CUSHING’S SYNDROME

THE “COMMON” DRUG THERAPIES

 

This month my article will focus mainly on the “common drug therapies” used for treating a dog with Cushing’s Syndrome.  Before starting Boomer on a course of treatment, I did extensive research into each drug that was available, the protocol for administration, the side effects, the warnings, and the dangers that sometimes accompany  “chemotherapy”.  

 

Below is what I discovered:

 L-Deprenyl (Anipryl)

This drug is sometimes considered first in the treatment of PD Cushing’s.  It has been show to only work for PD Cushing’s cases.  It is used for Parkinson’s disease in people and is also used to treat canine cognitive dysfunctions (CD).  In fact, a few of my friends had used this drug on their older goldens with canine cognitive dysfunction and did have success.  Another nice thing about this drug is that if your dog is elderly when diagnosed with Cushing’s, you may be able to successfully treat two diseases with ONE medication!!

Anipryl affects the hypothalamus and its interaction with the pituitary gland in relation to a chemical called dopamine.  There are minimal side effects.  Many dog owners who belonged to one of the various Cushing’s listservs that I had joined when Boomer was first diagnosed substantiated low to no side effects.  Unlike the other drugs used to treat PD Cushing’s, ACTH testing is of no value to monitor effectiveness.  The drug does not act on either the pituitary or the adrenal gland. 

The recommended dosage is given daily for 2 months.  If the symptoms don’t diminish within that time period, the dose is increased.  The majority of PD Cushing’s dogs will show improvement within the first 2 months.  If after an increase in dosage, there is still no improvement, then other illnesses need to be considered.  If other illnesses/diseases are not found, then other drug therapy should be instituted. 

A word of caution:  Anipryl should not be used if your dog is being treated for Demodex with Mitaban or with antidepressant medications or Prozac.

The most commonly used drug therapy used in the United States for dogs diagnosed with Cushing’s Syndrome is:

Mitotane (o,p’-DDD)

The trade name or name by which it is most familiar is Lysodren.  Lysodren works to control Cushing’s by  selectively destroying the zona fasciculate and reticularis, effectively limiting the amount of cortisol that these areas of the adrenal gland can secrete.  It should be administered with meals to enhance its absorption. This drug requires what is known as a “loading dose” for 7 – 10 days.

Side effects are NOT uncommon and may include:

·         lethargy

·         vomiting

·         diarrhea

·         anorexia (lack of appetite)

·         weakness

·         ataxia (incoordination)

The side effects are due to the cortisol level being reduced BELOW the normal levels.  Even when the cortisol levels do not go below “normal levels”, the rapid decease in the once “elevated cortisol levels” to the “normal range” can still cause the symptoms listed above.

It is imperative that you keep an eye on your dog for any of the side effects mentioned, when using the Mitotane therapy. If any of them should occur it is extremely important to immediately stop administering the medication and get in touch with your veterinarian. Most vets will also prescribe prednisone to have on hand at home, should the side effects be significant.

After the 7-10 days of “loading”, the cortisol levels are assessed with the ACTH stimulation test.  You will be instructed to not give your pet any supplemental cortisone on the day of testing.  If the pre and post cortisol levels come in “normal”, then a “weekly” Mitotane maintenance dose is prescribed and occasional ACTH stimulation tests are recommended by most veterinarians to ensure the cortisol levels are staying within the “normal” range.   

Unfortunately, two long-term effects can occur while on Mitotane maintenance therapy:

The drug can be so effective that the adrenal glands stop producing enough cortisol for normal physiology.  This is call iatrogenic hypoadrenocorticism.  When this occurs, all Mitotane therapy is stopped and supplemental prednisone is administered.  This side effect can be permanent and you’re your dog will need to be on supplemental prednisone the rest of his or her life. 

The second side effect is for a “relapse” to occur within 12 months, even while on the maintenance therapy.  Another “loading” dose is required, then a conversion to a maintenance dose when it is ascertained that the cortisol levels are again normal through the ACTH stimulation test.

Because of the side effects, the importance of continual monitoring of your dog must be emphasized!  This means close observation at home for clinical signs and ACTH stimulation tests every 3 to 6months.

Ketaconazole

Routinely used to control fungal infections.  This drug inhibits the production of cortisol in dogs and humans by preventing enzyme pathways from functioning properly.  It is prescribed for both PD and AT Cushing’s.  It is not as commonly prescribed as the previous 2 drugs.

A test dose is initially given with the owner told to watch for anorexia and/or vomiting. If tolerated, a “loading” dose is given for 7 – 10 days, after which an ACTH Stimulation test is performed.  If the cortisol is determined to be in the “normal” range, the drug is given every 12 hours for the rest of the dog’s life. 

I was not able to find much information on side effects, as this drug is not widely used in the United States . 

 
Surgery

Surgery to remove both adrenal glands can also be used.  It is an involved endeavor and should be performed by a specialized surgical hospital.  Post operative complications are common, and these dogs need lifetime prednisone replacement therapy.  As a result, this treatment is not commonly utilized.

Radiation
If after the initiation of the above therapies, symptoms of PD Cushing’s reoccur, this might be an indication of a large pituitary tumor.  An MRI might be recommended to identify this type of tumor and radiation may be recommended to prevent further progression of symptoms.  Unfortunately, radiation specialty centers that can perform this procedure are not widely available.

Iatrogenic Cushing’s (a/k/a drug induced)

This type of Cushing’s is the easiest to treat!  No medication is necessary; however, the “removal” of one is!  In most cases the elimination of exogenous cortisone will return your dog to normal function.  However, this may take several months and some of the skin changes associated with Cushing’s may take longer.  Some skin conditions may never correct themselves or return to a total normal state.  In some cases, your veterinarian may use a decreasing dose of supplemental prednisone for several weeks to give the adrenal glands time to resume to normal cortisol production.

Adrenal Tumor (AT)

Should your dog be diagnosed with AT Cushing’s, most likely he/she will require surgery.  The surgery to remove the cancerous adrenal gland is called an adrenalectomy.  It is a specialized surgery that is not routinely performed.  Post operative complications may occur and are somewhat common.

Due to the remaining adrenal gland being atrophied, the dog will need to be supplemented with prednisone until that gland returns to normal function.  ACTH stimulation tests are done every few months to determine when the gland is functioning normally again.  It can take up to 12 months for this gland to return to its normal functioning process.   

It should also be noted that adrenal tumors can be treated with Mitotane at high doses and for a long period of time.  Side effects are again common at this dose and, relapses may and can occur.  Dogs will also need to be supplemented with prednisone for the rest of their lives.

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Due to the length of this month’s article, I have decided to wait until next month to discuss the drug therapy I am using to treat Boomer.  It deserves the entire article!!  Let’s just say…I am extremely pleased with its results…and so is Boomer!! 

As always, the above information is based on my personal research and first hand experience with my golden retrievers.  My reference for the medical/technical information for this article is: http://www.lbah.com/Canine/cushings.htm.

I can be reached at boomer@trianglenet.net

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