the dosage change.

Thank you all for your help. Lady is a lovely dog who hasn't been apart from me for more than a day in 13 years and has spent a big part of her life mentoring service and therapy dogs. It really is her time of need now and I appreciate all the thoughtful help.

Mike

[Harley PoMMom]

Note: could I have screwed up the vet's test by giving 2 doses in 1 day a few days before the test? My impression is that it doesn't stay in the blood long enough for that.


Trilostane is administered orally and appears to be rapidly absorbed. Peak serum concentrations occur one-and-a-half to two hours after dosing and return to baseline within 18 hours; inhibition of steroid synthesis is reported to last less than 20 hours.8

http://veterinarymedicine.dvm360.com/vetmed/article/articleDetail.jsp?id=491107&sk=&date=&%0A%09%09%09&pageID=3


Hypoadrenocorticism can develop at any dose of VETORYL

http://www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Vetoryl.pdf




Yes, 2 ACTH tests (the 8 hour kind) were done before Trilostasne began and one after. (the brief kind where they just measure Cortisol and Cortrosyn) I definitely do not observe any increase in urination over the past year or, if any, so little as to be unobservable.

Sounds like Lady had a LDDS test, which takes 8 hours to perform, and an ACTH test.

Do you recall if her kidney values are within the normal ranges? These would be the Creatinine and BUN.

[apollo6]

welcome Mike and Lady
I am Apollo mom. Apollo is 12year old mini dachie. He has been on Trilostane since June 2010. Most doctors seem to go by rules and not the patient. Apollo weighs 10lbs. and is now on 12.5 compounded Trilostane. I insisted on starting real low because of the very thing that happened to your poor Lady. As to the hind leg weakness it is often a symptom of cushing muscle wasting of the hind leg muscles. It can take a few months until you see improvement , some areas will improve faster then others. Like you it took almost 2 years to come to the cushing diagnosis. Ask as many questions as you like. Will be praying for your Lady and you. Hang in there. You are doing all the right things.
Sonja and Apollo

[Squirt's Mom]

Hi Mike and welcome to you and Lady! :)

On the excess urination - that does not always mean the pup needs to go out more often, it could be that the pups pees longer and voids more during the same number of trips out.

The anxiety sounds a bit like thyroid problems. Has this been ruled out? Cortisol will upset the circadian rhythms in our pups causing them to be more restless at nite when the cortisol level will drop in a normal pup but doesn't in a cush pup, this is not the only cause for this behavior. Her hearing loss may be playing a part in this as well.

I assume no other abnormalities were noted on the ultrasound?

Keep asking questions! We have several Trilo moms and dads who will be along to share their experience with you I am sure. Meanwhile, here is a link to our Helpful Resource section where you will find lots of good info on Cushing's as well as other conditions.

http://www.k9cushings.com/forum/showthread.php?t=180

I'm glad you found us and look forward to learning more as time passes!

Hugs,
Leslie and the girls - always

[voss001]

Sonya - thank you for the informative reply.
Can you tell me aproximately how long Apollo was on Trilostane before you saw definite improvement?

I am glad to hear that maybe the hind leg issue is related and could improve. I watched my sister's 16 year old sheltie suffer the same problem the last year or 2 of her life and thoguht it was just a common aging issue in some breeds.

Best regards,

Mike

[Harley PoMMom]

Another thing I wanted to ask you...before Lady's hearing loss was discovered, did she have an ear infection and was she rx'd Gentamycin/Gentamicin? This antibiotic medicine is known to cause deafness in dogs.

http://www.peteducation.com/article.cfm?c=0+1451&aid=1421

[voss001]

Interesting. Lady did in fact get Otomax for an ear infection. We went through one bottle over the coures of maybe 2 years and it was before she lost her hearing. We've been using Tresaderm for the past 2 years as needed.

wow.

[Harley PoMMom]

One of the ingredients in Tresaderm is Dexamethasone; Dexamethasone is a member of the glucocorticoid class of hormones like cortisol. If Lady was on Tresaderm for a period of time when she had her ACTH stim test, this could have skewed her results.

[Squirt's Mom]

If Lady has been on these steroid containing or steriod-like products for very long, they can cause what is called Iatrogenic Cushing's which is caused by external forces like use of steroids and is treated by slowing stopping these meds.

How long has she been using products like these?

[voss001]

Generally, Lady has only received these meds when an ear was bothering her. her bottle of Otomax lasted around 2 - 2.5 years. She's gone through one 15 ML bottle of Tresaderm in the past year and just got a new one 2 months ago when vet found an ear infected during the ACTH test. Usually, if her ears are bothering her, evidenced by shaking her head a lot or pawing at one, I'll check them and give her the med daily for about a week or ten days and then stop.
I can certainly discontinue the Tresaderm altogether if it may be a cause. I can't believe my vet wouldn't have known this.

