Cushing's questions from a new member

[westcoastflea1]

interesting article ghrelin stimulation of acth cortisol any thoughts??

Abstract
Ghrelin, a peptide predominantly produced by the stomach, has been discovered as a natural ligand of the GH Secretagogue receptor type 1a (GHS-R1a), known as specific for synthetic GHS. Ghrelin has recently attracted considerable interest as a new orexigenic factor. However, ghrelin exerts pleiotropic actions that are explained by the widespread distribution of ghrelin and GHS-R expression. Besides strong stimulation of GH secretion, the neuroendocrine ghrelin actions also include significant stimulation of both lactotroph and corticotroph secretion; all these actions depend on acylation of ghrelin in serine-3 that allows binding and activation of the GHS-R1a. However, GHS-R subtypes are likely to exist; they also bind unacylated ghrelin that is, in fact, the most abundant circulating form and exerts some biological actions. Ghrelin secretion is mainly regulated by metabolic signals, namely inhibited by feeding, glucose and insulin while stimulated by energy restriction. The role of glucocorticoids on ghrelin synthesis and secretion is still unclear although morning ghrelin levels have been found reduced in some patients with Cushing's syndrome; this, however, would simply reflect its negative association to body mass. Ghrelin, like synthetic GHS, stimulates ACTH and cortisol secretion in normal subjects and this effect is generally sensitive to the negative glucocorticoid feedback. It is remarkable that, despite hypercortisolism, ghrelin as well as synthetic GHS display marked increase in their stimulatory effect on ACTH and cortisol secretion in patients with Cushing's disease. This is even more intriguing considering that the GH response to ghrelin and GHS is markedly reduced by glucocorticoid excess. It has been demonstrated that the ACTH-releasing effect of ghrelin and GHS is purely mediated at the central level in physiological conditions; its enhancement in the presence of ACTH-secreting tumours is, instead, likely to reflect direct action on GHS receptors present on the neoplastic tissues. In fact, peculiar ACTH hyperresponsiveness to ghrelin and GHS has been observed also in ectopic ACTH-secreting tumours.

[westcoastflea1]

has anyone tried using taurine alcar and calcium to combat possible leptin resistance in hypothalamus? it seems that leptin reduces cortisol and helps in appetite regulation so am wondering if anyone has tried thinking outside the box and if it has worked for pdc?
my Declan is pdc and hungry all the time he is on 90 mg vetoryl a day and while he is no long drinking all day then getting me up 4x a night to pee on the 90 mg the hunger etc is still a problem

leptin seems to reduce hunger signals and also reduces cortisol


cushings is just such a nasty disease and no one seems to really have the answer for it all the vets do is give toxic meds that are no longer used for humans there must be a better way.

[labblab]

Hello and welcome to you and Declan! As you will see, I've merged your two new posts into this single consolidated thread. I've also taken the liberty of giving it kind of a generic new name -- we can change that to something else, but this seemed like an easy place to start. We generally like to "corral" peoples' posts in a single thread so that all the related information/discussion is easy to locate and review in one single place.

I know you were asking for feedback re: the article that is abstracted in your first post, and you are also asking for some input re: using some supplements to combat hunger? I must confess that the abstract is too technical for me to understand, and I really do not know anything about the use of taurine alcar and calcium. So I'm afraid I cannot add to your understanding about either of those specific questions. :o

However, I would like to learn more about Declan's health history, Cushing's diagnosis, and treatment. I will cut this short so that I can go ahead and quickly post this reply -- I want you to know why and how your threads have been merged. But any additional specifics about Declan will be very much appreciated!

Marianne

[Renee]

cushings is just such a nasty disease and no one seems to really have the answer for it all the vets do is give toxic meds that are no longer used for humans there must be a better way.

Yes, it truly is a nasty disease, however, these medicines are generally only toxic when misused. It's unfortunate that there really is no 'cure' for cushings, but the medications (when used properly) are absolutely life-saving for many, many dogs, my own included.

Much of your abstract is above my technical understanding, but I did want to comment on the usage of calcium supplement to combat hunger. I would strongly urge you not to that, as dogs needs a certain ratio of calcium to phosphorus balance in their bodies for health. In addition, many cushings dogs (my own included!) may already have an imbalance in calcium and/or phosphorus.

We would love to know more about your pup so we can offer meaningful advice to help.

[westcoastflea1]

hi
thanks for the merge :)
you're right info is quite daunting.
im trying to take it in, digest it , then put it out there and see if anyone has any experience with thinking outside the box, any endocrinologists, nutritionists, scientists,chemists, anyone who can add a piece to the puzzle, we have nothing to lose, from what i can see current treatment is very expensive and medications are toxic. cortisol levels seem to be the biggest issue so how can they be lowered without using vetoryl or lysodren?

how can we help them feel better ?

declan is a 6 year old basenji, unadoptable foster i have had since he was 2 years old, huge bite history, he didnt just bite he attacked and would bite 5 or 6 times before you could move.
declan is always on guard, doesnt trust anyone to put their hands towards him, i have to wonder how much of his personality may have been shaped by a tumor that is just now making itself known?

declan was diagnosed with pdc several months ago.
he is currently on 90 mg vetoryl daily 60 in the am and 30 in the pm
and only improvement seems to be in water consumption and urination( back to normal )
if he is not sleeping he is looking for food.
declan has indigestion prompting me to start making a mix of orijen fish dog food combined with a small amount of rice and lots of veggies so he can eat more and taken in less calories (orijen is almost 500 calories per cup)
Declan currently weighs 42 pounds, about 20 pounds over what he should be. Gall bladder has some debris im going to start him ursodiol to clear it up and keep it from forming a full blown mucocele.

his first uccr test showed cortisol levels of 234 on urine taken at home. i skipped the stim test and went directly to the ultrasound which showed an enlarged left adrenal gland, diagnosis was pituitary tumor.
liver and everything else is good
before diet change he would throw up bright yellow bile 2 or 3 times a week first thing in the morning i fixed that by making sure he gets food right before bed, he hasnt thrown up since.
last vet visit was a limited cortisol test showing 6.6 (normal 1-5) vet said it really didnt give any info beyond making sure he wasnt below normal so no info on whether vetoryl had lowered cortisol
he is going for a stim test wednesday
has anyone tried taurine to get leptin cells to work and lower cortisol and hunger pangs?
feel free to edit this i could go on for a lot longerhttp://www.k9cushings.com/forum/images/smilies/biggrin.gif

[westcoastflea1]

trilostane was withdrawn from human use in the United States market in April 1994. The drug was previously available in the United Kingdom for use in humans under the brand name Modrenal for the treatment of Cushing's disease and for breast cancer

[labblab]

Just to clarify for folks, trilostane has been used to treat Cushing's in humans and also has been investigated as a treatment for advanced breast cancer and for prostate cancer. It stopped being sold for human use in the U.S. in 1994, but it is still sold elsewhere in the world. When I first started treating my own dog for Cushing's back in 2004, I was actually importing Modrenal, the human form of the drug, from England. Here's a summarizing blurb:


Trilostane is an inhibitor of 3 β-hydroxysteroid dehydrogenase (3-β-HSD or delta 5-delta 4-isomerase), an essential enzyme for the biosynthesis of all classes of hormonal steroids. It has been used in the treatment of Cushing′s syndrome for stopping the production of cortisol, and is currently approved for dogs in the US, but is still a human drug in the UK and other countries. It is being investigated as a possible treatment for both breast cancer and prostate cancer to prevent the synthesis of estrogens and androgens from endogenous precursors. It has also been used to inhibit endogenous production of progesterone in research studies.

Like Renee, I do think that both trilostane and mitotane have the potential to vastly improve quality of life for dogs when they are used properly. However, I also agree it would be great if a newer generation of drugs is ever introduced that have fewer side effects and do more than only treat symptoms. In that vein, here's an article published last fall by Dr. David Bruyette that discusses some exciting new drugs that may be coming down the pipeline. What a gift if they actually materialize!

http://veterinarynews.dvm360.com/new-possible-cushing-s-treatments-work-root-cause

Marianne

[labblab]

Hi again, and it looks as though we were typing at the same time about the Modrenal. ;)

Thanks very much for the additional info about Declan. You are a jewel to continue to foster him, given his biting issues. I just have a couple of quick thoughts to add after reading more about his history.

First, you mention that the left adrenal gland was enlarged on ultrasound. Was the right gland able to be seen? Typically, pituitary Cushing's produces bilateral gland enlargement. So if only one gland is enlarged or mishapen, that would tend to point more to an adrenal tumor being the culprit. One reason why I mention that is because a functional adrenal tumor may necessitate higher doses of medication to gain symptom control. You'll know a lot more about Declan's cortisol level after the ACTH test, but I just wanted to mention this possibility.

However, if Declan does indeed suffer from a pituitary tumor, it seems possible that it could be exerting enough pressure on the hypothalamus to overstimulate his appetite. We more commonly see the opposite effect here: dogs with expanding macrotumors tend to lose their appetites. But I think you could see the reverse dynamic, as well, depending upon the exact nature of the intrusion into the hypothalamus.

Either way, the ACTH test results will be very interesting to see.

