Correlation of pituitary histomorphometry with adrenocorticotrophic hormone response to domperidone administration in the diagnosis of equine pituitary pars intermedia dysfunction.
Authors: Miller M A, Pardo I D, Jackson L P, Moore G E, Sojka J E
Journal: Veterinary pathology
Summary
# Editorial Summary The diagnosis of equine pituitary pars intermedia dysfunction (PPID) has historically relied on assays targeting the hypothalamic-pituitary-adrenal axis, yet this intermediate lobe is uniquely controlled by dopaminergic inhibition rather than the mechanisms regulating the anterior pituitary; loss of this dopaminergic tone permits the pathological growth characteristic of PPID. Miller and colleagues tested whether domperidone, a dopamine antagonist administered orally at 3.3 mg/kg, could serve as a diagnostic tool by blocking the inhibitory signal and triggering excess adrenocorticotrophic hormone (ACTH) release in affected horses, then compared the endogenous ACTH response (measured at 8 hours post-administration) against the histological severity of pituitaries examined post-mortem. The findings revealed a striking correlation: normal glands (grade 1) showed median ACTH of 20.0 pg/ml, whilst adenomas (grade 5) produced 720.5 pg/ml, with intermediate grades showing proportional escalation (focal hyperplasia grade 2: 27.1 pg/ml; diffuse hyperplasia grade 3: 64.4 pg/ml; microadenomas grade 4: 128.0 pg/ml). This work establishes that horses with pituitary histological changes at grade 3 or above mount a measurable ACTH response to domperidone, suggesting the test may effectively identify the functional pathology underlying clinical PPID before advanced adenomatous change develops. For practitioners, the domperidone challenge offers a physiologically sound approach to early diagnosis that directly targets the dopaminergic dysfunction central to the disease mechanism, potentially enabling intervention before severe adenomatous transformation occurs.
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Practical Takeaways
- •The domperidone stimulation test (3.3 mg/kg orally, measure ACTH at 8 hours) can help identify PPID cases with significant pituitary pathology, with values >64 pg/ml suggesting grade 3 or higher disease
- •PPID clinical signs correlate with objective pituitary pathology; horses showing poor response to domperidone may have earlier-stage disease requiring alternative diagnostic approaches
- •Age is a co-factor in PPID severity—older horses (>20 years) with clinical signs warrant more aggressive diagnostic investigation
Key Findings
- •Domperidone-stimulated ACTH concentration at 8 hours correlates with pituitary histologic grade: grade 1 (20.0 pg/ml) to grade 5 (720.5 pg/ml)
- •Pars intermedia cross-sectional area increases progressively with histologic grade: from 0.16 cm² (normal) to 2.1 cm² (adenoma)
- •Horses with histologic grade ≥3 show measurable ACTH response to domperidone administration
- •Median age increases with pituitary grade severity: 7.5 years (normal) to 24.9 years (adenoma)