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Quick Review
PPID = pituitary pars intermedia dysfunction = Cushing's Disease. It is caused by loss of neurons in the brain, originating in the hypothalamus, that send nerve endings down to the pituitary where they release dopamine. Dopamine inhibits/controls the release of the hormones that are elevated in PPID.
At this time, the goal of "treating" PPID is to control the symptoms and control the output of hormones caused by the tumor. The best way to assess ongoing treatment & medication requirements of horses with PPID is to test ACTH levels and to monitor the horse symptomatically. The level of circulating hormones reflects the size of the pituitary hypertrophy or adenoma. For the best long term prognosis, hormone levels should be kept as close to normal as possible, often requiring titration of medication during certain periods of the year.
DRUG THERAPY
Best current treatment of PPID is with the use of the drug, pergolide mesylate. Pergolide is a drug that was widely used in humans to treat Parkinson Disease which also involves loss of dopaminergic neurons but in a different part of the brain. This drug attaches to dopamine receptors on pituitary cells and mimics the action of dopamine. Pergolide is usually very effective in controlling symptoms. Veterinarians vary in their starting dose and in the time they wait between dosage adjustments. Starting dose is typically between 0.5 to 1.0 mg/day for an average sized adult horse. Dosages as high as 6+ mg/day have been used, and are still considerably below the dosages used in humans.
Pergolide Safety: Pergolide was withdrawn from the human market in the US and CA in 2007 because of concerns over heart valve fibrosis or lung fibrosis. As far as we know, this has not been reported in horses. Pergolide is derived from a class of natural compounds called ergot alkaloids which can cause hallucinations and bleeding tendencies or gangrene, but pergolide itself is Not an ergot alkaloid and does Not have these effects.
The most common side effects of pergolide are depression/lethargia and loss of appetite which EC and IR Group now refers to as the Pergolide Veil. These are usually temporary side effects and can be reduced and/or eliminated with a slow introduction to the drug. A typical dosing regimen might start with 0.5 mg per day for 3days, gradually increasing by 0.25 mg every 3 days until desired starting dose is achieved. By using this dosing regimen, EC and IR Group has seen far fewer reports of side effects. Side effects are not inevitable and many horses are showing rapid improvment with energy levels and attitudes, some within days of slowly introducing pergolide and with appropriate nutritional support.
When horses with seasonal elevation of ACTH and/or G:I ratio present with fall laminitis, it is the recommendation of the EC and IR Group that these horses be treated with pergolide, atleast seasonally (August to mid-December). Suggestions are to start at .5 to 1 mg pergolide during this period with follow up ACTH testing starting each Spring. These may be early PPID horses with exaggerated seasonal influences increasing laminitis risk that might otherwise be fine without pergolide during the rest of the year.
The drug Cyproheptadine was used at one time to treat horses with PPID. Cyproheptadine blocks serotonin, a brain chemical that stimulates POMC production. Cyproheptadine often works well for a while, then loses its effectiveness. This probably occurs because more dopamine producing neurons continue to be lost and the suppressing effect of blocking serotonin can't compensate for this after a while. The standard dose is 0.25 mg/kg of bodyweight once daily. There is no known documentation of higher doses and/or increased frequency of administering this drug.
The first drug tried in horses with PPID was bromocriptine. Like pergolide, bromocriptine mimics theinhibitory effects of dopamine on the pituitary. It worked, but the problem was it had to be given subcutaneouslyseveral times a day. Oral absorption wasn't reliable.
ALTERNATIVE THERAPIES
There are a variety of herbal supplements on the market for PPID horses. Some have immune stimulating or anti inflammatory ingredients but by far the most universally found herb is Vitex agnuscastus, aka Chastetree Berry, Monk's Pepper. Dr. Eleanor Kellon did the first field trial of this herb in PPID horses after researching its use in “female disorders” and finding it was a prolactin inhibitor that was a dopamine agonist.
The trial involved 10 horses and ponies with clinically obvious PPID, laminitis, long coats and depression. The shedding response started within two weeks and attitudes brightened considerably. Results were reported only as clinical observations and even in that trial it was suggested this not be used in very longstanding cases.
That preliminary field trial was published in the December 2000 issue of Horse Journal and attracted a good bit of attention.
The next study involved New Bolton Center and compared Vitex to pergolide, and another trial was done in the UK under the auspices of Dr. Robert Eustace of the Laminitis Trust. Each horse was followed for 12 months.
All three trials used liquid extracts of Vitex, Hormonise or Evitex. Some upward adjustment of dosage was allowed in the UK trial while Dr. Kellon's field trial and the New Bolton trial used 10 ml per 200 pounds of bodyweight. The UK trial reported the same good clinical responses Dr. Kellon saw originally but improvements in ACTH and insulin were varied. The preliminary study results through the Laminitis Trust are detailed here:
http://www.equinescienceupdate.co.uk/oct2001.pdf
Final results are not yet available and all results still need to be corrected for seasonal influences. Dr. Eustace continues to recommend and use Vitex. EC and IR Group, after being able to study & document many horses on Vitex over several years, have found that many cases respond well initially but then lose the response and need to be switched to Pergolide for better control. Since there is no cost advantage to Vitex over pergolide in North America at the moment, the recommendation is pergolide as first line treatment for obviously advanced and/or laminitic horses with PPID. If it's an early case and the owner wants to try Vitex first, it's a reasonable first step as long as the owner and veterinarian realize it may lose effectiveness.
Other alternative treatments may include homeopathic remedies. Regardless of whether you “believe in” homeopathy or have had a positive or negative experience trying it, there are no formal studies on the use of homeopathy to treat PPID. True homeopathy is a system of medicine first defined by the physician Samuel Hahnemann 300 years ago. In brief, the concept was to “treat like with like” or the Law of Similars (aka “the hair of the dog..”). The homeopathic remedies are supposed to be prescriptions that contain a variety of different substances that themselves would be expected to cause symptoms similar to what the patient is experiencing, and to patient's emotion and spiritual make up. Although it is rarely clearly stated this way, Hahnemann believed that suppressing symptoms would suppress the body's attempts to clear itself of the abnormality. A less complicated example of the Law of Similars at work would be putting hot compresses on an abscess to help make it come to a head. At this time, there are no homeopathic remedies currently recommended or suggested by the EC and IR Group.
The goal of EC and IR Group is No Laminitis. Therefore, it is the groups recommendation that horses with PPID be treated with pergolide and if also IR, that their diet be managed according to the DDT/E protocol.
Information Contained On this Page Adapted From
Equine Cushings & Insulin Resistance Course Offered by
Dr. Eleanor Kellon, VMD www.drkellon.com
EC and IR Group and Dr. Eleanor Kellon, VMD © 2009
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