Atypical Cushing's and Cushing's what's the difference? (Marie and Bruno)

[overfiffty]

Hi, my name is Marie and Bruno is my 13 soon to be 14 year old lab chow mix. I have joined this web site at the advice of Natalie from the K9 web site. Natalie has been a tremendous help to me with Bruno and she said I should log in over here and look around.

To begin with I realized back in November when home recovering from a knee replacment operation that this dog had diabetes. Being a former diabetic myself I knew the signs. We took him to our regular vet who confirmed what I already was sure of.

Bruno is going to be 14 years old sometime in April. He was originally 72 lbs but since he's had the diabetes he's lost weight and is down to around 61 lbs. He's tail which was always very bushy is now thin and frail. His back legs are not working well and he has quite alot of weakness in his back legs. He can no longer go upstairs and needs help. He has recently lost a great part of his eye sight not sure if due to cataracts or just from high glucose. He started out in the 600's and is currently down in the 300+ or minus, mostly +. We check his urine every day and it's +2000, ketones are negative. We are up to 35 units (just yesterday) has been on 33 units for the past week. Since his urine never varies and stays standard at +2000 Dr. Kimmel the specialist has been raising his insulin levels very slowly.


Well it's been a long trial and error but my regular vet was very reluctant to up his insulin dosages. He did many tests and did show that Bruno had Cushings. However, I felt we were running in place and getting no where. When my vet suggested a test where he was actually hoping that Bruno would crash I knew it was time to see a specialist. So I've been taking him to Dr. Susam Kimmel an Angel with wings on her that she doesn't even realize she has.

She took Bruno and I under her wings and really has been a tremenous help. She performed an ACTH test which was negative. So she sent the panel to the Univ of Tenn. I am going to post yesterday's e-mail to me. She was nice enought to send Bruno's panel to the Univ of Tenn and here are the results.

The adrenal function panel is back and shows mild elevation in cortisol, progesterone, but more significant increase in estrdiol (estrogen). This can be associated with insulin resistance. Therefore treatment is definitely recommended. A combination of products are recommended which help to inhibit the production of some of these hormones.

1. Flaxseed Hulls 3/4 tsp once daily
2. melatonin 6 mg twice daily
3. Ketoconazole twice daily

We should continue to monitor glucose curves and insulin dose adjustments as needed. Our hope is with control of some of these hormone elevations the insulin resistance will improve and less insulin would be needed than otherwise.

While on ketoconazole liver values should be periodically assessed. every 3 - 4 weeks. Glucose curves at home should be 1-2 weeks.

Well guys, I'm opening this up to everyone. Does this sound familiar and what is the difference between Cushings and atypical Cushings?

Any suggestions from anyone? Do meds sound ok? Is anyone dealing with these meds and having a terrifc result? :confused:
Please advise and thank you for your thoughts and responses.

Marie and Bruno

[Franklin'sMum]

Hi Marie
Welcome to you and Bruno from me and my furkids (Franklin- Cushings, and Bailey- Arrythmia).

I am so glad you have found a specialist- the thought of a vet wanting a pup to crash is terrifying to me :eek:. This is an amazing group of people, Marie, with all kinds of knowledge. The more experienced members play 20 questions, and meanwhile I'm still learning, but I'll start the interrogation :p:)
What tests were done to diagnose the cushings? You said the ACTH was negative, but then you say there's a mild elevation in cortisol, so I'm a little confused.

Ketaconzole is very hard on the liver, which is probably why they recommended getting it checked each month. We have another member (Jean and Snickers) who was just using ketaconzole, but due to a few issues, is needing to change.

The main difference between regular Cushings and Atypical Cushings is cushings is high cortisol, and atypical is one or more intermediate steroid sex hormones (estradiol, aldosterone, androstenedione, progesterone and 17OH progesterone) is elevated. And yes, a pup can have both cushings and atypical cushings at the same time.

If Bruno's cortisol is only mildly elevated, a number of people use melatonin and lignans-- these have the ability to lower cortisol and lower most of the intermediates (with the exception of estradiol, which is produced both in the adrenals, and also hair follicles and such). That may be all he needs to bring things under control.
You might like to check out Lori's (HarleyPomMom)and Leslie's (Squirt's Mom) threads, as their babies have atypical cushings. Recently Harley's cortisol became elevated, and now he has atypical and PDH cushings, and is on a maintenance dose of Lysodren, and is doing well.

