Cushing's Disease (Hyperadrenalcorticism) - Our Experience

I have written about Sunshade's Cushing's Disease before in a couple of our old posts, but I have decided to compile all the info into one post for convenience sake. So I apologize if you are reading repeated material....

Cushing's Disease and Atypical Cushing's Disease are two forms of hyperadrenalcorticism (increased activity of the adrenal cortices).

The adrenal glands, one located near each kidney are responsible for the production of the stress hormone - cortisol, as well as the production of other steroid & intermediate sex hormones. The stress hormone Cortisol is a hormone that is necessary for many body processes to occur. It is impossible to live without some form of this type of steroid, either made naturally by the body or given in the form of prescription steroids. However, too much cortisol and/or other steroid hormones circulation in the body over a prolong period of time can cause serious damage to the body and its organs. Secondary illnesses often arise as a result of uncontrolled Cushings/Atypical Cushings.

To differentiate between Cushings and Atypical Cushings:

Cushings (Typical hyperadrenalcorticism): The overproduction of the hormone cortisol from the adrenal glands.

Atypical Cushings (Atypical hyperadrenalcorticism): The overproduction of adrenal steroid hormones other than cortisol (ie, estradiol, androstenedione, progesterone, 17-hydroxyprogesterone, aldosterone).

If your dog is showing all the symptoms of having Cushings, and yet has tested negative for having Cushings, meaning the cortisol level is normal. I would strongly suggest you run a U of Tenn panel to rule out Atypical Cushings. This was the case with Sunshade. Her cortisol had been normal in all of her tests, but her intermediate sex hormones were elevated. U of Tennessee has a huge endocrinology department, and is the only place in the world that runs this particular panel for Atypical Cushings. Dogs from Australia are having their blood sent to U of Tenn!!! Please note, it is possible for a dog to start out with Atypical Cushing's and then progress to being typical with elevated cortisol as well. This was the case with Sunshade. 

Symptoms commonly associated with Cushings/Atypical Cushings Syndrome:

• Polyphagia (increased, excessive appetite) 
• Pot belly or distended abdomen


• Muscle wasting resulting in hind end weakness
• Lethargy
• Chronically elevated serum liver enzymes: ALP, ALT, AST
• Enlarged liver
• Enlarged adrenal glands
• PU/PD (excessive urinating; excessive drinking)
• Dilute urine
• Excessive panting, temperature intolerance
• Haircoat problems (baldness, hair loss, hair thinning, discoluration of coat)

• Skin biopsies that indicate presence of an endocrinopathy, such as calcinosis cutis (abnormal calcium deposits in and beneath the skin)

Both typical and atypical Cushings can be caused by either a tumor in the hypothalamic-pituitary area (85-90% ~ Pituitary Dependant) or in the adrenal glands (10-15% ~ Adrenal Dependent), or both. Typical Cushings can also be caused by cortisone medications (ie, Prednisone, Prednisolonde, Dexamethasone, etc) given in excess or over a long period of time. Cortisone induced Cushing's is called Iatrogenic Cushing's Disease. 


Cushing's Diseases causes elevation in liver enzymes due to the prolong "steroid" exposure. Sunshade's liver enzymes were off the charts, as in, in the thousands when I left it untreated for a year. As soon as we got control, the liver enzymes came all the way down. Cushing's Disease also digests muscle mass, so it makes the dog lose muscle tone, which in turn exacerbates existing orthopedic problems and/or make the dog look a lot older than he/she is.

Usually with Cushing's, you need two positive tests to confirm it. The cheapest, easiest test I think is the Urine Cortisol to Creatinine ratio test. If that's positive, you can either run a LDDS (Low Dose Dexamethesone Stimulation) or ACTH Stimulation test. The LDDS will most likely be able to tell you whether the Cushing's is pituitary dependent or adrenal dependent. Treatment depends on the type of Cushing's the dog has. ACTH Stim test tells you whether there is an increase in adrenal activity. If both of those tests come out negative, you can then test for Atypical Cushing's. Sunshade was Atypical for a year before she turned typical.


Treatment for Atypical Cushing's: 

It is simple, and cheap. Over the counter Flaxseed Lignan and Melatonin are the two agents commonly used in conjunction to treat Atypical Cushing's. Sunshade was Atypical for a year and was treated with the above. However, when her cortisol (typical Cushing's) became elevated, the Lignan and Melatonin did nothing to help. So bottom line, if your dog does NOT have elevated cortisol but has elevated sex/intermediate hormones with Cushingnoid symptoms, you could try using Lignan and Melatonin to treat. If the cortisol becomes elevated (with symptoms), you will probably need to go to a drug (see below). 

To test for Atypical Cushing's,

• U of Tenn Atypical Cushing's Panel (item G. you want on the list)
• Read more about the diagnosing of Atypical Cushing's (download file)

Treatment for Cushing's:

There are two types of drugs you can use for Pituitary Dependent Cushing's. They are, Lysodren (Mitotane), and Vetroyl (Trilostane). Trilostane is the one I have been using with Sunshade. We get it through a local compounding pharmacy due to the varying dosages.

Mechanisms behind the two drugs,

Lysodren (Mitotane): 

Cytotoxic drug like chemo. Can work on both pituitary or adrenal dependant Cushings. It works by directly eroding layers of the adrenal glands away to suppress the production of the steroid cortisol, which causes all the Cushingoid symptoms. Usually, dogs go through a "loading phase" where you try to erode as much of the adrenal glands as you could to get rid of the symptoms, and once you've achieved that, you go onto a maintenance dosage for the rest of the dog's life. The risk is that each dog's response to the drug is different, and sometimes if the dog is sensitive and the dose is too high for the particular dog, you end up eroding too much of the adrenal glands or killing them off completely. That's what they called the Addisonian crisis, which is life threatening. It is basically the opposite of Cushing's where the body isn't able to produce cortisol (stress hormone) and the body goes into shock. The dog could become critically ill and sometimes even die. If you choose to use Lysodren, I would suggest that you are available to observe the dog almost 24/7 during the loading phase. Any subtle change (ie, stopping to look around while eating), could indicate the dog is loaded and the medication should be stopped. An ACTH stim test should be performed soon after to monitor the control.

