Introducing Frodo--Typical and Atypical Cushing's Dx

[Shybuhund]

Hi everyone—time for me to introduce myself and my dog! I’ve actually been lurking here on and off since September when I first started thinking my boy could have Cushing’s, but it’s taken until now to get an actual dx—which is both atypical and typical HAC.

I’m horribly long-winded when I write (please forgive me!) so I’m going to try to shorten this post by using headings, lists and bullets. :o

I want to be clear—I have not yet started Frodo on any drug treatment. I will probably start melatonin tomorrow, and lignans when they arrive in the mail because I feel comfortable with those.

My concerns/questions for those with experience:

-The 30 mg twice-daily dosage of Trilostane my internal medicine specialist prescribed seems really high: it’s a bit less than 2 mg/kg BID (my dog is 36.6 lbs, or 16.6 kg). Has anyone given twice-daily dosages this high?

-The specialist doesn’t want to recheck for a month…that seems like a long time, doesn’t it? (My regular veterinarians both effectively said “hmm…that’s interesting” when I forwarded them the rx and dx info from the specialist—and each wants to talk with the specialist before dispensing the Trilostane)

-My dog is on a lot of supplements already—does anyone know of anything that could be a problem combined with the Trilostane?

Thanks and nice to meet you! –Monica
…
About my dog: Frodo—Norwegian Buhund, neutered male, age 12.5 years, weighs 36.6 lb (16.6 kg)
Diagnosis: Atypical AND Typical Cushing’s (PDH)

Prescribed treatment (by internal medicine specialist):
-30 mg Trilostane BID, recheck with ACTH stim in one month
-6-10 mg melatonin BID (start w/3 mg and increase gradually)
-40 mg SID HMR lignans (due to history of IBD, introduce gradually)

Symptoms: PU/PD, panting and restlessness at night, seemingly “age-related” decline
Clinical signs: elevated liver enzymes (monitoring since 2011); elevated cholesterol (since May 2014); low thyroid (treated w/0.3 mg Thyroxine BID since Sept 2014); abnormal ultrasound findings

Other health problems: hypothyroidism; mild inflammatory bowel disease (managed with diet and supplements); arthritis (related to cruciate tear in 2012 and compensatory pain); NSAID allergies

Tests run: multiple ultrasounds, thyroid panels, urine creatinine to cortisol ratio, U. Tennessee hormone and cortisol panel for atypical HAC, and general “senior screen” panels for liver/kidney/CBC values

Notable test results:

UCCR (results WNL according to my regular vet)
-Urine Creatinine: 140.3 mg/dL
-Urine Cortisol: 5.8 ug/dL
-Urine Cortisol/Creatinine: 13

Most-recent liver enzymes (December 2014)
-ALP 890
-ALT 104
-Cholesterol 237 (down from 451 prior to starting Thyroxine)

U. Tenn panel
-Cortisol (ug/dL):
baseline 10.9
post ACTH 20.4

-Androstenedione (ng/ml):
baseline 3.10
post ACTH 9.62

-Estradiol (pg/ml):
baseline 72.7
post ACTH 74.8

-Progesterone (ng/ml):
baseline 0.62
post ACTH 2.06

-17 OH Progesterone (ng/ml):
baseline 0.86
post ACTH 3.83

-Testosterone (ng/ml): baseline and post ACTH <15 (WNL for a neutered dog)

Ultrasound findings (basically there is slight organ enlargement and calcium/mineral deposits on liver, kidneys, and adrenals, but nothing the radiologists were thought could be tumors)
-Left hepatic nodule (5 mm); Heterogenous liver texture, U/S=guided aspirate yielded cells with mixed inflammation and vacuolarization
-Mineralized areas and hyperechoic corticies on both kidneys
-Adrenal nodules/mineralization and enlargement

[Squirt's Mom]

Hi and welcome to you and Frodo!

Real quickly, would you please enter the normal ranges for the labwork you have entered AND please double check the normal ranges from the TN lab. I copied ad pasted the ones from my dog's results but noticed the cortisol on her labwork is not measured in ug/dl. So that range was not entered. If you would, make sure the others match what is on Frodo's work just to be sure there haven't been other changes. ;)

Also, if the cortisol is elevated, and it appears Frodo's is, the pup is considered to have true, or conventional, Cushing's. Atypical applies when the cortisol is NORMAL but one or more of the five intermediates, or sex, hormones are elevated. So it looks as if Frodo is simply a cush pup, not Atypical. Most cush pups do have elevations in at least one of the intermediates. ;)

I'm sure others will be along soon to welcome you and talk about Trilo. My Squirt started out Atypical, with normal cortisol, so we used Lysodren when her cortisol did start to rise.

Hugs,
Leslie and the gang

[Shybuhund]

Leslie--thanks for the clarification and for posting your ref ranges! I will post the reference ranges from Frodo's results and double check the units.

