Current Diagnostic Options for PPID

Veterinarians can typically diagnose a horse with late-stage pituitary pars intermedia dysfunction (PPID, or equine Cushing's disease) easily. Diagnosing early stage PPID and, thus, allowing treatment to begin earlier in the course of the disease, remains more challenging. Fortunately, research is ongoing and more reliable diagnostic tests are being developed.

At the 2013 Western Veterinary Conference, held Feb. 17-21 in Las Vegas, Nev., Hal Schott II, DVM, PhD, Dipl. ACVIM, professor of equine medicine at Michigan State University's College of Veterinary Medicine, described the current diagnostic options for PPID.

PPID Basics

Schott first reviewed PPID, a disease caused by an enlargement of the pars intermedia of the pituitary gland (the central part of the pituitary gland located at the base of the brain) that affects all breeds and types of horses. Many affected horses are older than 20; however, the disease has been recognized in some younger horses, as well. There's no gender predilection.

Schott described some common clinical signs of horses with advanced PPID:

  • They have a characteristic long hair coat that fails to shed properly (a condition formerly known as hirsutism in these horses, but recently studied and renamed hypertrichosis, which means hair growth that is abnormal in quantity or location, Schott said);
  • Affected horses often have abnormal sweating patterns;
  • They experience polyuria and polydypsia (excessive urination and drinking, respectively); and
  • About 60% of affected horses experience muscle wasting with or without associated weight loss.

But, Schott said, there are some other less obvious clinical signs seen in affected horses that could possibly indicate early stage PPID, including:

  • Chronic infections;
  • Chronic laminitis (only about 50% of PPID horses develop laminitis, Schott said);
  • Poor wound healing;
  • "Silent" urinary tract infections;
  • Persistent mammary secretions;
  • Decreased fertility;
  • Abnormal fat depositions;
  • Insulin resistance; and
  • Type 2 diabetes mellitus.

He noted that suspensory apparatus breakdowns, "bizarre" neurologic signs, and blindness have also been associated with PPID onset; however, researchers still don't fully understand the connection between the signs and the disease.

The challenge with most clinical signs, Schott said, is that "it can be hard to separate the effects of PPID with the effects of aging."

Diagnosing PPID

"Practically, the diagnosis of PPID is most commonly made by the observation of hypertrichosis and other clinical signs in older equids," Schott said. "Establishing a diagnosis of PPID in less severely affected horses can be challenging."

Due to the need for better PPID testing protocol, Schott said the Equine Endocrine Society's (EES) PPID Diagnosis Working Group evaluated current diagnostic options, narrowed the options down to identify the most useful tests, and then developed a two-tier system of recommended evaluations. He explained that Tier 1 options are screening tests whereas Tier 2 options can be used to further evaluate horses with inconclusive Tier 1 test results.

Tier 1 Tests: The EES recommended two Tier 1 tests: a resting adrenocorticotropin (ACTH) plasma concentration test and an overnight dexamethasone suppression test.

When the pars intermedia becomes enlarged, it secretes excessive amounts of several hormones, including ACTH, which ends up in horses' blood plasma. "Measuring plasma ACTH concentration is a logical choice for a single simple screening test for initial evaluation of equids suspected to have PPID," Schott said.

He noted that the ACTH test has a few drawbacks; however, the test is still useful as long as certain factors are considered:

  • ACTH levels can change throughout the day. To combat this, Schott recommended taking two blood samples, 10 to 30 minutes apart, and submitting a mixed sample for testing.
  • Both healthy and PPID-affected horses experience a rise in ACTH levels in the autumn. However, PPID horses have an exaggerated ACTH level rise, and Schott recommended that fall might be the best time of year to test ACTH concentrations, especially in the earlier stages of the disease.
  • Assays and results vary between laboratories. Schott recommends using the same laboratory for ACTH testing to ensure consistent results.
  • Results are often normal for horses with early stage PPID.

The other Tier 1 test, the overnight dexamethasone suppression test (ODST), measures circulating cortisol (stress hormone) levels about 19 hours after administration of the steroid dexamethasone.

"Failure of dexamethasone to induce suppression of circulating … cortisol concentration is strongly supportive of PPID," Schott said.

The ODST was long considered the gold standard PPID test by many veterinarians, Schott said. However, more recent research indicates that the ODST is not superior to measuring ACTH to diagnose PPID or to detect earlier stages of the disease. Further, dexamethasone administration carries a slight risk of exacerbating laminitis in some PPID-affected horses, he noted.

Based upon the results of a Tier 1 test, Schott said, the attending veterinarian can begin treatment, conclude that the horse is not affected by PPID, or—if test results are inconclusive—employ another Tier 1 test or proceed to Tier 2 testing.

Tier 2 Test: Schott said The EES' Teir 2 test is a thyrotropin-releasing hormone (TRH) stimulation test. The TRH test stimulates the pars intermedia, resulting in a greater increase in plasma ACTH concentrations in PPID-affected horses when compared to normal horses. This test involves collecting two blood samples--before and 10 to 30 minutes after intravenous TRH administration--to measure ACTH concentrations.

Schott said that "the TRH stimulation test is currently being advocated as a more sensitive test for detection of PPID in the earlier stages of disease." However, additional research is needed, and the test should be employed in a larger number of horses, he added. Nonetheless, Schott said, the TRH stimulation test appears "promising" in confirming PPID in horses with "gray zone" test results from Tier 1 evaluations and those with earlier stage disease.

"A further reason that this test may be pursued, rather than an overnight dexamethasone suppression test, would be to alleviate owner concerns about possible exacerbation of laminitis following dexamethasone administration," Schott said.

Take-Home Message

Although PPID diagnosis remains a challenge for veterinarians, using the two-tier series of tests Schott described can help confirm a diagnosis. Still, owners must remain vigilant for changes in horses' behavior, appearance, and health status; alerting a veterinarian to clinical signs associated with PPID can help veterinarians make an earlier diagnosis and initiate treatment sooner.

Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.