Vetroyl (Trilostane): 

It is a newer drug, and works for pituitary dependent Cushings. As you know, pituitary dependent Cushing's is caused by a microtumour in the pituitary gland in the brain. The tumour causes the pituitary gland to send out too much ACTH signals to the adrenal glands, that in term, produce more cortisol than the body needs. So Trilostane works by blocking the ACTH signals sent out by the pituitary, so the adrenal glands don't receive them and therefore they don't over produce cortisol, thus controlling Cushings. This drugs sounds very benign and theoretically, should NOT cause corrosion of the adrenal glands since it had no direct action on the adrenal glands,  unlike Lydodren. However, since it became available in Canada and the US, vets are finding they are losing as many dogs on Trilostane as they did on Lysodren. Every dog's response to Trilostane is different, and they still don't know why adrenal necrosis occurs in some dogs (usually within days of starting the med). Another thing is that when Trilostane first became available to N. America, the insert that came with the drug had specific dosages for different size dogs. The vets have now realized those set dosages were way too high for a lot of the dogs, and was one of the reasons why dogs were dying on the drug. Now they have a Start-Low-Go-Slow protocol that is much much lower than the company insert. Dogs are doing better with the lower starting dose. Still, you do get some that just can't handle the drug and they crash even on the smallest dosage, much like Lysodren.

• Trilostane Twice A Day Dosing - everything you need to know

So that's about the two drugs, not one is better or less risky than the other unfortunately. I'm lucky that Sunshade never had a problem on Trilostane. Of the two drugs, Lysodren is much more affordable than Trilostane.

Our Cushing's Journey

Sunshade was dx with Cushings in June 2010 (about 10.5 yrs old), but looking back, she had been Cushingnoid for a good 5-6 months prior. She went untreated for almost a year because I was too afraid of the potential deadly side effects from the drugs commonly used to treat Cushing's. Then she got diagnosed with cancer in November 2010. We didn't start treating until December 2010. It has been two years since we have been treating Sunshade with Trilostane. I can honestly say looking back at the huge difference it has made in Sunshade's overall wellbeing as well as quality of life that I would NEVER allow Cushing's to go untreated for so long.

Sunshade went from having mild Cushingnoid symptoms to full blown Cushingnoid symptoms. All of her personality (what you see now) was GONE towards the end of that untreated year! She was a Sunshade shell that wanted food and that was it. Everything that made her "Sunshade" was no longer there anymore. I would take her to her favourite beach, or to play in the snow, and she would just stand there with a blanked look in her eyes, not wanting to walk at all. A squirrel/cat would run by, no reaction. A dog would jump on me, or try to get attention from me with her standing right next to me, still no reaction. She is normally quite possessive/protective of me, and  would get in between to keep dogs away from me. People running towards me at night, no reaction (would normally run up to block them from coming straight towards me). She didn't care for unneutered boy dogs, and no interest in her horsie/fat rat (*gasp* can you believe it!!). The only thing that existed in her world was food, and ONLY food. 

The Sunshade sparkle was gone. Light was out from those beautiful eyes. It broke my heart. That was when I realized I needed to take the plunge and start her on meds because I was losing my girl already. Two weeks after I finally decided to start treatment, she was diagnosed with cancer (November 2010), so we had to deal with that first. When cancer came, there was no other choice but to treat Cushings if we wanted to win the cancer battle. Prolonged steroid exposure to the body greatly compromises the immune system. Lots of things can go wrong when the immune system is compromised, including cancer.

Uncontrolled Cushing's made Sunshade do unthinkable things; things the "normal Sunshade" would have never considered doing. This was a dog that you could leave unattended, with food within reach on the coffee table and she would not touch it.

Picture below was Sunshade at the peak of her untreated Cushing's (10.5 yr old). I took her to a place she had never been before, and she did this. The normal Sunshade would have loved to explore new places being the curious girl that she had always been, and still is today. Notice the muscle loss, pot belly, thinned out coat (and she has a sheepcoat!!), and loss in colouring.

Once treatment started, I began to see little glimpses of my girl returning. It took quite a few months to get to the correct dosage. When she was fully controlled, my bossy, flirty, protective, loyal girl was back!! Now at 13.5, she is just as bossy as she was in her prime, still keeping the pups in check anytime and every chance she gets. I can't stress enough how easy it is for the lack of interest, sluggishness, laziness, lethargy, and dulled personality that are often associated with Cushing's Disease to be attributed to "simple aging". If your dog has other symptoms, get him tested and start treatment when appropriate. 

Pictures below were taken in November 2012, on Sunshade's 13th birthday (3 yrs after dx, 2 yrs being treated). She had lost over 10 lbs since treatment started, and is now back to her optimum weight of 62 lbs. Notice the difference in coat and colouring? Her muscle tone is good, and is more active now than she was 2-3 yrs ago. I can also see the sparkle and mischief in her eyes once again. My happy girl is back! Sunshade is back! 

I picked Trilostane to be our drug of choice based on the internist that I took Sunshade to in Seattle, WA. Dr. Matt Vaughan was UC Davis trained. UC Davis came up with the new Start-Low-Go-Slow Trilostane Protocol that many specialists are following now. My internist was the head of the research team for that protocol, so I went with a drug that he was very familiar with. We went very slow with testing every two weeks. It cost a fortune I must admit because of the slow increments we were doing with the drug. An ACTH Stim test must be performed every time there was a dosing change, and/or if over-control is suspected. 

To give you an idea, we started Sunshade at 15mg twice a day, we increased by 5mg every two weeks (that's VERY conservative, normally they go at least 10mg) with ACTH testing every two weeks. We had to increase all the way to 80mg twice a day before I started seeing reduction of some symptoms. The symptoms weren't all gone at 80mg, so we went up to 90mg. Then all of a sudden, Sunshade started showing signs of over control. She did not go into an Addisonian crisis (thank goodness!), she just lost her appetite, and her back became extremely sore back. Keep in mind steroid Cortisol masks pain, so when we try to bring it down, the aches in the body become more apparent. Anyway, the ACTH Stim test confirmed that she was being over controlled. We then had to back all the way down to about 40mg twice a day (10mg at a time), and that was where she was for a couple of months. Then over a period of 3 months, I felt the drug was building up in her system, and we again ran an ACTH Stim test which confirmed my suspicion. We lowered the drug again, and now she is at 25mg twice a day. She has been on that dose for the last year or so. Her recent ultrasound showed her liver looks completely normal, not the usual fatty/enlarged Cushingnoid looking liver. Her adrenal glands also went back down to normal size when it had been large and ever growing over the last two or so years. Liver enzymes are perfect. So this tells us we have her Cushing's under good control. 