I'm pleased to hear you reiterate what I initially thought--cortisol is high, so that's conventional Cushing's. While I'm on my lunch I think I'm going to find a different internal med specialist, I'm really starting to wonder about the one I saw. She insisted Frodo has both atypical and pituitary cushing's. I just double checked the TN lab paperwork, and in the comments it says "these results suggest typical HAC."

TN Lab with ref ranges:

-Cortisol (ug/dL):
baseline 10.9 Normal <1.0-5.6 ug/dL,
post ACTH 20.4 Normal 7.1-15.1

-Androstenedione (ng/ml):
baseline 3.10 Normal 0.05 – 0.36 ng/ml,
post ACTH 9.62 Normal 0.24 – 2.90

-Estradiol (pg/ml):
baseline 72.7 Normal 23.1 – 65.1 pg/ml,
post ACTH 74.8 Normal 23.3 – 69.4

-Progesterone (ng/ml):
baseline 0.62 Normal <0.20 ng/ml,
post ACTH 2.06 Normal 0.22 – 1.45

-17 OH Progesterone (ng/ml):
baseline 0.86 Normal 0.08 – 0.22 ng/ml,
post ACTH 3.83 Normal 0.25 – 2.63

-Testosterone (ng/dL): baseline and post ACTH <15 (WNL for a neutered dog)

[labblab]

If you do decide to treat Frodo's elevated cortisol with trilostane, the most current dosing recommendation issued by Dechra (manufacturer of brandname Vetoryl) is to begin with a daily total of 2 mg./kg. (or 1 mg./lb.). Since many dogs respond well to once daily dosing and it is an easier regimen to follow, Dechra still recommends beginning with a once daily dose and only moving to twice daily dosing if symptoms do not remain sufficiently well controlled throughout an entire 24-hour time period. However, some clinicians prefer twice daily dosing from the outset so as to maintain more consistent cortisol levels throughout the day/night. In that circumstance, though, the most generally accepted protocol is to halve the once daily dose rather than double it.

Given Frodo's weight, you could most easily start out with one 30 mg. Vetoryl capsule daily. Or if you prefer twice daily dosing, you could go with either 15 or 20 mg. twice daily. A 15 mg. dose would need to be compounded by a specialty pharmacy, however, since it is not available in Vetoryl capsules. And if you instead opt for 20 mg. twice daily, you may also want to explore compounded product because four boxes of 10 mg. Vetoryl capsules each month would be quite pricey.

Here's a link to Dechra's initial dosing recommendation for you discuss further with whichever vet you choose to oversee Frodo's care:

http://www.vetsonline.com/news/product-news/140722-new-lower-starting-dose-for-vetoryl.html


Marianne

[Harley PoMMom]

Hi Monica,

Welcome to you and Frodo!

I believe the UTK reference ranges for the ACTH stim test are lower than other labs, I think for the post the high normal range is around 22 ug/dl. Also I see that Frodo had an UC:CR test done and the result was 13, which I do believe is at the normal range and thus would rule out a diagnosis for Cushing's.

To me, those test results point to Atypical Cushing's where melatonin along with lignans is the treatment. Just be aware that this type of treatment takes several months, about 6 months, to show any improvements.

The melatonin used is the regular kind, not the rapid releasing or fast acting. We do have literature in our Resource Thread about this so I will provide a link to that information: "Atypical Cushing's"/Congenital adrenal hyperplasia-like syndrome/ Hyperestrinism (http://www.k9cushings.com/forum/showthread.php?t=198)

The Trilostane dose that the IMS recommended, 30 mg BID, is high for a dog weighing 36.6 lbs. Dechra, the makers of Vetoryl, have revised their starting dose protocol and now recommend initiating Vetoryl at 1mg per pound of a dog's weight. And just so ya know, and so I don't confuse you :eek: Trilostane is the active ingredient in Vetoryl. Here's a link to that info: New lower starting dose for Vetoryl (http://www.vetsonline.com/news/product-news/140722-new-lower-starting-dose-for-vetoryl.html)

Hugs, Lori

[Squirt's Mom]

Well, the ranges have changed so I deleted my edits. :D

[Renee]

Hi Monica and welcome!

I was thinking the same thing as Lori, that the reference range for the post cortisol on the ACTH is rather lower than most other labs, meaning more dogs would get a cushings diagnosis, but may not actually have it.

The LDDS is the preferred method of diagnosing cushings these days, and it may give you a more definitive answer in regards to what you are dealing with (typical or atypical).

For some perspective, my pug's ACTH results before treatment were on the border as well (post cortisol was 24). but her LDDS and the presence of CC (and other symptoms) were enough to confirm. Later a CT also confimed PDH.

