Equine Cushingʼs disease, also known as pituitary pars intermedia dysfunction (PPID), and Insulin Resistance (IR) are distinctly separate conditions. The often overlapping signs and symptoms can make diagnosis difficult.

Pituitary Pars Intermedia Dysfunction (PPID) - Equine Cushingʼs Disease

PPID / Cushing's Disease is a disorder of the pituitary gland and results in hormonal disturbances. The pituitary gland secretes high levels of the hormone ACTH which stimulates the production of cortisol, a stress hormone.

Recommended Diagnostic Test for PPID

Endogenous ACTH – a single blood draw to measure the level of endogenous ACTH (adrenocorticotrophic hormone) is diagnostic for Cushingʼs in equines. The sample requires special handling for accuracy. There are seasonal fluctuactions to consider for diagnosis of PPID, please review SEASONAL RISE.

In the United States, the EC and IR Group suggests Cornell University Laboratory. From Appendix C, Page 1, Specific Submission Guidelines ACTH:

An EDTA plasma tube (usually lavender top) MUST be used for specimen collection. Collect blood to the tube fill volume, gently mix by inversion, and chill immediately by refrigeration or immersion in an ice bath. Separate plasma from cells by centrifugation as quickly as possible for dogs and within 4 hours for horses. Centrifuge for 5-10 minutes (preferably in a refrigerated centrifuge) and transfer the plasma into a plastic (canine/equine) or coated glass (equine only) tube and freeze immediately. Ship on frozen cold packs using an overnight courier service. Plasma samples should arrive frozen (strongly recommended) or adequately chilled (i.e., kept near 4°C at all times).

http://diaglab.vet.cornell.edu/test/feeman/AppendC.pdf

In Canada, the EC and IR Group suggests Guelph University Labratory. From Page 28, 2009 Lab Services User Guide for Guelph University, E. Endogenous adrenocorticotropic hormone (ACTH) Assay:

Equine HAC. Endogenous ACTH assays are the most useful test for diagnosing pituitary tumors in horses. One limitation is that ACTH is a fragile hormone that requires meticulous care in handling. Blood should be collected in a chilled siliconecoated EDTA tube, centrifuged immediately, plasma collected in a plastic (nylon) tube and kept frozen until assayed.

http://www.labservices.uoguelph.ca/labserv/units/ahl/files/Users_Guide_2009.pdf

Other Diagnostic Tests for PPID

Dexamethasone Suppression Test (DST) – measures cortisol response to a dexamethasone challenge. While considered the “gold standard” by some, there is a risk of precipitating or exacerbating laminitis, especially for hoses that are also Insulin Resistant. The product is labelled identifying this risk [of triggering laminitis].

* Both Endogenous ACTH & DST are subject to “seasonal” elevation in late summer/early fall (August through December and sometimes longer in older individuals).

Domperidone Response Test - Still experimental but may be the PPID test of the future. This involves oral (or possibly intravenous) dosing with the drug domperidone, which causes an approximately 300% rise in ACTH in a horse with PPID but not in a normal horse. More information available on the research into this test here http://www.ivis.org/proceedings/aaep/2006/pdf/z9100106000320.pdf

TRH Stimulation Test - An older test for Cushingʼs, does not give consistent results alone but when combined with DST is more reliable than either test alone. However, this is also more time consuming and expensive.

Combined Dexamethasone Suppression/TRH Stimulation - Test for Cushingʼs Disease – involves both tests as above.

Urinary Cortisol:Creatinine Ratio - Test done on urine as a screen for Cushingʼs disease. Not 100% diagnostic but highly suggestive. More accurate than blood cortisol levels in detecting increased production of cortisol.

Cortisol Rhythm – this test is not diagnostic for Cushingʼs, considered to have 30%+ false positive readings.

For more specific questions on PPID testing, interpretation and Diagnosis please join the EC and IR Group.

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Insulin Resistance

Most veterinarians now know what insulin resistance is, and that horses may be insulin resistant without having Cushing's Disease (pituitary pars intermedia dysfunction – PPID). However, a lot of confusion remains about how to diagnose it.