[Renee]

Thank you for the correction on trilostane being used in humans. I would hate to pass about incorrect information, so I have edited my original post.

[westcoastflea1]

sorry it was the right adrenal gland 1.2 cm width is that enlarged? its obviously something since it was noted in the charts just not sure which

cabergoline WOW
just read the study it sounds great
42% of dogs saw improvements, tumor smaller, life expectancy is greater and the only side effects vomiting
sounds like a win win now to see if it is available :)

[westcoastflea1]

thats what is interesting why do they get so hungry ?
what causes that imbalance ? why arent they getting the signal that they are full?
leptin seems to be the "im full" signal but the brain can be leptin resistant, so you can have too much leptin in the fat cells but the body is not reading them because the brain has become leptin resistant
taurine is supposed to deal with the resistance so it seems to me that if you cure the resistance then the brain will get the leptin signals and the dogs will know they are full plus the cortisol levels will drop because leptin reduces cortisol
too simple??? worth trying?? i dunno

[labblab]

Your questions about hunger are really interesting, and are encouraging me to do some more research of my own. In truth, I've always just accepted as "fact" that elevated steroids are associated with increased appetite, but I've never actually investigated the mechanism in detail.

If you're willing, though, I'd first like to find out some more about Declan's Cushing's diagnosis. You've spoken about increased thirst, urination and appetite. Did he suffer from any other Cushing's symptoms, either overt or in terms of lab abnormalities? I'm guessing you're aware that the UC:CR is not a definitive test for Cushing's -- other conditions can also cause elevation in those results. And now I'm also wondering about those ultrasound results...were both adrenals visualized, and was only one enlarged? How much enlargement was actually noted? Just as is the case with the UC:CR, conditions other than Cushing's can result in systemic stress, cortisol release, and enlarged adrenals.

Since Declan weighs approx. 40 pounds, his daily dose of 90 mg. is more than twice the amount that is currently recommended as a starting dose for a dog of his size. So I don't know whether you have worked up to this dose, but if his cortisol level remains high on this upcoming ACTH testing, it does make me scratch my head a bit. It definitely seems counter-intuitive, but we have been told that with mitotane (the other Cushing's med), dogs who are dosed with the drug but don't truly have Cushing's can be resistant to the effects on the adrenal glands (in other words, cortisol levels remain high even in the face of ongoing treatment). I don't know whether the same is also true of trilostane.

But to cut to the chase, I'm interested in finding out the whole universe of factors that led to the Cushing's diagnosis: overt symptoms, abnormal blood tests, abnormal urine tests, actual ultrasound interpretation. I apologize for asking so many questions, but Cushing's is an easy disease to misdiagnose due to the lack of a single, definitive test.

[westcoastflea1]

im so glad you asked!!!
i finally found the paper work from his first visit to specialist realised he had had a stim test along with the ultrasound and also realised that we were never given the results of the stim!
so...... results for january 13 stim test was 1,380 normal being 220 - 550

his history as follows:

12-16 he first went to vet
cbc increased wbc (18.7k)
hct (60%)
platelets (519k)
chemistry panel:
alkp 415
alt 152
ck 288
phosphorus 6.8
ua-rare bacteria , trace protein
up:c o.6

12-30 test results
uccr 234

1-13 visit to specialist
Ultrasound abdominal liver: diffusely enlarged hyperechoic no focal lesions
Gall Bladder: moderately distended, small amount of settled echogenic debris uniformly thickened mucosa or mucoid bile adhered to walls
Spleen: normal
Left kidney: normal
Left adrenal: 1cm pole widths enlarged
Right adrenal 1.1 cm width enlarged
Right kidney normal
Bladder:
moderately distended normal
prostate stomach sm intestines duodenum pancreas all normal
Liver consistent with metabolic hepatopathy secondary to hyperadrenocorticism
Gall Bladder: consistent with early mucocele
Adrenal Glands consistent with pituitary dependent hyperadrenocorticism
systolic blood pressure 178 mmhg
ACTH test pending
PROBLEM LIST:
abdominal distension
muscle weakness
elevated liver enzymes
elevated urine cortisol creatinine ratio
bilateral adrenal gland enlargement
liver enlargement
mild hypertension
indigestion
STARTED ON 50 MG VETORYL 30 AM 20 PM
PLAN ON MONITORING HIS GALL BLADDER

SO THAT VISIT WAS 750.00 meds given at discount only to find they were expired by 2 years
february 9th purchased new vetoryl 30 mg 2xday

FEBRUARY 17TH VISIT TO SPECIALIST
limited blood baseline cortisol test 6x6ug/dl (normal 1-5)
limited ultrasound no change in gall bladder
Right adrenal gland 1.2 cm width
No real changes
Increased vetoryl to 90mg 60 am 30 pm
questioned vet why not treating gall bladder before it turns to mucocele was told we could start ursidiol waiting til vet visit this wednesday to start that
going back to my old vet on wednesday, do not like specialist at all
so i hope this gives you the info you were looking for??

[molly muffin]

So yes, I see where it is pituitary based on both adrenal glands being bilaterally enlarged. Not sure if a macro tumor though, since there are usually quite a few neurological signs associated with the macro tumors due to the pressure in the brain. Staring into space, stuck in corners, not able to lower head to head, lack of appetite, just to name a few. We have a thread that is just about macrotumors, created by and added to by those who have had their dogs diagnosed with them. http://www.k9cushings.com/forum/showthread.php?t=3567

The gall bladder sludge can definitely have an adverse affect on just about every organ surrounding it, especially liver, etc. So it could be affecting both the cortisol levels and the liver enzymes. I would expect it to anyhow and we've seen that before.

It certainly is strange that his cortisol would be so high on such a large dose of vetroyl.

Shame on anyone dispensing drugs that are expired. That's downright dangerous.

Oh and hello and welcome to the forum. :)

[westcoastflea1]

congrats on your wading through all that info!
vet seemed to think gall bladder was because of cortisol levels and would resolve once under control
but in doing some research on the internet studies seem to indicate that clearing the gall bladder out before it becomes solid is the way to go
i dont like this specialist so im going to my old vet wednesday she doesnt have much experience with cushings but i know from experience with my last basenji (cancer) this doctor will listen to you and let you have some control over treatment.
im going to see about a script for the cabergoline
how can you go wrong?
only side effect is vomiting after taking meds 42% were helped

im tired of giving meds that are dangerous and dont seem to be doing a whole lot (although i have to admit its nice being able to sleep thru the night ) it seems as though he has good days and bad days like the cortisol levels are going up and down today is a not so good day really hungry and drinking alot of water again
anyway more info on condition on wednesday doing another stim to see how the FRESH meds are working
thanks for taking the time to work thru the info i sent

[molly muffin]

I do t think that we have found that gall bladder sludge clears up if cortisol is controlled. Every dog I can think of that we've had on here have had to go on medication and I think one had gall bladder removed, at which point Cushing's symptoms disappeared and no longer needed treatment for that. Bit not the scenario that your specialist mentioned.
If it was me. I'd start the gall bladder meds. You don't want a blockage there.

You know it might be worth contacting Dr Bruyette about the Cabergoline in case there is anything you would need to know before using it other than what was mentioned in the Rticle etc. You can email him T the office in California. I don't have it right off the top of my head but he is very responsive and he's always been very interested in new remedy a for Cushing's and that really is his field of interest.

[westcoastflea1]

hi
thanks so much for the suggestion to email dr bruyette
i just did and then watched a couple of videos
it sounds like there are 3 drugs now to treat pdc depending upon where the tumor is in the pituitary, each drug acts on certain receptors? the cabergoline on dopamine the pasireotide on hormones and the som2 on another receptor, (alot more complicated but that seems to be the simple version)
declans 1380 level was before he started on the vetoryl, so tomorrow will tell whether its working.
has anyone noticed that symptoms seem to see saw day by day?
one day good the next not?
it really does sound like these new drugs are the way to go

[molly muffin]

Did you get a response back from Dr. Bruyette yet? I'd be very interested in seeing what he says about the new drug possibilities. We haven't seen any dogs being prescribed them at this point and we are always curious about any new treatments out there.

Radiation for macro tumors has come a long way in just a few short years from originally needing 12 treatments to now only needing a couple.

[Harley PoMMom]

Found this abstract from a study that used Cabergoline for the treatment of canine Cushing's:
To conclude, Cbg is useful in 42.5% of dogs with PDH, justifying its use as a treatment.http://www.sciencedirect.com/science/article/pii/S0034528807001920

[westcoastflea1]

HI
yes i did get several emails from dr bruyette.
ive decided to increase vetoryl to 120 mg per day
so far declan has shown no side effects and seems to be getting better on this dose.
declan is also getting 10mg famotodine and 250mg ursidiol per day. his last acth stim was 5.1 ug pre and 10.5 ug post aiming for about 4ug.
hope to get gall bladder cleared out liver back to normal and cortisol levels to where they should be.

