Atypical Cushings ?

gajopaJune 19, 2008

Can anyone tell me what the difference is between Cushings and Atypical Cushings? My poodle was diagnosed with chronic active hepatitus and is being treated for it but he doesn't have the usual symptoms. A lady who is very knowledgeable in canine problems thinks he has either hypothyroidism or atypical Cushings. She is a friend of Lew Olson, PhD (who is an author and is the owner of the K-9 Nutrition list at Yahoo) and sent his lab results to her. Lew replied that he has "Cushings, for sure, or hypothyroidism." So, I told my Vet of my concern and he said he has been checked and doesn't have hypothyroidism. He was checked for Cushings in '04 but the Vet agreed to re-check him and said he could have gotten a 'false negative'. His partner called with the results today and said he doesn't have Cushings. I was out and my DH didn't know what questions to ask so I don't know much more than I did. The lady I mentioned is with her DH at a hospital in another city so I won't be able to talk with her for a long time. He was in a motorcycle accident and has a critical head injury. I'm at a loss as to what to do next. Jett pants almost constantly although we keep the A/C on 69 so he shouldn't be hot. Also his hair is thinning. Any help will be appreciated.

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Atypical Cushings is an abnormal elevation in the sex hormones, not in steroid hormones like in typical Cushings. It usually has the same physical symptoms such as thin skin, bilateral alopecia (symmetrical hair loss), a pot belly, increased thirst and urination, panting. The University of Tennessee Endocrinology lab has a standard profile that tests for elevations in several reproductive hormones. It isn't cheap, but it can be useful especially when testing for typical Cushings comes out negative. The treatment is a bit different though.

How was the chronic active hepatitis diagnosed? Usually that requires a liver biopsy. One of my dogs was diagnosed with that, but she got over it with treatment. Speaking of which, the treatment for chronic active hepatitis is usually steroids- prednisone, dexamethasone, etc.- which can cause iatrogenic (the vet did it) Cushings. Stop the steroids and the Cushings goes away.

    Bookmark   June 19, 2008 at 8:19PM
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If you are second guessing your vet, go get a second opinion from another vet, or call your vet and ask for a more indepth assessment of your dogs symptoms.

    Bookmark   June 19, 2008 at 9:32PM
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Any help will be appreciated

It would be easier to help if you knew exactly what tests where performed as some are more complete than others and lessen the chance of false negatives. With that said here is an excellent link on cushings
scroll down to "screening" and see the up to date required testing methods, than if you have any more questions or would like good support join this group
By the way I have alot of faith in Lew, but you still want to know what exact tests were performed.

    Bookmark   June 20, 2008 at 7:03AM
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Thanks to each of you for replying.

Meg, (or is it Dr. Meg now?) thanks for explaining the difference. When I told the Vet I was concerned that it might be atypical Cushings he said he would retest. He did an ACTH test. Would that show if he has atypical? He was just sure it's not hypothyroidism. Jett has some bilateral alopecia, a pot belly and pants excessively. I have not noticed any thinning of the skin and really not that much increased thirst. Dr. Dodds will do an evaluation but she asks for a 7200 profile. When I asked my Vet for this he didn't know what I was talking about.

The Vet diagnosed hepatitus just by his lab work. His latest Alk Phos was 3303, ALT 153, Bile Acid, pre-19 & post-30. He does not want to sedate him to do a biopsy. He has been on Denamarin, Cochicine & URSO for 2-3 years. I feed him a variety of human grade food and give him liver support factor, Vit. E & glucosamine/chondroitin. Also give him Adequan injections because both his rear knees are out of socket. He eats well and never vomits and really until the 2nd knee popped out seemed to feel good. To my uneducated thinking he doesn't act like most liver dogs. If there is something I can do for him locally then cost doesn't matter. We are older people and are not able to take him elsewhere for treatment. Thanks for your thoughts on this.

Mazer, I will talk to my Vet Monday and see if he can offer anything further but I sort of doubt it. I may get a second opinion but I feel like anyone in the same city likely would not go against what he has told me.

Cindy, thanks for the links. I did not find the 'screening' you mentioned.

    Bookmark   June 21, 2008 at 5:53PM
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No, the ACTH stimulation test checks only for increases in steroid hormones and does not measure the sex hormones, so it cannot be used to diagnose atypical Cushings. I don't know what a 7200 profile is either, but any vet can send a blood sample to the Tennessee Endocrine lab.

Screening tests for Cushings only test for typical Cushings; they cannot be used to diagnose atypical Cushings. They are:

Urine cortisol:creatinine ratio- determines if there is enough extra cortisol being produced to spill into the urine. A negative test here pretty much rules out typical Cushings, but a positive test is not conclusive.

