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Thread: Harry, 11 y/o Irish Setter - Hyperestrinism to Cushing's/Diabetic - Harry has passed

  1. #1

    Default Harry, 11 y/o Irish Setter - Hyperestrinism to Cushing's/Diabetic - Harry has passed

    Hi,
    I have 11 year old Irish Setter boy named Harry.
    For a few years, Harry has had proteinuria (urine protein creatinine ratio of 1.6-2.8) - we have been controlling this with low protein diet (Natural Balance Reduced Calorie Formula). His blood pressure is normal. His kidney values so far have been normal. No protein deficiency in the blood numbers.
    Harry's routine blood panel in December showed slightly elevated Alk Phosphatase (208). His T4 was a low, but additional test (free T4?) ruled out hypothyroidism. We started Harry on Denamarin. Harry has had unusual hunger, so our vet and I debated Cushing's. Despite his age, Harry is still a very active and fit dog, being able to go on hours of trail runs. We decided to just monitor him closely.

    Early February, Harry had a non-recurring episode of vomiting. A blood test for pancreatis was negative. Blood chemistry showed even more elevated Alk Phosphatase (280) and ALT (128). Ultrasound done by a radiologist showed everything normal, including liver, stomach, gall blader, kidneys, testicles (Harry is intact). Some gas in his stomach. He has not had any vomiting since, so we attributed to one-time gasteritis.
    A follow-up blood test in early April showed even more elevation in Alk Phos (480!) and ALT (140).

    We did a tick panel, lepto and U Tennessee Adrenal Panel test. Tick was a very slight positive on Rocky Mountain Spotted Fever. Lepto was negative, and U Tennessee Adrenal Panel came back hyperestrinism.

    Cortisol - Normal, Baseline (9.5 vs range of 2.5-56.7), Post (107 range of 70.8-108.5).
    Androstenedione- Normal, Baseline (2.97 vs range of 0.21-4.26), Post (3.67 range of 0.68-7.92).
    Estradiol - Abnormal, Baseline (105.3 vs range of 30.5-66.6), Post (98.9 range of 30.0-65.6).
    Progesterons- Normal, Baseline (0.10 vs range of 0.03-0.40), Post (1.0 range of 0.55-1.70).
    17 OH Progesterone - Abnormal, Baseline (0.52 vs range of 0.08-0.84), Post (3.31 range of 0.37-2.87).
    Aldosterone - Normal, Baseline (50.4 vs range of 11-139.9), Post (196.5 range of 72.9-398.5).

    Other than hunger and begging Harry has not had any other symptoms. Some hair loss around his anal area (hair fell off when he has some skin rashes there a few months ago, has not grown back much). He has had some plant material embedded around his toes and got infected (due to thinnern skin? But then he is a trail running dog).

    Our vet does not think that we need to pursue additional diagnostics to dig deeper into liver (biopsy or bile acid test). She thinks that Harry's estrogen elevation is significant, and this could cause vacuolar hepatopathy that could elevate enzymes. She also thinks hypothyroidism is still a possibility given many Irish Setters are prone to this.

    For now, she is recommending melatonin and flaxseed hulls.

    Now, I also belong to a Yahoo Cushing's board, and the prevailing thought on that board seems to be that there is no such thing as Atypical Cushing's and that melatonin / flaxseed do not really work.

    I wanted to get your opinion on this issue and understand how to deal with this issue.

    I was also told that U Tennessee Adrenal Panel often results in elevated estrogen due to collection / testing method problems. Is Harry's estrogen even elevated?

    Are there any other procedures I should follow?

    As you can tell, I am very very confused and would appreciate any help.

    Harry's Mom
    California

  2. #2
    Join Date
    Apr 2009
    Location
    York, PA.
    Posts
    11,036

    Default Re: Introduction of My Harry - Atypical Cushing's?

    Hi Harry's mom and welcome to our cush family. When my boy Harley had his first adrenal panel done from the University of Tennessee he also showed very elevated estradiol levels.