[westcoastflea1]

my basenji declan was on 120 mg vetoryl and was doing quite well
he went to the vet for his stim test and after the test all of his symptoms came back, horrible gas increased water consumption indigestion and general discomfort
his symptoms did not improve until a week and a half later when his vetoryl was increased by 30 mg a day
it is as if the cosyntropin shot prompted high levels of cortisol and it didnt stop producing until his vetoryl was increased
has anyone experienced this after a stim test?

[molly muffin]

Usually we see about a 48 hour increase in symptoms as a normal reaction to the test due to the excess cortisol that is dumped into their system. Some dogs due take longer for it to come back to normal. Some have very little reaction. In that regard every dog is different but it does normally resolve on its own and they go back to the level they were at pre test. Out of hundreds of cases I know of that is the normal. What where the ACTH results? If he was a bit high in that then maybe the symptoms would take longer to resolve.

[westcoastflea1]

Declan's pre sample was 1.7 ug/dL (was 5.1 BEFORE LAST MED INCREASE) and his post sample was 6.2 ug/dL (was 10.7 BEFORE LAST MED INCREASE ). Ideally the pre and post values would be between 1.5-6.
im hesitant to do another stim on his next visit just thinking of having levels checked to make sure not too low

[molly muffin]

As long as symptoms are controlled, that result is a good one.
You mean you are just thinking of having a baseline since he had a reaction that required an increase due to the last stim test?

The pre number tends to fluctuate up and down throughout the day and in reaction to stimuli, so it isn't a good precursor of what his adrenal glands are doing, although I guess if it where way low, then you could go ahead with a full stim to check the post level.

[westcoastflea1]

im asking because declan is currently on 120 mg 2xday he weighs 47 pounds
my concern is whether nor not this will damage his organs
also has anyone tried the cabergoline yet?
with such a high dose of vetoryl im starting to think about trying the cabergoline

[judymaggie]

Hi! I have merged your latest post into your original thread. We like to keep all posts about each pup in one thread. That way it is much easier to keep up with the history for us as well as for you.

I can't recall anyone mentioning that they have tried cabergoline since you last mentioned it. I see that Lori gave you the link for a study on it. Did you ask Dr. Bruyette about it?

With regard to affecting organs with a high dose, the best way to determine this is to do regular chem panels and keep track of any differing symptoms. Has an ACTH been done since April? If not, it would be time to do another one along with a super chem panel.

[molly muffin]

No i don't recall anyone trying cabergoline either and agree with Judy that the best way to determine how the organs are being affected is with regular testing to check them. We do that with my molly's kidneys and liver enzymes.

[westcoastflea1]

i did speak with dr bruyette months ago i felt he was more interested in declan as a test subject then in helping him
he said get an mri taken him off vetoryl for one week then start cabergoline
my vet did say she has used cabergoline for diabetes and would do some research to see if they could be used together

friday i discovered what i think is an enlarged thyroid on declan

this might explain why almost none of his symptoms have cleared up on 240 mg vetoryl since many of the same symptoms are related to either cushings or being hypothyroid
since thyroid is part of hpa axis im also hoping that taking care of thyroid might lower cortisol and let me lower vetoryl dose
so hoping to see vet this week
wish me luck :)

[westcoastflea1]

in regards to test results for cabergoline dr bruyette said it works if the tumor is located in a certain area of the pituitary. i would try it now but 42% success is not nearly as high as vetoryl although cabergoline CAN get rid of tumor and has no damaging affects. its a hard decision to make which is why i would love to try both at the same time perhaps a synergistic effect would occur?
declan is still young so it is worth doing absolutely everything to take care of this
his blood and urine test results are a tad bit high in some areas
only areas really high are alp 415 when when high normal is 160 and alt at 152 with high normal being 121

[Harley PoMMom]

I have a couple questions, and forgive me :o I haven't had a chance to read Declan's whole thread, is Declan getting his Vetoryl with a meal and are those monitoring ACTH stimulation tests being performed 4-6 hours post pill?

Hugs, Lori

[molly muffin]

So is dr Bruyette saying they want to do an MRI to know if a tumor is in the right area?

[westcoastflea1]

i spoke with dr dodds recently she was very adamant that the acth stim test never be used. instead she said to have uccr done
my vet knows nothing about the creatinine cortisol ratio in determing whether meds have things under control. i emailed dr dodds but she is leaving for italy today not sure if she will get back to me
numbers are
TEST RESULT REFERENCE VALUE
Urine Cortisol 22.4 ug/dL 31.4
Urine Creatinine 28.2 mg/dL 41.9
Urine
Cortisol:Creatinine
ratio
ive read that you supposed to divide cortisol concentration umol/l by creatinine umol/l to get the results cant figure that one out and cant seem to find what a normal uccr should be to determine how far off his number is

thanks for any help you can give :)

[labblab]

I will come back later in hopes of adding some specific citations, but I'm afraid Dr. Dodds is misleading you if she has told you that a UC:CR alone can be used to make decisions about increasing a Vetoryl dose. That notion has held attraction but, unfortunately, specific research aimed at testing that proposition has come up empty-handed.

I have no idea why Dr. Dodds would insist that the ACTH stimulation test not be used for monitoring purposes. That is contrary to the advice of virtually all Cushing's experts, of which I must point out, Dr. Dodds is not generally recognized as being one, even with her long history of thyroid interest. The ACTH is not perfect, but as of yet, no reliable alternative has been validated.

Marianne

[labblab]

Here's a couple of quick references. The first relates to the inadequacy of using the UC:CR for judging Lysodren loading. It does not pertain specifically to trilostane, but still, you'll get the idea.

https://www.researchgate.net/publication/51316919_Use_of_the_urine_cortisol-to-creatinine_ratio_for_monitoring_dogs_with_pituitar y-dependent_hyperadrenocorticism_during_induction_tr eatment_with_mitotane_op'-DDD

Also, here's a textbook reference re: issues with UC:CR results in conjunction with trilostane treatment monitoring:

https://books.google.com/books?id=yDjDr_MLGSsC&pg=PT2965&lpg=PT2965&dq=uccr+test+for+monitoring+trilostane&source=bl&ots=Jo2TUNCfKj&sig=sBxxvSJdKoGmytuliOvKGocRVh0&hl=en&sa=X&ved=0ahUKEwiS4M6ZsY3PAhXEQiYKHaPlAag4FBDoAQgzMAk#v =onepage&q=uccr%20test%20for%20monitoring%20trilostane&f=false

I will add more references as I find them.

[westcoastflea1]

i think what she is saying is that the uccr tells you the amount of cortisol being produced using the creatinine as a sort of measuring device since it is produced steadily all day no ups and downs like cortisol if that makes any sense?
if a normal uccr is 50 and declan is 200 than it would seem clear that he has excess cortisol being produced? and if his number was 50 i would say that we have cortisol under control BUT.....i really dont know
it just seems logical

ive done a ton of research today and found studies that do say the uccr
is helpful since it shows high uccr numbers in cushings dogs across the board and that non cushings dogs have very low numbers across the board
i dont like the stim test last time he had one his cortisol shot up and stayed up for over a week until i finally had to increase his vetoryl to get it back to where it was
hes on almost 270 mg per day
be interesting to finally get to the bottom of this whole uccr thing
appreciate your taking the time to post :)

[westcoastflea1]

hi
thank you for the links
this is a quote from one

'The UCCR overlapped among the 3 categories of treatment response. Nevertheless, dogs with PDH receiving mitotane induction treatment and with UCCR > 79 x 10(-6) were always classified as having excess cortisol secretion. The UCCR failed to predict post-ACTH cortisol concentration during mitotane induction treatment sufficiently close to be a clinically reliable indicator of treatment control. Seemingly, however, UCCR > 79 x 10(-6) obtained from a dog with PDH during mitotane induction would indicate inadequate adrenal cortex destruction and the need for continued mitotane induction; UCCR < or = 79 x 10(-6) would be inconclusive.I WONDER IF THIS IS WHAT DR DODDS IS SAYING THAT UCCR IS IS A CLINICALLY RELIABLE INDICATOR OF TREATMENT CONTROL BUT NOT ACCURATE ENOUGH TO ACTUALLY MONITOR CORTISOL DURING MITOTANE INDUCTION
DOES THAT MAKE SENSE?

[labblab]

The UC:CR is well recognized to be a very helpful initial diagnostic screening test for dogs with possible Cushing's vs. dogs without the disease. But even for that, it has limitations in that an elevated result can be associated with conditions other than Cushing's.

As far as treatment monitoring, however, I believe there is too much overlap of UC:CR results for dogs in different treatment categories for the testing to have sufficient validity upon which to base dosing decisions. I am still searching for the specific research paper that I think I am remembering, but the links I've given you convey the basic idea.

Using the UC:CR for diagnostic purposes is a different proposition from using it for monitoring purposes. I do appreciate the fact that your dog had an unusually long reaction to the ACTH stimulation test. But I must tell you that his reaction is way outside the norm that we have experienced here. And I still must question Dr. Dodd's blanket warning against ever using an ACTH for monitoring purposes, ever. That is just way outside mainstream Cushing's treatment and monitoring protocol.

Marianne

[westcoastflea1]

I FOUND THIS AS WELL DO YOU THINK IT TIES IN TO THE GENERAL IDEA OF UCCR BEING USED AS A MONITORING TOOL BUT NOT AS A TOOL IN THE INDUCTION PHASE?