As far as diet wise, there isn't really a Cushing's diet. Go with lower fat content as most Cushing's dogs have livers that are somewhat compromised from the prolong exposure to cortisol. So lowering the fat content makes the liver's job a bit easier. The only supplement I give Sunshade as far as Cushing's is concerned is Denamarin tablets. It has SamE & Silybin (Milk thistle active compound) for liver detoxification and protection.

Good luck to everyone embarking on this journey. Yes, it can be frustrating, yes it can be overwhelming, yes it can be scary for some, but I do believe there will be light at the end of the tunnel if properly managed. Sunshade is a living proof.

Cheers,
Sunshade's mum

Consult with Internist and Oncologist

Hi Everyone, mum taking over. Prepare yourself for loooooooooong and booooooooring..... so sorry...

Love nibbles to all,
Miss Sunshade

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By Sunshade's mum

I took Sunshade down to Seattle on Wednesday, December 1st to see an Internist for her raging Cushing's Disease, as well as an Oncologist for her Soft Tissue Sarcoma. Kathy, a long time blog friend (mother of Jemma the Chihuahua Princess) so graciously offered to come with me for moral support, and back up in case I blank out during the consult. I have been doing things like putting both contact lenses into the same eye, and paying the cashier $40 at the gas station and then driving away without putting any gas in. So blanking out is not out of the norm for me these days. Derek stayed behind to work and look after my Jaffaman!

Many people have asked me why I have chosen to take Sunshade down to Seattle instead of going to our local specialists clinic 20 minutes away. The short answer is I have had one bad experience with them with Sunshade's first orthopedic surgery in 2001, and have heard many unpleasant stories involving them. The other short answer is I have had nothing but good experiences with specialists from three different specialty clinics in Seattle. I personally feel the veterinary expertise and bedside manner in the States are far more superior than most specialists here in British Columbia. Sunshade deserves nothing but the best.

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Cushing's Disease

Our first appointment was with Dr. Matt Vaughan at the Seattle Veterinary Specialists to discuss treatment options for Cushing's disease.

If you remember from our posts before, we were trying to avoid the use of the drugs commonly used to treat Cushings disease due to their potentially deadly side effects. However, we have tried the holistic approach to no avail, and now we need the help of conventional medicine to stop the physical deterioration, as well as the personality changes seen in Sunshade resulted from the uncontrolled Cushing's Disease. (Sunshade: mum says I'm not a b*tch anymore and don't like my beach walks.... What's a b*tch? ) (mum: Go ask Jaffa!)

I had chosen Dr. Vaughan as our Internist because through my research, I found out he had a special interest in endocrinology and spent much of his residency involved in research projects focused on canine Cushing’s disease and Diabetes Mellitus. I was delighted to hear that he was on the UC Davis research team that came up with the latest Cushing's treatment protocol that vets/specialists from all over the world are following. Not only was Dr. Vaughan very knowledgeable, he was also extremely genuine. He listened to my every concern, answered all my questions and came up with a treatment plan for Sunshade.

Don't get me wrong, I am still very wary of starting Sunshade on Trilostane (our chosen drug). However, I do feel much better and much more confident to have an experienced specialist on board with us.

Dr. Vaughan might have sensed my worries, as he wrote me a follow up e-mail that evening to basically reiterate what was said during the consult. To me, this shows a specialist who really cares, and is willing to work and communicate with general vets/owners.

Below is Dr. Vaughan's e-mail as well as his report to Dr. Crook (most of you know her as Auntie Janice LOL...),

Hello Elaine,

It was a pleasure to meet you and Sunshade today, hope you made it home OK.

The trilostane will be started at 30mg twice daily and a recheck ACTH stim test is recommended 1-2 weeks after starting therapy. This test needs to be started 3-4 hours after the morning trilostane dose is given (this is the "peak effect" time). The effectiveness of trilostane is based upon test results, but more importantly on resolution of her symptoms. Please keep an eye on these symptoms (thirst, urination, appetite, energy level) as I will be asking you how they compare to pre-treatment levels.

Things to watch for that would indicate too MUCH trilostane would be a lack of appetite, vomiting, diarrhea, lethargy or collapse. If you note any of these signs, stop giving any more trilostane and if possible have an ACTH stim test performed ASAP. Prednisone can be started at 10mg twice daily if she is very sick, however stopping trilostane is usually enough.

As we discussed, the starting dose of trilostane is fairly low (1 mg/kg twice daily) and will most likely need to be increased. We also need ot make sure that her signs are not actually worsening on the trilostane and if so the plan would be to switch to Lysodren.

Please don't hesitate to contact me by phone or email if you have any questions or concerns regarding Sunshade or if you have any problems obtaining a prescription of trilostane. I have copied a letter to Dr. Crook below for your records.

Take care,
Matt




Dear Dr. Crook,

I saw Sunshade today for evaluation of Cushing’s disease. I did review the recent thoracic radiographs with our radiologist and found no significant changes.

The recent low dose dexamethasone suppression test results and ultrasound findings are consistent with pituitary dependant hyperadrenocorticism. It may be that this began as an increase in cortisol precursors/sex hormones and progressed to involve cortisol, however 40% of dogs with Cushings will have normal cortisol levels on an ACTH stimulation test and so it is possible that this is a variation of "typical" hyperadrenocorticism.

Medical treatment options for the hyperadrenocorticism would include either Lysodren or trilostane. Theoretically, trilostane should (and does) increase some cortisol pre-cursors which can worsen atypical hyperadrenocorticism. That being said, I have had a number of cases that did respond clinically to trilostane despite this. I am also not convinced that this is truly "atypical" hyperadrenocorticism and so I think that a trial of trilostane would be reasonable.

The depressed activity level may be due to elevated cortisol levels or could potentially be related to a pituitary macrotumor. The stumbling may be related to a pituitary mass, however the duration of stumbling signs is quite long (over 1 year) and it would be unusual to not see a more rapid progression of signs if these signs were due to a macrotumor. An MRI could be considered to evaluate the pituitary gland and a recheck neuro consult would be recommended prior to proceeding with an MRI.

