Friday, March 29, 2013

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,

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.

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.


Sunshade's mum


Duke said...

What a very informative article! Thank you so much, Miss Elaine!
We are thrilled that you are back to being the superfun girlie that we all know and love, Sunshade!

Love ya lots,
Mitch and Molly

My Dog Sam - Ruptured Disk said...

Hi E: wow that's some post on Cushing's. This post goes to prove that you should consider becoming a vet. Maybe Janice is right.

Duke said...

Happy Easter, Elaine, Sunshade and Jaffa!

Love ya lots,
Mitch, Molly and Sue

Anonymous said...

Hi! Thanks so much for this post on Cushings! You've given all of us who have a dog diagnosed with this curious disease hope that with the right meds it can be controlled. I live in Victoria:) My 10yr-old Aussie Smudge is now entering week 4 on Vetoryl. So far so good!!!

Kera @ Nugget On A Budget said...

This article has giving me much more insight on what I think my own dog has. He has all of the signs, but they only started to really be shown this morning. I've been at our vet twice today, and after $400 they couldn't give me a diagnosis of anything and sent me home with a pain reliever and an anti-inflammatory. Our dog, Dallas, is 3 years old and recently was diagnosed with an auto-immune skin disease, that we are currently treating with antibiotics and steroids, both oral and topical. After reading your article, I'm convinced Dallas has Cushings, brought on by the prolonged exposure to the steroids. He has been restless ALL day, and will not sit or lie down while at our house. He did sit and lie down while at the vet's and during the car ride, however. He eats fine but is just not his usual self. He is like that "shell" of himself that you described. I'm not sure what to do. Our vet did run x-rays but no blood work. And I'm not sure how the meds that he may have to be on for Cushings {if that's what he has} will go with the meds he's taking for his auto-immune disease.