"With the recent changes in availability and pricing of synthetic corticotropin (cosyntropin), which is used in the ACTH response test, keep in mind that the UC:Cr also can be used as a monitoring tool. Although several studies have documented that it is not ideal to use the UC:Cr as a monitoring tool during the loading phase of mitotane treatment, it can be used safely during the maintenance phase because of the low risk of hypoadrenocorticism occurring compared with the risk during the loading phase. The problem with using the UC:Cr to monitor patients during the loading phase is its inability to differentiate between well-controlled and overdosed patients. This distinction is important as well-controlled patients would be switched to maintenance treatment but overdosed patients would require close monitoring and potential treatment for hypoadrenocorticism."

[westcoastflea1]

uccr test Normal range 2.8 - 4.8. A normal result effectively
rules-out hyperadrenocorticism,

so how do declans numbers get worked on to see how they compare to the normal range ?

[labblab]

The problem with using the UC:Cr to monitor patients during the loading phase is its inability to differentiate between well-controlled and overdosed patients.
This is exactly the kind of problem I am talking about. With trilostane treatment, there is no distinction between a loading phase and a maintenance phase. The risk of oversuppression remains a constant throughout treatment. So the inability of the UC:CR to reliably distinguish between dogs for whom the current dose is appropriate vs. inappropriate renders it unacceptable for trilostane monitoring purposes.

[westcoastflea1]

http://www.ncbi.nlm.nih.gov/pubmed/9108922
Use of the urine cortisol: creatinine ratio to monitor treatment response in dogs with pituitary-dependent hyperadrenocorticism.
im finding what seems to be a common thread uccr is not good for induction phase but is useful for monitoring purposes
does this seem right ??

[Harley PoMMom]

The UC:CR is not recommended for monitoring treatment. I'm including this excerpt from a study and was published in 2009 and titled: Urinary Corticoid : Creatinine Ratios in Dogs with Pituitary-Dependent Hypercortisolism during Trilostane Treatment


Conclusion and Clinical Importance: The UCCR cannot be used as an alternative to the ACTH stimulation test to determine the optimal dose of trilostane, but might be helpful in detecting dogs at risk for developing hypocortisolism during trilostane treatment.

http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2009.0374.x/abstract

Lori

[labblab]

RESULTS:
UCCR was not useful for identifying dogs with inadequate adrenal reserves at the end of the induction phase of treatment or during the maintenance phase. The UCCR was useful for identifying dogs in which control of cortisol secretion was not adequate.
CLINICAL IMPLICATIONS:
UCCR should not be used for evaluation of dogs during the induction phase of treatment, because the potential consequences of not identifying dogs with inadequate adrenal reserves are great. The UCCR may be useful as an adjunct means of monitoring treatment response during the maintenance phase of treatment. However, the ACTH stimulation test remains a necessary component when monitoring response to treatment in dogs with PDH receiving mitotane.

First of all, again, trilostane treatment does not distinguish between a loading and maintenance phase. Secondly, the very important point that is made is that, at no time does the UC:CR adequately identify dogs who are at risk of going Addisonian (cortisol reserves too low). This is a huge safety risk, in and of itself, and renders the UC:CR inadequate as the sole monitoring tool for a dog being treated with trilostane.

[labblab]

Thanks so much, Lori! That was the study I was trying to find!!!

[westcoastflea1]

thank you for all the useful info
i would like to see the paper you are searching for
declans reaction to the stim was atypical. as is his vetoryl dose its up to almost 300 mg for a 30 lb dog
im always looking outside the box for ideas since staying in the box doesnt seem to be doing a lot of good for anyone with a cushings dog

you cant trust the vets to stay current with the newest studies which is why im reading and questioning everything and soliciting advice from the members of this forum

ive put declan on melatonin lignans milk thistle vitamins bixbee immune booster ursidiol evo canned food (all meat) and he is doing better then he has since this whole nightmare started dec 2015

i can almost gauge cortisol control just by his appetite and water consumption , he gets his doses his hunger is under control ,he missed a dose last night (pill fell on floor next to food bowl and he was a hungry horror all night
alt and alp have dropped dramatically in the last year
alp went from 639 last year to 448 this last test
alt 152 down to 85
so hopefully you can find that article i just got an email from hemopet saying dr dodds was on her way to italy and would contact me
thanks again for all the good links and advice :)

[westcoastflea1]

my declan who weighed 45 pounds was on 300 mg of vetoryl a day before we finally got things under control cortisol level wise .(using uccr urine test that came back as a non-cushings dog ) but
still his physical symptoms consistent with not only cushings but hypothyroid were still present
dr dodds said thyroid was fine which might have been true but the cortisol decreases tsh so my argument was maybe thyroid is fine but not working the way it should. my vet refused to put him on thyroid meds so i took him to a new vet who started him on thyroid meds and within the last 2 1/2 months ALL physical symptoms are gone. he has a full coat. no pyoderma. no crepey skin, no blackheads on belly no darkening of skin, his energy is back. i also took declan off the vetoryl and started him on cabergoline its been almost 3 months now off vetoryl and i have seen no sign of cushings symptoms. he is back to under 30 pounds which is where he should be and is doing fine. i dont use stim tests to see if cortisol is under control rather i use several days of morning urine sent to lab to test uccr. since going off vetoryl i have not tested uccr but will do so soon. im just relating my personal experiences in hopes that someone might find them useful in some way

[Budsters Mom]

Do you mean 30mg., not 300mg.? That must be a typo?????:confused:


my declan who weighed 45 pounds was on 300 mg of vetoryl a day before we finally got things under control cortisol wise.

[Harley PoMMom]

my declan who weighed 45 pounds was on 300 mg of vetoryl a day before we finally got things under control cortisol level wise .(using uccr urine test that came back as a non-cushings dog ) but
still his physical symptoms consistent with not only cushings but hypothyroid were still present

Is the 300 mg a typo and you meant 30 mg instead?

[westcoastflea1]

no 300 mg per day 150 am 150 pm

[westcoastflea1]

no typo 300 mg per day

[westcoastflea1]

he is on vetoryl not trilostane we have found that uccr works just fine to monitor his cortisol levels, if lab results come back as non cushings then we are good with that

[westcoastflea1]

he is on vetoryl and regardless of studies we are finding that uccr is working just fine if he tests as non cushings we know cortisol levels are not too high thus meds are working it works for us not saying anyone else has to follow suit just relating what is working for us

[westcoastflea1]

declan has a pituitary tumor.
pars intermedia tumors account for approx 30% of cushings and interestingly enough the success for some of the new dopamine agonist drugs is also about 30%.
my thought is that perhaps vetoryl does not work as well on pars intermedia tumors which might be why declan was on 300 mg of vetoryl
dechra when testing vetoryl did not mri the dogs in the study so had no idea where tumors were located had no idea why some dogs responded and some didnt, cabergoline has been shown to shrink tumors and dogs have been in remission for 4 years on it so just interesting ideas for those whose dogs are not responding well to vetoryl

[Carole Alexander]

So many questions after reading your thread: Did Declan have an MRI? Is his tumor pars intermedia? What dosage of Cabergoline?

My dog responded poorly to increasing doses of Vetoryl beginning in 12/16 and finally at 60mg for 28 lb dog was intensely tremoring and very sick. He is also having significant cognitive issues, lethargy, low interaction, mostly sleeping - onset of cognitive issues coincided with Cushing's diagnosis. Stopped Vetoryl three weeks ago and BP has skyrocketed. I am now debating MRI or Lysodren so I am VERY interested in more detail about your experience with Cabergoline.

This seems like a miracle and you are an extraordinary advocate for Declan. By the way, how is his dog aggression now? Thank you in advance for any additional information. Best to you,

[Harley PoMMom]

I've been a member here for 7 years and have never seen a dog take a dosage that high, 300 mg is an enormous dose.

[labblab]

Hello again from me! I have only a moment to post right now, but I just want to clarify that Declan is not currently taking any Vetoryl -- is that correct? Here's a portion of one of your replies from yesterday, and I just want to make sure that we're understanding it correctly.


i also took declan off the vetoryl and started him on cabergoline its been almost 3 months now off vetoryl and i have seen no sign of cushings symptoms. he is back to under 30 pounds which is where he should be and is doing fine. i dont use stim tests to see if cortisol is under control rather i use several days of morning urine sent to lab to test uccr. since going off vetoryl i have not tested uccr but will do so soon. im just relating my personal experiences in hopes that someone might find them useful in some way

Thanks in advance for clarifying!
Marianne

[molly muffin]

So glad that Declan is finally on thryoid medication. That was found last July right, so glad it is being addressed.

yes to clarify, Declan is not on vetroyl now he is on Cabergoline. I can't remember if you had an MRI to verify the location of the pituitary tumor, but it is interesting that he is having such a good response to the Cabergoline. I believe you are our first to try this for cushings, so we are all going to be super interesting in how he is doing on it and any follow up testing to verify cortisol levels.

