ACTH, iron overload and WNV titer results for IR mare


 

I hope to get some insights on recent test results for my 10 yo TWH mare Cayuse. She isn't foot sore or otherwise in pain, so not your top priority! I've know for several years she is severely IR.  First and most troubling, her ACTH tested at 26.5 pg/ml, barely within Cornell's normal range. This is an elevation over 18.6 pg/ml that we had 2 years ago as a baseline. Do I need to engage my vets about treating her with pergolide now in anticipation of the rise? Her observable symptoms are elevated leptin and one slightly runny eye. Coat and muscle are normal. No footiness ever.


Second, I'd like to understand the KSU iron panel results. 

Serum iron- 299,  lab normal 75-228. 

TIBC - 506, lab normal 231-455. 

Ferritin - 178, lab normal 43-261. 

I don't know how to evaluate her iron overload status and what, if anything, I should do about it, since I'm already balancing her trace minerals, usually at a ratio of 3.5:1:3:3. Is there any benefit to dropping the ratio of Fe:Cu:Zn to 3:1:3? Dietary iron is 1242mg, including hay, Nuzu Stabul 1 and ODTBC, the last two being added because of low nutrient quality hay.


Last, because she is such a problematic vaccine reactor, this year I asked for both rabies and WNV titers. Rabies hasn't been received yet. Cayuse's last WNV vaccination was March, 2014. The Cornell WNV SN titer result was 512, described by my vet as "adequate." This is much lower than my other mare's titer of 2048, so I'm trying to  understand what it means - - is annual titration necessary? Is the result adequate for now? Do we have any idea how long it will remain adequate?


I can add hoof shots in a day or two, after Thursday's trim. 


Thanks for your time.


Cass for Cayuse

Sonoma County, Calif

Oct 12

https://groups.yahoo.com/neo/groups/echistory7/files/Cass%20in%20Calif/

body condition photos: https://groups.yahoo.com/neo/groups/echistory7/photos/albums/1837846198



Kerry Isherwood
 

".... Her observable symptoms are elevated leptin and one slightly runny eye. Coat and muscle are normal. No footiness ever. ..."


Fascinating! My mare's left eye has had chronic, clear discharge off/on for years. Bc of her pink sclera, as time wore on I'd resigned to the possibility of an eventual nasty cancer diagnosis but magically pergolide 'cured' the discharge for once and for all!

That's why I love this group!!

Sorry I can't offer any actual help...

Best of luck to Cayuse

Kerry in NY
Sept 2014


Lavinia Fiscaletti
 

Hi Cass,

Cornell's upper limit is 35pg/ml so 26.5 is solidly within normal range. If I had that result with Dante I'd be ecstatic. In and of itself it doesn't warrant pergolide. However, as this is a solid elevation from 2 years ago, I'd consider running blood work again in late Aug/early Sept to see what is happening when the actual seasonal rise period kicks in. Are the elevated leptin and slightly runny eye new? Maybe Cayuse will be a candidate for pergolide only during the seasonal rise period. Wish this was a" black and white" type issue but it seems to fall in one of those hmmm... grey areas.

Here is a post form Dr. Kellon addressing the iron panel results:

_____________________________
The tests in an iron screen are:

1. Serum iron - the amount of iron circulating in the blood. This
primarily reflects the amount the horse is absorbing from his diet.
Upper normal is between 150 and 190 for most labs.

2. TIBC - Total iron binding capacity. This is a measure of
transferrin, a protein in the blood that binds and carries iron.
Free iron is very damaging to the tissues. TIBC normally increases
as serum iron increases. Like serum iron, it can't be used as a
measure of body iron load. KSU has reported seeing them as high as
455, but I have several higher than that, in both the normal and the
IR group. Think of it as a "reaction" to the presence of iron in the
blood, like insulin going up is a "reaction" to blood glucose.

3. TSI - Transferrin saturation index. This is a calculation, iron
divided by TIBC x 100, that shows how much of the transferrin
protein is saturated with iron. TSI does correlate with body iron
burden, and also with how much iron is being absorbed. Upper normal
is somewhere in the low 40s.