My knowledge of diabetes would not over-flow a thimble, so I'll sit that one out ;) Hope this helps a bit,
Jane, Franklin and Bailey xxx
________
Wendie 99 (http://www.lovelywendie99.com/)

[StarDeb55]

Marie, welcome to you & Bruno. I, too, don't know much about diabetes, so I will leave that to other members with more experience.

Would you mind posting the actual results of the full adrenal panel, along with normal ranges & reporting units? It's not that we're doubting what yo have already posted, but we're just numbers kind of people around here, & really like to see those values. Also, were the 3 suggested treatments on the UTK sheet, the only ones? I'm asking as normally the treatment recommendations with results that show a mild elevation in cortisol will frequently include a maintenance dose of lysodren, if the melatonin/lignans don't help.

Now, when it comes to types of Cushing's, I need to clarify some of what Jane has already said. If there is no elevation of cortisol, but elevations in any or all of the 5 intermediate hormones, this is considered to be Atypical Cushing's only. If there is an elevated cortisol, even with elevations in any of the intermediate hormones, this is typical Cushing's. For instance, my Harley, has an elevated cortisol, along with elevations in all intermediates, so he has typical Cushing's with elevated intermediate hormones. Harley is not considered to be regular Cushing's + Atypical. The determining factor for diagnosis is whether or not the cortisol is elevated.

Melatonin + lignans are usually used to try to control non-adrenal production of estradiol. The other thing about melatonin + lignans, you will need to allow about 3-4 months for them to work. These 2 medications will have only a very small effect on the cortisol, if any. The 2 drugs that are used to lower cortisol are either trilostane or lysodren. I can't comment on ketoconazole usage as I have no experience with the drug. What I can tell you is that I have, now, successfully treated 2 pups with lysodren. What is Dr. Kimmel recommending?

Debbie

[Franklin'sMum]

Hi Debbie,
Thanks for clearing that up :)
________
Teen Sex (http://www.fucktube.com/categories/39/teen/videos/1)

[Harley PoMMom]

Hi Marie,

Welcome to you and Bruno from me and my boy Harley! I am so very happy that you decided to join our family also, although I am so sorry for the the circumstances that have brought you here.

Bruno's IMS, Dr. Kimmel, sounds like a top-notch doc to me and I am so happy you found her.

We do have another member here; Heather, that treats her pup, Zoe Claire, with the Ketoconazole, flax hulls and melatonin, now Zoe Claire is not diabetic. Here is a link to their thread if your interested, Zoe Claire is doing great on this treatment plan.

Re: Update on Zoe Claire "Atypical Cushing"

http://www.k9cushings.com/forum/showpost.php?p=25518&postcount=67

Update on Zoe Claire "Atypical Cushing" (Start of Thread)

http://www.k9cushings.com/forum/showthread.php?t=620

Marie, I think you are doing an excellent job of taking care of Bruno, and I do hope you keep us updated.

If you have any questions at all, please do not hesitate to ask, ok. We are here for you and Bruno too.

Love and hugs,
Lori

[k9diabetes]

Here is a link to Bruno's thread at the K9D forum: http://www.k9diabetes.com/forum/showthread.php?t=1617

I believe that Dr. K. is trying this route first in part because of elevated estrodial and in part because the cost of purchasing lysodren and monitoring lysodren treatment with ACTH tests would present a financial hardship.

Bruno has been running up quite a bill at the vet the past couple of months and Dr. K. has done an excellent job of balancing his diagnostic/treatment needs with the limits of the financial resources available. She's been very sensitive to that.

Natalie

[gpgscott]

Welcome Marie and Bruno.

It would be very helpful to see the results of the full adrenal panel.

If the cortisol is only mildly elevated and you have elevations of other hormones, (you mentioned estradiol) I think the Keto makes sense as it will affect all of the adrenal hormones and Lysodren is most active for cortisol elevations.

It is my understanding however that you still need to be aware of low cortisol when administering Keto and the only definitive method I am aware of for that is a stim.

Am very glad your Dr. is undertanding of the financial issues. I hope we can help you by giving you our experiences.

Scott

[gpgscott]

Marie,

I see you have not yet replied.

We have another member with a similar situation. Heather and her ZoeClaire. This link as already been mentioned by others because of the relevance.