ACTH stimulation test- pretty good diagnosis for Cushings, but 5% of tests are falsely negative

Low dose dexamethasone suppression test- False positives occur frequently with stress or other diseases, but a negative result pretty much rules out typical Cushings

None of these are helpful if steroid hormones are not being overproduced as with atypical Cushings though. All of those tests can be normal, but the adrenal gland would still be producing too much sex hormones.

There is no way to diagnose a specific liver disease just on lab work. All those results mean is that there is some sort of liver disease present, but it does not tell you exactly what is going on. In fact, those kinds of numbers are pretty commonly seen in Cushings, typical or atypical! Has a CBC been done? Usually dogs with typical Cushings have characteristic changes in the CBC, commonly referred to as a "stress leukogram."

A non-invasive way to maybe help determine what is going on in the liver is an ultrasound. While you can't make a specific diagnosis with it, livers that have steroid hepatopathy (as from Cushings, typical or atypical) have a characteristic vacuolar change on ultrasound. Ultrasound may be suggestive of other liver diseases that could explain those lab results as well. You can also look at the adrenal glands for changes in size and/or shape and see if there is evidence of Cushings that way. I can't remember any specific changes in atypical Cushings but we didn't see that many cases, even in school. But with typical Cushings you can almost always see changes in the size of the adrenals, with pituitary-dependent Cushings (most common in dogs) showing both adrenal glands enlarged, and adrenal-dependent showing one enlarged and one small adrenal gland.

I am a *huge* fan of ultrasound-guided liver aspirates. While it would require heavy sedation, unless your dog has any medical reason that he can't be sedated, I personally would do it. I would do a coagulation profile first, because the liver makes most of the coagulation factors and since your dog definitely has evidence of some sort of liver disease I would need to know if he can clot properly before sticking a big needle into his liver. But if the coagulation profile was normal and he doesn't have other problems that make him unable to be sedated, I would go for it. Using ultrasound guidance on the aspirate is very helpful especially if there are any lumps or bumps that specifically need to be sampled. Aspiration with a large needle for cytology has been shown to be a very sensitive and specific means of diagnosing liver disease; there is no need to get a larger sample such as with exploratory surgery. But even if you couldn't do a aspirate I think and ultrasound would be incredibly helpful.

None of the medications you are currently giving your dog are harmful, and it is possible that they may be helpful even if he doesn't have chronic active hepatitis, since he definitely has some sort of liver disease. Those medications are good for generally helping the liver no matter what the cause. I think that feeding him the human grade food is great for every dog, but especially for dogs with liver disease. You are doing a great job managing his joint disease without aggravating his liver with NSAIDs.

We got cases like Jet all the time in school. The vets know there is a problem, and Cushings was strongly suspected, but could not be proven conclusively. Even with all the wizz-bang toys and incredibly smart, board certified specialists, we couldn't always get a definite answer either. Since the Tennessee endocrinology lab started offering their sex hormone profile we have been able to get more cases figured out, but some are just mysteries and we don't know how to treat them.

Anyway, I would strongly suggest an abdominal ultrasound first, plus aspirates if possible, to help diagnose the liver problem. To specifically diagnose atypical Cushings, you need to measure the sex hormones which is most commonly done through the University of Tennessee lab. Any vet can submit a sample to them, and the results come back with a potential diagnosis and suggested treatments; it's a no-brainer for the most part.

I know how frustrating it is when you know there is a problem with your pet that isn't being addressed. Keep on bugging your vet until all of your concerns are addressed. It's their job. It sounds like you are doing everything in keeping Jet happy and healthy, and besides the panting he seems comfortable, so that is good. Good luck with a diagnosis.

Here is a link that might be useful: Diagnosing Liver Disease

    Bookmark   June 22, 2008 at 12:05PM
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Meghan, thank you so much for all the info. I was waiting for my Vet to call so I could let you know what he said but it appears he isn't going to. I intend to pursue a correct diagnosis for Jett, just haven't decided exactly how I'm going to do it.

Yes, Jett has had a CBC along with the superchem. The only thing out of range on the CBC is neutrophils being 12087 (high range 10600) and basophils 153 (high 150).

On the superchem in addition to the liver numbers mentioned above the things out of range are: glucose 64 (70-138), total bilirubin .6 (.0-.3), cholesterol 552 (92-324), BUN 29 (4-27), triglycerides 1206 (29-291) and magnesium 18 (1-12).

I'm sorry your K'Ehleyr is having a problem but glad it wasn't as bad as it appeared at first. She is so lucky to have you for a mommy.

