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Adjusting pergolide when base numbers are normal


Karen Anderson
 

Good morning all: 

Many thanks to Martha from Vermont, who has been extremely helpful to me!  I just updated Fhin's case history with the results of the latest tests. 

Fhinland is a PPID horse, diagnosed with TRH Stim, where the endogenous test result has been and continues to remain low (in the teens.)

 I have been advised that TRH stim testing is not generally done after a positive PPID diagnosis so how am I supposed to manage this horse’s pergolide dose?  Do I only pay attention to the pre-test numbers?  My vet agrees that his coat is not normal even though his last endogenous test was 11. Although he is clipped, his coat is a strange color and he shows guard hairs on his unclipped legs. 

Appreciate the advice of the group.
Karen
--
Karen and Fhinland in Maryland

Case Study:   https://ecir.groups.io/g/CaseHistory/files/Karen%20and%20Fhinland


 

Hi Karen,
Thanks for updating your case history and posting.  Your mention of a funny coat color brings possible iron overload to mind.  Would you be able to post some photos of Fhinland?  What does his coat look like in summer?  Does it look normal to you?  Do the guard hairs persist into summer?
--
Martha in Vermont
ECIR Group Primary Response
July 2012 
 
Logo (dec. 7/20/19), Tobit(EC) and Pumpkin, Handy and Silver (EC/IR)

Martha and Logo


 
 


Sherry Morse
 

Hi Karen,

Do you have copies of the actual test results or at least his pre-TRH numbers? Have you ever had a test that was sent directly to Cornell and not through Antech?




Lorna Cane
 

Hi Karen,

If Fhinland were mine ,I would pay attention to balancing his hay. From what I see in his CH ,for example,his trace minerals are not at sufficient levels,or ratios. Copper deficiency *can* be a reason for the hair coat colour being bleached out....not sure if that's what you mean by a strange colour.
The supplements being supplied are pretty minimal. I don't see iodine mentioned, and a salt block wouldn't suffice here.I didn't have time (sorry)to search all the products,except the Purina mentioned,so maybe one of them contains required magnesium , phosphorus and calcium,depending on the levels in your hay.
Can you test your hay ,to find out where it is deficient?
I think if you got the balancing nailed down,you'd see a positive difference.
In our Files is a list of members here who balance hay for people.
--

Lorna  in Eastern  Ontario
2002
Check out FAQ : https://www.ecirhorse.org/FAQ.php


 

Hi Sherry,
The pre TRH numbers are the ones before the commas, I believe.  
--
Martha in Vermont
ECIR Group Primary Response
July 2012 
 
Logo (dec. 7/20/19), Tobit(EC) and Pumpkin, Handy and Silver (EC/IR)

Martha and Logo


 
 


Nancy & Vinnie & Summer
 

I too posted the same question about how to determine if the current dose of prascend pergolide is sufficient when the bloodwork was always normal for endogenous acth.

Thx following as well.

Nancy 
--
Nancy and Vinnie and Summer
Oakley, Ca
Joined Nov 2018
https://ecir.groups.io/g/CaseHistory/files/Nancy%20and%20Vinnie 
https://ecir.groups.io/g/CaseHistory/album?id=245855

Summer
https://ecir.groups.io/g/CaseHistory/files/Nancy%20and%20Vinnie/Summer 
https://ecir.groups.io/g/CaseHistory/album?id=249104


Kirsten Rasmussen
 

I have been advised that TRH stim testing is not generally done after a positive PPID diagnosis so how am I supposed to manage this horse’s pergolide dose?  Do I only pay attention to the pre-test numbers? 

This question has been asked many times and I feel like we just don't have a good answer for it. However,  the 2019 EEG Guidelines on PPID do state in Table 5, under Initial Response, that you should see "decreases in basal ACTH and ACTH 10 min after TRH administration (but not necessarily to below cutoff values)"
https://sites.tufts.edu/equineendogroup/

This seems reasonable to me...the TRH Stim should show a reduction in both pre-and post-ACTH numbers, although how much reduction does not appear to be quantified.  There will also be a seasonal effect, so less reduction may be seen during the seasonal rise.  It may be best left to the owner and attending vet to decide if the drop is adequate at that time given that basal ACTH is normal in early cases.  Keeping basal ACTH in the lower-middle part of the range year-round might also be advisable since many PPID horses do best when their ACTH is tightly controlled in the middle to lower normal range.  Also, if the signs that prompted the use of a the first TRH Stim test in the horse improve or go away on medication,  that is another indicator that the pergolide dose is effective.