    There is a cushings known as Atypical Cushings and this is when one or more of the intermediate/sex hormones...Androstenedione, Estradiol, Progesterone, 17 OH Progesterone, and Aldosterone are elevated but the cortisol is not.

    Now if the estradiol is the only one elevated this is known as Hyperestrinism.

    Melatonin and lignans high in SDG is what is recommened for pups that have elevated hormone levels. My boy Harley's estradiol levels have dropped considerably...from 132.2 to 96.6 in 7 months...yes it does take time.

    I don't know if you would consider getting Harry neutered, considering his age, but this could take care of that high level of estradiol.

    Was diabetes ruled out?

    I am sure the others will be along to give their advice also, so hang in there, just remember you are not alone on this journey, we are here to help you in any way we can so ask all the questions you want and we will answer them the best we can.

    Congenital adrenal hyperplasia-like syndrome/ Hyperestrinism/ "atypical Cushing's"
    http://www.k9cushings.com/forum/showthread.php?t=198

    Love and hugs,
    Lori

  3. #3
    Join Date
    Apr 2009
    Location
    New Jersey
    Posts
    528

    Default Re: Introduction of My Harry - Atypical Cushing's?

    Atypical Cushings exists....and cases of "regular" cushings may involve most/all of the hormones being elevated (which is what I have been dealing with)....I am not sure why folks on the other board would say that Atypical does not exist. The UTK seems pretty reputable to me and you can find other citations of Atypical Cushings on the web. Many vets are not aware of atypical cushings nor the UTK testing procedures.

    I have been following a combo therapy of anipryl, melatonin and lignans for several (many?) months now with fairly good results. We are due for a checkup this month. I only added the melatonin and lignans after I had the UTK panel done (was already on anipryl alone for several months based on what was a "borderline" case of cushings at that time). I do feel they have helped, based on observation of symptoms and our last checkup in the fall (we had a "low" reading of cortisol on the UCCR screen using a multi-day sample...which was markedly better than 6 months prior before I started the melatonin & lignans).

    If you are curious and search the net, you can read a lot about melatonin's anti-cortisol properties; it is widely used by competitive body builders in fairly high doses. They too, want to reduce cortisol at all costs, because it adversely affects their ability to build muscle.

    Jeff

  4. #4

    Default Re: Introduction of My Harry - Atypical Cushing's?

    Lori,
    Harry's blood chemistry panel did not indicate diabetes. Just elevated Alk Phos, ALT and cholesterol (note that it was not a fasting blood panel). Everything else was normal.

    Sertoli Cell tumor was cited by U Tenn as a possible cause of hyperestrinism, but the ultrasound showed normal testis, and palpitation did not indicate any tumor.

    Fixing him is an option, but with his proteinuria and liver values, the vet is reluctant to put him under general anethesia. We also debated how neutering him at this point would impact his quality of life (energy levels, exercise tolerance, etc.). Something to keep in mind.

    Thank you for your kind words.

    Yunhee - Harry's Mom

  5. #5

    Default Re: Introduction of My Harry - Atypical Cushing's?

    Jeff,
    Thanks for your response. Our vet did say that U Tenn Adrenal Panel is the current gold standard for this kind of test, and even if the tests do have bias towards elevated estradiol, Harry's values were too high to attribute to false test results.

    I think some of the members on the other board feel that there is no Atypical Cushing's, and these turn out to be full blown Cushing's cases eventually - so it seems that some researchers believe that abnormal Adrenal Panel results are early indicators to Cushing's. Hard to say as I am just starting to research this.

    For whatever it's worth, after taking melatonin for the first time last night, Harry's had a very peaceful sleep (he usually wakes up a few times to jump up on bed, but not last night).

    Harry's Mom - Yunhee

  6. #6
    Join Date
    Apr 2009
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    York, PA.
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    Default Re: Introduction of My Harry - Atypical Cushing's?