That said - I have a question about the ultrasound findings: It states the adrenal glands have nodules / mineralization? Have they confirmed how many and the size of these nodules? Any discussion on how these may contribute to possible cushings?

[labblab]

I'm going to offer out a bit of a different slant from Lori and Renee by saying that even though Frodo's post-ACTH cortisol reading would not be considered elevated by labs using different norms, it is diagnostically elevated according to UTK's reference range. And that is the whole point of the necessity of seeing each lab's reference range -- the result has to be judged solely on each lab's individual analysis. Whether the differences have to do with preparation of samples or equipment used for analysis, I don't know. But UTK's diagnostic ACTH cortisol range has traditionally differed from other labs, and that doesn't make it any less accurate or trustworthy, just different.

Since Frodo exhibits multiple classic symptoms of Cushing's in addition to related lab abnormalities and enlarged adrenals on ultrasound, I personally would not have any particular reason to question UTK's finding of typical hyperadrenocorticism based on elevated cortisol within their reference range. The only outlier here seems to be the normal UC:CR. However, I think the result of an ACTH stim test would typically be thought to trump a UC:CR since the ACTH is actually a more specific test for Cushing's and there can be inaccuracies with urine testing unless samples are collected on multiple days and pooled.

So if Frodo were my dog and he was exhibiting worrisome Cushing's symptoms, I would opt to proceed with conventional treatment. But, of course, he is not my dog and you need to pursue whatever course of treatment seems best to you. Based on the symptoms and test results you have described, however, I will be surprised if you gain significant relief using melatonin and lignans alone.

Marianne

[Harley PoMMom]

I would still say the Cushing's diagnosis is questionable. Cushing's is not the only disease that will cause adrenal enlargement, any chronic health issue has that capability, such as Frodo's IBS.

Also when looking at IDEXX ACTH stimulation test flow chart it does state that a post between 18-22 ug/dl is equivocal.

https://ca.idexx.com/pdf/en_ca/smallanimal/snap/cortisol/cortisol-acth-stimulation-protocol.pdf

Both of these excerpt are from the dvm360 website and written by Nyssa J. Reine, DVM, DACVIM (small animal internal medicine):
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 and that you need to look for another possible cause for the patient's clinical signs.


http://veterinarymedicine.dvm360.com/practical-matters-urine-cortisolcreatinine-ratio-most-useful-normal-test-around?rel=canonical


Definitively diagnosing canine hyperadrenocorticism (Cushing's disease) can be exceptionally difficult because nonadrenal illness can affect the test results. However, I think that the urine cortisol:creatinine ratio (UC:Cr) serves an invaluable role in ruling out canine Cushing's disease since a dog with a normal UC:Cr almost assuredly does not have Cushing's disease.

http://veterinarymedicine.dvm360.com/nyssa-j-reine-dvm-dacvim-small-animal-internal-medicine

Just my 2 cents worth! ;):D

Hugs, Lori

[labblab]

The IDEXX flowchart norms only pertain to samples that have been submitted to IDEXX for their own analysis. I feel certain that UTK performs its analysis inhouse, and does not send it out to IDEXX or any other outside lab. That is why the samples are sent to UTK in the first place -- because they are the only lab in the U.S. that processes and evaluates full adrenal panels. So the normal range that IDEXX posts on its website for its own testing services bears no relation to normal ranges posted by other laboratories, including UTK.

Also, as far as the UC:CR, I am basing my comment on this quote from noted endocrinologist, Dr. David Bruyette:


Urine cortisols can be a problem. Many studies have shown that the only way to accurately gauge urine cortisol levels is to obtain the first morning voided urine sample on 3 consecutive days and then pooling the urine to run a UCCR. When done in this fashion it is likely an accurate test. Otherwise there is likely too much day to day variation to make a single random cortisol very helpful.

Perhaps Frodo's UC:CR was based on a pooled sample collected several mornings at home? If not, the result may be questionable.

Marianne

[labblab]

Frodo's parent, do you have access to UTK's printed test results? It would probably help us all to clarify things if you can tell us exactly what their interpretation consisted of. For instance, with the cortisol results, what was the commentary that accompanied Frodo's result? We know that the normal range was listed as being as high as 15.1. Was there anything above that listed as "equivocal," or was anything above 15.1 considered to be diagnostic of Cushing's?

[Shybuhund]

Frodo's parent, do you have access to UTK's printed test results? It would probably help us all to clarify things if you can tell us exactly what their interpretation consisted of. For instance, with the cortisol results, what was the commentary that accompanied Frodo's result? We know that the normal range was listed as being as high as 15.1. Was there anything above that listed as "equivocal," or was anything above 15.1 considered to be diagnostic of Cushing's?