Karen, I personally would be satisfied with your latest bloodwork numbers for now, but the real test will be if his coat regrows normally and if his airway issues recur on his current dose.  Of course the skin irritations could be a sign that a higher dose would be beneficial, as we know from Martha and Logo's experience, but coat abnormalities in colour could be due to minerals not being balanced to his hay.

--
Kirsten and Shaku (IR) - 2019
Kitimat, BC, Canada
ECIR Group Moderator
 
Shaku's Case History
Shaku's Photo Album


Eleanor Kellon, VMD
 

There is absolutely zero published information on what to expect  with TRH stimulation after pergolide is started. Zero. There is also no way to accurately predict it.

When pergolide is started the goal is to re-establish the "brakes" on hormonal output from the median lobe. A test like the dexamethasone suppression test should also normalize because dex suppression only affects normal  ACTH output and that will have taken over when you got the median lobe under control again.

Stimulation tests are different. How effective TRH is in stimulating the output depends on both how unregulated it is without pergolide and also potentially on how enlarged/hypertrophied the median lobe has become. If pergolide shrinks these growths like it does in humans it would be reasonable to expect the post TRH numbers to be lower after treatment but we don't know if it does shrink them. Until someone does a study that shows what happens to ACTH levels after TRH when on pergolide we can't make any assumptions.

There is also more overlap between PPID positive and negative for post TRH stimulation values than for baseline ACTH at some times of the year https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848300/ and a huge difference in post TRH depending on the time of year.

--
Eleanor in PA

www.drkellon.com 
EC Owner 2001


Maxine McArthur
 

On Wed, Feb 24, 2021 at 09:06 AM, Eleanor Kellon, VMD wrote:
When pergolide is started the goal is to re-establish the "brakes" on hormonal output from the median lobe. A test like the dexamethasone suppression test should also normalize because dex suppression only affects normal  ACTH output and that will have taken over when you got the median lobe under control again.
Goodness me. I read this and had a massive light-bulb moment. THIS is why we like our PPID horses on pergolide to have tests within normal range--because it shows that the median production has been suporessed and the anterior lobe ACTH output has taken over again. Correct? 

But this raises the question--if normal ACTH output from the anterior lobe increases during the seasonal rise in all horses, why do we want to keep our medicated PPID horses right down in the lower end of the range rather than accepting that their anterior outputted ACTH rise is normal and being satisfied with them sitting in the same range as normal horses for the rise? (hopefully my question is clear)
 
--
Maxine and Indy (PPID) and Dangles (PPID)

Canberra, Australia 2010
ECIR Primary Response

https://ecir.groups.io/g/CaseHistory/files/Maxine%20and%20Indy%20and%20Dangles 
https://ecir.groups.io/g/CaseHistory/album?id=933

 


Eleanor Kellon, VMD
 

The seasonal ACTH rise is from the median lobe too. The other median lobe hormones like alpha-MSH also go up seasonally.
--
Eleanor in PA

www.drkellon.com 
EC Owner 2001


Maxine McArthur
 

I see. So the anterior lobe (in a normal horse) does the everyday job of producing ACTH, while the median lobe jumps in for special occasions, so to speak? And in a PPID horse, the over-production from the median lobe drowns out (or does it actually prevent?) the normal production from anterior lobe. 

Sorry to over-simplify, I do realise other hormones are involved. Just trying to get the mechanism clear in my mind. 
--
Maxine and Indy (PPID) and Dangles (PPID)

Canberra, Australia 2010
ECIR Primary Response

https://ecir.groups.io/g/CaseHistory/files/Maxine%20and%20Indy%20and%20Dangles 
https://ecir.groups.io/g/CaseHistory/album?id=933

 


Eleanor Kellon, VMD
 
Edited

It's actually the distal lobe, pars distalis, that normally produces ACTH under the influence of CRH. CRH secretion is linked to the circulating cortisol level. In the normal, every day function of the median lobe, a tiny amount of ACTH is produced as an intermediary in other reactions https://flipper.diff.org/app/pathways/info/2863 . The median lobe is normally under the control of dopamine. When that control is lost, the levels of all its hormones is increased but ACTH is actually the lowest.

When ACTH from the median lobe shoots too high, it triggers cortisol production just like ACTH from the pars distalis. That increased cortisol then inhibits CRH and ACTH normal production.
--
Eleanor in PA

www.drkellon.com 
EC Owner 2001


Nancy & Vinnie & Summer
 

This may be a dumb question, but how does insulin come to play in this myriad of hormones? Is it related to the elevated cortisol?