The soft tissue sarcoma was not discussed in detail today as there is a pending appointment with an oncologist. I did recommend that if radiation therapy for the sarcoma is considered, an MRI of the brain might be a good idea as a pituitary mass could potentially also benefit from radiation.

The plan is to start trilostane at 30 mg PO BID. This is a relatively low dose and the goal is to slowly increase the dose based upon clinical signs and ACTH stim results (cortisol-only is sufficient). The goal is resolution of clinical signs and a post-stim cortisol between 1-5. An ACTH stim test is recommended 1-2 weeks after starting therapy as well as 1-2 weeks after any dose change. Timing of the ACTH stim test is critical and should be performed 3-4 hours after the morning dose of trilostane. I am more than happy to continue to help with interpretations of lab results and dosage changes if you fax test results to me.

Thank you for the referral. Please let me know if you have any questions or concerns regarding this case.



Sincerely,

Matt Vaughan, DVM, DACVIM

We plan on starting Sunshade on Trilostane on a Sunday. According to Dr. Vaughan, we'd probably see a response before the end of the week and can test during regular veterinary operation days if necessary.

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Cancer - Soft Tissue Sarcoma

Our next appointment was with Dr. Bob Rosenthal at the Animal Cancer Specialists. I had heard many good things about the clinic and Dr. Kari Meleo, the founder of ACC. Unfortunately, she books 3 months in advance. Dr. Rosenthal was new at the cancer center, but not new at practicing oncology and I was very pleased with our appointment.

Just a recap:

November 10th, 2010: jelly bean sized lump removed under local anesthetic from left thoracic region. Biopsy showed Grade 1 Soft Tissue Sarcoma (low mitotic index)

November 17th, 2010: marginal surgery - 3cm X 3 cm skin around the tumour site removed along with some adjacent fat tissue. Pathology showed one plane did not achieve wide margin, all other margins were clear.

I will put the summary of our consult in Q & A format:

Q: Does a successful "clean margin" surgery eliminate the possibility of recurrence?

A: No, clean margin doesn't guarantee no recurrence as we are talking about microscopic level. There will be some residual cancer cells left at the microscopic level.

Q: Does a clean margin surgery reduce the probability of a recurrence?

A: Having a clean margin does technically reduce the recurrence rate by a bit, because you are leaving less cancer cells in. However, it doesn't make a huge difference.

(The answer above was very specific to Sunshade's particular type and grading of the tumour, as well as the fact that all of the margins were clean except one plane. I'm sure the answer would be different if we were talking about a Grade 3 Mast Cell Tumour.)

Q: What is the best method for getting rid of all cancer cells?

A: Radiation is best option to clean up at the microscopic level. The location of Sunshade's tumour site makes it possible to have full range/spectrum radiation without damaging major organs.

Q: How likely is it for Soft Tissue Sarcomas to recur?

A: Recurrence rate to the same site is high due to the locally aggressive nature of this type of tumour. However, the timing for at which a recurrence may happen varies anywhere from 10 days after surgery to months, to years depending on each individual tumour. He told me it is unlikely for Sunshade's particular tumour to return soon given its low mitotic index.

(Janice also talked to the two pathologists that worked on the tissue from the marginal surgery. They gave her an estimate of recurrence at 3-4 years with the dirty margin. Sunshade is 11 right now, 14-15 is very good for an Airedale if I'm being realistic.)

Q: Would the tumour be harder to remove should there be a recurrence?

A: The surgical procedure would yield a bigger wound and the patching job would be a bit tougher as we would be removing yet more skin. However, the removal of the tumour itself should not be more difficult.

Q: If radiation is held off this time around, would future radiation be less effective should the tumour return?

A: Doing radiation the second time around is JUST AS successful as if radiation were performed the first time. It will NOT be less effective at killing the cancer cells.

(Very comforting to learn that.)

Q: Should I choose to have a second margin surgery done, would having a board certified surgeon perform the surgery lead to a higher success rate?

A: The success rate is usually a little higher with board certified surgeons because they tend to be more aggressive. However, it doesn't mean that a general vet practitioner can't be as aggressive.

(He said from the looks of Sunshade's scar, he thought we were being pretty aggressive already given that the tumour was only the size of a jelly bean. So he was sure that the same vet would be just as aggressive with the second surgery.)

In conclusion, Dr. Rosenthal felt that given the type (low metastatic rate, recur at same location) and grading of Sunshade's tumour, radiation is not urgent. While he would recommend radiation for a young dog/healthy dog, he believes Sunshade's Cushing's disease should take priority for now. Great to see an oncologist who is able to look that the whole picture!

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My plan right now is to treat the Cushings, and "maybe" do a second margin surgery given that we know where the dirty margin is (which we think we do as Janice marked the tissue sent in with sutures). I will not pursue radiation for now.

Again, I can't say enough good things about the following specialty centers in Seattle. I would highly recommend them to anyone in WA and Western Canada.

• Animal Surgical Clinic of Seattle (Sunshade's TPLO knee surgeries were done there - great success)
• Seattle Veterinary Specialists (Sunshade's neurology & internal med consultations)
• Animal Cancer Specialists (Sunshade's Soft Tissue Sarcoma consultation)
  

Please continue to keep Miss Sunshade in your thoughts, and cross your fingers (and paws) that we don't run into complications with Cushing's treatment.

Thank you again for being in on the ride with us, you have helped "me" more than words can describe!! I feel so much better now that we have a plan and Sunshade can start getting better. I slept for more than 5 hours last night for the first time in the last 3 weeks. Actually, I slept for 12 hours!

Ear scratches to all your fur-kids,
Sunshade's mum

Labour Day Weekend Day 4 - Neurology Consult

Mum took me to this place after my date with the 4 B's,

She said I was going to see the Stumbling Doctor about my stumbling, (mum: she meant a neurologist.)

I waited patiently in the hoooge waiting area,

When will it be my turn??

Then a nice lady came and took us to a room. She listened to my SuperHEART, and violated my MUSCLE BUTT..... (mum: she had her temperature taken)


The lady told us that the Stumbling Doctor was coming soon. See the drawing of the weird Dog X Snake creature behind me on the white board?


The Stumbling Doctor came in, his name was Dr. Sanders. He was very nice, and he thought I was very funny because I dragged mum's backpack down from the chair and started opening the zipper while he and mum were talking. (mum: there was a small bag of cheese and one boiled egg inside.)