Hi Marianne, here are the comments from UTK:

"These results indicate presence of increased adrenal activity (significant)

History: > liver enzymes, PU/PD, abnormal nocturnal behavior, rule out atypical vs typical HAC

Cortisol, androstenedione, estradiol, and progestin concentrations are elevated, which suggests typical HAC. Deviation from the reference intervals is marginal (estradiol) to significant. Various treatment options are attached for your consideration."

(The attached sheet is the one that talks about everything including all four drugs, lignans, and melatonin)

All the pertinent info is here (not sure if a dropbox link will work)
https://www.dropbox.com/s/x1ao3fi5oye2qlk/UTK_Frodo.pdf?dl=0

Lori and Renee: thanks for bringing up the possibility that it may not be Cushing's. I'm thinking an IDEXX ACTH and maybe an LDDS might be in order before I start Frodo on meds.

I'll send a more thoughtful reply later--just a quick update for now.

TTFN
--Monica

[labblab]

Monica, thanks very much for this additional information, and yes the dropbox link works. :)

From their interpretation sheet, it does appear that UTK considers Frodo's cortisol level to be diagnostically elevated. So if you are wanting to perform another test for your peace of mind, I'd suggest an LDDS over simply repeating an ACTH elsewhere. UTK is considered the premiere veterinary endocrinological testing lab in the U.S., and there is no reason why an ACTH performed by IDEXX would be any more credible than what you've already got. If you opt instead for an LDDS, you are testing a different parameter of the disease since it is a suppression test rather than a stimulation test.

One last word about the difference in ranges: if the very same blood sample had been submitted to IDEXX, the likelihood is that the reported result would have been higher than the 20 reported by UTK. In other words, there is an actual difference in the way the two labs analyze the samples, and that is what accounts for the corresponding difference in the reference ranges. It is not that UTK has simply selected a lower diagnostic threshold.

Marianne

[Harley PoMMom]

So the normal range that IDEXX posts on its website for its own testing services bears no relation to normal ranges posted by other laboratories, including UTK.
Marianne

I see your point and yep you're right. However, I would still like to know why UTK's reference ranges are so much lower than IDEXX and Antech. :confused:

I just looked at Harley's UTK results and at that time the RR for the post ACTH stim test were 6-18 ug/dl.

[labblab]

Dunno what accounts for the difference in analysis, but I don't think it's necessarily all that unusual. For instance, there's quite a difference in the reference ranges for some of my family's blood values depending on whether the blood is drawn at the doctor's office and sent off for analysis vs. being drawn and analyzed inhouse by the hospital's lab.

[labblab]

Back again this morning, and here are a couple quotes that may better explain the differences in ranges:


Quoted reference ranges depend on the method used in the laboratory, and the population from which the reference range was derived. The results from one method may be systematically different from those of another and therefore the reference ranges will be different.


In general, reference ranges are specific to the laboratory that produces the test results. For many analytes, different laboratories use different kinds of equipment and different kinds of testing methods. This means that each laboratory must establish its own reference ranges using data from its own equipment and methods. The laboratory must supply your test result with an accompanying reference range on the laboratory report. Consequently, there is no such thing as a standard reference range...

...That being the case, however, for a few specific tests, such as the electrolytes, there is a high degree of consistency if not standardization, among clinical laboratories in the methodologies and procedures used for these particular tests. These laboratory methods have been in use for many years now so their reference ranges have been well-established and typically reflect numbers that are very similar to the theoretical reference range...

As to why UTK's reference range for cortisol differs significantly from that of IDEXX and Antech, I'd have to assume that UTK is indeed utilizing some sort of different methodology since they are the only lab capable of offering analysis of the full panel of adrenal hormones. Plus, the profiles of the patients who end up being referred to them for full analysis may also differ fairly significantly from the patient populations upon which the other labs are deriving their norms. I think that both these features would have an effect on their respective reference ranges.

[Shybuhund]

That said - I have a question about the ultrasound findings: It states the adrenal glands have nodules / mineralization? Have they confirmed how many and the size of these nodules? Any discussion on how these may contribute to possible cushings?

Hi Renee! The ultrasound findings are something I'm curious about too. this link contains a blood-chem and urinalysis history and images of the ultrasound findings.
https://www.dropbox.com/s/ax1xlsgac984iki/Sonograms_and_chemistry-Frodo.pdf?dl=0

Let me know if you have any thoughts!
Trying to remember wayyy back to my undergrad coursework, the term "hyperplasia" refers to increased cell proliferation, but these are otherwise normal cells without the abnormalities that define neoplasia/cancer (e.g. loss off the normal cell life cycle including programmed cell death).

In this context I don't know what that means--I will definitely be asking my veterinarians about it. So far when I did ask following the ultrasounds, the response was something along the lines of "nothing to be concerned about." Even if that's the case, I'd like to know what's behind it if I can. I'm still hoping to get into veterinary school eventually, so I like to use my dog's health issues as a way to keep up my biology knowledge, haha.

