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

Laser Treatment

Well, I am getting better and better everyday. Mum took me to see my Auntie Gail today to have my back adjusted. I had been very sore everywhere since the ER clinic, so a chiropratic adjustment was in order. Then I had to wait for my turn for Auntie Gail's hubby to do laser treatment on me.

I waited with mum, and thought I would play a game of tug with her,


That's a bag of tripe treats I was tugging btw!


My turn to use the SuperCOOL Laser Machine!! It increases cellular activity, which in turn will reduce inflammation and promote healing. You have to enter the weight, hair type in the machine for it to calibrate,


We used it on my wound first to reduce the inflammation,

Then we worked on my sore shoulders and sore back. I could feel the heat penetrating, and it was very relaxing....


I felt really good after the treatment. Once we got home, I told mum to FEEEEEED me!


Yogurt just doesn't cut it any more!!

Roade to Recovery from Sepsis

THANK YOU friends for all your e-mails, phone calls, Facebook messages to me and mum. All the prayers and healing thoughts have helped me recover, but I think they've helped mum more, and I thank you for that!

Now I just want to keep you updated on my recovery since I know not everyone is on Facebook. I know a lot of you care about the SuperDALE, so I am going to keep you in the loop!!

TUESDAY:

MY vet clinic opened on the Tuesday following the Bun Bun long weekend. Mum rushed me in first thing in the morning to get checked by Auntie Sue, my other vet.

Before leaving though, I told mum that she should really serve me breakie in bean bag. I had just started eating the night before, so I don't think breakie in bean bag is too unreasonable of a request.

Ready to eat NOW!


Yum Rotisserie chicken,


Chop chop, I don't have all morning, Auntie Sue and Auntie Jen are waiting for me!


That's more like it!


Now go get me a straw for that chicken juice,


When I arrived at the clinic, the first thing Auntie Sue said to mum was "poor baby, she's really not feeling well is she?". She checked me all over and she said my elbows, my shoulders, my back were all so SuperSORE, and I still had a low grade fever, so she went all out with her acupuncture needles to try to make me feel all better.



She said it should bring my fever down too,


Auntie Kate, my other vet tech came to hook me up to IV to continue my fluid therapy. (mum: She was being pumped full of sedative at the ER, we were trying to help flush her organs out. The vet, and all the techs were all furious at the use of Acepromazin on Sunshade, and the way she was dosed.)


At around lunch time, mum thought all my wonderful Aunties deserve some treats,


While mum went to buy treats, MY Auntie Jen sat with me,


Mum bought me an eggie for lunch,


I ate it and mum was happy,


(mum: This was the update I put on Facebook for Tuesday (04-10-12):

As many of you know, I brought Sunshade in to our own vet clinic to have her examined and evaluated by Sue, the attending vet at our clinic. Other than Jen and me, everyone else at the clinic thought Sunshade looked pretty out of it. She was walking, but very gimpy. She was looking around, but not woofing and bossy like her normal self. So Sue freaked out a little bit, she didn't expect Sunshade to be this weak. The receptionist also came up to me and tentatively asked "so she is looking good???". To them, the way Sunshade looked was so much weaker/worse than how she is normally. Only Jen and I knew Sunshade was actually "improving" given the condition she was in prior to today.

Sunshade had been having a low grade fever (39.4ish) for the last day or so. When Sue did acupuncture on Sunshade today, she did a point that would help with fever. Prior to acup treatment, Sunshade was at 39.4. Three hours after Sunshade's acupuncture treatment, her temperature was back to normal at 38.8!! She wasn't on anything other than IV.

We stayed at the clinic until 5pm. Sue sent us home with another liter of fluids to get into Sunshade. She also wants to recheck Sunshade tomorrow (Wednesday), once she gets all the blood results back from today.

I just took Sunshade's temperature, and she is holding steady at just under 39. Normal is 38-39. Hopefully, there will be yet more improvement tomorrow!

She ate breakfast, lunch, dinner no problem. Had a stool that was a bit soft.

While I was at agility with Jaffa, Sunshade apparently walked D-Guy to Bosley's pet store again. Unfortunately, they were closed and we had one disappointed girrrrlie. It's great that she's feeling well enough to walk :-)

THANK YOU for continuing to pray for Sunshade. She will come around, i know it!!)

WEDNESDAY:

I ate my breakie and we headed out the door to go see my Auntie Jen and Auntie Sue again. Before leaving, I grabbed a rockie on my way down!!


(mum: Another GOOD sign - she grabbed a rock on her way down the ramp when we left the house to go to the vet!!!

All those rocks lined up on the rails were hand picked by Sunshade from various places. She would carry them back to the car and well....yes I put them in the car... Just don't have the heart to not bring them home with us lol.....

Anyway, her ritual is that everytime she walks down that ramp, she has to grab a rock on the way down. A lot of the times she would just chill in the yard with a desirable rock in front of her, or she would drop it on the way out the gate to go for a walk. Every few days she would run out of rocks to take and I have to go hunt down every single rock and put them back ob the rails.

She stopped doing that when she got sick, didn't do it yesterday, but did it just now!!!! Very happy :-))

Once we arrived at MY clinic, I had a talk with my Auntie Jen. I LOVE my Auntie Jen!!!