I am placing a link

Scott

http://www.k9cushings.com/forum/showthread.php?t=620&highlight=Claire

[overfiffty]

Hi,

I did reply but when I hit the submit button, nada, zero, zilch. It would not let me post any reply. Let me just say thanks to one and all who responded to my thread/post. Unfortunately I had the same problem over the weekend with K9 diabetes. Therefore I personally e-mailed Natalie who was nice enough to send my link from there over to here. I have visited the two other sites for people who are sitting in the same boat as Bruno and I.

I am waiting to speak with Dr. Kimmel regarding the three meds she prescribed she is not in on Sun., Mon, or Tues. When my husband had the drug store call the hospital they told him that only Dr. Kimmel could prescribe the medicine Bruno needs. I do not believe that but since Dr. Kimmel and I haven't had a chance to chat I want to hold off on the meds till I'm at least home during the day and can watch him on a Saturday and Sunday. Therefore I have a small window of time to pick up all the drugs. Not only that but Dr. Kimmel is leaving on vacation this Saturday so I really want to speak to her about using all these meds in conjunction with his insulin of 35 units 2x a day. And if necessary if an emergency crops up can I bring him into their hospital or do I bring him into my regular vet?

I have posted results to his tests in the diabetes web site so if you are truly looking for numbers you will find the test results over there. :rolleyes:

I hope to post and have her fax to me the entire results from the panel done at the Univ of Tenn on Wednesday after I speak with her.

I will keep everyone advised as I move along. Thanks again to everyone and most of all thanks for the warm welcome.

Marie and Bruno:)

[lulusmom]

Admin Note: This is a copy of Marie's 3/28/10 post on k9diabetes relative the UTK adrenal panel results.


Well Guys Here Goes:

The adrenal function panel is back and shows mild elevation in cortisol, progesterone, and more significant increase in estradiol (estrogen). This can be associated with insulin resistance. Therefore treatment is definitely recommended. A combination of products are recommended which help to inhibit the production of some of these hormones:

1 Flaxseed HULLS: WWW.FLAXSEEDHULLS.COM recommended give 3/4 teaspoon (which is equivalent to 1/2 of a "red scoop' provided) once daily.

2 Melatonin (can be purchased over the counter at a health food store) recommended give 6 mg twice daily use regular melatonin NOT rapid or extended release product.

3 Ketoconazole 200 mg twice daily (prescription required) I will call her and she will call the prescription in for us. This is an antifungal drug but is also used in adrenal hormone excess because it inhibits an enzyme in the pathway where adrenal hormones are made.

We should otherwise continue as we have been (monitor glucose curves and insulin dose adjusted as needed) toward the goal of improved diabetes control. Our hope is with control of some of these hormone elevations, the insulin resistance will imiprove and less insulin would be needed than otherwise.

While on Ketoconazole, ideally liver values should be periodically assessed (q1-2 months) as it has rarely been associated with liver toxicity. As both diabetes AND Atypical Cushing's can contribute to elevations in liver values (ALP and also ALT to a lesser extent) this may be a subjective determination. I usually watch for elevations in ALT or AST that are incongruous to the elevatsions seen with ALP (which with diabetes or Cushing's is usually the main liver value elevated). Clinical signs are typically also present (vomiting, diarrhea, lethargy, inappetance) in the face of a ketoconazole "toxicity" so if this is ever observed you should notify us.

Depending on response, Lysodren is another drug that can also be considered. However, I have opted to start with Ketoconazole as its monitoring would be less intensive and less expensive.

Follow up: Once we start the drugs above, recheck liver values (blood test) in 3 - 4 weeks. Do glucose curve at home q1-2 weeks and continue to say in touch with me about results and dosage adjustments we may need to make.

Well that's the e-mail she sent to me. We will try to purchase the first two items on the list and I will call today and see if I can get one of the hospital doctors to call the other prescription in. I would like to start all three on Wednesday of this week if possible. Dr. Kimmel will only be there Wed, Thursday, Fri and Sat. Then I understand she's off for a week's vacation. So I also need to discuss with her who do I call in case of an emergency. Although in all honesty I did e-mail these results to Dr. Melhrose. Although he's not active in Bruno's diabetes care I still use him as a vet for Miss Starr, and my son uses him for his cat, Lana so he's still involved with our family of animals. :D

Anyone have any suggestions or idea's????