Just out of curiosity, what prompted doing the CT for your pug? Seizure?

Thanks and nice to meet you!
--Monica

[Shybuhund]

I would still say the Cushing's diagnosis is questionable. Cushing's is not the only disease that will cause adrenal enlargement, any chronic health issue has that capability, such as Frodo's IBS.


Hi Lori! Thank you for posting the links. Before treating for Cushing's, I definitely want to rule out all other possibilities. I am certain all of Frodo's various ailments are related on some level--his IBD and arthritis both have chronic inflammation/autoimmune components, and he's always stressed out over something, and he was neutered at not quite five months--in terms of endocrine feedback loops those factors could all have an influence.

It's nice to meet you! I really appreciate how thoughtful and thorough everyone here is--you're quite the team! :)
--Monica

[Shybuhund]

As to why UTK's reference range for cortisol differs significantly from that of IDEXX and Antech, I'd have to assume that UTK is indeed utilizing some sort of different methodology since they are the only lab capable of offering analysis of the full panel of adrenal hormones. Plus, the profiles of the patients who end up being referred to them for full analysis may also differ fairly significantly from the patient populations upon which the other labs are deriving their norms. I think that both these features would have an effect on their respective reference ranges.

Marianne, thanks for your thoughtful research. This is a great point, and I'm sure partly why the IMS I used chose to run the UTK panel in the first place.

I have scheduled to do an LDDS with my regular vet, and depending on the results might do an ACTH stim through IDEXX before starting trilostane as well. It's extra expense (thank goodness Frodo has great insurance), but for monitoring purposes I would like to have the IDEXX numbers--it's just easier if we don't have to try to guess/convert to compare it with the UTK results.

I'm so happy for all the help I have on hand here!
--Monica

[Squirt's Mom]

Something else for you to keep in mind. Cortisol is the body's natural response to stress - internal or external. A pup who gets very nervous just going to the vet can test positive simply from the stress of the vet, clinic, and test. My Squirt tested positive for the pituitary form on 5 different tests - LDDS, HDDS, ACTH, UTK panel, and abdominal ultrasound. However, the ultrasounds showed a tumor on her spleen. Once that tumor was removed, her cortisol returned to normal and remained within range for several years while being treated for Atypical. This is one reason Cushing's is so difficult to accurately diagnose - so many things can cause the cortisol to rise. Frodo has other issues so you will want to keep this in mind as you consider Cushing's. ;)

[Harley PoMMom]

I see that one of the conclusions from the ultrasound is that Frodo may have chronic kidney disease which would explain the increased drinking/urination.

I recently found an article stating that IDEXX has a test that will detect kidney disease in dogs months or years earlier than standard screening technologies, if this were me I would have the kidney disease ruled out/in before any more testing is done to diagnose Cushing's.

Here's a link to info regarding that kidney test: http://www.k9cushings.com/forum/showpost.php?p=170039&postcount=1

Hugs, Lori

[Renee]

Just out of curiosity, what prompted doing the CT for your pug? Seizure?

Thanks and nice to meet you!
--Monica

The CT was prompted by a combination of things. For one, the ultrasound machine up here is not of the quality needed and it is administered by the only available IMS in Alaska, whom I do not have a great relationship with. I knew I wanted good imaging though to check her organs and so on, so I opted for the CT rather than the ultrasound. The difference in expense was approximately $600 more for the CT than the US. I have paid for an ultrasound from this IMS in the past and I was not very impressed. She did not provide good feedback. Not sure if that was a function of her or the machinery. Either way, I am glad I did the CT because we have since referred back to it for other items and having it available like that is very helpful. I'm not sure if ultrasounds are recorded for reference later on, but I don't believe so.

[labblab]

It is very rare for Lori and me to be at odds with one another re: work-ups and treatment, but this seems to be one of those unusual times. Overall, I think she is much more skeptical of the Cushing's diagnosis than I am. As you've already learned, the hardest part about Cushing's diagnostics is that there is not any single, definitive test that can tell you for sure whether or not a dog is suffering from the disease. So you are stuck looking at all the puzzle pieces and trying to fit them together in the manner that seems to offer the best explanation for the combined abnormalities. There is no way in which I am an expert and can say for certain that Frodo has Cushing's, but when looking at his whole picture (outward symptoms, abnormal lab values, ultrasound irregularities), untreated Cushing's is the one thing that could theoretically be connected to most if not all of them. So to me, that increases the likelihood that it is truly an underlying culprit here and I would continue to pursue diagnostics.

