EQUINE CUSHING’S DISEASE
What is Equine Cushing's Disease?
Equine Cushing’s Disease, also known as Pars Pituitary Intermedia Dysfunction (PPID), is a disorder of the endocrine system affecting older horses (>15 years old) and other equidae and is certainly the commonest old age syndrome in horses.
Cushing’s Disease is caused by enlargement of the middle section of of the pituitary gland. This gland is located at the base of the brain and is an important endocrine organ that produces a variety of different hormones. Dysfunction results in the increased release of several hormones, including ACTH (adrenocorticotropin hormone), which leads to overproduction of cortisol (type of steroid). It is this over production of cortisol that affects the horse and can explain the majority of clinical signs seen in this condition.
What are the clinical signs?
The most common clinical signs (in order from most common to least):
inappropriate lactation can occur in mares
Why do Cushing’s Disease horses get laminitis?
Between 50% and 80% of horses with Cushing’s Disease will have clinical laminitis although the severity of the disorder may vary widely and indeed may vary in an individual horse from episode to episode.
Laminitis associated with PPID has been attributed to the effects of overproduction of cortisol and the development of insulin resistance; in this respect the syndrome has marked similarities with the Metabolic Syndrome although the latter is driven by a different metabolic pathway. Insulin and cortisol have opposing actions on glucose metabolism such that hyper-insulinemia and insulin resistance are both potential consequences of corticosteroid treatment.
Supporting the importance of the development of insulin resistance in the pathogenesis of laminitis is the importance of insulin as a prognostic indicator for survival in horses with PPID. Horses with abnormally high levels of insulin are much more likely to develop laminitis and survive less than two years after diagnosis, than those with only moderate elevations or normal insulin levels.
NB: Laminitis associated with iatrogenic corticosteroid administration is rare in normal horses – the rather irrational fear of steroids in horses has largely been driven by a few “high profile cases” and the occasional horse which certainly does develop a severe laminitic syndrome following corticosteroid administration. The common link between both PPID and iatrogenic corticosteroid administration is the ability of cortisol to induce insulin resistance.
How is Cushing’s Disease diagnosed?
1. Plasma ACTH concentration
Plasma ACTH is increased in the presence of pituitary hyperactivity and hyper-secretion. A single blood sample is collected between 8 am and 5.30 pm (no special precautions are necessary although the horse should not be stressed unnecessarily – e.g. transport, vigorous exercise, etc.). Special sample handling is required so this test is best done Monday to Wednesday (in order to reach laboratory without deterioration of the sample)
2. Overnight dexamethasone suppression test
First sample is collected around 5 pm, followed by administration of dexamethasone. Second sample is collected following day (16-24 hours later). A normal horse is expected to have almost complete suppression of endogenous cortisol in the second sample whereas horses suffering with PPID have the same or only slightly reduced levels of cortisol.
3. Insulin levels
Although not specific for PPID, insulin levels can help with prognosis and monitoring of recurrent laminitis associated with PPID
Less commonly used tests:
4. TRH stimulation test – not commonly performed and limited data preclude statistical analysis of its reliability
5. The combined TRH stimulation and dexamethasone suppression test – improved accuracy of the TRH stimulation test; however, it does not appear to be any more sensitive or specific and is less practical than the overnight dexamethasone suppression test.
Treatment and management of Cushing’s Disease:
1. Medical treatment:
Unfortunately, there is no cure for Cushing’s Disease but there are a couple of drugs available that can help reduce the effects of the disease and aid in managing the affected horse.
Pergolide (Prascend®) – by far the most effective medication. It is a dopamine agonist which reduces the over-production of cortisol and has been reported to be up to 80% successful in reducing the severity of signs of Cushing’s Disease. Low dose regimen (0.002 mg/kg/day) has proven to be effective in many cases; however, some horses will require a high dose (up to 0.01 mg/kg/day). Treatment is generally initiated at the low end of the dose range and gradually increased if required based on clinical and endocrinological responses. Adverse effects of pergolide include anorexia, diarrhoea and colic; however, the latter problems are more often associated with higher doses of the drug. Transient anorexia does occur occasionally even in low dose regimens.
Trilostane (Vetoryl®) – is another drug often used to control signs of PPID in horses. It acts by inhibiting cortisol and has been used successfully at a dose rate of 1mg/kg once to twice daily.
Other drugs, such as cyproheptadine (Periactin®) and bromocriptine (Parlodel®), has been used in past but recent studies did not prove their efficacy and they are not readily available anymore.
2. Nursing and diet:
Management of laminitis (see the separate article covering this)
Management of secondary infections (including internal and external parasitism). Frequently inspecting for wounds and the evidence of any kind of infection and ensuring prompt veterinary attention is very important as affected horses have reduced levels of immunity and often need more intensive and prolonged treatment than other horse.
Clipping of coat hair to prevent excess sweating and ensure the comfort of the horse
Careful attention to teeth and diet (good quality diet with sufficient mineral and vitamin intake). Regular dental checks along with routine vaccinations and a de-worming program involving frequent faecal egg counts are vital to ensure the health of Cushing’s affected horse.
Follow-up evaluation after 6-12 months of treatment includes overall assessment of whether the horse’s condition has improved, remained unchanged or deteriorated. Body condition, hair coat, hyperhidrosis, and severity of laminitis can be assessed and owners can also be asked about excessive water consumption.
Many of the clinical signs should improve on medication (although not all will disappear), generally body condition and hair coat improves significantly in almost all cases, and amount of drinking/urinating and severity of laminitis improves in the majority of cases treated with pergolide.
It is important to remember that no treatment for Cushing’s Disease can actually reverse the pathology that is occurring so veterinary monitoring is essential. Monitoring of clinical signs, basal ACTH concentration and fasting insulin will provide the best information.
In all cases, treatment of PPID is lifelong so embarking on treatment means a significant financial commitment. Additionally, medical therapy does not completely stop the progression of the disease, but can alleviate clinical signs and improve the quality of life of animals on treatment. Not all horses will respond to therapy, but many horses can continue in comfort for many years.
Copyright. East Kent Equine Ltd. 2014