Cushings or Something Else?

[deesatt]

Hi, my name is Pam and my pride and joy is a male German Sheppard/Lab/Chow mix. We took him in as a pup abandoned at camp ground 10 years ago. He has showed gradual changes over the last 6 months which are much more apparent now. They are
[1] Panting
[2] Lethargic, no longer meets us at the door when we come home, rarely moves unless he thinks food is involved, rarely wags his tail,
[3] Huge appetite, 1st time ever trash raiding & jumping up on counters for food.
[4] Vomiting, not daily but once every week or two.....hard to tell exactly how often
[5] Moody, we thought because of old age he was just getting ornery
[6] Some head pressing
[7] "Talking" to me, slight slow wine....
[8] Drinking water & urinating frequently, almost not making it off the porch.
[9] Stomach enlarging w/fluid, pot belly

Took to vet and they informed me that last July 2011, his blood work from his geriatric work-up came back with high: 1)Alk Phosphatase 647 (norm 5-131), 2)Cholesteral 364 (norm 92-324), & 3)Triglycerides 561 (norm 29-291)……..so they were high she said, but not alarmingly so.

Took him back to the vet March 2012 and his
Alt 194, and Alp in exess of 1981. They give us antibiotics first to see if there is an infection in the liver, clavamox 375mg & Flagyl (metrodidazole) 750mg, for 14 days. We also started giving him Denamarin 425gm twice daily, Glyco Flex 3 & senior canine vitamins. …………RESULTS: Nothing changed, he did appear to be vomiting less though.

Took him back to vet 5 weeks later May 5, ran blood work:
Alt 287 & Alp …couldn’t break down – still in excess of 1981……

May 7- ACTH test. RESULTS: Cortisol Sample 1 – 1.9 ug/dL & after Cortisol Sample 2 - 20.2ug/dL

IN HERE IS OUR PROBLEM! According to my vet if Bud was cushionoid his resting/or Sample 1 should have been way in excess of 1.9! So we aren’t so sure he has cushions yet.

May 15 – Ultrasound ……..RESULTS: Liver “abnormal” – “Numerous hypo echoic lesions throughout liver – some as large as 1.6 cm dia” & “Left Adrenal 3cm long, 0.9cm wide…..slightly abnormal & Right Adrenal 2.6cm long & 0.9cm wide….slightly abnormal” - “Adrenal are of normal appearance but slight enlarged”

May 15 – urinalysis…RESULTS: all normal except w/ “ xxxx high Protein”

May 15 – Bloodwork Alt 245 & Alp in excess of 2967

May 15 – Cytology of 5 samples of liver- RESULTS: “Moderately cellular with moderate homodilution. It consists of occasional clusters of hepatocytes, which are oval to polygonal with distinct cell borders. They contain basophilic to deeply basophilic, moderately wispy cytoplasm. Nuclei are round with stippled chromatin and sometimes with small distinct nucleoli. Few cells are bi-nucleate. No overt criteria of malignancy seen.” “Microscopic Findings: Moderate hepatocellular vacuolar change” Comments: “The cytologic findings are consistent with steroid hepatopathy, which is a non-specific finding resulting from various forms of liver pathology. If a clinical concern for neoplasia exists or better define liver pathology, recommend biopsy and histopathology.” Vet said this was "inconclusive"

Vet asked for a 17 Hydroxy Projesterone test May 21/Monday. It is now Friday 48hrs later and they haven’t gotten us the results back…….

We do not want to do surgery on him for either a biopsy or to remove any tumor. We just think he is too old. But if he doesn’t have cushions, like his ATCH cortisol sample could suggest then what could this be? And how long does it take to get a 17-Hydroxy result back? How much more testing are they going to require? My vet prefers the tried & true drug Lysodren (vet has never used Trilostane) but we are leaning more towards Trilostane because of less side effects and less trips to the vet for blood testing.

[Squirt's Mom]

Hi Pam and welcome to you and your sweet Bud! :)

Bless you for taking him in and giving him such a caring home!