I wonder if the reason that he has a prolonged reaction to the acth test is because his of his unaddressed thyroid issues at that time? I think I mentioned at the time that normally the spaz situation resolves within about 48 hours and cortisol goes back to normal, but for Declan the spaz response went on for almost 2 weeks wasn't it?

I call it spaz as that was how I felt my molly reacted. But it's an increase in all cushings systems until the cortisol that is dumped in the body by the ACTH test works it way to normal levels.

[LaurieS]

I am also very interested in your experience with cabergoline. I have mostly the same questions as Carole posted. My Charlotte couldnt tolerate vetoryl and has been off of it for a couple of months and some of her cushings symptoms (exessive hunger and pu/pd) have not returned. Her current symtoms are lethargy, tremoring, pacing, cc, anorexia and now she wont drink on her own. We suspect a pit macro tumor but havent had a mri to confirm. She is day to day at this point. We have her on prednisone and several holistic supplements to reduce inflammation and boost immune system. Yesterday was a good day, today not so good. I would love to feel like there is some hope as she is only 7 years old. But i also dont want to treat her like an "experiment" and need to think of her quality of life.

I anxiously await your answers to some of Carole's questions. Thanks for sharing all your experiences with Declan.

Laurie

[westcoastflea1]

[QUOTE=Carole Alexander;200030]So many questions after reading your thread: Did Declan have an MRI? Is his tumor pars intermedia? What dosage of Cabergoline?DECLAN DID NOT HAVE AN MRI SO I DONT KNOW IF HIS TUMOR IS PARS INTERMEDIA CABERGOLINE DOSE AT PRESENT IS 0.05MG 2 TIMES A WEEK COST IS 120.00 FOR THE MONTH JUST MADE SENSE THAT IF HE HAD TO BE ON SUCH A HIGH DOSE OF VETORYL HE WAS ATYPICAL AND PARS INTERMEDIA TUMOR IS ONLY 20 - 30% OF PITUITARY CASES, SO IT SEEMED LOGICAL DECHRA DIDNT MRI DOGS IN TRIALS SO THEY HAVE NO IDEA WHY IT WORKS FOR SOME BUT NOT ALL DOGS.

My dog responded poorly to increasing doses of Vetoryl beginning in 12/16 and finally at 60mg for 28 lb dog was intensely tremoring and very sick. He is also having significant cognitive issues, lethargy, low interaction, mostly sleeping - onset of cognitive issues coincided with Cushing's diagnosis. Stopped Vetoryl three weeks ago and BP has skyrocketed. I am now debating MRI or Lysodren so I am VERY interested in more detail about your experience with Cabergoline.CABERGOLINE IS GREAT BECAUSE IT DOESNT REALLY HAVE SIDE EFFECTS, SOME NAUSEA IS REPORTED, DECLAN HASNT HAD ANY NAUSEA. DECLAN IS ABOUT SAME AGE AS YOUR DOG. CABERGOLINE, IF IT WORKS, SHRINKS TUMORS SO IF YOUR DOG HAS A MACRO TUMOR CABERGOLINE MIGHT HELP SHRINK IT DEPENDING ON SIZE OF TUMOR. ALSO HAS YOUR DOGS THYROID BEEN TESTED? HIGH CORTISOL LEVELS INTERFERE WITH THRYOID STIMULATING HORMONES SO WHILE THYROID GLAND MAY BE NORMAL IF HIS TEST LEVELS ARE BELOW NORMAL OR LOW NORMAL THYROID MEDS MIGHT HELP WITH MOST OF YOUR DOGS SYMPTOMS. DECLAN WAS TIRED, NOT PLAYFUL, HIS CHEST WAS BALD, THINNING HAIR IN T SHAPE ON BODY, BLACKHEADS PYODERMA AND CREPEY SKIN ON BELLY HE WAS A MESS AND VETORYL DID NOTHING TO RESOLVE ANY OF THESE PROBLEMS

This seems like a miracle and you are an extraordinary advocate for Declan.FOUND OUT THE HARD WAY THAT VETS DONT ALWAYS TELL YOU THE RIGHT THING TO DO, DOING RESEARCH ON INTERNET OF RESEARCH PAPERS, DRUG TRIALS AND GENERALLY TRYING TO FIGURE OUT THE HPA AXIS IS WHAT IVE DONE AND EVERY CUSHINGS OWNER SHOULD DO, YOU JUST CANT COUNT ON YOUR VET TO KNOW EVERYTHING ABOUT CUSHINGS AND EVEN THE SPECIALISTS CANT BE COUNTED ON By the way, how is his dog aggression now? WHEN DECLAN WENT OFF THYROID MEDS HE WAS CRANKY AND BIT ME HE GROWLED GAVE WARNING BUT I WAS ON THE PHONE WITH THE VET AND DIDNT PAY ATTENTION. SINCE STARTING THYROID MEDS HE IS BACK TO HIS NORMAL SELF SO AGAIN WHILE DR DODDS SAYS THYROID IS FINE, DECLANS TEST RESULTS SHOWED BELOW NORMAL, SO REGARDLESS OF WHAT MY VET SAID I FOUND ANOTHER VET WHO WOULD PUT HIM ON THYROID MEDS AND START CABERGOLINE, CHANGES IN DECLAN SINCE STARTING THYROID MEDS HAS BEEN AMAZING.IF I WERE YOU I WOULD CHECK TEST RESULTS FOR THYROID GET HIM ON BLOOD PRESSURE MEDS AND START ON CABERGOLINE. I HAVE NOT HAD DECLANS CORTISOL LEVELS CHECKED YET BUT IT HAS BEEN 2 1/2 MONTHS AND IVE SEEN NO CUSHINGS SIGNS AT ALL HOPE THIS HELPS? LET ME KNOW ?

[westcoastflea1]

it is scary high and makes you wonder why so high to get results? dechra has no answers since they didnt do mri on trial dogs to see why vetoryl worked in some dogs but not all

[westcoastflea1]

declan has been off vetoryl completely for about 3 months. currently his meds have been 0.05 mg of cabergoline 2 times a week and dermal thyroid meds 2 times a day i have not tested cortisol levels but will be doing so in the next couple of weeks to determine what adjustments if any are needed in cabergoline dose

[westcoastflea1]

so glad that declan is finally on thryoid medication. That was found last july right, so glad it is being addressed. YES HE HAD THE TEST and the vet would not prescribe the meds needed since dr dodds said thyroid was normal i had to find another vet to prescribe thyroid and cabergoline.

Yes to clarify, declan is not on vetroyl now he is on cabergoline.RIGHT i can't remember if you had an mri to verify the location of the pituitary tumor,NO
but it is interesting that he is having such a good response to the cabergoline. I believe you are our first to try this for cushings, so we are all going to be super interesting in how he is doing on it and any follow up testing to verify cortisol levels.WILL KEEP EVERYONE POSTED WHEN UCCR IS DONE

i wonder if the reason that he has a prolonged reaction to the acth test is because his of his unaddressed thyroid issues at that time? I think i mentioned at the time that normally the spaz situation resolves within about 48 hours and cortisol goes back to normal, but for declan the spaz response went on for almost 2 weeks wasn't it? HIGH CORTISOL LEVELS mess with thyroid stimulating hormones so possible that thyroid wasnt producing what it should and led to symptoms worsening
but not sure what thyroid does in terms of appetite water consumption gas etc

i call it spaz as that was how i felt my molly reacted. But it's an increase in all cushings systems until the cortisol that is dumped in the body by the acth test works it way to normal levels. yes declan didnt go back down stayed higher which caused me to have to increase vetoryl

[westcoastflea1]

[quote=lauries;200081]i am also very interested in your experience with cabergoline. I have mostly the same questions as carole posted. My charlotte couldnt tolerate vetoryl and has been off of it for a couple of months and some of her cushings symptoms (exessive hunger and pu/pd) have not returned. Her current symtoms are lethargy, tremoring, pacing, cc, anorexia and now she wont drink on her own.HAS HER THYROID BEEN CHECKED?? AND IF SO WHAT WERE THE TEST RESULTS? ? THEY MAY SAY THYROID IS FINE BUT IF ACTUAL LEVELS ARE BELOW NORMAL I WOULD PUT ON THYROID MEDS THEY CANT HURT AND MAY VERY WELL HELP . HAVE YOU HAD A GALL BLADDER ULTRASOUND? DECLAN WAS THROWING UP YELLOW BILE SOME MORNINGS HIS GALL BLADDER WAS SLUDGY PUT ON MEDS AND CLEARED IT OUT IF NOT DONE IT CAN BURST.
THYROID MEDS SHOULD HELP WITH APPETITE, LETHARGY AND NOT DRINKING, GET DERMAL THYROID SINCE GETTING A PILL INTO A DOG WITH ANOREXIA IS IMPOSSIBLE, COMPOUNDING PHARMACY CHARGES ME 50.00 A MONTH FOR IT we suspect a pit macro tumor but havent had a mri to confirm. I DONT SUPPOSE IT MATTERS IF YOU HAVE AN MRI OR NOT IF VETORYL IS NOT WORKING TRY CABERGOLINE IF THAT DOESNT WORK GO WITH ANOTHER DOPAMINE AGONIST NONE OF THE DRUGS HURT YOUR DOG OR CAUSE ANY NEGATIVE EFFECTS, AND IF THEY DO WORK THEY CAN SHRINK A PIT TUMOR he is day to day at this point. We have her on prednisone and several holistic supplements to reduce inflammation and boost immune system. STEROIDS FOR POSSIBLE PIT TUMOR REDUCTION? Yesterday was a good day, today not so good. I would love to feel like there is some hope as she is only 7 years old. But i also dont want to treat her like an "experiment" and need to think of her quality of life.YOU AND YOUR DOG HAVE NOTHING TO LOSE BY STARTING CABERGOLINE AND POSSIBLY THYROID MEDS. NO NEGATIVE SIDE EFFECTS WITH EITHER THEY ARE NOT HARMFUL LIKE THE OTHER CUSHINGS DRUGS THERE IS HOPE! YOUR DOG IS STILL YOUNG CHANCES ARE GOOD THAT ORGAN DAMAGE IS NOT EXTENSIVE THE SOONER YOU START THE BETTER YOUR DOG MAY FEEL
i anxiously await your answers to some of carole's questions. Thanks for sharing all your experiences with declan.