--
Nancy and Vinnie and Summer
Oakley, Ca
Joined Nov 2018
https://ecir.groups.io/g/CaseHistory/files/Nancy%20and%20Vinnie 
https://ecir.groups.io/g/CaseHistory/album?id=245855

Summer
https://ecir.groups.io/g/CaseHistory/files/Nancy%20and%20Vinnie/Summer 
https://ecir.groups.io/g/CaseHistory/album?id=249104


Maxine McArthur
 

Thank you!! I think I've got it.
--
Maxine and Indy (PPID) and Dangles (PPID)

Canberra, Australia 2010
ECIR Primary Response

https://ecir.groups.io/g/CaseHistory/files/Maxine%20and%20Indy%20and%20Dangles 
https://ecir.groups.io/g/CaseHistory/album?id=933

 


Nancy C
 

Hi Nancy

Try this

https://www.ecirhorse.org/physiology-EMS.php

There is a short paragraph about cortisol and insulin onthispage

https://www.ecirhorse.org/physiology-ppid.php

Have your cyber dictionary open.
--
Nancy C in NH
ECIR Moderator 2003
ECIR Group Inc. President/Treasurer  2020-2021
Join us at the 2021 NO Laminitis! Conference, August 13-15, ECIR Virtual Conference Room


Nancy & Vinnie & Summer
 

I think I have read these passages probably 50 times and finally I am beginning to get a better understanding:)  thank.  This thread helped so much!
--
Nancy and Vinnie and Summer
Oakley, Ca
Joined Nov 2018
https://ecir.groups.io/g/CaseHistory/files/Nancy%20and%20Vinnie 
https://ecir.groups.io/g/CaseHistory/album?id=245855

Summer
https://ecir.groups.io/g/CaseHistory/files/Nancy%20and%20Vinnie/Summer 
https://ecir.groups.io/g/CaseHistory/album?id=249104


Nancy C
 
Edited

This conversation has made me go archives surfing. Some nuggets I found, all from Dr Kellon posts. Some may help your questions, some not.

https://ecir.groups.io/g/main/message/255735

There is no direct link between ACTH  and insulin levels.  Studies have shown cortisol is often normal and much of the measured ACTH  may be inactive. However, we use ACTH as an indicator of control over the PPID.  ACTH is actually  only a small fraction of the hormones released by the intermediate lobe, and all of them can have a negative effect on insulin sensitivity.

https://www.ncbi.nlm.nih.gov/pubmed/6141515 
https://www.ncbi.nlm.nih.gov/pubmed/3035302
***
https://ecir.groups.io/g/main/message/212887

Insulin can be elevated as a result of high cortisol production, which is stimulated by ACTH.  If that is the only cause of the high insulin and if the Prascend is keeping ACTH normal, the insulin will also be normalized. However, in most cases Prascend without an insulin resistance diet will not get insulin back to a good level.

****

https://ecir.groups.io/g/main/message/254265

There's no consistent rise in cortisol with chronic pain, which is presumably the mechanism behind insulin rise in pain, but we don't have any studies on chronic pain and insulin per se.

***
https://ecir.groups.io/g/main/message/252431

This one has really great stuff and I'd recommend reading the whole post, but this jumped out at me:

IR – Insulin Resistance. This is a specific cause of elevated insulin levels where the insulin sensitive cells (liver, muscle, fat) do not respond normally to insulin. Insulin's job is to signal those cells to take up glucose. When glucose does not drop enough in response to normal insulin levels, the pancreas secretes more to get the job done.

It may be genetically determined or occur as a result of drugs (classically corticosteroids) or as a response to infection, starvation, surgery or trauma – virtually any major assault to the body. IR in the face of challenges helps preserve glucose for the most critical tissues, the heart and lungs.

and

PPID – Pituitary Pars Intermedia Dysfunction (aka Cushing's Disease). This is an age-related hypertrophy of the middle lobe of the pituitary gland and hypothalamus. One of the consequences can be increased ACTH leading to increased cortisol which in turn causes insulin resistance. The other hormones produced in excess in PPID can also change insulin sensitivity.

The insulin resistance caused by PPID can cause many signs that are the same as EMS but this is a distinct cause which requires unique treatment and these horses should be called PPID, not EMS.

***
This is another good one

https://ecir.groups.io/g/main/message/220577


In no way do I claim to have my brain around the hormonal chain, but what I think I know is that IR -- a metabolic condition -- can be made worse by a disease state like PPID. Increase is cortisol and other hormones can worsen insulin sensitivity in some individuals to the extent it causes laminitis.

I may not be answering your question, but you may find more that will by searching the archives.

--
Nancy C in NH 2003
ECIR Group Inc. President/Treasurer  2020-2021
Join us at the 2021 NO Laminitis! Conference, August 13-15, ECIR Virtual Conference Room


Nancy & Vinnie & Summer