Cushing's - Treatment

Many of you who are reading this may have heard or read the statement that a Cushing's dog lives only about 2 years after diagnosis, and some of you may have even heard that the 2-year prognosis is with or without treatment. Well, we're here to tell you that it's not really true. We know of many dogs who have lived 5, 6, 7 years or more after having been diagnosed with Cushing's. And here's why the 2-year prognosis is not really correct as pertains to all Cushing's dogs.

Although it may have been an accurate statistic when arrived at some years ago, we have to remember that it is just a statistic, an AVERAGE which is based on data collected from a fairly small group of dogs who were diagnosed with Cushing's Disease (Hyperadrenocorticism).

We must also remember that most Cushing's dogs are already quite "senior" by the time they are diagnosed, and many would not have lived much longer than 2 more years even if they did not have Cushing's or any other health issues.

The data on which the 2-year prognosis is based also includes:

• Some dogs who were not treated at all for the Cushing's Disease
• Some dogs who may have been diagnosed and treated by inexperienced Vets or Vets who were perhaps too conservative in their treatment of the dogs and never really got the dogs' Cushing's well-controlled
• Some owners who quit treatment at the first sign that the dog didn't feel well (when it may have been only a dose adjustment that was needed to get the dog feeling well again and to maintain good control of cortisol production)
• Some owners who were not observant or not diligent about giving the prescribed medication and/or were not having the dog monitored as recommended with periodic ACTH stim testing to check cortisol production and to know for certain if or when dose adjustments might be needed etc.
• Some dogs who were diagnosed only by the time the Cushing's was quite advanced and by then some irreversible organ damage (liver, kidneys, heart etc) may have already occurred

When you take scenarios like the above-mentioned ones into consideration and add that data all together with the available data on the Cushing's dogs who are successfully treated and have successful outcomes, many of whom live 5, 6, 7 years or more after diagnosis with an excellent quality of life, well, you may actually get an AVERAGE 2-year prognosis, but that does not mean that a dog who is correctly diagnosed and treated for Cushing's will only live 2 more years from the time of diagnosis.

That statistic is only an "average" and we must remember what data that average is based on.

The statistic includes, for various reasons as described above, some dogs who lived only a few months after diagnosis as well as dogs who lived many years after diagnosis.

There are quite a few excellent websites about Canine Cushing's but many do throw in that "2-year" prognosis statistic without explaining how it was arrived at ... nor do they qualify that statistic by explaining that it does NOT mean that every Cushing's dog diagnosed will probably only live another 2 years.

When correctly diagnosed and treated by a knowledgeable Vet who has experience in successfully treating and managing dogs with Cushing's, a Cushing's dog can live out a normal lifespan with an excellent quality of life.

Here is a link to some photos of a beautiful dog named Cleo, taken "before and after treatment with Lysodren".

Cleo can be an inspiration to us all and these photos can give hope to folks who are just learning that their dogs have Cushing's and who are wondering if treatment can really help.

It is my understanding that Cleo was not diagnosed early, but she did do very well on Lysodren after treatment began. A picture is worth a thousand words and in these photos you can actually see the huge difference in Cleo's appearance before and after treatment.

Go take a look at beautiful Cleo and you'll see what a difference treatment with Lysodren can make, even for a dog who is already in poor shape at the time of diagnosis.

http://web.archive.org/web/200805091...eo-alison.html

http://packageinserts.bms.com/pi/pi_lysodren.pdf

Also see here for Lysodren product information:

https://www.sunnysidevetclinic.com/cushing

https://vcahospitals.com/know-your-pet/mitotane (describing Lysodren)

GENERAL GUILDELINES FOR ACTH RESPONSE TESTING

1. Monitoring Lysodren therapy: ACTH stimulation testing is recommended after the initial induction period (7-10 d of daily Lysodren). If additional induction phases are required, an ACTH stimulation should be done at the end of each phase. Once the dog is on maintenance, an ACTH stimulation should be done 3 months and 6 months later. Periodic retests at 6 month intervals are recommended, if the patient is responding well to treatment (earlier if not).

2. Monitoring ketoconazole therapy: The initial dose of ketoconazole is 5 mg/kg bid for 7 days. If there are no adverse effects, the dose is increased to 10 mg/kg bid and an ACTH stimulation should be done after 14 days. If cortisol levels are not within the ideal range, the dose should be increased to 15 mg/kg and an ACTH stimulation again done after 14 additional days. The ACTH stimulation test should begin within 1-3 hours of the last dose of ketoconazole.

3. "Ideal" values: in a Cushings dog receiving either Lysodren or ketoconazole are pre-ACTH cortisol, 30-100 nmol/L and post-ACTH cortisol, 30-110 nmol/L. In other words, we like to see measurable cortisol levels which do not rise above 110 nmol/L after ACTH.
Interpretation of specific results with the ACTH stimulation test during therapy with Lysodren

At completion of induction therapy (daily loading therapy):

1. If both cortisols (pre and post ACTH) are between 30 and 110 nmol/L, go to maintenance therapy.

2. If both cortisols (pre and post ACTH) are above 110 nmol/L, continue daily Lysodren and repeat ACTH stimulation in 5 days. Continue daily therapy until cortisols are between 30 and 110 nmol/L.