[LaurieS]

Thanks for your response and yes we have checked Charlotte's thyroid. Although they don't feel there is anything wrong I do know it's a very misdiagnosed problem in people so I suppose she could be having thyroid issues that we aren't treating. I don't have her test results in front of me right now but I will ask my vet again about it. Also, it doesn't seem like we have much to lose trying the cabergoline. Even without a mri it's pretty apparent she has a pit tumor that has enlarged and is putting pressure on the hypothalamus which is what controls hunger, thirst, blood pressure and so many other things. I'm so glad Declan is doing better and I sure hope the cabergoline will work for other dogs on this forum.

Laurie

[LaurieS]

One more question for you. How long did it take you to see the cabergoline start to work?

Laurie

[westcoastflea1]

[QUOTE=LaurieS;200130]Thanks for your response and yes we have checked Charlotte's thyroid. Although they don't feel there is anything wrong I do know it's a very misdiagnosed problem in people so I suppose she could be having thyroid issues that we aren't treating. I don't have her test results in front of me right now but I will ask my vet again about it.I WOULD HAVE YOUR VET EMAIL TEST RESULTS TO YOU, THAT WAY YOU CAN SEE WHAT THE LEVELS ARE ON T3 T4 TSH ETC .MY VET SAID THYROID WAS FINE DR DODDS SAID THYROID IS FINE, BUT UNTIL YOU SEE ACTUAL LEVELS T3 T4 AND TSH LEVELS YOURSELF YOU WONT KNOW. HAVE YOU HAD RECENT BLOOD WORK DONE? SO YOU KNOW ORGAN FUNCTION IS GOOD OR BAD WHITE BLOOD CELL COUNT ETC ETC AND HAVE YOU THOUGHT ABOUT ADDISONS DISEASE? WHEN WAS THE LAST TIME YOU HAD CORTISOL LEVELS CHECKED? I WOULD HAVE CORTISOL LEVELS CHECKED BEFORE STARTING CABERGOLINE TO MAKE SURE YOUR DOG HASNT GONE ADDISONS DUE TO VETORYL SHE WAS TAKING Also, it doesn't seem like we have much to lose trying the cabergoline. Even without a mri it's pretty apparent she has a pit tumor that has enlarged and is putting pressure on the hypothalamus which is what controls hunger, thirst, blood pressure and so many other things. I'm so glad Declan is doing better and I sure hope the cabergoline will work for other dogs on this forum.

[westcoastflea1]

one more question for you. How long did it take you to see the cabergoline start to work?

Laurie i took declan off vetoryl 3 months ago, as far as beginning to work i dont have an answer for you. All i can say is that no symptoms of cushings have returned.when i get a uccr done that will tell me if he is still testing as a non cushings dog which is where he was at after last test. Then i will know meds are definitely working or if we need to increase his dose. Again if i were you i would have blood work done cortisol levels tested and get copy of THYROID test results showing where all the levels are at if you are below normal or low normal for most levels then you know that thyroid meds might be good . And again addisons has most of the symptoms your dog is showing so super important to get cortisol levels asap IS YOUR DOG ON MEDS FOR BLOOD PRESSURE?

[labblab]

OK, per my note posted elsewhere, I wanted to return to your thread to try to clarify thyroid recommendations. I do not disagree at all with urging folks to request complete thyroid panels for their Cushpups in order to explore the likelihood that low thyroid readings are a primary problem in their own right, vs. being secondary to the Cushing's ("sick euthyroid syndrome"). I would also agree with giving thyroid supplementation to any dog for whom hypothyroidism is judged to be a primary problem. But I think you are also recommending that supplementation be started for any Cushpup with a low thyroid reading, even if the thyroid abnormality is thought to be secondary to the Cushing's. Am I right about that, or am I misunderstanding you?

In that situation, I believe most specialists recommend against starting thyroid supplementation prior to having the opportunity to gauge whether thyroid results normalize once cortisol levels have been therapeutically lowered with Cushing's treatment.

Here are some excerpts from Michigan State University's veterinary thyroid testing page. It addresses a pattern of results that may commonly occur in Cushpups.


My patient has low thyroid hormone concentrations, but thyroid stimulating hormone is not elevated. What does this mean?

Depending on the clinical presentation, one of two main possibilities is likely.

The more common explanation is that T4 values often decline in animals with non-thyroidal illness and in animals receiving certain drug therapies (some glucocorticoids or anticonvulsants). Non-thyroidal illness may suppress TSH release from the pituitary via glucocorticoid-mediated inhibition or lower T4 concentrations by altering serum protein binding affinities...

...With this pattern of test results, a trial with T4 supplementation is suggested only if there is a strong clinical presentation consistent with hypothyroidism and if no non-thyroidal illness can be detected...

...While the administration of thyroid hormone to animals which do not have hypothyroidism is generally considered to have minimal risk, large scale studies in human medicine have shown detrimental effects of such treatment in patients that have decreases in serum thyroid hormone concentrations due to non thyroidal illness. (Brent GA and Hershman JM. Thyroxine therapy in patients with severe non-thyroidal illness and low serum thyroxine concentrations. J Clin Endocrinology and Metabolism. 1986, 63:1)

https://www.dcpah.msu.edu/sections/endocrinology/Thyroid_Canine.php#19

As I say, I may be misunderstanding your recommendations, so I wanted us to have a chance to clarify further.

Marianne

[westcoastflea1]

a thyroid test may show that the thyroid is normal BUT the problem is that the thyroid stimulating hormone is suppressed by high cortisol which keeps it from putting out what it needs to put out, which causes many of the symptoms you see in both cushing and hypothyroidism.
THIS is why you need to see the entire thyroid panel not just listen to your vet tell you the thyroid is normal. until cortisol is under control you have a thyroid that tests as normal but is in actuality not working correctly so you have hair loss, skin infections, etc etc i put declan on thyroid meds and within a month all hair had grown in no more skin infections, he had more energy, he was playful, when i took him off thyroid meds for 2 weeks he got grumpier and grumpier until he bit me. I got dermal thyroid meds and he is fine now SO the point im making is you need to see entire panel and if all numbers are low except t4 you should put on thyroid meds. when cortisol levels are under control then have thyroid panel taken again and see where numbers, then make decision as to whether or not to continue or discontinue it took a year to get declan on the right dose of vetoryl 300mg so that is a year in which skin infections were happening every day hair was falling out he was grumpy, his immune system was weak.HPA axis is complicated so getting thyroid levels where they should be might help with other issues there is just no point in not putting on thyroid meds if numbers are for the most part low until cortisol levels are under control

[westcoastflea1]

declans thyroid panel was low with the exception of free t4 which was 80 range is 70 -1.70. so they said thyroid was good whats funny is both thyroid tests he had one like 4 years ago and this one said possible non thyroidal illness but the vet never mentioned it or suggest exploring what else could be wrong needless to say i have a new vet now that test showed low normal so in 4 years he went from low normal to below normal makes you wonder what we could have done 4 years ago if we acted on the non thyroidal aspect

[westcoastflea1]

I need to point out that we are unaware of any research that suggests that UCCR analysis is preferable to ACTH monitoring for dogs being treated with either trilostane (Vetoryl) or mitotane (Lysodren). In fact, clinical testing thus far suggests the reverse: that UCCR analysis cannot reliably be used as the basis for decisions regarding dosing increases. Here's a related reply posted by another one of our staffers.


Although perhaps not a perfect monitoring tool, the ACTH stimulation test remains the preferred method for evaluating the appropriateness of dosage increases during the course of trilostane and Lysodren treatment.

Marianne
uccr is the first test that should be done when trying to diagnose a possible cushings dog although it does have false positives its negative results are much more reliable. so if i have a uccr done and the lab says my dog is negative for cushings than i have a pretty good idea that cortisol is under control. here is one quote from a vet "Although the UC:Cr is more frequently elevated than it is normal, when it is normal, you know that your patient does not have Cushing's disease" pub med www.ncbi.nlm.nih.gov states that " Using the cutoff of 12.27 nano mol/ micro mol(based on data of normal subjects) for the urine cortisol creatinine ratio we get a sensitivity of 93.75% and a specificity of 100%. Also the positive and negative predictive value as calculated with this cutoff is 100% and 93.3% respectively.