Don't be in a rush to start treatment - there are too many other factors that could at play here to risk treating a condition that may not exist. ;) The ACTH appears to be borderline or just above (no normal ranges given so this is a guess based on other ranges tho labs do differ so providing those ranges will help :)) and based on that and the ultrasound alone, I would not start treatment if it were me. It is not the pre number on an ACTH that matters, it is the post number (last number of 20.2).


...his resting/or Sample 1 should have been way in excess of 1.9! So we aren’t so sure he has cushions yet.

The labs and ultrasound do sound like Cushing's and combined with the ACTH post result, this would suggest the condition is present. HOWEVER, there are many things that present like Cushing's which is why thorough testing is important.

Has hypothyroidism been ruled out? diabetes? These as well as liver and kidney issues can cause many of the same signs as Cushing's and can cause false-positives on the cush tests. My Squirt tested positive on five different tests but it turned out she had a tumor on her spleen and once it was removed, her cortisol returned to normal and remained that was for over three years. ;)

Don't be fooled into thinking Trilostane (Vetoryl) is any safer than Lysodren (Mitotane) - it is not. What makes it seem safer is the short life in the body - in other words, it and it's effects do not stay in the body as long as Lysodren does. BOTH have the exact same potential side effects - the keys are 1) your knowledge, 2) your vets experience with Cushing's and the chosen treatment approach, 3) a vet that will work with you as a team. And, of course, you now have us on your side! :)

For now, take your time, learn all you can, gather all Bud's medical history and tell us all about it. To get you started here are a few questions - How much does Bud weigh? Is he on any other medications? If so, what, how much, and for what? How is his appetite - is it increasing? Is he still vomiting? How are his bowel movements? Is he exhibiting any other neurological signs other than the head-pressing like circling, getting stuck in corners, seeming confused or not recognizing familiar things/places/people? The more you can tell us, the better. We LOVE details and you are off to a great start there.

The most important thing I can share with you this morning it to tell you that you and Bud are no longer alone - we will be with you every step of this journey. I'm glad you found us and look forward to learning more as time passes.

Hugs,
Leslie and the gang

[labblab]

Pam, from everything you've written so far, I do believe that Bud probably suffers from Cushing's. I am basing this on the assumption that Bud's glucose reading was not elevated on his labwork (a high glucose level signals diabetes). I am not sure why your vet is testing the 17-Hydroxy level alone. When dogs do not show evidence of high cortisol but otherwise exhibit symptoms of Cushing's, then we often suggest to folks that they have an analysis of all the adrenal hormones in addition to cortisol (including 17-Hydroxy). Elevated hormones other than cortisol can also cause symptoms consistent with Cushing's. But I'm not sure about the value of testing only the 17-Hydroxy level. Did your vet explain why this was done?

Also, virtually all labs and specialists advise disregarding the "pre" value (baseline cortisol) on a diagnostic ACTH test. It really doesn't matter how high or low the "pre" value is. It's the "post" value that has significance in signalling Cushing's. So I'm puzzled by your vet's concern over Bud's "pre" value, too.

If it were me and I was considering any additional testing, I would ask for a low dose dexamathasone test. It is an alternative diagnostic blood test to the ACTH, but it is more likely to give a definitive "positive" result in a dog who truly does have the disease. If you can give us the "normal" range for Bud's ACTH test, that will also be helpful to us. It may be that Bud's ACTH already falls within a range consistent with Cushing's, and if so, I really do not question the diagnosis given his symptom profile,labwork, and the ultrasound results. But as Leslie says, different labs have different normal ranges. And if Bud's ACTH result is only borderline, given all of his classic Cushing's symptoms, I'm willing to bet that the LDDS will come back positive. And I believe that would give you the confidence to move forward with treatment. Based on the ultrasound results, it is most likely that Bud suffers from the pituitary form of Cushing's. And for that form of the disease, treatment with medication (rather than surgery) has historically been the norm.

So see if you can get back to us with the "normal" range for that ACTH, OK? And also, tell us why your vet is performing the 17-Hydroxy test...

Marianne

[deesatt]

Leslie thanks for your reply!
I wrote a rather lengthy reply then I lost my internet connection & ...........gone.

