Correlation of pituitary histomorphometry with adrenocorticotrophic hormone response to domperidone administration in the diagnosis of equine pituitary pars intermedia dysfunction.
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 cm(2); grade 2 (focal hypertrophy or hyperplasia), n = 9, 14.5 years, 27.1 pg/ml, 0.27 cm(2); grade 3 (diffuse adenomatous hyperplasia), n = 5, 21.0 years, 64.4 pg/ml, 0.48 cm(2); grade 4 (microadenomas), n = 12, 23.3 years, 128.0 pg/ml, 0.87 cm(2); grade 5 (adenoma), n = 4, 24.9 years, 720.5 pg/ml, 2.1 cm(2). Results suggest that horses with pituitary histologic grade > or =3 respond to domperidone with increased plasma ACTH concentration.
Publication Date: 2008-01-15 PubMed ID: 18192571DOI: 10.1354/vp.45-1-26Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article explores the relationship between the physical structures within the pituitary gland and the hormone response to a medication called domperidone in diagnosing a pituitary disorder in horses. The study determines if the levels of a hormone called ACTH increase in response to domperidone, suggesting a higher grade of pituitary disorder.
Understanding Equine Pituitary Pars Intermedia Dysfunction
- Central to this research is Equine Pituitary Pars Intermedia Dysfunction (PPID), a progressive disorder in horses’ pituitary glands, more common in older horses
- This condition is characterized by the overdevelopment (hypertrophy and hyperplasia) of pituitary cells.
- One leading theory proposed involves the loss of dopamine regulation in the affected parts of the pituitary gland.
The Role of Domperidone
- The researchers explored the use of domperidone, a dopamine receptor antagonist, to test its effect on horses with PPID. In simple words, it blocks the inhibitory effects of dopamine.
- The expectation was that domperidone would increase the endogenous adrenocorticotropic hormone (eACTH) released from the cells in the affected region of the pituitary – the pars intermedia (PI).
Research Test and Results
- The PI was assessed in both normal horses and those showing PPID symptoms. These assessments were done at 0, 4, and 8 hours after oral administration of domperidone.
- The pituitary was also evaluated postmortem by grading and measuring its tissues to observe any changes in morphology.
- The correlation was made between the age of the horses, ACTH concentration 8 hours after administering domperidone, and PI area per grade designation.
- The research observed a trend where horses with a histologic grade higher than 3 demonstrated an increased ACTH concentration in response to domperidone administration.
Implications of the Study
- This study could provide a diagnostic criterion based on hormone response to medication for PPID.
- The study also reinforced the theory that PPID manifests due to loss of dopaminergic inhibition.
Cite This Article
APA
Miller MA, Pardo ID, Jackson LP, Moore GE, Sojka JE.
(2008).
Correlation of pituitary histomorphometry with adrenocorticotrophic hormone response to domperidone administration in the diagnosis of equine pituitary pars intermedia dysfunction.
Vet Pathol, 45(1), 26-38.
https://doi.org/10.1354/vp.45-1-26 Publication
Researcher Affiliations
- Animal Disease Diagnostic Laboratory, Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA. pegmiller@purdue.edu
MeSH Terms
- Adrenocorticotropic Hormone / metabolism
- Animals
- Domperidone
- Dopamine Antagonists
- Female
- Horse Diseases / diagnosis
- Horse Diseases / metabolism
- Horses
- Male
- Organ Size
- Pituitary Diseases / diagnosis
- Pituitary Diseases / metabolism
- Pituitary Diseases / veterinary
- Pituitary Gland, Intermediate / metabolism
- Pituitary Gland, Intermediate / pathology
Citations
This article has been cited 13 times.- Zapf AM, Fey K, Büttner K, Gröf M, Staszyk C. Periodontal structures in horses with pituitary pars intermedia dysfunction: A histological evaluation.. Front Vet Sci 2023;10:1114445.
- Kirkwood NC, Hughes KJ, Stewart AJ. Prospective Case Series of Clinical Signs and Adrenocorticotrophin (ACTH) Concentrations in Seven Horses Transitioning to Pituitary Pars Intermedia Dysfunction (PPID).. Vet Sci 2022 Oct 17;9(10).
- Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses.. Vet Sci 2022 Oct 10;9(10).
- Hinrichsen SL, Yuen KY, Dryburgh EL, Bertin FR, Stewart AJ. Short-Term Effects of Temperature and Thyrotropin-Releasing Hormone Stimulation on Adrenocorticotropin Stability in Horses.. Animals (Basel) 2022 Jan 28;12(3).
- Nitzsche AM, Fey K, Büttner K, Gröf M, Staszyk C. The Gingiva of Horses With Pituitary Pars Intermedia Dysfunction: A Macroscopic Anatomical Evaluation.. Front Vet Sci 2021;8:786971.
- Fortin JS, Hetak AA, Duggan KE, Burglass CM, Penticoff HB, Schott HC 2nd. Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy.. Sci Rep 2021 Aug 6;11(1):16036.
- Tatum RC, McGowan CM, Dean RS, Ireland JL. Equine pituitary pars intermedia dysfunction: Identifying research priorities for diagnosis, treatment and prognosis through a priority setting partnership.. PLoS One 2021;16(1):e0244784.
- Horn R, Stewart AJ, Jackson KV, Dryburgh EL, Medina-Torres CE, Bertin FR. Clinical implications of using adrenocorticotropic hormone diagnostic cutoffs or reference intervals to diagnose pituitary pars intermedia dysfunction in mature horses.. J Vet Intern Med 2021 Jan;35(1):560-570.
- Fortin JS, Benskey MJ, Lookingland KJ, Patterson JS, Howey EB, Goudreau JL, Schott HC 2nd. Restoring pars intermedia dopamine concentrations and tyrosine hydroxylase expression levels with pergolide: evidence from horses with pituitary pars intermedia dysfunction.. BMC Vet Res 2020 Sep 25;16(1):356.
- Reynolds A, Keen JA, Fordham T, Morgan RA. Adipose tissue dysfunction in obese horses with equine metabolic syndrome.. Equine Vet J 2019 Nov;51(6):760-766.
- Morgan RA, Keen JA, Homer N, Nixon M, McKinnon-Garvin AM, Moses-Williams JA, Davis SR, Hadoke PWF, Walker BR. Dysregulation of Cortisol Metabolism in Equine Pituitary Pars Intermedia Dysfunction.. Endocrinology 2018 Nov 1;159(11):3791-3800.
- Hart KA, Wochele DM, Norton NA, McFarlane D, Wooldridge AA, Frank N. Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses.. J Vet Intern Med 2016 Mar-Apr;30(2):653-63.
- Rendle DI, Duz M, Beech J, Parkin T, Durham AE. Investigation of single and paired measurements of adrenocorticotropic hormone for the diagnosis of pituitary pars intermedia dysfunction in horses.. J Vet Intern Med 2015 Jan;29(1):355-61.
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