[labblab]

I believe you continue to miss the point that we staffers are making: there is a difference between using the UCCR as an initial diagnostic test for Cushing's in general, vs. using the UCCR as a monitoring tool for dosing changes once trilostane treatment has begun. We are fully aware of the value of the UCCR as a diagnostic tool. However, as we have now written to you repeatedly, as yet we are unaware of any studies that validate the use of the UCCR to monitor trilostane. If you are aware of any such studies, we would be grateful to see the citations. In the meantime, I will once again quote Lori's comment in full:


The UC:CR is not recommended for monitoring treatment. I'm including this excerpt from a study and was published in 2009 and titled: Urinary Corticoid : Creatinine Ratios in Dogs with Pituitary-Dependent Hypercortisolism during Trilostane Treatment


Conclusion and Clinical Importance: The UCCR cannot be used as an alternative to the ACTH stimulation test to determine the optimal dose of trilostane, but might be helpful in detecting dogs at risk for developing hypocortisolism during trilostane treatment.

http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2009.0374.x/abstract

Lori
Lori's link doesn't seem to be working for me right now, so here's an alternative link to the same study:

https://www.ncbi.nlm.nih.gov/pubmed/19709356

I do acknowledge that I am unaware of the monitoring protocol that clinicians may be using with cabergoline treatment. Perhaps UCCRs are indeed being used for monitoring purposes with that medication. But you have been repeatedly offering the UCCR as a monitoring tool to our members whose dogs are being treated with trilostane, and as stated above, we are currently unaware of any support for that use. Due to its greater ease and lesser expense than an ACTH, clinicians had been hopeful for some time that the UCCR could be validated for trilostane monitoring purposes, and I cannot argue that it would be great if it had worked out. But as far as I know, the research evidence just isn't there.

Marianne

[Squirt's Mom]

Please listen to what Marianne, Lori and others have been trying to get thru to you. This are some of our Admins and moderators who hold those positions because they have years, YEARS, of experience and knowledge under their belts....and for no other reason period.

Your repeated posts telling members to forego the ACTH in favor of the UC:CR is very, very confusing to new members and carries the potential to cause harm to their babies. I hope, HOPE, your intent is good but the fact that you continue to post this erroneous information after being repeatedly corrected is concerning to us all. I BEG you to educate yourself further on this matter. You will find a wealth of solid information in our Helpful Resource Section to get you started.

Please listen.....please.

[westcoastflea1]

i post information in regards to new studies and medications.i also post about my own experiences one of which is the use of uccr to monitor declan for all but the first few months after being diagnosed. it is pure simple logic if a uccr comes back as negative non cushings dog then the dose of medication i have my dog on is working as it should because uccr says my dog is non cushings which is the point of putting him on the meds to begin with isn't it???.
so if it is working for me and is an experience i have had why are you so upset about it?? people have brains on this forum i dont think they need any protection from new ideas that differ from yours
If you want to stay within your narrow box of current cushings treatments i have no objection, however when you object because you underestimate the intelligence of the people here on this forum thats a problem. pointing out new meds, studies etc will hopefully encourage people to step outside the box by researching things brought up on this forum, and making their own informed decisions for their pets. The current treatments and protocols for cushings are not working for many people on this forum im simply giving them the stepping stones to start exploring the disease and letting them know what alternatives may exist that certainly are not found on this forum, and appear to be objectionable to you. before declan was diagnosed i thought my vet knew everything, little did i know they knew nothing except standard protocols and procedures, people need to realize that they cannot in all cases blindly follow their vets advice. hopefully my posts will them explore other possibilities in the treatment of cushings and once informed to make good decisions. isnt that what a forum is for? new thoughts. ideas. personal experiences? i thought it was but apparently not, so if you want to keep your little kingdom enclosed because you feel the members of this forum are not entitled to new information that goes against what you and other admins believe, something you feel the members here are incapable of understanding you are only hurting the people and pets that are in need because typical cushings treatments have failed them or they cant afford them.

[labblab]

You have raised a lot of different issues in your reply, and I will come back later on to address more of them. But for the moment, I want to continue to focus on your insistence that the UCCR is a good method for monitoring trilostane dosing. This is what you tell us:


it is pure simple logic if a uccr comes back as negative non cushings dog then the dose of medication i have my dog on is working as it should because uccr says my dog is non cushings which is the point of putting him on the meds to begin with isn't it???.

so if it is working for me and is an experience i have had why are you so upset about it??

So, you are advising folks that this can be a good method for them to use simply because it seems logical to you and has "worked" for your dog. The huge problem is that the research we keep citing that was specifically designed to test that logic says that it does not hold. Here are the "Results" taken from the citation we keep giving you:


RESULTS:
The UCCRs were significantly higher before treatment (11.5-202.0 x 10(-6); median, 42.0 x 10(-6)) than at rechecks 2 months after optimal dosing, but they did not decrease below the upper limit of the reference range in the majority of dogs. The UCCRs of 11 dogs that initially were dosed insufficiently (range, 7.5-79.0 x 10(-6); median, 31.0 x 10(-6)) did not differ significantly from UCCRs when the dosage was optimal (8.2-72.0 x 10(-6); median, 33.0 x 10(-6)). Post-ACTH cortisol concentrations did not correlate significantly with UCCRs at rechecks during trilostane treatment. Long-term follow-up indicated that the decrease in UCCR below the upper limit of the reference was associated with hypocortisolism.
So, according to this study, if dogs taking trilostane had UCCRs that dropped back into normal range, this actually signaled cortisol levels that were dropping too low with treatment -- i.e., dogs were risking bring overdosed. I'm sure the authors of the study were just as surprised by this as you might be. It's not what they expected or what "logic" would dictate. But those are the results they obtained, and unless you have a research citation that states otherwise, your recommendations to folks here about using the UCCR is unsafe. You are lucky that Declan did OK, but others might not be so lucky.

Absolutely, we support the exchange of thoughts, suggestions, research results, and personal experiences. But when we are aware of specific research that contradicts personal recommendations that are being made here, we will continue to bring that research to the attention of our members, especially when safety is at stake. Again, if you are aware of newer research that draws a different conclusion about using UCCRs to monitor trilostane dosing, we are really anxious for you to bring it to our attention. But that is a different matter than your insistence that just because your personal theory is logical, it must be right.

Marianne

[westcoastflea1]

[QUOTE=Squirt's Mom;200534]Please listen to what Marianne, Lori and others have been trying to get thru to you. This are some of our Admins and moderators who hold those positions because they have years, YEARS, of experience and knowledge under their belts....and for no other reason period.
Your repeated posts telling members to forego the ACTH in favor of the UC:CR is very, very confusing to new members and carries the potential to cause harm to their babies. I BELIEVE YOU SERIOUSLY UNDERESTIMATE THE INTELLIGENCE OF THE MEMBERS ON THIS FORUM
'I hope, HOPE, your intent is good'
ARE YOU FOR REAL??
"but the fact that you continue to post this erroneous information after being repeatedly corrected is concerning to us all. I SEE SO ANY NEW INFORMATION OR EXPERIENCE THAT A MEMBER HAS THAT YOU DO NOT AGREE WITH IS CONSIDERED ERRONEOUS AND SO SHOULD BE CORRECTED? "you need to educate yourself further on this matter. You will find a wealth of solid information in our Helpful Resource Section to get you started. I HAVE SPENT MONTHS AND MONTHS HUNDREDS OF HOURS EXPLORING EVERY STUDY AND TRIAL, THE HPA AXIS AND ENDOCRINE SYSTEM AND STILL HAVE NOT STOPPED, THE INFO IN YOUR RESOURCE SECTION HAS NOTHING NEW TO ADD TO CONVERSATION SORRY. THE CURRENT MEDICATIONS ARE NOT WORKING FOR MANY MANY DOGS SO OWNERS NEED TO START THINKING OUTSIDE THE BOX
IF YOU FEEL THAT MY PERSONAL EXPERIENCE WITH A CUSHINGS DOG AND THE THE NEW INFORMATION I BRING TO THE TABLE FOR OTHER MEMBERS TO EXPLORE AND RESEARCH IS A THREAT TO YOU THATS FINE
BUT ....
A. DONT QUESTION MY MOTIVES IN POSTING INFO ABOUT MEDS OR TRIALS OR MY OWN EXPERIENCE WITH A CUSHINGS DOG TO MOTIVATE MEMBERS TO STARTED RESEARCHING ON THEIR OWN

AND

B REALIZE THAT YOU ARE DOING AN ENORMOUS DISSERVICE TO MEMBERS WHO HAVE LISTENED TO YOU, READ YOUR HELPFUL RESOURCE GUIDE AND TRIED ALL CONVENTIONAL TREATMENTS AND NEED SOMETHING NEW BECAUSE NOTHING IS WORKING AND THEIR DOGS ARE SICK WHY ARE YOU SO THREATENED BY SOMEONE WHO INJECTS NEW THOUGHTS, EXPERIENCES AND IDEAS INTO THE MIX? THE WHOLE IDEA IS TO GET PEOPLE TO START RESEARCHING ON THEIR OWN, THINK OUTSIDE THE BOX DONT JUST GIVE UP WHEN THEIR VET SAYS THERE IS NOTHING MORE THEY CAN DO THEIR DOG

[labblab]

OK, since I'm a site administrator, I get to make a definitive statement here. You are way over the top and way over the line in your complaints about us. You are correct that the purpose of a forum like this is to broaden perspectives, offer information (sometimes old, sometimes new), and to challenge members to educate themselves so as to be the very best advocates possible for their dogs.