It seems to me that the kidney changes on the ultrasound are noted as being "mild," and perhaps even just age-related. Was your IMS concerned about the renal changes noted on the ultrasound, thinking that they looked serious enough to be causing significant symptoms? I do see some protein loss noted in this most recent urinalysis, and that may truly warrant some additional investigation once the UTI is fully cleared. Other than that, I don't know how much more you could do diagnostically right now other than a kidney biopsy which is a fairly risky procedure. But even if there is a smoldering chronic kidney issue at play, one of the things that a nephrology specialist would look to see is whether there is some unaddressed systemic issue that could be causing or contributing to the kidney damage. And as it turns out, Cushing's is one such condition. So in that situation, the recommendation is usually to proceed to treat the underlying condition in the hope that it will lessen damage being caused to the organ.

Even re: Frodo's GI issues, my IMS told me that uncontrolled Cushing's can be responsible for causing diarrhea and GI irritation. My own Cushpup suffered from chronic diarrhea and we had high hopes that it would settle down after he started treatment. Unfortunately, it did not. But apparently for some dogs the issue can be related to elevated steroids and some do improve after treatment is begun.

Without a crystal ball, of course it is impossible to know for certain in advance whether Cushing's treatment is actually the correct choice or not. I think it's great that you are moving forward with some additional testing beforehand (although I must warn you that the LDDS is even more likely than the ACTH to falsely return a "positive" result for a dog who is actually suffering from an illness other than Cushing's). Who knows, maybe both of those tests will come back negative and typical Cushing's will be thrown out the window. But if not, I think you will reach a point where you and your vet will just have to look at the whole big picture and decide whether or not Cushing's offers a reasonable explanation for enough of the combined abnormalities to proceed with giving treatment a try, regardless of whether or not there are also other issues at play.

Marianne

[Shybuhund]

Oh goodness, I'm sorry to stir up trouble!But sometimes the best information comes when there's a bit of conflict though.. so... :)

I do feel like I'm chasing rabbits to some degree by not immediately accepting the cushing's diagnosis, but nothing with Frodo's health has ever been black-and-white. Back when he was younger, he needed pred acetate eyedrops for his pannus (autoimmune eye disease), and within about six weeks on the drops he packed on 7 pounds and developed a thin coat with bald patches. Thinking back, he should have been tested then for Iatrogenic Cushing's! I weaned him off the eye drops based on some tidbit I picked up in an anatomy class and never even consulted a vet (oops) but he recovered fully (dropped the weight, coat came back).

Lori--I'm excited about the new IDEXX SDMA test! As soon as it's available I will have Frodo tested. His great-grandmother died of CRF (but she was also 17.5 years old) so it is possible that he's genetically predisposed. I'm just excited about the new test though, lol, because I know so many folks with CRF pets who could have done a lot more for their furbabies with earlier detection.

Leslie--yes, I have no doubt that Frodo's stress levels (he hates car rides, new people, and most of all the vet's office) significantly elevate his cortisol. My holistic vet comes to our house, so I may see if it would be possible to do some of the tests at home to see if it makes a difference. I'm glad to hear Squirt's spleen tumor was detected and removed! Those can be so scary.

Marianne--yes, the sonographer was not extremely concerned about the renal changes, but the changes she noted and the PU/PD plus the protein in the urine (still there, and elevated, months after the UTI was treated with no recurrence) did prompt taking Frodo to the IMS. The IMS thought the mineralization seen on the organs was an additional sign that it could be Cushing's more likely than renal disease and so we started with the UTK panel. Like you said... it's so hard because there's no one test that works best! I'm really happy I have pet insurance, and that the company is really quick about pre-approving procedures so that I can afford to run additional diagnostics. I might rethink the LDDS a bit, maybe opt for the ACTH stim only. Lot's of conferring with vets!

I put in a call personally to the IMS today to ask why she chose such a high dosage of the Trilostane to start with. She felt that the literature supported starting with a higher dose, as did the dosing range from Dechra, but did offer me an alternate prescription for a lower dose if I prefer to start lower. She feels the trilostane will help even if there is another underlying issue.

I like that this IMS is really accessible (she answered her own phone!) and good at explaining things, but I did schedule an appointment with another IMS for a case review. More opinions probably can't hurt.

Renee--I have heard ultrasounds are really expensive in most areas--it's wild that the price difference between that and a CT was only $600. I'm spoiled living in Colorado where all the veterinarians graduate CSU and then want to stay here... it really helps keep prices down. The US I had done most recently was recorded in little "snapshots" using a newer machine from IDEXX and a computer, but the images were in no way as useful as a CT would be.

As an aside, if you ever need to make a whole room full of veterinarians laugh, just suggest doing a full-body CT on your dog. :D

[labblab]

You certainly have not stirred up any trouble, and absolutely, that is the point of posting on a forum like this -- in order to garner the widest possible range of thoughts and opinions! ;) :)

It sounds as though you are approaching all these issues very methodically and carefully, and all with Frodo's best interest in mind and heart. You are doing a great job, and no matter what you end up deciding to do next, the information you gain will help move you a few further steps along the diagnostic journey.