So here is a shorter version.
Bud weighs 75lbs has gained 5 of that over the last few months.
His eats enough for 3 dogs and has started trash raiding & he has NEVER done that. The vet didn't say she ruled out or suspected any other disease.

The only next step after result of the 17hydroxy is back is open him up for liver biopsy of which we have already stated we want no surgery. He is just too old. We did get a second opinion last week and that vet told us based on his file that she would go ahead and start treatment for cushions.

As I mentioned in my symptoms list he has some head pressing but no on any other neurological damages. He doesn't seem confused & recognizes people & places.

I mentioned "We also started giving him Denamarin 425gm twice daily, Glyco Flex 3 & senior canine vitamins. …………RESULTS: Nothing changed, he did appear to be vomiting less though" I've listed the medicine & how long he took each in my post.....but currently he is only taking the above mentioned.

We were told in less than a 5 day span his liver has gotten much worse but that there is no prediction on how long he would have. So we feel like time isn't on our side and that we need to try something because doing nothing was for sure going to kill him.

[labblab]

Pam, I think we were typing at the same time, so I don't know if you saw my earlier reply. But after reading your new info, I wanted to come back and add this, too. I definitely agree with you that I would NOT pursue a liver biopsy as this time. To me, this is the significant part of the ultrasound report in that regard:


Comments: “The cytologic findings are consistent with steroid hepatopathy, which is a non-specific finding resulting from various forms of liver pathology.

Cushpups can have huge elevations in some of their liver enzymes, but without actually causing life-threatening damage. Everything about Bud points to Cushing's, and if it is indeed Cushing's that is causing the liver abnormalities, then treatment should help ease them. My own dog had his Cushing's diagnosed by a specialist to whom he was sent to have a liver biopsy done. My dog's liver values were really elevated, too. But when the specialist reviewed his history and symptoms, he said "I'm going to test for Cushing's this afternoon, not do a biopsy." As it turned out, the biopsy was never performed, because the testing that day was positive for Cushing's.

Does your current vet have much experience with actually treating Cushing's, though? Some of the things he's said make me wonder :o. How about the second vet you saw?

Marianne

[deesatt]

Hi Marianne!

Thank you so much for your post!!

I asked for the LDDS test and was told if I was not necessary. From everything I read that was the next test normally given when trying to diagnose this disease. I was fustracted. So we moved on & went straight to the ultrasound and then was told the 17-hydroxi was the next step. She explained it to me that the 17-hydroxi was the breakdown of all the hormones to tell us exactly what hormones were effected. Very interesting info on the pre-cortisol levels to disregard. I'm feeling like my current vet may not have near the experience needed in diagnosing this particular disease.

Normal range for the ACTH test is pre 1.- 5.0...Bud's was 1.9 And post ACTH levels is 8-17...Bud's was 20.2

His last test result the glucose was 78. Normal range/70-138

Thanks,
Pam

[deesatt]

Yup we are typing at the same time!

[deesatt]

Second vet said that all the findings were consistant of haveing Cushions and if it were her dog she would feel 100% move forward with the Trilostane or Lysodren. The second vet also stated that she didn't understand the 17-Hydroxy test either. My husband and I have already decided to go back to our old vet, which is who we got the second opinion from. We just had a new animal hospital open right down the street and our dog gets car sick so we moved a few years back to it.

[labblab]

Normal range for the ACTH test is pre 1.- 5.0...Bud's was 1.9 And post ACTH levels is 8-17...Bud's was 20.2
Since the "normal" post-ACTH range was as low as 17, then personally, I too would consider a result of 20.2 as being consistent with Cushing's given all of Bud's symptoms, labs, and ultrasound. If you do have reservations, though, I still think the LDDS would be the way to go.

I have to say that in all my years on this forum, I have never heard of anybody testing 17-Hydroxy, in isolation, as part of the diagnostic process. But I do keep learning new stuff all the time, so maybe this is something else of which I'm just unfamiliar!

I hope that some other folks will also chime in. But if it were me, I'd either ask to go forward with the LDDS or go ahead and start treating. But who was the second vet you saw? Is this somebody who you think may have more experience with Cushing's? I agree that I feel nervous about the experience level of your first vet.