You have brought some new and very interesting info to the table here. For instance, I had known nothing about cabergoline until you introduced it to us, and I am grateful for your having done so. As I said earlier, UCCR monitoring may even be appropriate for cabergoline treatments -- I truly don't know enough about it. There are several things you've spoken about that are both interesting and potentially quite helpful. But as I've also pointed out above, you've additionally introduced some treatment considerations that concern me in terms of actual safety (specifically, the UCCR monitoring and certain thyroid treatment suggestions). For that reason, I have challenged you about those statements, as have some other staffers. That is our job as custodians of the site -- to assess the safety of info that is being presented. If you wish to discuss our concerns in a civil manner, we'll be happy to proceed. But rude and argumentative conversations are prohibited by our forum rules and will not be tolerated.

Marianne

[Whiskey's Mom]

Sorry , have to comment. I've read through your posts more than once. I consider myself a person of reasonable intelligence, and I find them confusing, misleading, and very hard to follow. ESPECIALLY WHEN YOU TYPE IN ALL CAPS!!
I have gotten a wealth of extremely helpful, honest and reliable info from this forum, not to mention unconditional love and support, even after I realized that my dog was misdiagnosed with Cushings by a vet I trusted. Without question, the people in charge on this forum saved my dog's life.

[Budsters Mom]

Your findings regarding Cabergoline treatment are to be applauded. I have been in contact with Dr. B several times. He has advised on my Buddy's course of treatment. In my opinion, he is the foremost authority on everything regarding canine Cushings.

Having said that, your posts are very hard to follow, extremely technical, without much explanation.

I am an out of the box thinker also. To be perfectly honest, I was probably never in the box in the first place. However, I air on the side of safety and need proven citations for changes in protocol. I am not saying that you process doesn't work. And yes, Regular ACTH monitoring for dosage adjustments are damn expensive. I understand why you have decided to pursue your course of action and hope it all works out for you and Declan.

The administrators and moderators on this forum strive to stay up with current protocol and get extremely excited when members share new, proven studies and protocol. They do this on their own time, without pay, just to support members the best way they are able. Most of them have lost their own Cush babies, but remain here to support others through their journeys. Yes, there have been times where I have disagreed with their advice, but I have never questioned their intentions.

We are thrilled to have you on this forum. You have gotten our brains tuned and thinking of potential new protocols for battling this horrendous disease. Please continue to share your thoughts in a way that we all can benefit.

Kathy


I've read through your posts more than once. I consider myself a person of reasonable intelligence, and I find them confusing, misleading, and very hard to follow.

[westcoastflea1]

well thank you kathy but since my posts will now be reviewed before being posted i wont be posting here thank you

[westcoastflea1]

please let me know how to cancel my registration to the forum or perhaps you can take care of it thank you

[Carole Alexander]

I am sorry I missed this kerfuffle as I was buried in my dog's macro. But I want to commend each of you, Marianne, Kathy, Sharlene, Annie and whomever I missed, for your thoughtful and helpful clarifications regarding testing after starting Vetoryl or Lysodren and for your comments about the need for clarity and evidence when proposing treatment protocols that are out of the box as I think was your term, Westcoastflea1. I am new here, but as you all know only to well, this is a forum where people come with only the written word, often through tears, frustration, fear and a lack of knowledge about the endocrine system, Cushing's and the many, many complications that ensue with the diagnosis and progression of this disease. It is a delicate balance to respond to the myriad pleas for help in light of these issues that color our ability to hear, take in and utilize the feedback provided. Westcoastflea1, it can't be done with a hammer, unless you think every problem is a nail. Many of your comments and citations are helpful and I appreciate you raising Cabergoline again as a potential treatment option, but please do so with caution so as not to raise people's hopes that it is a miracle drug; there is simply no evidence to support such an assertion. And, unless you know differently, the vast majority of the other experimental drugs are unavailable or exorbitantly expensive. My same comment applies to the question of low thyroid in Cushing's dogs. Finally, I agree with others that formatting of your posts and the use of CAPS serves only to confuse and not to enlighten. Bullets, paragraphs, highlighting could be other options. I believe that your goal is to clearly communicate what is often helpful and valuable information; challenging others or making emphatic statements without evidence, be it to the forum administrators or members, doesn't serve your own ends. If you think the resource section is weak, contribute your research to strengthen it. While I have raged a few times on this forum, I'm sorry I have done so because then it's about me and not what I'm trying to communicate. We are all on the same team here with one goal, to help our dogs' survive Cushing's and whatever else ails them. Our time and knowledge are not limitless and the dedication of those who sustain this forum is remarkable. Please join with them and me to help make us all smarter, wiser, more empathetic, and capable of taking this journey on behalf of all of our dogs. Thank you and my best to you.

Carole

[labblab]

I have noticed that people are continuing to direct questions to "westcoastflea1" on their own threads, frequently in conjunction with cabergoline treatment. However, she will no longer be available to reply since she has asked to end her membership here. Due to the interest, however, we have started a new thread about cabergoline on our "Everything Else" subforum. Here's a link to our new thread:

http://www.k9cushings.com/forum/showthread.php?t=8551

Also, once again, here's a link to the article authored by Dr. David Bruyette that first prompted westcoastflea1 to pursue cabergoline treatment for her own dog.


Like Renee, I do think that both trilostane and mitotane have the potential to vastly improve quality of life for dogs when they are used properly. However, I also agree it would be great if a newer generation of drugs is ever introduced that have fewer side effects and do more than only treat symptoms. In that vein, here's an article published last fall by Dr. David Bruyette that discusses some exciting new drugs that may be coming down the pipeline. What a gift if they actually materialize!

http://veterinarynews.dvm360.com/new-possible-cushing-s-treatments-work-root-cause

Marianne

For anyone who wishes even more information about cabergoline or one of these other novel treatments, here is Dr. Bruyette's email contact in Los Angeles: David.Bruyette@vca.com.

[Carole Alexander]

Thank you Marianne for this info. I am sorry that Westcoastflea1 decided to withdraw and I hope my comments didn't offend her; that was certainly not my intent. Thank you for Bruyette's email as I want to inquire about the cost and availability of the drugs he mentions in his article and other drugs mentioned in studies posted online.

[labblab]

Carole, if you write to Dr. Bruyette, do mention that you're a member here. He was also an active member for a while here, himself. Also, westcoastflea1 made her decision prior to anything you wrote, so you need not have any concern about that.

We'll be anxious to hear what you learn from Dr. B!

Marianne

[Budsters Mom]

Hi Carole,

I found Dr. B to be extremely helpful and down to earth. So much in fact, that he'd sign his emails just "Dave". :p This was several years ago and I'm sure he's super busy, but do give it a try. His replies were always prompt and spot on. His recommendations are what eventually led to Buddy's course of treatment. The neurosugeon who oversaw Buddy's treatment, which was implemented through his regular vet, even contacted him herself for clarification and dosages. ;) Dr. B explained in a way that was understandable without giving false hope. That is exactly what I needed at the time. I needed to realistically know what to expect in order to proceed with Buddy's care. Contacting him gave me peace. He was the foremost authority on all things Cushings. I didn't need to continue to frantically search for a cure after that. There wasn't one.:o

As far as Dr. B, he likes all the facts in some kind of precise order. The more organized and precise your details are, the better he will be able to help.

Keep us posted on Skippy's thread, okay?

Kathy


if you write to Dr. Bruyette, do mention that you're a member here.

[Carole Alexander]

Kathy, thanks for your post; I do understand and accept that there is no cure for Skippy's macro. I hope I'm not grasping at straws but I want to
ask Bruyette about the various drugs that are being tested. Are they commercially available? Are any within the realm, beyond Cabergoline, of affordability? Are there any current clinical trials of these drugs?
The two treatment options offered are, to my mind, either a quick or a slightly slower death sentence. Surgery by a surgeon who has never removed a pit tumor or radiation that likely will put him down in six months. Sort of a Sophie's Choice. I know that doing nothing but treating with the Cabergoline is likely to lead to an abrupt crisis, stroke, inappetance, blindness and so on. So, before that occurs, I want to explore every avenue while there still may be time. Just my stubbornness I guess.

[labblab]

Since westcoastflea1 is no longer here with us, we are going ahead and closing this thread for further posting from this point onward.

As a reminder, here's our new interactive thread about cabergoline (and other experimental pituitary Cushing's treatments) on our "Everything Else" subforum:

http://www.k9cushings.com/forum/showthread.php?t=8551

Marianne