Some good points were raised during TheHorse.com's Ask the vet live: Equine Cushing's Disease sponsored by Boehringer Ingelheim on 18 September, with questions being answered by Dr Nicholas Frank and Dr Marian Little.

In particular:
- important to recognise early and advanced PPID symptoms, early signs are often subtle and variable and include late shedding of winter coat, patchy longer/lighter coloured hairs, regional fat deposits, loss of topline, easy keeper becomes hard to keep weight on, depression & lethargy, footsoreness and chronic laminitis.
More advanced signs include "woolly mammoth" hair coat, recurrent infections e.g. hoof and tooth abscesses & sinusitis, excess drinking/urination, abnormal sweating.

- Miller graded pituitary glands into 1 and 2 = normal, 3 = mild PPID, 4 = moderate PPID and 5 = advanced PPID.  Diagnostic blood tests only picked up grade 5 and some grade 4 cases of PPID, but mild and moderate PPID cases are generally not detected by current testing.  If a horse has clinical signs but negative test results, keep testing as eventually a positive result is likely.

-  Horses that are obese and have EMS are predisposed to PPID. 

- ACTH is the easiest screening test and autumn is the best time to test using seasonal reference ranges for ACTH.  TRH stimulation test (of ACTH) may be a more sensitive test for diagnosing early PPID cases.

- Horses may need increased pergolide during the autumn seasonal rise - test ACTH to check control of PPID.  Even when diagnosis is obvious from clinical signs, testing ACTH gives a measure of severity and response to treatment.

- caring for the PPID horse includes giving pergolide, checking insulin levels, good nutrition (vitamin E and anti-oxidants), hoof care, clipping, deworming, regular dental checks, exercise if possible.

- not all horses with PPID are insulin resistant - insulin should be tested (basal insulin and glucose and/or oral sugar test) to make informed decisions about nutrition, e.g. able to graze or not.  Not all horses with PPID will get laminitis - laminitis is connected to insulin resistance.  If not insulin resistant, many older horses do better on grass.

- every case of PPID is different and must be managed individually.

Listen to the archived recording at www.thehorse.com

Read notes of the session

A few things to note:

I chose to do a non-fasting insulin and glucose test - this was only because we had previously had negative results for both from a fasting test.  Fasting tests are easier to interpret because they will not be affected by recent feed, and are recommended  by many vets for initial diagnosis and for follow up tests at least until the horse tests negative.

I purposely wanted to compare the glucose results from glucometers and lab tests.  Following these results, I'm not sure I would place too much faith in all glucometer results - they are likely to be useful for monitoring increases and decreases in glucose (using the same glucometer), but not necessarily for giving an accurate glucose concentration.  I would want to know that a glucometer had had results in line with (correctly handled) lab results before accepting a glucometer result in lieu of a lab result. 

I particularly wanted to have Homer tested for PPID during the peak of the seasonal rise (September), because according to the latest thinking, he could be said to be showing early signs of PPID:
- long hair on his chin/under his jaw, down his gullet and on the backs of his legs,
- early to get winter coat and later than my other "finer" horses to shed his coat in the spring, although no patchy shedding,
- decreased athletic performance and lethargy - he's never been the most enthusiastic chap to work, he's the sort of horse that tells you the way home out hacking, and keeps asking if it isn't time to stop or take a break in the school!
So it was great to have 2 resoundingly negative ACTH results - and I suspect it's changes in these symptoms that we need to watch out for, or starting to have them for the first time later in life, whereas Homer, who is a very easy keeping Irish cob who doesn't waste a scrap of energy and could easily be related to a yak, has always, since he came to us at the age of 7, been hairy, slow to lose his winter coat (which is much thicker than most other horses), and not too keen on work - no change there in over 10 years!  So for the moment I am going to happily accept that that's "just how he is", and not go looking for PPID in every long hair (but I will keep monitoring him regularly, because if he does start to show signs, I'll be doing all I can to arrest the neurodegeneration for as long as possible)!