Marianne

[labblab]

HA -- we've got to stop typing at the same time!!!!!!! :p

I definitely agree with you -- I'd head back to my original vet!

[Squirt's Mom]

With the ranges given, I agree, the post is consistent with Cushing's when combined with the ultrasound findings and other info provided. I wouldn't do the biopsy either, tho.

I wonder if the vet is talking about the full adrenal panel from the Uni. of TN in Knoxville (UTK panel) that looks at all the hormones that can come into play with Cushing's - the 17-OH being one of them, along with Estradiol, Androstenedione, Progesterone and Aldosterone. That was my thought when reading that the vet wanted to test this hormone but I may be off base. But with the post cortisol level on the ACTH, the UTK panel might be a big waste of money. UTK does not recommend the use of Trilostane in pups who have elevations in these hormones but we have pups who do just fine on this approach in spite of that. So unless it will affect the choice of treatment, I don't think I would have this done either. ;)

And back to the vet who seems to know a bit more would also be my choice.

Hugs,
Leslie and the gang

[lulusmom]

The vet who wanted to check the 17 hydroxyprogesterone concentrations may be pretty astute. If you take a look at the study for which I've included a link below, you'll probably be able to follow the vet's rationale. Bud's symptoms are overt, liver enzyme pattern and cytology report are consistent with cushing's but the diagnostics are still equivocal, meaning the results definitely point to cushing's but they aren't quite convincing enough without validation. I think your vet is being very cautious and I personally appreciate that. My dogs had every test in the book before a diagnosis was confirmed and treatment started.

http://www.vetcontact.com/en/art.php?a=1196&t=

[labblab]

Well, as I said earlier, darned if I don't learn something new every day! ;) Thanks very much for this citation, Glynda!

But I'm still left with questions. Why would you not first run an LDDS before you shifted to this back-up method? And since this study was published in 2005, wouldn't you think that the gurus would be mentioning/using it more if they thought it was really useful?

It still seems odd to me that a vet would pick this method over an LDDS for initial confirmation...

Marianne

[lulusmom]

Well, as I said earlier, darned if I don't learn something new every day! ;) Thanks very much for this citation, Glynda!

But I'm still left with questions. Why would you not first run an LDDS before you shifted to this back-up method? And since this study was published in 2005, wouldn't you think that the gurus would be mentioning/using it more if they thought it was really useful?

It still seems odd to me that a vet would pick this method over an LDDS for initial confirmation...

Marianne

That I really can't answer. Perhaps it might be because an acth stimulation test is less likely to yield false positive results if something else is going on with Bud? Maybe Pam would be willing to ask the vet to explain.

[labblab]

But Bud already had the diagnostic ACTH test early in May, with the elevated result of 20+. That part of things I understand, as to why the ACTH would have been ordered originally. It's the 17-hydroxy test ordered on May 21, apparently all by itself and as opposed to an LDDS at that later time, that still seems very weird to me. Plus from your article, it sounds as though it needs to be run in conjunction with a stim? I dunno. I am confused.

I would definitely welcome more info from the vet!

Marianne

[deesatt]

To all that have responded, you’re correct that the 17 hydroxyprogesterone concentrations are only done at UTK and this is the test the vet was referring to. She said that she was being cautious. But she is a real advocate for surgery and is pushing a liver biopsy. We don't want surgery for either removal of a tumor or a biopsy. She wants to rule out any other liver disease that might be present in conjunction with possible cushions.

I have just got back from the NEW (but really our old vet) with the Vetoryl/Trilostane Capsules in hand.

In our part of town we have only had one vet clinic and they have many years of experience between 7 vets working there. However, they are in an upscale area and their prices started to reflect this. Getting in for an appointment was difficult too. However, 7 years ago we had an animal hospital open less than a mile away and started taking our dogs there. Being an animal hospital you would think their prices would be much higher but they were very reasonable. Since then our old vet has adjusted their pricing (as we just found out) and I'd imagine their clientele has evened out among the new Vet Clinics & Animal Hospitals that have opened in area.