Symptomatically, most IR horses have a body condition score of 6 or higher (or a history of being easy keepers), abnormal fat collections such as fatty crests, fat in the eye hollows or other fat pads and often are brought to the vet's attention because of laminitis. The blood tests for insulin resistance are insulin and glucose.

Most university and commercial labs offer these tests. Horses should not be fasted before this testing (this is only done for human tests)! If a horse is "meal fed", which basically meaning there are periods in excess of 6 hours when the horse has nothing to eat, the first meal after the fast will generate a larger insulin spike than subsequent closer together feedings even if the meal is exactly the same. To avoid a false positive result, the horse should have hay or pasture available at all times the night before and day of the testing. If that's not possible (e.g. a ravenous horse that will inhale as much of anything you put out as quickly as possible), make sure the blood is drawn at least 4 hours after the first meal of the day and feed at 4 hour intervals or keep some hay in front of the horse until the testing is done. The horse should not be fed any grain prior to testing. The horse also should not be exercised within 4 hours of the test and avoid shipping before testing if at all possible. Stress and exercise influence glucose and insulin dynamics.

Some important facts to remember:

• Insulin resistant horses do not usually have an elevated blood glucose.
• A horse can be insulin resistant and still have an insulin level that is within the lab's normal range.

If the feeding restrictions above are followed and the horse tests with a normal glucose and elevated insulin, it is insulin resistant. Upper limit of normal for glucose in a horse that has not been fed anything but hay is around 100 mg/dL (5.6 mmol/L) by definition – in other words, it is taking a larger amount of insulin to maintain a normal blood glucose. It is important to also know that the horse could have an insulin result inside the lab's normal range and still be insulin resistant. This is determined by the use of calculations called “proxies”.

GLUCOSE:INSULIN RATIO – G:I RATIO

Based on human studies and data from our group member's horses, we have been using the G:I ratio for many years now. It's very easy to do. Simply divide the glucose result in mg/dL by insulin in uIU/mL. (If your insulin is reported in pmol/L you have to convert it to uIU/mL by dividing by 7.1.). A value below 4.5 is uncompensated insulin resistance, high risk of laminitis. Values between 4.5 and 10 represent compensated insulin resistance – less risk of laminitis but still needs tight diet control.

IR Calculator is the tool designed to the calculate G:I Ratio, RISQI and MIRG.

RISQI

The RISQI is a proxy developed by researchers at Virginia Polytechnic Institute. RISQI stands for “reciprocal of the square root of insulin”. It is calculated by the equation 1/square root of insulin. A RISQI value of less than 0.2 indicates uncompensated insulin resistance and the horse is at high risk of laminitis. RISQI 0.2 to 0.32 = compensated insulin resistance and a lower risk of laminitis.

IR Calculator is the tool designed to calculate the G:I Ratio, RISQI and MIRG.

MIRG

Horses that have elevated blood glucose, or abnormally low insulin responses, may have RISQI and G:I results that are normal because they have actually crossed the line from insulin resistance to actual diabetes.

MIRG = modified insulin:glucose ratio. It is calculated by: [800 – 0.3 x (insulin – 50)2] /(glucose – 30)]. If G:I ratio or RISQI are positive, there is no need to do this calculation, but if the horse has symptoms of IR and those equations are normal, you should check the MIRG, especially if blood glucose is elevated. A MIRG result greater than 5.6 means the horse is IR and at risk of laminitis.

IR Calculator is the tool designed to calculate the above G:I Ratio, RISQI and MIRG.

References
Use of proxies and reference quintiles obtained from minimal model analysis for determination of insulin sensitivity and pancreatic beta-cell responsiveness in horses
Kibby H. Treiber, MS; David S. Kronfeld, PhD, DSc, MVSc; Tanja M. Hess, DVM, PhD; Ray C. Boston, PhD; Pat A. Harris, VMB, PhD AJVR, Vol 66, No. 12, December 2005

Insulin resistance in the horse: Definition, detection, and dietetics1,2
D. S. Kronfeld*3, K. H. Treiber*, T. M. Hess*, and R. C. Boston
J. Anim. Sci. 2005. 83(E. Suppl.):E22–E31

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EC and IR Group and Dr. Eleanor Kellon, VMD © 2009