    Bookmark   June 24, 2008 at 6:12PM
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I understand about not being sure what to do next. It can be frustrating when your vet doesn't have all the technology you need, especially if nobody in the area has what you need either. I'm lucky to be near Raleigh; not all places can do an MRI on a dog within a day.

Mature neutrophilia, high neutrophil count without band cells, is common with steroid-induced hepatopathy, but it could just be a stress reaction. High basophils are probably not significant. If there are bands or nucleated red blood cells (nRBCs) they would be more supportive of Cushings. But not having them doesn't rule out Cushings.

The high cholesterol and triglycerides are interesting. They are common with hypothyroidism. What were Jett's thyroid levels? Was there a full panel or just a total T4?

High total bilirubin is common with liver disease, but not specific for any particular liver disease.

The glucose is slightly low. I don't think I would worry about that unless it was repeatable. I've seen *very* low glucose levels in animals with end-stage liver failure and pancreatic beta cell tumors (insulinoma) but these animals were clearly very sick.

A high BUN can be a couple of things- mild dehydration, kidney disease, high protein diet. Since we don't have a urinalysis dehydration can't be ruled out. Since you are feeding homecooked meals, it may be higher in available protein than a commercial food; that can elevate the BUN. Kidney disease is a concern too. Unfortunately a mild elevation in BUN isn't very specific without a urinalysis.

I'm not sure what to make of the magnesium. I've seen it low, but never high.

Was this the lab work back from 2 years ago when Jett was diagnosed or from recently? What were his symptoms when he was diagnosed? Are there any changes?

I'd still want that ultrasound LOL! Lots of things to look at now- liver, adrenals, pancreas, kidneys.

I don't mean to second guess your vet- he's seen Jett and I haven't, so hepatitis might make a lot of sense. Just from numbers, it it impossible to diagnose any particular liver disease, but it sure does look like Cushings or hypothyroidism to me too. It's rare that 2 ACTH stimulation tests would come back negative unless it was atypical Cushings. If the total T4 is borderline low, that could still be part of Jett's problem, but based on his chemistry panel he certainly has (had?) something wrong with the liver too. Vets like to blame all problems on one disease whenever possible, and Cushings certainly fits a lot of Jett's problems.

K'Ehleyr is doing a bit better today, just got her home. We changed some medications, and hopefully that will help her out. I'm lucky to be her mommy, she's a sweet old girl.

    Bookmark   June 24, 2008 at 7:03PM
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Meghan, sorry I'm slow getting back with the answers. It's house guest season and everything that goes with it.

Jett had a T4 done 3/05. All it has is 2.0 (1.0-4.0) so I'm assuming it's not a full panel.

Looking back as far as I have his lab which is 3/02 the Alk Phos was 490 but nothing was diagnosed then. 3/03 his chemistry panel had several high #'s with the Alk Phos being 447, cholesterol 752, triglyceride 2113 but the Alt being normal. 3/04 is when he was diagnosed with hepatitis. He had no clinical symptoms. Alk Phos was 1303 & ALT 189. They remained about the same in '05. A urinalysis that year showed protein ++/100 with the comment - ERD = high positive. We had a negative ACTH that year as well as last week. In 3/06 his Alk Phos went up to 3060 with most of the chem #'s being high, tested again 4/06 Alk Phos 3360. 3/07 it was down to 1477, then 3/08 back to 3303. Glucose fluctuates, being low one year then normal the next.

Jett has never eaten kibble. I've always fixed him boiled chicken breast with skin & fat removed and either chicken or beef liver. This past year I've added more variety to it. He has ground beef, pork, turkey, occasionally lamb, along with the chicken. He also gets bones in his diet. I tried him on raw but he wouldn't eat it. I give him a bit of coconut oil most days.

Jett has never been active even when he was young. Until his 2nd knee went out a few months back he appeared to feel fine. He only recently started the panting. The Vet said he would get to where he wouldn't eat and from reading on the Yahoo liver board it seems that is true of their dogs. Jett likes his food and stays overweight.

Thank you again Meghan for your help.

    Bookmark   June 27, 2008 at 4:04PM
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I understand about the houseguest thing. That time of year is here for me too, only now I am also getting ready to put the house on the market. Argh.