[Harley PoMMom]

Also wanted to add that recurring ear infections and extreme thirst are some of the symptoms of Hypothyroidism.

[Squirt's Mom]

I am not sure that intermittent use would cause Iatrogenic Cushing's but it is worth keeping in mind for the future.

Is Lady spayed? The ultrasound was normal other than the adrenal being bilaterally enlarged, correct? No tumors, or other abnormalities found? The reason I ask, my Squirt tested positive on 5 cushing's specific tests but when a splenic tumor was found and removed, her cortisol returned to normal. Cushing's is not the only reason for elevated cortisol which is why I like to see a number of tests done to confirm diagnosis before starting treatment.

I assume Lady had a CBC done? Did it show a T-4 test and do you know what that number was? This is a test for thyroid function that can indicate if there is a problem with this organ.

Hugs,
Leslie and the girls - always

[zoesmom]

Hi and welcome -

IMHO, I think 3 weeks is too long to wait for another ACTH test. The recommendation is to do one within 10-14 days after starting the trilo and whenever there is a dose change. And until you know where the cortisol levels are, it's hard to say what could be going on. Too high or too low cortisol, that is. Addison's can produce increased thirst, just like cushings and that's one of the symptoms you are seeing, right? If it were that, she might only be 'borderline low', since she doesn't seem to be displaying other signs of addison's. Here in the states, they now say to also test electrolytes, every time you are doing an ACTH. Did your vet mention doing that with the last ACTH?

As to the other advice - those are all good things to ask about (low thyroid, diabetes, steroidal ear drops, etc.) Sue

As to tweaking the dose on your own, that is probably not a good idea in the beginning. The cushings drugs are very serrious drugs. Some dogs take several weeks to stabilize on a dose and achieve the right numbers. And while the drug trilo is supposed to leave their systems rather quickly, I suspect that it can take several days sometimes, depending on circumstances and I do feel that there can be a slight cumulative effect that takes longer than one day to resolve. Doubling Lady's dose may have been a little much for her, even though it wasn't daily. That said, once my Zoe was stable and well into her treatment, I did tweak her dose myself on occasion. It was after we'd done many many ACTH tests and I had gotten so that I could interpret her symptoms pretty well. I also did a lot of measuring of her water consumption over the years and found that to be a good indicator. And when I did tweak her dose, I only made very very slight changes in the dose.

[voss001]

Leslie - Lady was spayed at about 1 yr of age when I found her. (she was a stray.) Nothing else unusual on the ultrasound. Lady has one egg - sized tumor in her belly which appeared about 2 years ago and has not changed at all in size - I watch it closely. All vets have expressed no concern and believe it to be a simple lipoma. Lady has been tested for thyroid function and diabetes and come up clean.

Zoesmom - I agree that tweaking lady's dosage was a bad idea and I blame my impatience due to her bad symptoms. The good news is that I have not varied whatsoever from the new every 12 hours dosing and today I have observed different results. It's now 4 PM and Lady's panting and water intake since the 7AM dosage have been much lower than any day in the past week. Only one 20 oz bowl of water and only panting 2 times for about a minute. She also slept a lot, which is unusual, and has been a bit more calm all day. It's obviously early to say, but I am hopeful that maybe her blood levels are
stabilizing. We'll see how we do up to and after the 7PM dose. We also skipped our 3 mile hike today as I didn't want to interrupt her peaceful rest, so I'm not sure if/how that fits in.

[voss001]

Hello everyone and Happy New Year,

Lady has been doing better since having her Vetoryl dosage adjusted and split into 2 daily doses. I think one more adjustment will still be necessary based on our last test, but it looks like we're almost there.

My concern now is her back legs. Until coming to this site, I had no idea that wasting in the hind legs was something related to Cushing's. Lady is almost 15 and I have seen other older dogs have their back legs start giving out, so I had thought she was just finally getting old. Now that I think about it, her weakening in the legs really became pronounced over the past 2 months. During that time, she stopped jumping up on my bed and lost the ability to jump up into the car. Looking closely at her back legs, I can definitely see that there is some degree of atrophy.

So, what can I do? Is there anything to be done in addition to Vetoryl and exercise? We hike 3 miles daily and she is very strong there. Is there anything else that can be done? Is it maybe possible to give vet steroids to a Cushing's dog?

Thanks,

Mike

[caroleh]

Hello and Happy New Year.
I am Carole and I currently have my Fritz in a Dallas ICU unit with Diabetes. Fritz also has Cushings but his right hind leg started giving him trouble and he couldn't get up. Once I held him in a upright position for a few minutes he was able to motivate. Has your little sweets been tested for Diabetes? I am sorry to say there seem to be many vets that are not educated in Cushings nor Diabetes where I live. I don't know if that is your case or not. I am just adding my two cents worth and I hope your baby will be o.k.