Marie and Bruno:rolleyes:

[overfiffty]

Hello everyone;

I haven't been on line for a few days and decided to check the K9 diabetes and Cushings forums. I've posted on both. The meds are on order for the Cushings and I hope to start the Cushings meds on Saturday. I am also doing a curve on Saturday. Dr. Kimmel said if he's still in the 300+ to increase his insulin to 39 units. He was switched last night to 37 units. I certainly hope that with the new medicines for the Cushings that we will see a marked improvement in him. I do not expect him to act like Starr who just turned a year old but I'd like to see him with a better quality of life.

I want to thank whomever was able to move the last e-mail I posted on K9 diabetes to here. I am quite techincally challenged with that sort of thing. I have called Dr. Kimmel's office and requested that they please forward the entire panel result to my home. I hope that they do that because you'd think you are dealing with HIPPA Laws. They are telling us in order to get anything we need from our dogs' file we need to fill out a form. I can see that for a human but not an animal. I'm a legal secretary and even clients can have anything they want from their file they paid for it and technically it's theirs. Anyway happy holiday to one and all.

As soon as I get the entire panel back I'll post it here.

Marie and Bruno:)

[Harley PoMMom]

Hi Marie,

According to the AVMA:
http://www.avma.org/issues/policy/ethics.asp#VIII


VIII MEDICAL RECORDS

A. Veterinary medical records are an integral part of veterinary care. The records must comply with the standards established by state and federal law.

B. Medical Records are the property of the practice and the practice owner. The original records must be retained by the practice for the period required by statute.

C. Ethically, the information within veterinary medical records is considered privileged and confidential. It must not be released except by court order or consent of the owner of the patient.


D. Veterinarians are obligated to provide copies or summaries of medical records when requested by the client. Veterinarians should secure a written release to document that request.

E. Without the express permission of the practice owner, it is unethical for a veterinarian to remove, copy, or use the medical records or any part of any record.

Love and hugs,
Lori

[overfiffty]

;)Here's the results: UNIVERSITY OF TENN RESULTS!!!!
TEST
Cortisol ng/ml
RESULT
(baseline) Normal range result post ACTH NORMAL RANGE
56.6* 2.0-56.5 202.3* 70.6-151.2

Androstenedinoe ng/ml
0.27 0.05-0.36 0.63 0.24-2.90

Estradiol pg/ml
143.6 23.1-65.1 141.2* 23.3-69.4

Progesterone ng/ml
0.51* 0.03-0.17 1.6* 0.22=1.45

17OH Progesterone ng/ml
0.2 0.08-0.22 1.54 0.25-2.63

Aldosterone pg/ml ***
79.1 11-139.9 241.7 72.9-398.5

*above or below reference range
** mean normal rnage valuses for neutered mald dogs (N- 37).
QNS = INSUFFICIENT SAMPLE
*** normal range valuses for mal and femal dogs (N=72, baseline, N-23 post-ACTH.)

These results indicate presence of increased adrenal activity (mild-moderate)

COMMENTS; History diabetic enlarged ADs @ US, LDDST + Estradiol elevation is sugnificant and it may be linked to insulin resistance. Various treatment option considerations are attached some veterinarians consider 2-5, 8 depending on the severity of clinical signs.

Obviously they left the sencond page off. I have to call the hospital to get it sent to me. Unfortunately Dr. Kimmel is off this week and Dr. Melhrose is closed at this time so page two will have to follow.

Any thoughts and/or suggestions from ANYONE?????????

[Harley PoMMom]

My boy Harley had his first UTK panel done in April 09, his estradiol was very elevated...a post of 132.2 pg/ml. At that time his cortisol was within the normal ranges so his treatment consisted of just the flax hulls with lignans and melatonin.

In Nov. 09 we ran another UTK panel on my boy and his estradiol dropped to a post of 96.6 pg/ml. Still on the high side but a significant drop for just treating him with the lignans and melatonin.

I really believe you are going to see very good results with your treatment plan. It will take time, that estradiol can be a bugger to get lowered, so just be patient...yeah right! :p:) Patience is not one of our virtues, at least it is not one of mine!

Wishing you and Bruno the best of luck and keeping you both in my thoughts and prayers.