Dr. Sanders and SVS came highly recommended to us. My friend Darwin saw Dr. Sanders when she had an owie back, and my other friend Sam had his owie back surgery at SVS.

Dr. Sanders flipped my toes, hit my knees with a hammer, and looked at my eyes with a bright light. (mum: reflex exam.) Mum had her laptop there to show Dr. Sanders videos of me stumbling. I just waited patiently for the boiled egg and cheese,


Dr. Sanders drew some funny picture on the white board. He said this is a doggie brain, and the purple ball is something bad in the brain. (mum: Pituitary Macroadenoma (type of brain tumor that causes Cushings).)


That's not my brain! I'm sure my SuperBRAIN is prettier than that.

Then he drew an X on the Dog X Snake creature. He said that's where he got an ouchie response from me, (mum: Dr. Sanders got a bit of a pain response from Sunshade at the thoracolumbar/lumbar junction (T13-L1) in the spine.)


I got bored from looking at the drawings and listening to them talk, so I thought I would show them how great my SuperBRAIN was working so they could stop saying how I might have something bad in my SuperBRAIN,


I scored an egg. See, brain working perfectly! (mum: That's Atypical Cushings acting, not normal Sunshade behaviour.....)


Mum and Dr. Sanders talked some more (while I finished the cheese chunks), and then we left the clinic.

(mum: While we were in Seattle, I took Sunshade to see a Neurologist about her stumbling.

Well, the result is inconclusive. Sunshade passed the neurological exam. Dr. Sanders said he couldn't pin point or localize anywhere that he could confidently say ok, this is what's making her stumble. Basically, Sunshade's history didn't really fit with his findings to come up with a firm hypothetical diagnose. He said he could make sense that her lower back pain (probably a chronically herniated disc or DDD) is causing her hind legs to stumble, but couldn't tie that to front end stumbling. At any point on the spine where an injury happens, you would expect functions below that injury point to be affected, not above. The "X" in the picture below is the spot where a pain response was perceived. If Sunshade had a chronically herniated disc in her neck, then the front + back end stumbling could then be explained. Sunshade's neck was fine upon palpation.



Dr. Sanders said he could make sense that a Pituitary Macroadenoma (tumor in the pituitary gland that also causes Atypical Cushings) is causing the front + back stumbling, but usually a dog develops severe neurological symptoms and is gone within a year's time untreated. That puts Sunshade at 4-6 months untreated if she does have a tumour.

The diagram on the bottom shows a normal brain with a normal Pituitary Gland (red arrow). The diagram on the top shows a Pituitary Macroadenoma (purple ball) that's putting pressure on the brain. The blue area is the part of the brain responsible for motor function. A macroadenoma can interfere with the motor function signals causing retardation in the motor function of the patient.



Sunshade was rated normal in the neuro exam performed. Her first stumble happened over 3 years ago, so that didn't really fit the Pituitary Macroadenoma profile - UNLESS the stumbles that happened 2-3 years ago were of a different origin (ie, ortho), then we could say it's of two unrelated sources causing the same symptom (stumbling). In that case, a Pituitary Macroadenoma might still stand. Another possibility is that its a separate brain tumour, unrelated to the Pituitary (Cushings), but that's stretching it a bit.

Dr. Sanders did mention the stumbling could very well be from the built up of the various orthopedic issues that Sunshade has had throughout her life, and at age 11, she's dealing with what naturally (for her) comes with that age. Front end stumbling could just be from an 11 year old with tired biceps muscles from years of over compensating due to the bad elbow. Hind end stumbling from the thoracolumbar/lumbar sacral region of the spine. He must have felt those were the more likely causes as he got his colleague, Dr. Kirkby, an orthopedic specialist to examine Sunshade as well. Dr. Kirkby had similar findings as Dr. Sanders. He also seemed to feel the front end stumbling was due to muscular weakness and aging.

I asked Dr. Sanders if there were tests I should do that would play a factor in Sunshade's longevity. He told me at this point, the only thing he would consider would be an MRI. The MRI would be able to tell us if a Pituitary Macroadenoma is present. If she does indeed have it, then we can do radiation therapy. The success rate for radiation on this type of tumour is apparently very high. The radiation therapy involves 18-25 rounds of radiation over a 3-4 week period. According to Dr. Sanders, dogs treated with radiation therapy are often older dogs, and they go on living anywhere between 2-5+ years of quality life without major neurological problems. Almost all of those dogs pass away from old age or other unrelated illnesses.

11 + 5 = 16 (years), not bad for an Airedale (not nearly enough for Sunshade...). MRI would also give us a better picture at what's going on in her lower back. Dr. Sanders mentioned back surgery could be considered if the pros out weigh the cons, and if I was willing to take the risk since back surgery could make a patient worse than before.

As far as I'm concerned, there will not be any back surgery for Sunshade, doesn't matter what the MRI say. So for me to do an MRI, it would solely be for the possible Pituitary Macroadenoma. But would I be willing to put her thorough 18-25 rounds of radiation therapy? I have no idea at this point.... SIGH..

Here is the full report for anyone that's interested, (click to enlarge)





One thing that had me quite excited from our consult was that, neither Dr. Sanders nor Dr. Kirkby got any pain response from Sunshade's bad right elbow. Some of you might recall, she had the stem-cell replacement procedure done on the bad elbow back in April of this year. Well, I'm so happy to report that the elbow that had been my main source of worry over the last 10 years is now clinically sound, even after days of being active!!! Dr. Sanders was genuinely surprised to find out about Sunshade's bad elbow and the subsequent stem-cell procedure. He said the elbow felt excellent and he was going to tell Dr. Kirkby that the dog he just examined (Sunshade) had a very successful Vet-Stem procedure. Apparently Dr. Kirkby had been wanting to take the Vet-Stem course.

For anyone with a dog/dogs with arthritis, or Elbow/Hip Dysplasia, or torn ACL (repaired or not), Vet-Stem is a great procedure to consider.)

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(mum: I was utterly speechless when I saw what Sunshade had done. To me, that was a whole new level of food obsession. The Atypical Cushings Disease is sending out signals that's making the body think its always being starved. Therefore, Sunshade goes into frantic food scrounging mode.