    Hi Yunhee,

    My boy Harley is a 13 y/o Pomeranian with PDH cushings and elevations in all his intermediate/sex hormones. He also has high blood pressure, which he takes meds for; still has protein loss in his urine. He also has pancreatitis. In Nov. 2009 his ALP levels were 761 (5-131) and his ALT were 272 (12-118). His vet and I noticed that his teeth needed a good cleaning and maybe some extractions, and even with these liver enzymes numbers she put my boy under a general anesthesia and extracted 3 of his teeth and cleaned the ones that were left! They do have general anesthesia's that are not as hard on our cush pups systems.

    Estradiol is produced from the adrenals but also is formed in other places, like fat cells, hair follicles and the liver.

    I really would suggest that your vet contact Dr. Oliver who heads the lab at the University of Tennessee. He is a saint! Harley's vet has talked with him, via email, many times about my boy and he always responds very quickly.

    Here is his email address: joliver@utk.edu
    Love and hugs,
    Lori

  7. #7

    Default Re: Introduction of My Harry - Atypical Cushing's?

    Thanks, Lori. I will mention it to my vet. Actually, I have been very happy with my vet - she has been very thorough through this entire ordeal (starting with proteinurira about a year ago and then elevated liver enzymes). I am sure she will be happy to reach out to Dr. Oliver.

    Yunhee, HarrysMom

  8. #8
    Join Date
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    Default Re: Introduction of My Harry - Atypical Cushing's?

    Quote Originally Posted by HarrysMom View Post
    His T4 was a low, but additional test (free T4?) ruled out hypothyroidism.
    Was this additional test done, was it the FreeT4 by Equilibrium Dialysis to rule out the Hypothyroidism?

    Love and hugs,
    Lori

  9. #9

    Default Re: Introduction of My Harry - Atypical Cushing's?

    Free T4 was done, and it ruled out hypothyroidism.

    Yunhee

  10. #10
    Join Date
    Apr 2008
    Location
    Tennessee
    Posts
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    Default Re: Introduction of My Harry - Atypical Cushing's?

    Hi Harry's Mom and a belated welcome to you and Harry.

    I have a few questions and comments and in order to keep things organized, I've posed them in blue text within your post below:

    Quote Originally Posted by HarrysMom View Post
    Hi,
    I have 11 year old Irish Setter boy named Harry.
    For a few years, Harry has had proteinuria (urine protein creatinine ratio of 1.6-2.8) - we have been controlling this with low protein diet (Natural Balance Reduced Calorie Formula). His blood pressure is normal. His kidney values so far have been normal. No protein deficiency in the blood numbers.

    I just wanted to point out that the mild proteinuria can be caused from strenuous exercise so with Harry being a trail running dog, this may be normal for him. I would be more concerned if his urine specific gravity was low. Do you have copies of urine tests and if so, what was the USG and PH?

    Harry's routine blood panel in December showed slightly elevated Alk Phosphatase (208). His T4 was a low, but additional test (free T4?) ruled out hypothyroidism. We started Harry on Denamarin. Harry has had unusual hunger, so our vet and I debated Cushing's. Despite his age, Harry is still a very active and fit dog, being able to go on hours of trail runs. We decided to just monitor him closely.

    Early February, Harry had a non-recurring episode of vomiting. A blood test for pancreatis was negative. Blood chemistry showed even more elevated Alk Phosphatase (280) and ALT (128). Ultrasound done by a radiologist showed everything normal, including liver, stomach, gall blader, kidneys, testicles (Harry is intact). Some gas in his stomach. He has not had any vomiting since, so we attributed to one-time gasteritis.
    A follow-up blood test in early April showed even more elevation in Alk Phos (480!) and ALT (140).

    Believe me, 480 Alk Phos is not that high for a cushdog. We've actually seen numbers in the thousands. To touch on Harry's intact status, the gonads are at the top of the list of body tissue where you can find estradiol so this can be contributing to the elevations you see on the UTK panel.

    We did a tick panel, lepto and U Tennessee Adrenal Panel test. Tick was a very slight positive on Rocky Mountain Spotted Fever. Lepto was negative, and U Tennessee Adrenal Panel came back hyperestrinism.