[Harley PoMMom]

Hi Mike,

Vet steroids are definitely a no-no when dealing with muscle atrophy and a Cush-pup, what you may want to try is L-Glutamine, but please ask your vet first.

Here is an article about L-Glutamine: http://www.scribd.com/doc/23752319/Role-of-Glutamine-in-Health-and-Disease

Glad to hear Lady is doing well, please do keep us updated.

Love and hugs,
Lori

[Squirt's Mom]

Hi Mike,

Giving steroids to a pup with Cushing's is not a good idea. Giving steroids to a pup with Cushing's who is under treatment is defeating the purpose of the treatment. ;)

First, determine what the cause of the weakness is if possible. That is one result of untreated Cushing's but weakness typically shows up before treatment and then gets better on treatment. But there are those babies who just will not follow the rules! :D

Does she appear to be in pain or have stiffness that improves with movement? That could be arthritis showing up as the cortisol is lowered. The excess cortisol often "treats" inflammatory problems like arthritis, then when the cortisol is lowered to more normal levels with treatment the inflammation rears it's head.

A very rare occurrence with Cushing's is a condition called myotonia, in which the muscles actually atrophy.


In rare cases of hyperadrenocorticism (<1%), dogs develop a myotonia (pseudomyotonia) coincident with the onset of Cushing’s disease.2 This syndrome is characterized by muscular hypertrophy and a stiff disabling gait (particularly of the pelvic limbs), in contrast to the typical clinical signs of muscular atrophy and weakness. The muscular rigidity may be so pronounced that the dog is non-ambulatory, and flexion of the hindlimbs may not be possible even under general anesthesia.3 In addition to the pelvic limbs, myotonia of the epaxial and thoracic limbs may also be apparent. Generally these animals are nonpainful and have an otherwise unremarkable neurologic examination. Percussion of the muscles may also produce a characteristic “myotonic dimple.”

http://www.vmsg.com/canine-hyuperadrenocorticism-and-pseudomyotonia

Another consideration is the Trilo itself.


ADVERSE REACTIONS:
The most common adverse reactions reported are poor/reduced appetite, vomiting,
lethargy/dullness, diarrhea, and weakness.

In a US field study with 107 dogs,...Additional adverse reactions were observed in 93 dogs. The most common of these included
diarrhea (31 dogs), lethargy (30 dogs), inappetence/anorexia (27 dogs), vomiting (28 dogs),
musculoskeletal signs (lameness, worsening of degenerative joint disease) (25 dogs), urinary
tract infection (UTI)/hematuria (17 dogs), shaking/shivering (10 dogs),...an additional four dogs were removed from the study as a
result of possible trilostane-related adverse reactions, including collapse, lethargy, inappetence,
and trembling.

http://www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Vetoryl.pdf

Keep in touch and let us know how Lucy is doing!

Hugs,
Leslie and the girls - always

[voss001]

Thank you this is very interesting. I definitely recall that a few years back after x-rays a vet said Lady had the very early signs of arthritis. This coupled with the rapid onset of difficulty with her legs coinciding almost exactly with the starting Vetoryl leads me to believe that the excess cortisol may very well have been helping her arthritis.

If that turns out to be the case, is there anything for dogs similar to Celebrex or such for helping with arthritis?

[Harley PoMMom]

Adequan shots are what some members use for their furbabies, Cosequin, I believe, is another, plus the L-Glutamine that I mentioned before.

[Squirt's Mom]

Several members here have had luck with Adaquan. It is an injection that the pup starts out on with a frequent dosing, then gradually reduces to an optimal level.

Also there are supplements and herbs that can help like Omega 3, SAMe, glucosamine, condroitin, Vitamin C, CM (cetyl myristoleate), DGM (dimethyl glycine), hyaluronic acid, Boswellia, evening primrose, borage oil, to name a few. I gave my pitty who had numerous skeletal problems many of these things and they seemed to help.

Diet-wise avoid plants from the nightshade family like white potatoes as they have been shown to be inflammatory and, if she will eat them, give her papaya (for papain) and pineapple (for bromelian) as these have anti-inflammatory properties among other foods out there.

Again, you want to be sure what is causing her problems before you start giving her any supplements or herbs - they are drugs in their own right and as such should be respected. ;)

Hope this helps!
Hugs,
Leslie and the girls - always

[frijole]

My Haley had adequan shots - she was over 16 at the time and they did give her some relief. You can actually buy them and give them yourself to save money if you like. Plus its more convenient than going to the vet every few weeks.

Annie, my other dog has an adrenal tumor and may or may not have cushings (long story) and the head of the department of small animal medicine at K State Univ suggested I give her Duralactin for her hind leg weakness - really bad at times. I have had great success with it. If you google it you will read alot of positive things. It is fairly new and alot of vets have not heard of it yet. Here is a thread I posted on it:

http://www.k9cushings.com/forum/showthread.php?t=2635

Kim