Sunshade had her chiro + acupuncture appointment on Wednesday. We saw Dr. Gail Jewell first for chiro adjustments. Gail mentioned upon seeing Sunshade that her stomach looked a lot smaller than 2 weeks ago when she saw her last. So that was good news to me although I knew grooming usually makes Sunshade look like she'd shed a ton of weight. After the chiro appointment, I brought Sunshade to be weighed. Surprisingly, she weighed 70 lbs, down from 74 lbs two weeks ago (ideal weight is about 65 lbs). That was excellent news. Then it was time to see Janice for Sunshade's acupuncture treatment. Janice and I usually talk a little bit about life and how Sunshade's been doing before she starts to put needles in Sunshade. The entire time we were talking, Sunshade was opening one of Janice's drawers. The one that the dehydrated liver treats were being kept. Yes she knows its the middle drawer, and she only goes for that drawer. She hooks her nails to the handle and pulls. Maybe I'll take a video next time we go in. Janice, Sunshade's Auntie Janice totally ADORES Sunshade's smarts. So every time Sunshade opened the drawer, Janice would tell her how smart she was followed by a piece of liver treat. Janice and Jen the vet tech TOTALLY spoil Sunshade. She can do no wrong in their eyes. Finally, the first acupuncture needle went in on top of the head, and Sunshade fell asleep (thank you head meridian). Janice felt Sunshade was doing well with the Atypical Cushings because she had a lot of "spunk". However, I wondered if that spunk was actually food obsession.

After our session with Gail and Janice, I brought Sunshade to the natural pet food store next door to get some treats and 4 cans of Tripet canned tripe. I use the Tripet as enticement for Jaffa on his picky days. I also give Sunshade her lemony fish oil in a spoonful of the canned tripe. Since Derek was going to have the kidney stone removal procedure the next day, he needed to drink a lot of fluids. He doesn't like plain water, so I thought I would go to the grocery store quickly to get some juice. Before leaving the car, I took all the treats I had just bought, everything that I thought was rip-able with me. Basically, I carried what looked like a large bag of groceries into a grocery store. I left the 4 cans of Tripet in the car as it never occurred to me that she would go through all that trouble to "find food". I have left cans with her many times before, she never touched them. Anyway, I came out 10 minutes later to her grinning from ear to ear with a can of chewed up Tripet in between her paws. There were bits and pieces of aluminum lying around her.

The first thought that went through my mind was Thank doG I was only a block away from the vet. I thought for sure the inside of her mouth was going to be a bloody mess. Much to my surprise though, there were no cuts on her tongue or gums. No blood visible. WHEW!

So what do I think? Since Sunshade never scrounged for food, never begged like crazy, never counter surfed, never opened cupboards, never chewed through cans until the last few months, I think the Atypical Cushings might be getting worse...... We haven't re-tested her yet because we wanted to allow enough time for the holistic approach to work (if they do work). I'll give it another 3-4 weeks given her symptoms don't get worse, and then retest. The fact that she lost 4 lbs is monumental as dogs with uncontrolled Cushings/Atypical Cushings don't usually lose weight despite the efforts.

It is hard for me to watch Sunshade always feeling and thinking that she's hungry. I can just imagine how much harder this is on her not understanding why she's feeling this way all the time.... Furthermore, I am becoming a little more worried about the extend she goes to find food and doing things that can potentially cause harm to herself. I never needed to worry about things like this with her before. She had always been a very sensible dog, knew what was ok, what wasn't...... SIGH....)

I'm a GENIUS!! + Health Updates

LOOK EVERYBUDDY!!

I've learned to OPEN CUPBOARDS while mum was out!!! It wasn't STINKY, it was alll ME because I'm the GENIUS of the family!!


(mum: Ever since Jaffa's Advil incident, he has been fairly well trained when left alone. He may counter surf once in a blue moon if something really yummy (ie, dehydrated liver treats) has been left on the counter, but never would he go to the extend of causing such catastrophic scene.)

This was the first time in 10 years I've opened a cupboard!! Aren't you proud of me my fellow canines??


(mum: Sunshade has never done anything remotely close to this, not even when she was a pup. I could leave food on the coffee table and she would not touch it. Same thing with garbage left out. However, things are a little different now... I'll explain more later in this post.)

I dragged the garbage out (and devoured everything that was devourable),


Then I dragged the rice bag out. Unfortunately, the rice wasn't cooked and it wasn't too yummy.....


So I moved on to the Ziggies. These were Kong stuffings mum bought when STINKY first arrived, almost 4 years ago. (mum: I don't even want to know what the expiration date was....)


I recall mum mentioning something about how she didn't like the ingredients, so she decided to stop giving them to STINKY. Those treats were basically left forgotten inside the cupboard.

Well, in the times of economic recession, we mustn't waste any foodables,


So, am I a considerate GENIUS or what?

Now, mum is going to post something very very very long & boring below (about me being a Genius opening cupboards). So I thought I would summarize her essay in two sentences for you - Mum says that there is something a little bit wrong with me that causes my body to constantly think I'm starving. The result of that is me searching for food all the time, and begging for food all the time.

*******************************************************************************

(mum: Sunshade has an endocrine disorder called Atypical Cushings Disease. Some of you might be familiar or have heard of "Cushings Disease". Both Cushings and Atypical Cushings are forms of hyperadrenalcorticism (increased activity of the adrenal cortices).

The adrenal glands, one located near each kidney are responsible for the production of the stress hormone - cortisol, as well as the production of other steroid & intermediate sex hormones. The stress hormone Cortisol is a hormone that is necessary for many body processes to occur. It is impossible to live without some form of this type of steroid, either made naturally by the body or given in the form of prescription steroids. However, too much cortisol and/or other steroid hormones circulation in the body over a prolong period of time can cause serious damage to the body and its organs. Secondary illnesses often arise as a result of uncontrolled Cushings/Atypical Cushings.

To differentiate between Cushings and Atypical Cushings:

Cushings (Typical hyperadrenalcorticism): The overproduction of the hormone cortisol from the adrenal glands.

Atypical Cushings (Atypical hyperadrenalcorticism): The overproduction of adrenal steroid hormones other than cortisol (ie, estradiol, androstenedione, progesterone, 17-hydroxyprogesterone, aldosterone).