    I'm not sure of the significance of a very slight positive on Rocky Mountain Spotted Fever would be. I know that you can see elevated cholesterol, Alk Phos and Alt with this condition so am wondering what your vet had to say about this.

    Cortisol - Normal, Baseline (9.5 vs range of 2.5-56.7), Post (107 range of 70.8-108.5).
    Androstenedione- Normal, Baseline (2.97 vs range of 0.21-4.26), Post (3.67 range of 0.68-7.92).
    Estradiol - Abnormal, Baseline (105.3 vs range of 30.5-66.6), Post (98.9 range of 30.0-65.6).
    Progesterons- Normal, Baseline (0.10 vs range of 0.03-0.40), Post (1.0 range of 0.55-1.70).
    17 OH Progesterone - Abnormal, Baseline (0.52 vs range of 0.08-0.84), Post (3.31 range of 0.37-2.87).
    Aldosterone - Normal, Baseline (50.4 vs range of 11-139.9), Post (196.5 range of 72.9-398.5).

    Other than hunger and begging Harry has not had any other symptoms. Some hair loss around his anal area (hair fell off when he has some skin rashes there a few months ago, has not grown back much). He has had some plant material embedded around his toes and got infected (due to thinnern skin? But then he is a trail running dog).

    Our vet does not think that we need to pursue additional diagnostics to dig deeper into liver (biopsy or bile acid test). She thinks that Harry's estrogen elevation is significant, and this could cause vacuolar hepatopathy that could elevate enzymes. She also thinks hypothyroidism is still a possibility given many Irish Setters are prone to this.

    Hyperestrinism can cause vacuolar hepatopathy but this is usually apparent on abdominal ultrasound and Harry's liver appeared to be normal. I assume that the adrenal glands were also normal? PU/PD (excessive drinking and peeing) is also the norm in most dogs with this condition so with Harry lacking this symptom, I think your vet's thinking that hypothyroidism shouldn't be ruled out just yet is understandable. In my opinion, Harry seems to have more lab abnormalities and physical symptoms consistent with hypothyroidism and until you absolutely rule it out, there's no way to tell which condition is causing the symptoms. Can you post the results of the Free T4 test that was done?

    For now, she is recommending melatonin and flaxseed hulls.

    Now, I also belong to a Yahoo Cushing's board, and the prevailing thought on that board seems to be that there is no such thing as Atypical Cushing's and that melatonin / flaxseed do not really work.

    Atypical cushing's, also known as pseudo or occult cushing's, does exist. More than a few reknown endocrinologists use these tags when defining a dog that has clinical signs and blood chemistry indicative of cushing's yet circulating serum cortisol levels are normal on the LDDS and acth stimulation tests. I'm therefore not sure why the folks at ccac feel that atypical cushing's does not exist. It may be because it's a highly controversial subject and the veterinary medical community seems to be split as to whether or not it's truly the elevated sex hormones that are at the root of the problem.

    It is known that efficacy for melatonin and flaxseed treatment is slow and low in comparison to the conventional treatment used for typical cushing's; however, we have seen some good results here.


    I wanted to get your opinion on this issue and understand how to deal with this issue.

    I was also told that U Tennessee Adrenal Panel often results in elevated estrogen due to collection / testing method problems. Is Harry's estrogen even elevated?

    I've personally never heard about problems in collection methods skewing test results but this can easily be clarified by Dr. Oliver at UTK. FYI, estradiol is an estrogen.

    Are there any other procedures I should follow?

    I think you should follow your vet's plan of action and I also agree with Lori that your vet should contact Dr. Oliver to discuss Harry's case. It doesn't cost a cent and Dr. Oliver may have some sound recommendations based on Harry's full medical history presented by your vet.

    As you can tell, I am very very confused and would appreciate any help.

    I understand how confusing all of this is and everybody has their own opinion based on their own experience and research. It took me a very long time after my first cushdog was diagnosed to get my arms around the disease and I didn't form my own opinions about anything for months. Try to catch your breath and go easy on yourself. We're here to help you in any way we can and I promise that the more you learn, the more unconfused you will become.

    Harry's Mom
    California

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