It isn’t difficult to presumptively diagnose a geriatric horse with hypertrichosis, delayed shedding and a pot belly or very lean body condition as one that is affected by pituitary pars intermedia dysfunction (PPID or Cushing’s). Yet by that point, the horse has reached an end-stage progression of the syndrome. It would be ideal if a horse in the beginning stages of PPID could be recognized as early as possible and started on pergolide treatment to mitigate lasting adverse effects from endocrinological dysfunction. Abnormalities associated with PPID range from thermoregulatory disturbances, immune dysfunction, delayed healing, severe weight loss, epaxial muscle atrophy and laminitis.
Lab Testing Procedures for Early Diagnosis of PPID in Horses
An Australian study reviewed lab testing procedures that might help with early diagnosis of PPID in horses [Kirkwood, NC.; Hughes, KJ.; Stewart, AJ. Prospective Case Series of Clinical Signs and Adrenocorticotropin (ACTH) Concentrations in Seven Horses Transitioning to Pituitary Pars Intermedia Dysfunction (PPID). Veterinary Sciences 2022, 9, 572 https://doi.org/10.3390/vetsci9100572].
Testing for Basal and TRH-Stimulated ACTH Concentrations
In the study, 113 light-breed horses were tested every month for a year for basal and TRH-stimulated ACTH concentrations. The horses were divided into three groups: PPID (n = 34); normal (n = 72); and equivocal (n = 9). Measurements of both ACTH testing concentrations were performed from October 2017 to November 2021. (Even though seasons are reversed in Australia, the same seasonal patterns occur, and all months were accounted for.)
Grading for Degree of Hypertrichosis
A subjective grading system for degree of hypertrichosis was formed with a scale of 0 – 5. Early stages of PPID were associated primarily with subtle signs of delayed shedding. Four of six horses identified with subclinical PPID experienced delayed shedding for two years before developing hypertrichosis. An important point is that even those horses with mild hypertrichosis don’t have basal or TRH-stimulated ACTH concentrations that exceed the diagnostic cut-off value.
Other Subclinical Signs
Other subclinical signs might be a tip-off to PPID: recurrent infections, delayed healing, thermoregulatory disruption, heat stress and exercise intolerance. White blood cell counts often show abnormalities such as lower lymphocyte counts and impaired neutrophil function. Ocular tears of PPID horses tend to have increased cortisol concentrations. Corneal sensitivity might also be less than normal.
Horses with pathognomonic hypertrichosis had basal ACTH concentrations higher than the diagnostic cut-off value in nearly 96%. TRH-stimulation tests in these horses exceeded the diagnostic cut-off value in 89%.
Value of TRH-Stimulation Testing
It has previously been recommended not to use the TRH-stimulation test in autumn. The authors suggest that despite greater variations in TRH-stimulated ACTH concentrations in autumn, this test still yields diagnostic accuracy when using appropriate reference values for those months. In fact, the authors report, “TRH-stimulation tests identify most transitional cases in late summer and autumn.” In contrast, basal ACTH concentration is less accurate in autumn due to normal elevations during that season. Horses with severe end-stage disease don’t need testing with the TRH-stimulation test.
With equivocal lab results, it is important to repeat testing every 3-6 months based on clinical signs in order to identify horses in transition as soon as possible. Because there have been false positive results for basal ACTH, basal ACTH concentration testing in clinically normal horses might not be appropriate.
While measurement of basal alpha-MSH is a more sensitive predictor of early PPID than basal ACTH, this test is not commercially available at this time.
Conclusions About Early Stages of PPID in Horses
The authors conclude that in the early stages of PPID:
- Clinical signs can be subtle or absent.
- Basal ACTH concentrations are variable between months and often equivocal in the early stages of PPID.
- Increases in ACTH concentrations, especially in fall months, can be markedly increased prior to clinical signs of hypertrichosis.
- TRH-stimulation testing in late summer or fall is more sensitive in identifying most transitional cases.
In summary, the authors advise that laboratory testing with basal ACTH or TRH-stimulation test is recommended when subclinical or clinical disease is suspected, in cases where horse owners are able to afford treatment, and as a screening test for horses over 15 years of age, since 20-25% of horses in this age category develop PPID. The authors state, “Even in the absence of clinical signs, subclinical disease can be identified, and horses will subsequently transition to clinical PPID within 1 – 3 years.”