Original Research
Extrapituitary and Pituitary Pathological Findings in Horses with Pituitary Pars Intermedia Dysfunction: A Retrospective Study

https://doi.org/10.1016/j.jevs.2009.01.004Get rights and content

Abstract

The objective of this study was to describe the histopathologic changes observed in extrapituitary organs as well as the pituitary glands of horses with pituitary pars intermedia dysfunction (PPID). Adrenal gland, thyroid gland, liver, lung, kidney, heart, and pituitary gland from 32 horses with clinical and histologic evidence of PPID and 20 control horses were reviewed histologically. Ten of the control horses were aged animals (≥15 years), allowing those changes attributed to age to be identified. In addition to previously reported changes in adrenal gland and liver, an association was established between PPID and several extrapituitary histopathologic changes, namely bronchiolitis, proliferative glomerulopathy, and myocardial lipofuscinosis and fibrosis. The potential biologic significance of these changes is discussed and, although the retrospective design of the current study precludes establishment of causal relationships between the observed extrapituitary changes and PPID, these findings suggest that further investigations are warranted.

Introduction

Equine pituitary pars intermedia dysfunction (PPID), also known as equine Cushing's disease, is a spontaneously occurring, slowly progressive disorder of horses, ponies, and donkeys. Although it is a well-recognized clinical disease of aged horses and ponies, the cause and pathophysiology of this condition remain poorly understood. Clinically, horses with PPID have many signs including hirsutism, muscle wasting, laminitis, hyperhidrosis, polyuria and polydipsia, and general debilitation.1 Many complications have been reported in horses with PPID, including secondary infections, insulin resistance, infertility, delayed wound healing, blindness, and seizures.1, 2, 3, 4 At necropsy, affected horses have hyperplasia or adenoma of the pituitary pars intermedia, which results in compression of adjacent structures and overexpression and disproportionate amounts of circulating pro-opiomelanocortin (POMC)-derived peptides such as α-melanocyte stimulating hormone (α-MSH), β-endorphin, corticotrophin-like intermediate lobe peptides, and adrenocorticotrophic hormone (ACTH).5

Few reports characterize extrapituitary pathologic changes in horses with PPID.2, 3, 4 Because the pituitary gland secretes a battery of hormones that collectively influence virtually all cells and physiologic processes in the body, significant histopathologic changes in the extrapituitary organs would be expected in horses with PPID. The objective of this study was to describe the histopathologic changes observed in tissue sections from extrapituitary organs of horses and to determine whether such changes could be related to pituitary pars intermedia dysfunction.

Section snippets

Source of Histologic Sections

Histologic sections of pituitary gland, adrenal gland, thyroid gland, liver, lung, kidney, and heart were collected from the Veterinary Teaching Hospitals of the University of California at Davis (UCD), USA (28 horses) and the Atlantic Veterinary College (AVC), Prince Edward Island, Canada (24 horses) (Table 1). Other tissues of interest, such as hypothalamus and pancreas, were not available in a sufficient number of cases to include in the study. Hospital records were consulted to document

Animal Ages

There was no difference in age between the PPID (mean age ± SD = 20.88 ± 5 years, n = 32) and age-matched control groups (mean age ± SD = 21.8 ± 5.5 years, n = 10, P = .62); however, the young control group (mean age ± SD = 9.8 ± 2.3 years, n = 10) was significantly younger than both the age-matched control (P < .0001) and PPID (P < .0001) groups.

Pituitary

Twenty-one of 32 horses with PPID had a pars intermedia adenoma; the remaining 11 PPID horses had pars intermedia adenomatous hyperplasia. Pituitary

Discussion and Conclusion

This study examined histologic changes in the pituitary gland and six extrapituitary tissues (adrenal gland, thyroid gland, liver, lung, kidney, and heart) of horses with and without PPID. Similar to a previous report3 in which 68% (13/19) of PPID horses had an adenoma (>1 cm), in this study 66% (21/32) of the PPID horses had an adenoma, with the remaining 34% having adenomatous hyperplasia. This distribution may reflect a bias toward selecting end-stage cases for study rather than a true

Acknowledgments

The authors thank Darlene Jones at the Pathology and Microbiology Department, Atlantic Veterinary College for her technical assistance and Dr Melanie Breshears at Oklahoma State University for her help with the photomicrographs.

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    Dr Glover's current address is: ITR Laboratories Inc. (International Toxicology Research), 19601 Clark Graham Boulevard, Bai d'Urfe, QC Canada H9X3T1.

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