4. Ferritin - This is the protein that binds iron in the tissues and
has been proven in horses to correlate very well with body iron
burden. It can also be elevated with inflammation, malignancy,
severe trauma, etc. but in that case the serum iron and TIBC go down.
Horses in the IR study that were actively laminitic and showed the
pattern of high ferritin but low iron and TIBC were not included so
that there would be no false elevation of ferritin values. Serum
ferritin of normal horses in Dr. Smith's study showed a mean of 152
with a standard deviation of 54.6, which means 152 was the average
and most (95%) of the horses fell within a range of 97.4 to 206.6.
My normals were similar, 139 plus or minus 43.9.
__________________________________

More info in the file on iron here:

https://groups.yahoo.com/neo/groups/EquineCushings/files/Iron%2C%20Iron%20Testing%2C%20Iron%20Overload/

Check the folder Iron: Dr. Kellon on Iron Overload.doc

Can't help with the vaccination/titre part of your question but as this has come up before, here is one previous message:

https://groups.yahoo.com/neo/groups/EquineCushings/conversations/messages/176564


Lavinia, Dante, Georeg Too and Peanut
Jan 05, RI
EC Support Team


 

Thanks, Lavinia, for your response. On ACTH, I focused on the combination of the ACTH increase from 18.6 two years ago to 26.5  and the shockingly high leptin that has risen every year, from 4.7 to 5.8 to 8.7 - - even tho the blood draws were taken at the same time of day and the horse had tested low sugar hay in front of her for  4 hours before the test.  The runny eye started last fall and hasn't subsided.

On iron overload, like serum iron and TIBC, it is outside the range of normal, while ferritin is within the range. Does this mean Cayuse has iron overload? I read the files before posting and still don't know if there is any additional benefit (or detriment) to reducing the ratio of Fe to Cu and Zn from 4:1:3 to 3:1:3. If anyone knows the answer, I'm all ears. The increase in Cu and Zn wouldn't bring the total amounts of up into any kind of problem ranges for toxicity or palatability. 

On the titers,  My concern is that vaccinations are a ticking time bomb.  For rabies, I added the result from last year's titer, 3 iu/ml, which is 6 times higher than 0.5. I'm fairly comfortable with that result, especially if it hasn't changed much since last year.

It's the WNV titer of 512 that I'd like to understand better. WNV is commonly found in birds in the area, but there were only two equine cases in this part of the state last year. The number of cases is fairly constant but resulting euthanizations steadily declined over the past 6 years. http://www.cdfa.ca.gov/ahfss/animal_health/wnv_info.html   I cannot find where on Dr Kellon's lists I read about the WNV titer. I asked my vet to request the WNV Plaque Reduction SN test, but he did not. The result is given as a fixed number that represents antibodies, and the explanation from Cornell doesn't inform me what the result means in terms of even short term immunity. Because she has not had WNV or the Recombitek vaccine, presumably she doesn't have cellular immunity.  Is this antibody result useless because I didn't get WNVPRSN?  I recall reading somewhere that results up in the 1000's (4000?) indicated earlier infection with WNV and good lifelong immunity. So where is a titer of 512 likely to fall in the scale? I'm not looking for a yes/no answer, just a better understanding of the risk I'm taking. 

Cass for Cayuse
Sonoma County, Calif
Oct 12 (Satra)

---In EquineCushings@..., <shilohmom@...> wrote :

Cornell's upper limit is 35pg/ml so 26.5 is solidly within normal range.... However, as this is a solid elevation from 2 years ago, I'd consider running blood work again in late Aug/early Sept to see what is happening when the actual seasonal rise period kicks in. Are the elevated leptin and slightly runny eye new? Maybe Cayuse will be a candidate for pergolide only during the seasonal rise period. Wish this was a" black and white" type issue but it seems to fall in one of those hmmm... grey areas.

Here is a post form Dr. Kellon addressing the iron panel results:
_____________________________
The tests in an iron screen are:

1. Serum iron - 
2. TIBC - 
3. TSI - Transferrin saturation index. This is a calculation, iron
divided by TIBC x 100, that shows how much of the transferrin
protein is saturated with iron. TSI does correlate with body iron
burden, and also with how much iron is being absorbed. Upper normal
is somewhere in the low 40s.
4. Ferritin - 
__________________________________

Check the folder Iron: Dr. Kellon on Iron Overload.doc

Can't help with the vaccination/titre part of your question but as this has come up before, here is one previous message:


Nancy C
 

Hi Cass

I will take a stab at your iron concerns. 

I reposted Dr Kellon's comments about the four ares of concern in the KSU labs   While your ferritin is within normal lab limits, you probably saw that it is above what both Dr Kellon and Dr Smith found to be normal in their studies. 