If your dog is showing all the symptoms of having Cushings, and yet has tested negative for having Cushings, meaning the cortisol level is normal. I would strongly suggest you run a U of Tenn panel to rule out Atypical Cushings. This was the case with Sunshade. Her cortisol had been normal in all of her tests, but her intermediate sex hormones were elevated. U of Tennessee has a huge endocrinology department, and is the only place in the world that runs this particular panel for Atypical Cushings. Dogs from Australia are having their blood sent to U of Tenn!!! Please note, it is possible for a dog with Atypical Cushings to also have elevated cortisol. Right now Sunshade's cortisol level is still within the normal range, but I do see it creeping up compared to tests performed last year and the year before.

Symptoms commonly associated with Cushings/Atypical Cushings Syndrome:

• Polyphagia (increased, excessive appetite) - see photos from earlier in the post ;-)
• Pot belly or distended abdomen


• Muscle wasting resulting in hind end weakness
• Lethargy
• Chronically elevated serum liver enzymes: ALP, ALT, AST
• Enlarged liver
• Enlarged adrenal glands
• PU/PD (excessive urinating; excessive drinking)
• Dilute urine
• Excessive panting, temperature intolerance
• Haircoat problems (baldness, hair loss, hair thinning, discoluration of coat)

• Skin biopsies that indicate presence of an endocrinopathy, such as calcinosis cutis (abnormal calcium deposits in and beneath the skin)

Both typical and atypical Cushings can be caused by either a tumor in the hypothalamic-pituitary area (85-90%) or in the adrenal glands (10-15%), or both. Typical Cushings can also be caused by cortisone medications (ie, Prednisone, Prednisolonde, Dexamethasone, etc) given in excess or over a long period of time.

Sunshade had an ultrasound in March 2009 that showed both her adrenal glands were on the small side of normal, blood panel negative, and she had none of the Cushingoid symptoms listed above at that time.

Looking back, I realized she actually started showing symptoms of having Cushings/Atypical end of last year, early this year. The excessive begging was the first sign. I ignorantly chalked it up to behaviour. She also started to gain weight, 10+ lbs to be exact (from 65 lbs to 75 lbs), and started having a pot-belly or pendulous look to her stomach. Energy decreased, was pretty lethargic most of the time. I again, thought it was due to me giving her lots of treats and table scraps whenever she begged which resulted in the weight gain, hence the lethargy. Then she had her first UTI (Urinary Track Infection) of her life, followed by another one shortly. At the same time of her UTI, she started drinking excessively (normal when having an UTI). However, after her UTI's were resolved, the excessive drinking did not go away. This was when I put 2+2 together and had my vet run an Atypical Cushings test.

After Sunshade tested positive for Atypical Cushings in June 2010, we had another ultrasound done. This time it showed both of her adrenal glands had doubled in size in just a year's time. They were still considered normal because they were small to begin with. However, this confirmed that there was increased adrenal activity, thus the clinical symptoms. Her liver enzymes have become slightly elevated for the very first time in her life as well. Her coat isn't as profuse or healthy looking as usual, and the colouring is off. I know Sunshade has never had the standard blk and tan Airedale colourings, but her coat has always looked thick, healthy to the touch, and quite a bit darker. She usually grows a full coat in 6 weeks time, now her hair is growing slower. We suspected that she was heading towards typical Cushing's with elevated cortisol as well. 

Since both her adrenal glands increased in size synchronously instead of one being bigger than another, adrenal tumor is unlikely. We believe Sunshade's Cushings is either caused by a tumor in the pituitary gland like mentioned above. Most of the pituitary tumors are benign micro-tumors at less than 3mm in diameter. However, if they start to grow and becomes a macro-tumor, on top of the damage that comes with Cushings, they may also start to cause other problems (blindness, incoordination, seizures, neurological problems, etc) due to the pressure on the brain tissue. 

The conventional drugs commonly used to treat Cushings are Lysodren (mitotane) and Vetroyl (Trilostane). Both are *scary* cytotoxic (kills cells) drugs, in the same family as drugs used in chemotherapy. Their function is to kill off layers of the adrenal glands to reduce their ability to produce cortisol and intermediate sex hormones. Both drugs require close monitoring via specialized blood test as well as close observation in changes in behaviour and/or clinical symptoms. When well monitored and controlled, the Cushingoid dog can live a normal life span and be symptom free. However, those cytotoxic drugs can also kill off too much adrenal tissue or even the entire gland that would in term send the Cushingoid dog into life threatening crisis called Addisonian Crisis (little or no cortisols being produced, detrimental to life). Some dogs recover, some don't and they die from not having enough cortisol.

That being said, uncontrolled Cushings/Atypical Cushings will speed up aging as well as creating other secondary illnesses (ie, Diabetes, Chronic Renal Failure, Cataracts, Hypothyroidism, just to name a few). Most dogs with uncontrolled Cushings end up dying from one or more of the secondary illnesses resulted from the Cushings.

Right now we are trying things holistically with Sunshade because both me and my vet hate the idea of giving drugs that eat away at an organ, not to mention the risks involved in using such drugs. While Sunshade does have most of the symptoms listed above, I feel like I have a little bit of time to try out different holistic approaches with her because her condition isn't severe yet. However, should the holistic approach fail, I do believe I need to go the conventional route in order to keep Sunshade comfortable and maintain quality of life.

I hope I'll never have to see those scary drugs...... Please keep Sunshade in your thoughts that the holistic approach will work.

Some links for Cushings Syndrome:

• Canine Cushings Disease
• Canine Atypical Cushings Disease
• Yahoo Canine Cushings Autoimmune Care Group (very informative & experienced group of people who are either dealing with or have dealt with Cushings/Atypical Cushings and related autoimmune illnesses)
• University of Tennessee Endocrinology Department

Lastly, a few updates on Sunshade's hearing and Vet-Stem:

Hearing Update:

Sunshade's hearing isn't back to what it was prior to the tire popping incident, and I doubt it ever will. She still has discomfort in her left ear whenever our vet tries to have a look at the ear drum. The ear drum according to our vet should long be healed. She has no discomfort in the right ear. She can definitely hear, but sometimes not very well. She still seems to have problem locating the direction the sound is coming from. The loss in hearing however doesn't seem to be effecting her at all. In fact, it is actually easier on her during the fireworks/firecracker season. She doesn't get stressed and pant non-stop.