[marie adams]

Hi Pam and welcome to you and Bud!! :)

It is amazing how different vets can be!!!:rolleyes:

I remember seeing the changes my Maddie made, but didn't relate it to anything that I could find online. She never got food off the table or counters before and that was puzzling. She would every now and then get into the trash, but after I figured out she had Cushings everything made sense. Her appetite, licking the rugs and floor in the kitchen.

I am so glad you found us and everyone has helped you make a good informed decision along with your new/old vet. :)

Bud and you are in good hands as Leslie said.

Take care!!!

[deesatt]

Bud is on day 6 of Trilostane and we take him back to the vet this morning for a ATCH test again. It wasn't supposed to be till day 10 but he is eating slightly less, drinking slightly less, urinating slightly less & more lethargic. But not drastic changes.

Here is my question I got back the 17 Alpha OH Progesterone test that Vet #1 requested. Although I've already started treatment with Vet #2. I'm wondering if anyone else has had this test done & what their knowledge of the test means. Vet #1 is doing test based on another vet in the area's suggestion. Basically Vet #1 said it is cushions. I show the test results to Vet #2, who we are using now, but they aren't familiar with this test to comment on results. (although they are looking into)

17 Alpha Hydroxy Progesterone Normals
Male, Castrate Bud's #'s
Pre (Baseline) = 0.06 - 0.30 ng/mL 0.78
Post ACTH = 0.32 - 1.67 ng/mL 2.57

???????????????

[labblab]

Hi again, Pam.

I'm sorry but I cannot shed any light on that 17 Alpha Hydroxy result. I went back and re-read the article that Glynda found, but it is very confusing to me. Maybe somebody else can read it and figure out what Bud's result may indicate. :o

But aside from that, I'm curious as to why your vet decided to perform the ACTH after only six days. Was she concerned that he was seeming to be too lethargic? Definitely let us know once you find out the results. And if his cortisol has dropped too low in this short amount of time, that would definitely prompt a dosing change. But if the reverse is the case -- his cortisol has not yet dropped all that much -- I hope your vet will not rush to increase his dose at this early stage. Cortisol levels can continue to drift downward throughout the first month of so of treatment. So as long as you are seeing some improvement in hunger/thirst/urination, the manufacturers of brandname Vetoryl recommend that you hold off on a dosing increase until at least that 30-day mark.

Marianne

[deesatt]

Vet just wanted to make sure that is levels hadn't gotten to low. So the results from 2nd ACTH test after 5 full days of Vetoryl is:
Pre - .7 Norm 1 - 5
Post - 2.4 Norm while on Vetoryl 1.5 - 8

I did just read something about the dogs should not be fasting the morning of taking the ACTH test. We were told not to feed him after midnight. I think this is good results. Vet said not to put much weight into the pre #'s but that 2.4 was good. We aren't changing anything at this time. Bud has shown signs of "eating slightly less (but still very interested in food/treats), drinking slightly less, urinating slightly less (he did pea for the 1st time in the house while thinking about jumping through patio dog door) & slighty more lethargic." Which must be a side effect of the medicine. We did a urine test & don't think he has a urinary track infection but she put him on an antibiotic just in case he was starting to get one. He only had traces of blood, it was cloudy & had some bacteria in his urine.

So I think that his test results was good news.

[labblab]

Can you tell us how much Bud weighs and how much trilostane he is taking? Actually, I am worried that this dose may turn out to be too high for him since the test was performed after he had been fasted. Since trilostane is metabolized more efficiently when dosed with food, there is reason to believe that the ACTH results would have been even lower had Bud eaten breakfast that morning as he usually does. And after only five days of dosing, we can expect that his cortisol level will continue to move downward throughout the first month or so on the medication. Since Bud is already nearing the bottom limit of the therapeutic dosing range at this early stage, he can risk getting into trouble if his cortisol consistently falls much lower. At a minimum, you will want to continue to watch him very, very carefully. And since he was fasted prior to the ACTH test, if it were me, I'd want to talk to the vet about actually decreasing his dose somewhat.

Marianne