If you do the calcs outlined in Lavinia's post your TSI comes up as 59 Percent.  That is above what Dr Kellon found to be upper normal, which was low 40s. 

Your serum iron shows that she's got too much in her diet and the TIBC is the reaction to that.

So bottom line for me would be, yes, I would tighten the trace minerals.

In some instances, Dr Kellon has recommended adding more copper and zinc than the 3;1;3;3 ratios we typically use for IR horses.  I would want her to comment on that use for your situation, but it may be in order.

Nancy C in NH
ECIR Moderator 2003
FACT: Iron overload has been identified as a significant factor in IR horses that are not receiving a mineral-balanced diet. (Nielsen, BD, Vick, MM, Dennis, PM, 2012. A potential link between insulin resistance and iron overload disorder in browsing rhinoceroses investigated through the use of an equine model. J Zoo Wildl Med. 2012 Sep;43(3 Suppl):S61-5.)
See  E. M. Kellon, VMD, Iron Overload and Insulin Resistance, 2013 NO Laminitis! Proceedings, Equine Cushing's and Insulin Resistance Group Inc.

 



From Dr Kellon:
The tests in an iron screen are:

1. Serum iron - the amount of iron circulating in the blood. This
primarily reflects the amount the horse is absorbing from his diet.
Upper normal is between 150 and 190 for most labs.

2. TIBC - Total iron binding capacity. This is a measure of
transferrin, a protein in the blood that binds and carries iron.
Free iron is very damaging to the tissues. TIBC normally increases
as serum iron increases. Like serum iron, it can't be used as a
measure of body iron load. KSU has reported seeing them as high as
455, but I have several higher than that, in both the normal and the
IR group. Think of it as a "reaction" to the presence of iron in the
blood, like insulin going up is a "reaction" to blood glucose.

3. TSI - Transferrin saturation index. This is a calculation, iron
divided by TIBC x 100, that shows how much of the transferrin
protein is saturated with iron. TSI does correlate with body iron
burden, and also with how much iron is being absorbed. Upper normal
is somewhere in the low 40s.

4. Ferritin - This is the protein that binds iron in the tissues and
has been proven in horses to correlate very well with body iron
burden. It can also be elevated with inflammation, malignancy,
severe trauma, etc. but in that case the serum iron and TIBC go down.
Horses in the IR study that were actively laminitic and showed the
pattern of high ferritin but low iron and TIBC were not included so
that there would be no false elevation of ferritin values. Serum
ferritin of normal horses in Dr. Smith's study showed a mean of 152
with a standard deviation of 54.6, which means 152 was the average
and most (95%) of the horses fell within a range of 97.4 to 206.6.
My normals were similar, 139 plus or minus 43.9.



---In EquineCushings@..., <cbernstein@...> wrote :


On iron overload, like serum iron and TIBC, it is outside the range of normal, while ferritin is within the range. Does this mean Cayuse has iron overload? I read the files before posting and still don't know if there is any additional benefit (or detriment) to reducing the ratio of Fe to Cu and Zn from 4:1:3 to 3:1:3. If anyone knows the answer, I'm all ears. The increase in Cu and Zn wouldn't bring the total amounts of up into any kind of problem ranges for toxicity or palatability. 


Cass for Cayuse
Sonoma County, Calif
Oct 12 (Satra)


 

Thanks, Nancy, you've confirmed my concern that dietary iron is too high. I'll do what I can to reduce it. Hay quality has been terrible over the past year because of severe drought. 

I'm looking at even slower slow feeding nets to forestall grubbing around the dry lot in our high iron soils. 

On the ratios, I somehow managed to miss information about the reduction of the Fe:Cu:Zn:Mn ratio to 3:1:3:3 for IR! Is this in Files? This nugget never made it into the balancing when my balancing was reviewed several years ago, probably because I didn't have blood work to confirm IR at the time.

Cass for Satra and Cayuse
Sonoma County, Calif Oct 12

---In EquineCushings@..., <threecatfarm@...> wrote :

If you do the calcs outlined in Lavinia's post your TSI comes up as 59 Percent.  That is above what Dr Kellon found to be upper normal, which was low 40s. 

Your serum iron shows that she's got too much in her diet and the TIBC is the reaction to that.

So bottom line for me would be, yes, I would tighten the trace minerals.

In some instances, Dr Kellon has recommended adding more copper and zinc than the 3;1;3;3 ratios we typically use for IR horses.  I would want her to comment on that use for your situation, but it may be in order.