Vet Stem Update:

Sunshade's right elbow, the one problem that has been my biggest source of concern over the last 8 years or so has been doing FABULOUS since the Vet Stem procedure 4 months ago. Like I had mentioned before, she wasn't crippled nor was she in extreme pain in that elbow prior to the procedure. She did get stiff, and would sometimes hobble a little upon rising before walking it off. However, nowadays, she is almost never ever stiff in that elbow, not even after bunny chasing. She rises from her sleep soundly and is able to walk away normally. She has not limped since Vet Stem. She also has full range of motion in that elbow. All in all, I would give her an 11 out of 10 on the elbow.

Another one of the reasons we decided to go with Vet Stem was because Sunshade was having mild neurological problems that was causing her to stumble (hind + front) from time to time. The neurological problem was thought to stem from narrowing of the spinal canal in the Lumbar region of the spine (L4-6). We were told ahead of time by the Vet Stem representative to not hold our breath on the procedure helping neurological problems. Well, it is true, her stumbling did not go away. She is still stumbling. Sunshade's chiro vet feels that the extra weight (10 lbs) Sunshade is carrying in her pot belly due to Cushings is weighing her spine down, and therefore, exacerbating the neurological problem. I do feel like she is stumbling in the front more now, some have resulted in severe face plants. She has also skidded on her wrist a few times due to front end stumbling. Each time causing the wrist to be scrapped raw. So if Cushings is really causing her neurological problem to be worse, that's another reason why we need to get it under control ASAP.

There is another possibility that her stumbling/neuro issue isn't actually caused by the spine, but by a tumor on the pituitary gland that's causing the Cushings. In that case, it might be a growing tumor that's compressing other brain compartments, causing neuro issues at the same time. Drugs for Cushings unfortunately would not help reducing the tumor or the neuro problem. Only an MRI or cat scan will tell if there is a tumor present. I however will not put her under for an MRI/cat-scan since even if the tumor is confirmed, it won't change my course of action.

If you are still with me right now, Thank You! Please keep Sunshade in your thoughts, she has been through so much in her life, and in this past year.

Ear scratches to all the fur babies,
Sunshade's mum)

*UPDATE on Cushing's Disease (March, 2013):

Please note, the above post was written in June 2010, before anything had happened, before cancer hit. 

Sunshade was dx with Cushings in June 2010 (about 10.5 yrs old), but looking back, she had been Cushingnoid for a good 5-6 months prior. She went untreated for almost a year because I was too afraid of the potential deadly side effects from the drugs commonly used to treat Cushings. Then she got diagnosed with cancer in November 2010. We didn't start treating until December 2010. It has been two years since we have been treating Sunshade with Trilostane. I can honestly say looking back at the huge difference it has made in Sunshade's overall wellbeing as well as quality of life that I would NEVER allow Cushing's to go untreated for so long. 

Sunshade went from having mild Cushingnoid symptoms to full blown Cushingnoid symptoms. All her personality (what you see now) was GONE towards the end of that untreated year! She was a "Sunshade shell" that wanted food and that was it. Everything that made her "Sunshade" was no longer there anymore. I would take her to her favourite park, and she would just stand there and refuse to walk. A squirrel would run by, no reaction. A dog would jump on me, or try to get attention from me with her standing right next to me, no reaction. She is normally quite possessive/protective of me, and  would growl her way to keep the dogs away from me. People running towards me at night, no reaction (would normally run up to block them from coming straight towards me). She didn't care for unneutered boy dogs, and NO HUMPING horsie/fat rat (*gasp* can you believe it!!). The Sunshade sparkle was gone. Light was out from those beautiful eyes. It broke my heart. That was when I realized I needed to take the plunge and start her on meds because I was losing my girl already. Two weeks after I finally decided to start treatment, she was diagnosed with cancer (November 2010), so we had to deal with that first. When cancer came, there was no other choice but to treat Cushings if we wanted to win the cancer battle. Prolonged steroid exposure to the body greatly compromises the immune system. Lots of things can go wrong when the immune system is compromised, including cancer. 

This was Sunshade at the peak of her untreated Cushing's. I took her to a place she had never been before, and she did this. The normal Sunshade would have loved to explore new places being the curious girl that has always been, and is today. Notice the muscle loss, pot belly, thinned out coat (and she has a sheepcoat!!)

Once treatment started, I began to see little glimpses of my girl returning. It took quite a few months to get to the correct dosage. When she was fully controlled, my bossy, flirty, protective, loyal girl was back!! Now at 13.5, she is just as bossy as she was in her prime, still keeping the pups in check anytime  and every time. Pictures below were taken in November 2012, on her 13th birthday. Notice the thick coat, dark colouring, well muscled, svelte waisted, happy girl with light and mischief in her eyes? She has also lost over 10 lbs, and is back to her optimum weight of 62 lbs. 

Cushing's Diseases causes elevation in liver enzymes due to the prolong "steroid" exposure. Sunshade's liver enzymes were off the charts, as in, in the thousands when I left it untreated for a year. As soon as we got control, the liver enzymes came all the way down. Cushing's Disease also digests muscle mass, so it makes the dog lose muscle tone, which in turn exacerbates existing orthopedic problems and/or make the dog look a lot older than he/she is. 

One thing I have to mention is that once we were beginning to get control of Cushing's, Sunshade's arthritis pain became more noticeable. This meant we had to up her supplements, more frequent acupuncture/laser treatments, etc. Some dogs may even need to go on opiate pain control meds or NSAID's. 

There are a few different forms of Cushings disease. Pituitary dependent Cushing's, adrenal dependent Cushing's, and iatrogenic Cushing's. Iatrogenic Cushing's is usually caused by steroid use, so by removing the steroid agent, the Cushing's should resolve. 

Usually with Cushing's, you need two positive tests to confirm it. The cheapest, easiest test I think is the Urine Cortisol to Creatinine ratio test. If that's positive, you can either run a LDDS (Low Dose Dexamethesone Stimulation) or ACTH Stimulation test. The LDDS will most likely be able to tell you whether the Cushing's is pituitary dependent or adrenal dependent (two different types, different treatment plans). ACTH tells you whether there is an increase in adrenal activity. If both of those tests come out negative, you can then test for Atypical Cushing's. Sunshade was Atypical for a year before she turned typical. 

Good luck to everyone embarking on this journey. Yes, it can be frustrating, yes it can be overwhelming, yes it can be scary for some, but I do believe there will be light at the end of the tunnel. Sunshade is a living proof. Please don't hesitate to contact me via e-mail below if you have any questions. 

Sendittoelaineplease@gmail.com

Cheers,

Sunshade's mum