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Correlation of Pituitary Histomorphometry with Adrenocorticotrophic Hormone Response to Domperidone Administration in the Diagnosis of Equine Pituitary Pars Intermedia Dysfunction

Animal Disease Diagnostic Laboratory (MAM, IDP1), Departments of Comparative Pathobiology (MAM, IDP, GEM) and Veterinary Clinical Sciences (LPJ, JES), Purdue University, West Lafayette, IN

Abstract

Functional evaluation of the pars intermedia (PI) is required for the early diagnosis of equine pituitary PI dysfunction (PPID), yet most assays target the hypothalamic-pituitary-adrenal axis, which regulates the pars anterior. In contrast, the PI is regulated by dopaminergic tone from hypothalamic neurons. Loss of dopaminergic inhibition is hypothesized to cause the PI hypertrophy and hyperplasia that result in the clinical manifestations of PPID. Domperidone, a dopamine receptor antagonist, should exacerbate the loss of dopaminergic inhibition in horses with PPID and increase the release of endogenous adrenocorticotrophic hormone (eACTH) by PI melanotrophs. To test this, plasma eACTH concentration was determined in horses with or without clinical signs of PPID at 0, 4, and 8 hours after oral administration of 3.3 mg domperidone/kg. Pituitary glands were evaluated postmortem by histologic grading and morphometry. In the 33 horses, median age, plasma ACTH concentration 8 hours after domperidone, and PI area in median sagittal sections were associated with histologic grade as follows: pituitary grade 1 (normal), n = 3, 7.5 years, 20.0 pg/ml, 0.16 cm²; grade 2 (focal hypertrophy or hyperplasia), n = 9, 14.5 years, 27.1 pg/ml, 0.27 cm²; grade 3 (diffuse adenomatous hyperplasia), n = 5, 21.0 years, 64.4 pg/ml, 0.48 cm²; grade 4 (microadenomas), n = 12, 23.3 years, 128.0 pg/ml, 0.87 cm²; grade 5 (adenoma), n = 4, 24.9 years, 720.5 pg/ml, 2.1 cm². Results suggest that horses with pituitary histologic grade 3 respond to domperidone with increased plasma ACTH concentration.

Key words: ACTH; adrenocorticotrophic hormone; domperidone; dopaminergic inhibition; equine; histomorphometry; horses; pituitary adenoma; pituitary hyperplasia; pituitary pars intermedia dysfunction.

Request reprints from Dr. Margaret A Miller, Animal Disease Diagnostic Laboratory, 406 S. University St., Purdue University, West Lafayette, IN 47907 (USA). E-mail: pegmiller{at}purdue.edu