Regarding the persistent protein loss -- has that been quantified by advancing to performing UPC analysis (urinary protein:creatine ratio)? If so, is the protein level high enough to warrant adding medication? Since Cushing's can contribute to causing/worsening protein-losing nephropathy, we do have several dogs here who have the condition and are being treated for it in order to minimize further kidney damage. So if you have questions about that, feel free to ask away.

And yep, we are all excited about the new renal test that Lori has told us about. Wish we didn't have to wait until summer for it to be widely released. I have a senior nonCushpup that I'd love to have tested in this way -- ASAP!

Marianne

[Harley PoMMom]

You certainly have not stirred up any trouble, and absolutely, that is the point of posting on a forum like this -- in order to garner the widest possible range of thoughts and opinions! ;) :)
Marianne

I totally agree with Marianne, we don't always agree with each other but we are a family here and families do have different sets of opinions. ;) And now you and Frodo are part of that family!!

Another thing I wanted to know, has Frodo's blood pressure been checked recently? High blood pressure is very hard on the kidneys and unfortunately vets do not regularly check a dog's blood pressure.

Hugs, Lori

[Shybuhund]

Hey everyone!

I just wanted to check in. I finally got my second opinion on Frodo, although in a bit of a round-a-bout way. The second IMS I had scheduled to see had to cancel my appointment last minute, but agreed to do a records review on my case. My regular vet did the tests I requested--renal panel (no SDMA, sadly), urine (first catch and cystocentesis), blood pressure, ACTH stim...

Blood pressure was high-normal (but Frodo HATES the vet so that's reasonable). Out of curiosity/wanting to establish a baseline, I'm going to buy a doppler and start monitoring his BP at home.


ACTH Stim--Cortisol (IDEXX)
Pre: 10.7 ug/dL (ref range for normal canines = 2-6 ug/dL)
Post: 22.4 ug/dL (ref range for normal canines = 6-18 ug/dL)
(ref range for HAC dx is 18-22 ug/dL)

For comparison, his UTK numbers (from Dec 31) were:
Pre:10.9 ug/dL (ref range for normal canines = 1.0-5.6 ug/dL)
Post: 20.4 ug/dL (ref range for normal canines = 7.1-15.1 ug/dL)

...so post was on the high end of the IDEXX reference range for Cushing's.

Urinalysis (from Cysto)
Specific Gravity: 1.012
pH: 6.5
Protein: Trace
Blood/Hemoglobin: Trace
No bacteria or white blood cells


Full results are here: https://www.dropbox.com/s/k7dfwdb3ksqirto/FRODO-2015-01-27-705PM.pdf?dl=0

Basically, his kidneys look fine other than he isn't concentrating urine well, but he drinks so much that's really no surprise--will run urine again when we do the first or second ACTH stim on the trilostane to see if there's clinical improvement in that area.

The first IMS I saw re-wrote the trilostane prescription for 15 mg BID (30 mg total). Since Frodo is 16.5 kg, that puts us on the low-end of the Dechra starting dose of 2 mg/kg. If I go with that dose, I will order it compounded from Diamondback.

Another option is to start with 10 mg tabs BID (20 mg total). The thinking here is just that anecdotally "less is more" with Frodo and drugs, and that is a bit closer to the UC-Davis protocol of starting with 1 mg/kg.

Either way I will recheck in 14 days.

Which way would you go?

Thanks!
--Monica and Frodo

[labblab]

Hi again, Monica!

I am glad you've gotten some additional info and feedback, and now have a gameplan in place. Just so you'll know, I've edited your post in order to add UTK's ACTH reference range, as well, so that it will be clear that Frodo was also higher than the normal range on their testing, too. It does seem that the IDEXX result is pretty much consistent with the UTK result in terms of magnitude of elevation in comparison to the respective reference ranges. But just so you'll know to double-check if you wish, that 18-22 interval on IDEXX testing corresponds to "equivocal" results, with a result higher than 22 being diagnostic for Cushing's. So Frodo was just a tiny bit into the "diagnostic" zone according to their interpretation.

Re: your trilostane dosing options:


The first IMS I saw re-wrote the trilostane prescription for 15 mg BID (30 mg total). Since Frodo is 16.5 kg, that puts us on the low-end of the Dechra starting dose of 2 mg/kg. If I go with that dose, I will order it compounded from Diamondback.

Another option is to start with 10 mg tabs BID (20 mg total). The thinking here is just that anecdotally "less is more" with Frodo and drugs, and that is a bit closer to the UC-Davis protocol of starting with 1 mg/kg.

