Equine Pituitary Pars Intermedia Dysfunction (PPID)

Equine Cushing’s Disease (ECD) or Equine Cushing’s Syndrome (ECS)

PPID is commonly known as equine cushing’s disease/syndrome (ECD/ECS) and is caused by hyperplasia of the pituitary pars intermedia. This produces excess secretions of a variety of closely related peptides derived from pro-opiomelanocortin including alpha-MSH, B- endorphin and CLIP, and smaller amounts of ACTH, which results in increased adrenocortical production of cortisol. It is a disease of the older horse, usually >15 years. The most obvious clinical sign is the characteristic long curly coat (hirsutism) and abnormal shedding patterns. Other common clinical signs include weight loss, weight distribution (pot belly, loss of epaxial musculature, increased supraorbital fat) lethargy, laminitis, polyuria, polydipsia and hyperhidrosis. Single basal cortisol levels are often within or below the normal range unless the animal is acutely stressed due to pain possibly caused by an attack of laminitis. Insulin levels are frequently raised but insulin alone should not be used to diagnose ECS. Endogenous ACTH is considered to be a very sensitive test and can be done alone or in conjunction with either the regular overnight Dexamethasone test or the combined TRH/overnight Dexamethasone test.

Overnight Dexamethasone Suppression Test

  1. Take a basal blood sample at about 17.00 hours (5 pm).
  2. Inject 0.04 mg/kg Dexamethasone i/m.
  3. Take a further blood sample 20 hours later.
  4. Label samples clearly and request cortisol.


Normal horses should suppress cortisol levels to below 30 nmol/L and ideally <20 nmol/L. Horses with high baseline values (>150 nmol/L) usually have less suppression and values below 40nmol/L would be considered normal.
Important Note: Normal horses may give false positive results if the test is done in the autumn months (August, September, October).

Combined Dexamethasone/TRH Stimulation Test

Recent studies have shown this test to be a more sensitive dynamic test for the diagnosis of PPID in equidae.

  1. Take basal blood sample.
  2. Inject 0.04 mg/kg Dexamethasone i/v.
  3. Take another blood sample 3 hours later.
  4. Immediately inject 1.1 mg TRH (Cambridge Laboratories) i/v. slowly over one minute.
  5. Take two further blood samples 40 minutes and 19 – 21 hours later, (22 – 24 hours after Dexamethasone).
  6. Label samples clearly and request cortisol.


Normal and ECS animals show depression from basal levels at 3 hours (usually > 50%).
40 minutes after TRH, normal horses depress further but ECS horses show a significant rise in cortisol (> 50% from 3 hour sample).
At 22 – 24 hours normal horses suppress below 30 nmol/L and ECS horses remain elevated, usually above the value of the 3-hour sample.

Insulin – The analysis of Insulin on a basal serum sample is very useful as this detects the presence of peripheral insulin resistance. Insulin levels are often very high (>250 μU/mL) in ECS. Insulin levels in equine metabolic syndrome (EMS) are raised but there can be considerable variation over a 24-hour period.
Normal horses and ponies have insulin levels less than 65 μU/mL.

ACTH – In horses and ponies a single sample analysed for ACTH has been shown to be a very sensitive (100%) test for equine ECS. However, this level of diagnostic accuracy requires strict sample handling procedures are followed (see canine section page 20). Normal ACTH levels vary according to the time of year and are significantly increased in the autumn (August, September, October) so this must be taken into account when interpreting results for the diagnosis of ECS. However very high levels (>300pg/mL) are still highly suggestive of ECS and a normal level in the autumn (<100 pg/mL) is more likely to be truly negative. Horses with EMS may have elevated ACTH due to the stress of their laminitic condition but levels will still not be as high as expected with ECS. Samples for equine ACTH estimation can be submitted without the use of a freezer pack, simply collect the sample into an EDTA tube (plastic if possible), mix very well and centrifuge to separate off the plasma and send to the lab within 24 hours of collection.

Following extensive sample comparisons using our very specialised eACTH RIA assay we are now able to accept samples as WHOLE BLOOD EDTA submitted through the post and received at the lab within 24 hours of collection.

Cortisol/Creatinine Ratio (CCR) – This can be useful as a screening test to exclude ECS but must not be used to diagnose ECS as it is not very specific and other factors such as exercise may give a positive result. A morning urine sample is collected for analysis.
Normal horses have a CCR less than 20 x 10-6.