I was hooked on IV again,


I told mum that since I've been soooo SuperPERFECT....


I really should get a big treat!!


Starbucks Oat Bar all gone.....


By the end of the day, I was doing so SuperAWESOME that my catheter was able to finally came out!!



Auntie Jen giving me a nice face rub for being soooooo good,



No more home IV means no more x-pen means I get to sleep on the big bed!!


(mum: Facebook update for Wednesday (04-11-12):

Sunshade and I came home not long ago from another day at our vet clinic. Sunshade had one last day of IV before the catheter came out. All her blood results are excellent. Kidneys and liver functions were fantabulous. She had another acupuncture session since the session she had yesterday helped so much. Like I had said before, the low grade fever that she had had for the last couple of days went away within three hours of the acupuncture session. Her sore joints were moving so much better. The leg swelling was completely gone too by the end of the day yesterday.

The wound is healing well from the inside out. However, Sue decided that with an infection that went systemic, she would like Sunshade to be on another 7 days of antibiotics on top of what the ER had prescribed. Sue is a holistic vet, when a holistic vet is pumping your dog with antibiotics, you know how serious the condition is. Our clinic finally had to get the wound Culture & Sensitivity report directly from the lab because the ER never sent us the report even though we had asked for it. Then report came back showing that the bug was sensitive to both of the antibiotics that were prescribed by the ER. This meant that Sunshade really only needed to be on one antibiotic. So once she's finished this 7 day round, we will drop one of the abx to make things easier for her tummy and continue with the other one for at least 7 days. Will need to be re-evaluated then to see if more is needed.

Sunshade was cheeky as ever at the clinic today :-) She was sticking her head in between the staffs' legs to demand ear rubs, and then onto all the different treat drawers throughout the clinic, barks in front of them until someone comes and FEEDS her! Physically, she still isn't 100% yet, but mentally, she is pretty darn close!

I will continue to update Sunshade's wound progress, but I imagine the updates won't come nearly as frequent as it had been over the last 6 days. I am looking forward to catching up on some sleep, and of course, catch up with the rest of you :-)

Thank you again to my big FAMILY (including all you blog readers too) for coming back day after day for updates, and sending prayers, love, and healing thoughts to us. I think most of you have realized that we have something truly special going on here, and I'm so grateful to be the beneficiary this time. I know I would do the same for other family members if and when they are needing the support. ((((BIG GROUP HUG))) )

THURSDAY:

Auntie Helen came to visit me, CAN YOU BELIEVE IT?? (look at my face)


Helen does Reiki, so she came to do Reiki on me to make me feel better. I said how about a treat first? Look at my SuperPAW on Helen's leggie!


She said no, and I said YEAH!!


And I WON,


While Helen was treating, I asked Helen's son Shawn if he wanted to try and take MY Truman away?


Mum decided to see if I would eat some food since I didn't really want to eat anything today.

Surrrrrrre I'll take spoon feeding!


Then I took over,


And finished the entire bowl!!!


After eating, I did what a true lady would do following a meal, I wiped my SuperMOUTH!



(mum: Facebook update Thursday (04-12-12):

Well, Sunshade had a hard night last night. Not sure why. She kept waking up every hour, hour and a half panting and whining. Every time she did that, I would take her out to the yard to pee, and then bring her back in to settle her down. Same thing would start again an hour or so after. I took her temperature the second time it happened, and it was 38.9, which is borderline normal, but still normal. She also drank a ton of water in the middle of the night too, which was VERY unusual. She's never drinks any water in the middle of the night!

Morning came, she didn't want to eat the special cooked food that she normally would go nuts for. She ate it fine last night after coming home from the vet. Tried giving her some of her favourite treats, turned most of them down with the exception of a small piece of dehydrated liver. Took her temp again, it was still 38.9. Checked her wound, looked great, wasn't more red or warmer.

Called our clinic to give them an update. Jen, our tech called me back to say to put her back on pain meds. We had taken her off them all day yesterday because she was feeling and acting so bright. She and the vet Sue wondered if Sunshade's body was adjusting to not having IV to help flush everything. She had been on IV for 6 days. Maybe weaning her off the IV would have been a bit better. Anyway, Jen told me to keep taking her temperature, give her the pain meds, keep an eye on the wound, and lots of rest. Before we hung up, she told me "You've got my number at home, and I'm not going anywere!"... poor Jen.....

In the evening, my friend Helen, who is a Reiki practitioner came over to give Sunshade a treatment. Just before Helen arrived, I offered Sunshade some food, she turned it down. As soon as Helen walked in the door, Sunshade started throwing her Truman (dale stuffy) around, went to treat drawer to bark for treats. Mid-way through treatment, I offered her food again, and she started eating it off the spoon. Then she licked the bowl clean, and went to wipe her face along the doggie bed after she was done eating. All of a sudden her energy and appetite was back upon seeing Helen?? Maybe she was just so bored and tired of me and being stuck at home with me???

I took her out to the yard for a pee just earlier, and she walked me to her hole and started digging. Of course, that meant she had to get a rinse down!)