If your vet collects blood and takes it away to process it, you could easily underestimate the amount of work involved and therefore perhaps question their charges.  The blood collection is (generally) the easy bit!  Every tube of blood (for EMS/PPID tests) has to either clot and/or spin in a centrifuge to separate the plasma or serum from the cells.  The plasma or serum then has to be drawn off using a clean needle and syringe for every tube, and put into a clean tube, which has to be labelled with the horse's name, the contents of the tube and usually the test required.  And then submission forms filled in and the tubes packed up correctly and dispatched to the testing lab.  A lab result is only as good as the sample submitted, so use the most experienced vet you can and be prepared to pay for good service.  If you don't believe me, ask your vet whether it might be possible to watch your blood being prepared sometime - you may be surprised!

Finally, I cannot thank the lab staff at Liphook enough for their friendly and efficient service.  Since I first contacted them over 2 years ago to ask them if they would test blood from France, they have helped us through every aspect of collecting and testing blood, and answered unending questions.  We can rely on getting accurate results, reported by whatever means we choose (phone, email, text..) often within a few hours of the samples arriving at Liphook, 6 days a week, and at excellent prices, and enjoy knowing that our samples may be contributing to their research and helping horses in the future.

And I'd like to thank my vets here in France who are great to work with, very open to new ideas, have excellent horse handling skills, speak very good English and even pose for photos for the website!  They are all equine specialists, are investing in equipment for the benefit of all horses in the area and appear to have made a huge difference to horse survival rates in the short time they have been in this predominantly beef-producing region of France - we are very lucky to have them!

For more about blood testing at Liphook, and the protocol in French and English, see:
http://www.thelaminitissite.org/l.html

Notes from Boehringer Ingelheim webinar 04 September 2012   
Andy Durham - Current thoughts of where we are with PPID diagnostics ​

Changes in the PI precede clinical signs and abnormal lab results 
Dianne McFarlane (ACVIM 2012) examined 120 horses before and after death, 48 normal and 72 PPID according to post mortem histology. 
Of the horses with grade 3 PIs (hypertrophy/hyperplasia), only 2/34 (6%)had clinical signs of PPID; 
of the horses with grade 4 PIs (microadenomas), only 3/27 (11%) had clinical signs; 
many grade 3 and 4 horses had negative ACTH and DST results, the mean ACTH and DST results for grade 3 and grade 4 horses were normal. 
The normal horses (grades 1 and 2) all had negative blood results.   
All the horses with grade 5 (macroadenomas) PIs had abnormal ACTH and ODSTs, and all but one had clinical signs.   
This suggests we are likely to be missing a lot of early PPID cases - 79% of horses with histopathology of PPID had no clinical signs of PPID.  Early detection and treatment may help to slow neurodegeneration. 

NB RIA was used for ACTH testing, 58 pg/ml cut-off is equivalent to 29 pg/ml with CIA (as used by Liphook) - RIA has higher results than CIA. 

TRH stimulation test 
The TRH stimulation test (testing ACTH) currently appears to be the best test for “grey-area” cases (TRH testing cortisol is now largely discredited). 
Horses are injected with 1 mg TRH IV, normal horses show very little response to TRH, PPID horses have big surge in ACTH production in response to TRH.  Research suggests ACTH tested 10 minutes post TRH uses 100 pg/ml cut-off (30 minutes post TRH uses 35 pg/ml cut-off).  Currently no seasonally adjusted reference ranges for TRH stimulation of ACTH. ​

Using CIA (cut-off 29 pg/ml outside of autumn), results under 20 pg/ml are likely to be negative for PPID, results over 40 pg/ml are likely to be positive, results between 20 – 40 pg/ml fall into a “grey area” – these may be early PPID cases. 
Testing ACTH 10 minutes post TRH, Liphook found that TRH results generally confirmed negative basal ACTH (<20 pg/ml) and positive basal ACTH (>40 pg/ml).  For basal ACTH results between 20 and 40 pg/ml, around 50% of TRH results were positive and 50% negative. 