Love and hugs,
Lori

[Squirt's Mom]

UTK Treatment Option Sheet:

http://www.vet.utk.edu/diagnostic/endocrinology/pdf/Steroid%20Profiles%20for%20Diagnosis%20of%20Atypic al%20Cushing%27s.pdf

[acushdogsmom]

Hi Marie,

I am copying my reply to you below, that I posted at the k9diabetes forum yesterday. :)

http://www.k9diabetes.com/forum/showthread.php?t=1617&page=16

__________________________________________

Hi Marie,

The UTK treatment options sheet (the page they didn't send you) is actually available as a pdf file on the UTK website. :)

The most recently updated version there is from January 2010.

http://www.vet.utk.edu/diagnostic/endocrinology/pdf/TreatmentInfoAtypicalCushingsRevised201001.pdf

Here is a quote from that document regarding treatment options 2-5 and 8:


2) Melatonin. Often used as a first treatment, especially if alopecia is present, since it is cheap, has few side effects and is available in health food stores or via nutrient suppliers on the Internet. Typically, a dose of 3 mg is given q12hrs (BID) for dogs <30 lbs; a dose of 6 mg is given q12hrs (BID) for dogs > 30 lbs. Regular melatonin is usually used rather than rapid release or extended release products. Melatonin has anti-gonadotropic activity (effective for ferret adrenal disease), and it inhibits aromatase enzyme (decreases androstenedione and testosterone conversion into estradiol) and 21-hydroxylase enzyme (effectively lowers cortisol level). Monitor treatment effectiveness by improvement in clinical signs, biochemistries or by repeat of steroid profile.

3) Melatonin Implants. Available for dogs and ferrets. (WWW.MELATEK.NET). Sizes are 8, 12 and 18 mg for <25, 25-50 and >50 lb dogs, respectively. Effects last 3-4 months. NOTE: Melatonin and flax hull product with lignans are used together when estradiol is increased.

4) Lignan. Lignan has phytoestrogenic activity, and competes with estradiol for tissue estrogen receptors, with less biological effect. Lignan also inhibits aromatase enzyme (lowers estradiol) and 3-beta HSD enzyme (lowers cortisol). Use lignan from FLAX SEED HULLS (or HMR lignan). DO NOT USE flax seed oil as the lignan content is very low, and the flax oil can exacerbate pancreatitis in dogs (triglyceride levels may increase). Search for standardized products (via Google or health food stores) that allow determination of lignan content. Available products allow for flexible dosing, and the suggested approximate daily dose of lignan is one milligram (mg) per pound of body weight.

5) Maintenance dose of Lysodren. Often useful in combination with melatonin and lignan to help lower sex steroid levels other than estradiol, along with suppressive effect on cortisol level. NOTE: MONITOR CORTISOL LEVELS AS FOR TYPICAL CUSHING’S TREATMENT.


8) Ketoconazole. Alternative Cushing’s disease treatment. Effective for increased cortisol and sex steroid levels. Consider 6 to 12 mg/kg, BID along with melatonin and lignan as above. See write-up at our website (and the recent article on ketoconazole treatment at JAVMA, 233:1896, 2008).

I think that the suggested treatment plan options on the treatment options sheet would include either a maintenance dose of Lysodren OR the ketoconazole. (not both)

And here's another link to a page on the UTK site where they do seem to explain a bit about Ketoconazole and the combination of Melatonin, Lignan, and low-dose ketoconazole. I think that may be the "writeup at their website" to which they refer on the treatment sheet above..

http://www.vet.utk.edu/diagnostic/endocrinology/treatment.php


Hope this helps.

[hfurlotte]

Hi Marie,
I have been away off site for awhile and just starting checking back in with K9 group this weekend. I was quite interested to read the new information that Dr. Oliver has released and I was extremely pleased to see Ketoconizole being used more readly in Atypical cases. As with any medication there are side effects that you want to watch for but this has been a wonderful treatment option for us. We have had our Zoe Claire on Keto for almost two years now and she is doing extremely well with absolutely no signs of "Liver Toxicity"
matter of fact her liver enzymes all are sitting middle of the normal range :) We have on a couple of times had to increase her keto and a total max she was at was 400mg a day for about 3 weeks then we reduced her when symptoms started to disappear. She is maintaining 200 mg a day with 6mg of Melatonin twice a day. Zoe is 70 lb lab/shep cross. All her hormone levels have decreased so I can only think the Keto and Melatonin are doing their jobs :)