Cushing’s Disease Explained

Pony Bramble at Burford equine centre

Cushing’s Disease, or Pituitary Pars Intermedia Dysfunction (PPID) is an endocrine disease that creates hormonal imbalances. PPID can occur in horses of all ages but is more likely to occur in those over 20 years old. This disease is closely related to Parkinson’s Disease and has several of the same symptoms, including lethargy and poor athletic performance.

Simply put, PPID is nerve degeneration in the hypothalamus. The Pituitary Gland is located directly below the hypothalamus and contains three different pieces, all of which release hormones (Figure 1). Dopaminergic neurons are sent from the Substantia Nigra Pars Compacta (SNc) to receptors in the Pars Intermedia, which slow the production of hormones. The Pars Intermedia releases a peptide called Pro-opiomelanocortin (POMC), which is converted to Adrenocorticotropic Hormones (ACTH). Almost all of the ACTH is split into derivatives and released into the bloodstream as α-Melanocyte Stimulating Hormone,β-Endorphin and CLIP. The remainder of the ACTH is also released into the blood.

ppid
Figure 1: Pituitary Gland

In a horse without PPID, the Dopamine prevents the Pars Intermedia from producing too many hormones. When a horse has PPID, the Dopaminergic neurons have become damaged and the cells have begun to die off. There is not enough Dopamine to slow hormone growth, and the Pars Intermedia starts producing more and more ACTH and releasing it and its derivatives into the bloodstream. As more hormones are produced, the Pars Intermedia expands and compresses the other pieces of the Pituitary Gland. Symptoms can arise due to both the lack of Dopamine and the surplus of hormones. Dopamine plays a role in controlling several behavior processes, such as mood and stress levels, and is needed for the horse to function properly. Just as with Parkinson’s Disease, the death of Dopaminergic neurons can lead to mood swings, and in the worst cases, restrict voluntary movement.

 

Cause

Although we don’t understand exactly what causes the Dopaminergic neurons to die, studies have shown that those found in the SNc are more likely to have mitochondrial dysfunction and synuclein. Dopaminergic neurons also use a lot of oxygen and are susceptible to stress when there is a lack of oxygen. There has also been a positive correlation between dead neurons and the presence of Lewy bodies nearby.

Symptoms

  • Lethargy and poor athletic performance
  • Muscle wasting, especially on the topline
  • Excessive Sweating
  • Wavy coat that doesn’t shed at normal times
  • Hyperglycemia
  • Chronic Laminitis

Diagnosis

There are two types of tests to diagnose PPID, both of which measure the ACTH level in the blood. The most common test is a simple blood draw. The blood needs to be handled very carefully because ACTH degrades quickly and can give false low results. ACTH levels in the blood can also be elevated by stress and pain and give a false high reading. Once the blood draw is complete it will be sent to a lab and tested for ACTH. Horses that have PPID are also likely to be insulin resistant and should be tested for that as well.

Treatment

prascendPergolide is the most common drug used to treat horses with PPID and can be found in the Prascend medication, sold by Boehringer Ingelheim. Pergolide acts as dopamine would and tricks the receptors on the Pars Intermedia into slowing the production of ACTH and its derivatives. Although it may take a few months, ACTH levels in the blood will decrease by at least half on the correct dose of Prascend. The hope is that the ACTH levels will return to normal at some point, but even if they do, the horse will likely have to continue taking the medication for the rest of his life. The dose may have to be increased to make sure the ACTH levels stay in the right range. My horse needs 1 ½ pills per day to prevent the excessive hormonal growth.

In addition to Prascend, many horses need NSAIDs for pain management, especially if they have laminitis. Check with your vet to decide which pain medications will be best for your horse.

 

Managed properly, PPID does not have to be a career or life-ending disease. If you find the disease early, Prascend can do wonders for your horse and will help to keep symptoms at bay. My horse has had several complications from PPID, including chronic laminitis, but he is doing very well on Prascend and is slowly healing. Remember, this medication takes time to work, so don’t be disappointed when symptoms aren’t resolved immediately.

Keep riding and keep working to ensure your horse’s well-being. Cheers!

 

Sources:
https://www.prascend.com/prescribe.html
http://www.thelaminitissite.org/articles/pituitary-pars-intermedia-dysfunction
https://www.ncbi.nlm.nih.gov/pubmed/20696315
https://www.sciencedirect.com/science/article/pii/S1357272504003711?viewFullText=true
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