When possible, my personal preference is to start out with brandname Vetoryl until a dog is stabilized on a given dose. At that point, if the wish is to switch to a compounded product, you have a basis of comparison re: efficacy. So in Frodo's case, I think the safest way to maintain twice daily dosing with Vetoryl would be to start out low with 10 mg. twice daily (rather than going higher and doubly expensive with 20 mg. twice daily). I'd personally be willing to give that a try instead of starting with a compounded product right out of the gate. But we have many members who have been satisfied with compounded trilo, even from the beginning.

In terms of Vetoryl, one other option that has not been discussed is to start with a single 30 mg. capsule once daily in the morning. Since many dogs do fine on once daily dosing, that protocol remains the "default" for Dechra and many clinicians, only switching to twice daily dosing if symptoms end up rebounding in the evening. It is certainly an easier protocol for the owner since you are not having to dose every 12 hours with a meal.

Anyway, definitely keep us updated as to what you decide, and also how Frodo does!

Marianne

[Shybuhund]

Hi Marianne,

Thank you for the edits and correcting my statement about the IDEXX reference range!


When possible, my personal preference is to start out with brandname Vetoryl until a dog is stabilized on a given dose. At that point, if the wish is to switch to a compounded product, you have a basis of comparison re: efficacy. So in Frodo's case, I think the safest way to maintain twice daily dosing with Vetoryl would be to start out low with 10 mg. twice daily (rather than going higher and doubly expensive with 20 mg. twice daily). I'd personally be willing to give that a try instead of starting with a compounded product right out of the gate. But we have many members who have been satisfied with compounded trilo, even from the beginning.

I feel a little more comfortable with the brand name myself, so I'm glad to hear you feel that way too!


In terms of Vetoryl, one other option that has not been discussed is to start with a single 30 mg. capsule once daily in the morning. Since many dogs do fine on once daily dosing, that protocol remains the "default" for Dechra and many clinicians, only switching to twice daily dosing if symptoms end up rebounding in the evening. It is certainly an easier protocol for the owner since you are not having to dose every 12 hours with a meal.

We did talk about the 30 mg SID option, and it may be what we end up doing if the 10 mg BID is too low. Both the vets feel that twice daily dosing will be better for Frodo since his symptoms are worse at night (he drinks and rests normally during the day). But I guess we'll see how things go!

Thanks again! --Monica

[Shybuhund]

I hope everyone out there is warm and safe--lots of crazy weather out there right now!

Just a little update on Frodo: Started 10 mg trilostane BID on 2/14. So far, no "scary" side effects, just a temporary ramp-up of arthritis pain--it lasted about two days, and then his body seemed to adjust. Right now he seems to be having more exercise-induced pain than usual, but it could be the cold temps more than the endogenous cortisol drop.

ACTH Stim results on 2/26:

Pre: 6.9 ug/dL
Post: 7.7 ug/dL

Ref range (canine) in ug/dL:

Pre-ACTH (resting) cortisol: 2-6 ug/dL
Post ACTH cortisol: 6-18
Equivocal Post ACTH cortisol: 18-22
Post ACTH cortisol consistent with HAC: >22
Desired pre and post ACTH cortisol on lysodren therapy: 1-5

So he's not in the "desired" range, but my vet wasn't sure if we should give it more time or increase the dose.

What would you do?

Thanks!
--Monica

[Harley PoMMom]

The therapeutic ranges for trilostane/Vetoryl are 1.5 ug/dl - 5.5 ug/dl, with the post being as high as 9.1 if symptoms are controlled.

I advise not to increase the dosage as of yet becuase a dog's cortisl can continue to drift downward during the first 30 days of treatment.

That ACTH stim post number of 7.7 ug/dl is great. How are Frodo's symptoms?

[Shybuhund]

Oh good! That's what I was thinking, but it's so easy to get confused with all of this. So far his symptoms have improved. He is still drinking more than what I consider "normal," but has only had one leak in his sleep and has not awakened me throughout the night at all. Keeping close tabs on the drinking and I'm hoping to get urine results back today to see if he is concentrating his urine better now.

[molly muffin]

I wouldn't increase yet either. There should be further improvements over the next couple weeks. See how his ACTH numbers and his symptoms are then.
I think it's looking very good!

[ShibaMom]

Agreed on not increasing, either. Great improvement, though! Hurrah!

BTW: Just a quick note, you mentioned that your vet said the 30mg BID was in line with Dechra's dosing. They changed their initial dosing recommendations last year, which I know someone provided a link for a few pages back, but just in case:
http://www.vetsonline.com/news/product-news/140722-new-lower-starting-dose-for-vetoryl.html

You may want to share that with your vet, in case she hadn't seen it. Mine hadn't, and I know others' haven't, either. People have mentioned that the box inserts haven't been updated with the latest information (neither has their main page?! Very strange).

Also, since Frodo does have some possible early kidney disease, that can also cause PU/PD, so it could be a result of a combination of things.

Regards,
Samantha and Zanya