Cushing's disease
Equine Cushing’s disease, more correctly called pituitary pars intermedia dysfunction (PPID), is a disorder of the pituitary gland in the horse that results in hormonal imbalances in the horse causing a variety of clinical signs:
- A long, wavy coat that fails to shed with the normal seasonal patterns
- Excessive sweating or abnormal sweating patterns
- Lethargy
- Poor athletic performance
- Chronic recurrent laminitis
- Infertility
- Weight loss
- Abnormal fatty deposits, most commonly along the crest of the neck, the head of the tail, around the sheath and above the eyes
- A pendulous abdomen
- Muscle wasting, particularly along the top-line
- Consumption of large amounts of water
- Passing of large amounts of urine
- Delayed wound healing
- Susceptibility to infections (e.g. hoof abscesses, skin infections)
- Depression
The disease most commonly occurs in middle-aged and geriatric horses and ponies, with an average age of approximately 20 years at the time of diagnosis. Ponies are more commonly affected than horses but there is no difference in the prevalence in mares or geldings. Current estimates suggest that between 20 and 33% of all horses and ponies develop PPID by the age of 20 (Kentucky Equine Research Center). This makes PPID the most common endocrine condition of horses worldwide. Without treatment, symptoms get worse over time and many horses are euthanized because of laminitis.
What causes the condition?
In dogs and humans, Cushing’s disease is caused by a hormone-secreting tumour in the front part (pars distalis) of the pituitary gland, which is found at the base of the brain. In horses, on the other hand, the disease involves the intermediate part of the pituitary gland (pars intermedia). This part of the gland is comprised of different hormone-secreting cells than the front part of the pituitary gland. Therefore, equine Cushing’s disease looks quite different to Cushing’s disease in dogs and humans. It is for this reason that many vets now prefer to refer to the condition in horses as PPID.
In horses with the disease, the pars intermedia of the pituitary produces excessive amounts of pro-opiomelanocortin (POMC) and several hormonally-active derivatives of this substance, including adrenocorticotropic hormone (ACTH). Function of the pars intermedia is normally kept in check by the body through dopamine-secreting nerve cells that arise from the hypothalamus, a nearby part of the brain that regulates a variety of important body functions such as thirst, hunger, body temperature, water balance and blood pressure. In most cases of equine Cushing’s disease the intermediate section of the pituitary gland does not have a true ‘tumour’ but instead is just enlarged and overactive due to the faulty regulation by the hypothalamus. In fact, the most effective treatment for the condition, pergolide, works by mimicking the inhibitory effect of the hypothalamic nerve cells on the pituitary.
Diagnosis
In very advanced cases of the disease, where the horse has developed the long, wavy haircoat and the classical fatty deposits the diagnosis tends to be relatively straightforward. However, cases which are earlier in the process are considerably more difficult to diagnose. Two main tests are used in the diagnosis of the condition, but neither is 100% accurate. The two tests used are 1) the measurement of plasma ACTH concentration and 2) the thyrotrophin-releasing hormone (TRH) test. In South Africa, we currently rely on the plasma ACTH concentration test.
The ACTH test is the most commonly used test worldwide and involves the collection and analysis of a single blood sample from the horse. The pituitary gland in horses with Cushing’s disease often secretes excessive amounts of ACTH into the bloodstream, and this can be measured with this blood sample. However, the blood samples must be handled very carefully once taken, as ACTH can degrade in the sample giving a falsely low reading. In some cases of equine Cushing’s disease ACTH is also not elevated. Stress, pain, seasonal variations and high starch diets in horses can also cause a horse to test positive with this test, even if they have not got Cushing’s disease.
Outside of South Africa, in cases where the vet is uncertain about the ACTH test results, the thyrotrophin-releasing hormone test can be used. The test involves obtaining a baseline blood sample, administering thryotrophin-releasing hormone (TRH) intravenously and collecting a second blood sample exactly ten minutes later. If ACTH levels in the blood increase excessively when the TRH is administered then the test is considered positive for Cushing’s. Once again, however, this test is not 100% reliable.
Other tests that are said to be useful include the measurement of blood glucose and of insulin levels. Many horses that are affected with Cushing’s disease are also insulin-resistant and some are chronically hyperglycaemic (have very high levels of sugar in the blood).
Treatment
Optimal management of Cushing’s disease generally involves a combination of medical and supportive measures. In both cases the management required will be life-long as there is no way to reverse the Cushing’s disease process. In the early stages of the condition, medication may not be required and more conservative measures like clipping to remove the long hair coat, nutritional management and strict attention to the feet may be sufficient to give a good quality of life.
Medications used to treat Cushing’s disease focus on reducing the amount of ACTH and other POMC derivatives. The drug of choice is currently pergolide, which is administered daily by mouth. The dose is tailored according to the response of the horse, and the progression of the disease. It is considered effective in 65-85% of cases, but can have unpleasant side effects including diarrhoea, depression, anorexia and colic.
In terms of other important aspects of management:
- As affected horses are often insulin resistant, sweet feed and other feedstuffs high in soluble carbohydrates should be avoided in favour of high fibre and fat diets. Feeds designed specifically for older horses and highly recommended, but those with high levels of sugar or molasses should be avoided.
- Lush green grass should also be avoided.
- Regular farrier visits are an absolute must to keep the feet in optimal condition, and to check for early signs of the onset of laminitis.
- In both mildly and severely affected horses, it is vital that bacterial infections are diagnosed and treated aggressively and quickly.
- Clipping is necessary – particularly in a climate like ours here in South Africa.
Take-home message
Cushing’s disease, more correctly termed PPID in the horse, is a manageable, but not curable, condition primarily occurring in older horses. If managed correctly and proactively, these horses can go on to have long and enjoyable careers and lives. If you suspect your horse may have Cushing’s disease, contact your vet for advice. The earlier the condition is detected, the faster management can be instituted and the better the prognosis and outcome.