It may be time to retest for hypothyroidism. Just because his test was normal 3 years ago doesn't mean that it is now. Unless you have had it done since 3/05. You don't necessarily need a full panel if the T4 results are unequivocal. If he was at 2.0 again, then I wouldn't get the full panel because it is unlikely that he is hypothyroid. But if his T4 was less than 1.2 or so, I would get the full panel because he could be truly hypothyroid. The T4 antibodies (gotta make sure the panel has T4AB) interfere with total T4- the test can't separate the 2 things- but if you measure T4AB then you can just subtract that number from total T4 and get the true T4. OTOH, my K'Ehleyr had a borderline T4 at 1.02 and when I did the full panel she had 0 T4AB. But since she had other clinical signs of hypothyroidism- a dry brittle haircoat, high cholesterol, had slowed down a bit- I put her on a low dose of thyroid supplement anyway. Her activity picked back up, cholesterol is now normal, and her coat is getting better. I don't think it's wrong to make a dog feel better, even if there isn't a specific diagnosis, as long as the treatment doesn't have negative side effects. I did remeasure her T4 after 6 weeks of starting the thyroid supplement, and her T4 was 2.4 which is good- don't want to make her hyperthyroid!

Ignoring Jett's bloodwork results for now, he may be panting because of pain in his knees. I think that what you are doing supplement-wise and diet-wise is excellent, except that you really need to get that extra weight off him. You can cut the amount of food back by up to 25% safely. The extra weight puts so much extra stress on their knees, getting him back down to normal may be all he needs to feel better. In the meantime, given his bloodwork and not knowing exactly what is going on with his liver, it does limit what you can give him for pain. One medication that may help is Tramadol, which is a synthetic morphine-type medication, only it is not addictive. Most animals do fine on it, may cause some sedation at first but that tends to go away. One poster here has a dog that had major GI distress on it, but that is rare. It is safe for his liver though, unlike NSAIDs such as rimadyl or deramaxx.

I really doubt that Jett ever had chronic active hepatitis. He just never had any clinical signs. B'Elanna was an extremely rare case, having completely recovered from it- I don't know of any other dog that has done that. But even she was not eating and she was very jaundiced when she was diagnosed. You're right that most dogs tend to eventually stop eating and die from hepatitis- once the liver fails that's it; it's one of those organs you really need. Some are managed for a long time, others go quickly, but I'd say most dogs eventually die from it. They are certainly sick pups until they are treated though, not at all like Jett.

New treatment plan: retest T4, ultrasound +/- aspirates.

Jett sure is lucky to have such a dedicated owner. I'd love to see pictures of him if you get a chance.

    Bookmark   June 28, 2008 at 10:55AM
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Thank you so much for your advise, Megan. I think you are right on target with everything you've suggested. I wondered if it wasn't a good idea to do a thyroid panel but I didn't know just doing a T4 first would tell me if it was needed. I have also wondered if the panting is from pain. Usually when he starts it I put a towel from the freezer over him and if that doesn't stop it I give him 25mg tramadol. I had forgotten to tell you I was giving that (against my Vet's advise, BTW) and he has done fine on it. I asked the Vet about it at the last visit. He wasn't familar with it and looked it up in the PDR, then told me it was as bad as the Deramaxx and it would be better to give Deramaxx. I know I need to find another Vet but I don't know where to find one that's any better. This one is considered to be one of the better ones in this city and has the highest tech clinic. He & my DH have been friends/acquaintances for most of his life (not that we would put this ahead of Jett's welfare) and he does understand that we will not leave our dogs there overnight or for any proceedure.

So what it boils down to is you really need to relocate here for your practice and Jett will be your first patient. We are getting a hugh tourist attraction shortly so this not so large city will be booming. Also, we are close to the gulf.

I have a gazillion pictures of Jett but I don't have a clue how to put one on this board. He's an adorable little guy. Thanks again, Meghan, for your expertise and concern.

    Bookmark   June 28, 2008 at 5:24PM
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I have been reading your posts regarding Jett. I have a dog that just won't test positive for Cushings though his symptoms
all seem to point in this direction. He is PU/PD, pot bellied, increased appetite, pants and generally is anxious most the time. He has had 2 ACTH stim tests, urine cortisol/creatinine, LDDST, water deprivation test,urinalysis, general blood work ups and ultrasound. The general thought is that he is Atypical Cushings. I have been told that even though you can diagnose the sex hormone problem there is not a good treatment for it currently. Could I get an opinion on this. He has an enlarged liver and I am told this is due to the Cushings. He is currently on Clomipramine to help with the anxiety until I can find a treatment I am comfortable with.

    Bookmark   January 24, 2009 at 12:02PM
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I have a 5 yr. old rescued greyhound dx'd with atypical cushings and chronic kidney disease. She has to eat Hills K/D exclusively for the kidneys, and is taking melatonin, flax hulls and lysodren for the atypical cushings. Has anyone used Lysodren and I am wondering if there is a specific kidney diet other than Hills that anyone is successfully feeding. I posted more details earlier but did not mention that Gracee has a lot of anxiety also and that my Vet said that sometimes this is related to the adrenal hormones in play with atypical cushings.

Here is a link that might be useful: Gracee & Henry

    Bookmark   July 31, 2009 at 8:56AM
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