Dopamine Antagonist Stimulation Test in Horses (Effect of Dose and Testing Interval on Plasma Endogenous ACTH)
ACVIM 2008
L.P. Jackson; J.E. Sojka; G.E. Moore; B.D. Denton; M.A. Miller
Purdue University
West Lafayette, IN, USA

Equine pituitary pars intermedia dysfunction (PPID) is a chronic progressive disease that occurs secondary to lack of dopaminergic inhibition on pituitary melanotrophs. It was our hypothesis that administration of a dopamine antagonist, domperidone, would result in an exaggerated increase in endogenous adrenocorticotropic hormone (ACTH). A pilot study demonstrated that ACTH levels are significantly elevated after domperidone administration in PPID horses, but the appropriate test dosage and interval have not been determined.

The response of ACTH to different doses of domperidone was evaluated in 8 horses (5 PPID and 3 control). While horses were initially classified by clinical signs, definitive classification was made by pituitary histopathology. Blood was collected immediately prior to an 8 AM dose of domperidone and every 2 hours for 8 hours following one of 4 doses (control, 0.5 mg/kg, 1.25 mg/kg and 5 mg/kg PO). Blood was collected in silicon coated EDTA tubes. Endogenous ACTH concentration (pg/ml) was determined using a chemiluminescent immunoassay. Receiver operating characteristic (ROC) curves were generated to quantify test accuracy, and area-under-the-curve (AUC) was calculated for the different domperidone doses and time points.

There was an increase ACTH in the PPID horses 2 and 4 hours post domperidone administration. The median(range) baseline ACTH in PPID horses was 53.8 pg/ml (15, 528) and 25.6 pg/ml (15.5, 30.9) in control horses. Following an oral 1.25 mg/kg dose of domperidone the median(range) ACTH was 145 pg/ml (29.7, 303) in horses with PPID versus 23.4 pg/ml (12.7, 105) in control horses at 2 hours; and 150.5 pg/ml (48.1, 365) in horses with PPID versus 33 pg/ml (26, 38.8) in control horses at 4 hours. After an oral 5 mg/kg dose of domperidone the median (range) ACTH was 144.5 pg/ml (80.9, 662) in horses with PPID versus 28.9 pg/ml (12.1, 63.4) in control horses at 2 hours and 170.5 pg/ml (43.6, 808) in horses with PPID and 29 pg/ml (13.5, 57.9) in control horses at 4 hours.

Table 1. Area under the ROC curve (95% CI) at 2 and 4 hrs

Time

Dose

AUC (95% CI)

2 hr

1.25 mg/kg

0.899 (0.631-1.000)

5 mg/kg

1.000 (1.000-1.000)

4 hr

1.25 mg/kg

1.000 (1.000-1.000)

5 mg/kg

0.944 (0.790-1.000)

In conclusion the changes in ACTH in response to the medium (1.25 mg/kg) and high dose (5mg/kg) domperidone were able to differentiate PPID horses from control horses at both 2 and 4 hours post domperidone administration.

Speaker Information
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Paige Jackson


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