NB "grey-zone" now identified for resting ACTH - 20-40 pg/ml if using CIA with 29 pg/ml cut-off outside of autumn.  Generally "grey zone" suggested as cut-off +/- 10 pg/ml. 

Treatment and Monitoring 

Dose of pergolide 
No consensus as to the “correct” dose of pergolide - a horse with mild hyperplasia may respond well to 2 mcg/kg (1 mg/500 kg horse), whereas a horse with a macroadenoma may need a much higher dose.  PPID is different in every horse, plus there may be differences in absorption of pergolide between individual horses.  Lab tests can be used to monitor response to treatment, but clinical signs must be taken into account as well. 

NB interesting to note that Orth et al. 1982 used 10 µg/kg pergolide and this dose was considered safe. 

Response to treatment with pergolide 
Liphook measured the response to (0.5 – 1 mg) pergolide in over 600 horses. 
Follow up tests after 4 – 12 weeks pergolide treatment showed ACTH decreased in 91.8% of horses.  37% had normal ACTH, 38% had a > 50% reduction in ACTH with ACTH remaining above normal, and 25% had a < 50% reduction in ACTH with ACTH remaining above normal.  When some of these horses were tested after 6+ months, the response was poorer and 42% had ACTH that had decreased by < 50% from the pre-treatment ACTH.  Reasons put forward for this: disease progression (most likely - disease initially controlled and then over time becomes less controlled? (was seasonal rise taken into account?)), increasing tolerance to pergolide, selection bias (poor responders more likely to be retested). 

How quickly do horses respond to pergolide? 
Liphook found that of 33/39 horses that showed a good or partial response to pergolide, the majority (average 63%) responded within 1 week of starting treatment, an average of 80% showed a response within 2 weeks, and all but one horse (average 91%) had responded within 4 weeks of starting treatment. 

When should follow-up testing be carried out? 
Follow up testing is recommended 4 weeks after starting pergolide and the dosage should be increased if the response is disappointing. 

Regular monitoring of ACTH is recommended, ideally every 3 to 6 months with one test between August and October to see whether PPID is controlled through the seasonal rise. 

What about horses that don’t respond to pergolide? 
Most horses that do not respond to an initial (2 mcg/kg) dose of pergolide do tend to respond to an increased dose.  Some horses may respond in the long-term: 
Hal Schott reported at ACVIM 2012 that of 8 PPID horses that had not responded to 2 mcg/kg pergolide at 3 months and 4 mcg/kg at 6 months, but continued to receive 4 mcg/kg, 5 had responded 2 years later, and 6 had responded 3 years later - appears there is potential for horses to respond to pergolide in the longer-term. 
Some cases respond when 0.25 mg/kg/12 hrs cyproheptadine is added to a high (10 µg/kg?) dose of pergolide. 

Conclusions 
Diagnostics 
ACTH is preferred to ODST for routine diagnosis. 
Early PPID cases are being missed – we can diagnose full-blown PPID with macroadenomas but early cases are not showing characteristic clinical signs or lab tests outside of normal ranges. 
TRH stimulation test (of ACTH) might detect cases earlier, could be used following “grey-area” resting ACTH results (20 – 40 pg/ml CIA), but we don’t yet have seasonal references ranges. 
Better PPID tests are needed – Liphook are investigating. 

Monitoring 
Recheck ACTH after a month and adjust dosage of pergolide as required. 
Maximum dose is probably 10 µg/kg BW - happy this is safe. 
Horses that don’t respond to the maximum dose (10 µg/kg) could either carry on with an affordable dose in the hope that they will eventually respond, or try adding cyproheptadine (0.25 mg/kg every 12 hrs) to the pergolide. 
When horses are stable and the PPID appears controlled, it may be possible to reduce the dose – retest to monitor. 

This webinar was presented by bi-academy on 04 September 2012 (login required): 
http://live.webcasts.unique-media.tv/bil019/interface 
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