3. If both cortisols (pre and post ACTH) are below 30 nmol/L, stop Lysodren, wait 3 weeks, retest with ACTH stimulation and start maintenance when cortisols increase into 30-110 nmol/L range. Dog may require glucocorticoid supplementation, especially if stressed. Also, monitor Na/K to see if Addisons is present.

During maintenance therapy:

1. If both cortisols (pre and post ACTH) are between 30 and 110 nmol/L, continue as is.

2. If both cortisols (pre and post ACTH) are below 30 nmol/L, stop Lysodren, retest with ACTH stimulation at 3-4 week intervals until cortisols increase into 30-110 nmol/L range, then resume maintenance. Dog may require glucocorticoid supplementation, especially if stressed. Also, monitor Na/K to see if Addisons is present.

3. If both cortisols (pre and post ACTH) are well above 110 nmol/L, re-initiate loading Lysodren at 50 mg/kg on a daily basis for 5 days. Retest with ACTH stimulation after 5 days to see if cortisols have dropped, and continue daily Lysodren until they do. Once cortisols are between 30 and 110 nmol/L, restart weekly maintenance at a dose 50% above that used previously.

4. If both cortisols (pre and post ACTH) are slightly above 110 nmol/L, increase weekly Lysodren dose by 25% and retest with ACTH stimulation in 4-6 weeks.
[/QUOTE]

From the proceedings of the Italian Association of Companion Animal Veterinarians at the Congresso Nazionale Multisala SCIVAC, 2005, Rimini, Italia

Follow the links below to access the excerpts from various proceedings.

Auburn University College of Veterinary Medicine
Endocrine Diagnostic Service
Cushing's Therapy Recommendations

Guidelines for monitoring Lysodren (or ketoconazole) with ACTH Stimulation Response Testing

(Previously posted at the old Auburn site, no longer online. Now this treatment guideline is back online and just slightly revised from the guidelines which were posted on their old webpage)

http://web.archive.org/web/200609041...mendations.pdf

Quote:

---

Auburn Endocrine Diagnostic Service
ACTH Response Testing in Dogs with Cushing’s Disease

Periodic ACTH response testing is recommended in all dogs with Cushing’s disease treated with either lysodren or ketoconazole.

General guidelines for ACTH Response Testing

1. ACTH response testing is recommended after the initial induction period (7-10 days of daily lysodren), then 3 months, and 6 months later. Periodic retests at 6 months intervals are recommended, if the patient is responding well to treatment (earlier if not).

2. “Ideal” values in a Cushing’s dog receiving either lysodren or ketoconazole are pre-ACTH cortisol, 30-110 nmol/L; post-ACTH cortisol, 30-110 nmol/L. In other words, we like to see measurable cortisol levels which do not rise above 110 nmol/L after ACTH.

Interpretation of Specific Results With the ACTH Response Test (circled number indicates recommendation).

At completion of induction therapy (daily loading therapy):

1. Both cortisols are between 30-110 nmol/L; go to maintenance therapy.

2. Cortisols are above 110 nmol/L; continue daily lysodren and repeat ACTH response in 5 days. Continue daily therapy until cortisols are between 30-110.

*3. Cortisols are below 30 nmol/L; stop lysodren, wait 3 weeks, retest with ACTH, start maintenance lysodren when cortisols increase into 30-110 nmol/L range.

During maintenance therapy:

1. Cortisols are between 30-110 nmol/L; continue as is.

*2. Cortisols are below 30 nmol/L; stop lysodren, retest with ACTH at 3-4 week intervals until cortisols increase to 30-110 nmol/L range, then resume maintenance.

3. Cortisols well above 110 nmol/L; re-initiate loading lysodren at 50 mg/kg on a daily basis for 5 days. Retest with ACTH after 5 days to see if cortisols have dropped, and continue daily lysodren until they do. Once cortisols have dropped into “ideal” range, restart maintenance (weekly) therapy, but increase dose 50% above that used previously.

4. Cortisols only slightly above 30-110 nmol/L; increase weekly lysodren dose by 25%, retest with ACTH in 4-6 weeks.

*Dog may require glucocorticoid supplement, especially if stressed. Also, monitor Na/K to see if Addison’s has occurred

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.
Test values conversion - please note: The values of measurement used in the Auburn guidelines (nmol/L) are the units of measure commonly used in Canada and the UK and in most other countries in the world, but for the folks in the USA and any other countries where ACTH stimulation test results are given in ug/dl values, here's how to convert nmol/L to ug/dl:

Simply divide nmol/L by 27.59 and that gives you the value in ug/dl

examples:

30 nmol/L = 1.09 ug/dl

110 nmol/L = 3.99 ug/dl

Canine Cushing’s Syndrome: Diagnosis and Treatment
Rhett Nichols, DVM, ACVIM

Part 1: Typical, Atypical, and Pseudo-Cushing’s Disease

Part 2: Medical Treatment of Cushing’s Disease

Attachment 473

Medical Management of Pituitary-Dependent Hyperadrenocorticism: Mitotane versus Trilostane
Nyssa J. Reine, DVM, ACVIM (Internal Medicine)

Pituitary-dependent hyperadrenocorticism is a common endocrine disorder in dogs in the United States. Once a diagnosis is established, a decision must be made whether or not to pursue treatment, and if so, which medication to use. Historically, mitotane (Lysodren, o,p’-DDD, Bristol-Myers Squibb, New York) has been the most commonly used treatment for medical management. Its use is complicated and comes with many potential side effects, making many practitioners wary of its use. Recently, trilostane has been proven to be an effective treatment of pituitary-dependent hyperadrenocorticism and is approved for use in other countries. Treatment with trilostane is somewhat simpler and the incidence of side effects seems to be less when compared with mitotane therapy. Either treatment can be a safe and effective method of treatment for pituitary-dependent hyperadrenocorticism when the practitioner and client are well educated regarding their use and an appropriate monitoring protocol is used.

ACTH stimulation test
https://www.idexx.es/files/cortisol-...n-protocol.pdf

Low Dose Dexamethasone Suppression test:
https://www.idexx.co.uk/files/low-do...t-protocol.pdf

High Dose Dexamethasone suppression test:
https://www.idexx.co.uk/files/high-d...t-protocol.pdf

IDEXX Lysodren dosing/monitoring flow chart (on page 4)
https://www.idexx.com/files/snap-cor...g-guide-en.pdf

Trilostane: A therapeutic consideration for canine hyperadrenocorticism
Audrey K. Cook, BVM&S, MRCVS, DACVIM, DECVIM-CA

February 2008 issue Veterinary Medicine "nxtbook" version:
http://www.nxtbook.com/nxtbooks/advanstar/vm0208/

The article starts on page 104 in the above "nxtbook" version

Or, the same article in regular format, here:
http://veterinarymedicine.dvm360.com....jsp?id=491107

Comparing therapies for canine hyperadrenocorticism
By: Johnny D. Hoskins, DVM, PhD, Dipl. ACVIM
DVM Newsmagazine, Oct 1, 2007

page 1 of DVM Newsmagazine article:
http://www.dvmnews.com/dvm/Small+ani.../detail/460965

or http://veterinarynews.dvm360.com/dvm.../detail/460965

page 2 of DVM Newsmagazine article:
http://www.dvmnews.com/dvm/article/a...date=&pageID=2

or http://veterinarynews.dvm360.com/dvm...date=&pageID=2

page 3 of DVM Newsmagazine article:
http://www.dvmnews.com/dvm/article/a...date=&pageID=3

or http://veterinarynews.dvm360.com/dvm...date=&pageID=3

*Thanks to Glynda for the links

Inefficacy of selegiline in treatment of canine pituitary-dependent hyperadrenocorticism
JA BRADDOCK, DB CHURCH, ID ROBERTSON and ADJ WATSON
Australian Veterinary Journal, 2004;82:272-277

http://www.ncbi.nlm.nih.gov/pubmed/15181926

http://www3.interscience.wiley.com/j...45516/abstract


Full version can be seen online here:
http://web.archive.org/web/200609272...5/04050272.pdf

Quote:

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Conclusions: Selegiline was confirmed as a safe drug with no important side effects in dogs but was not effective for treating canine PDH at the dose used in this study. Due to the availability of other more reliable treatments, it cannot be recommended for treating this disease in dogs. In some dogs, selegiline may have an effect in increasing the activity levels and general alertness, possibly reflecting dopaminergic effects on the brain unrelated to treatment of PDH. It is conceivable that dogs with known pars intermedia tumours could respond better to selegiline, but premortem identification of tumour location in animals is not possible at present with imaging modalities available.

---

How I Treat Pituitary Dependant Hyperadrenocorticism
David B. Church, BVSc, PhD, MACVSc, MRCVs, ILTM
Department of Veterinary Clinical Sciences, The Royal Veterinary College
North Mymms, Hatfield, Hertfordshire, UK

http://www.vin.com/proceedings/Proce...3874&O=Generic

"What are your trilostane dosing and monitoring recommendations in dogs with hyperadrenocorticism?"

"Should I switch treatment from mitotane to trilostane in dogs being treated for hyperadrenocorticism?"

Video Presentation By: David S. Bruyette, DVM, DACVIM
VETERINARY MEDICINE, Feb 1, 2009

http://veterinarymedicine.dvm360.com.../detail/567360

Here is a link to a 2011 abstract published by Dr. Edward C. Feldman of University of California at Davis:

https://www.ncbi.nlm.nih.gov/pubmed/21627507

Tables of study can be found here:

https://www.semanticscholar.org/pape...2#paper-header


Here is a link to a more streamlined summary of Dr. Feldman's key reasearch findings:

https://www.dvm360.com/view/hot-lite...lostane-answer

A collection of links on one topic. The same links and more are available individually in this forum.